Brief History of Important Immunologic Discoveries and Developments

Year Event Author(s)

1798 Cowpox vaccination Edward Jenner 1866 Wound disinfection Joseph Lister 1876 Discovery of B. antracis, foundation of Robert Koch bacteriology 1880 Discovery of attenuated vaccine by Louis Pasteur invitro passages 1883 Phagocytosis, cellular immunity theory Elie I. I. Metchnikoff 1888 Discovery of bacterial toxins P. P. Emile Roux and Alexandre E. J. Yersin 1890 Discovery of antitoxins, foundation of Emil A. von Behring and serotherapy Shibasaburo Kitasato 1894 Immunologic bacteriolysis Richard F. J. Pfeiffer and Vasily I. Isaeff 1894 Discovery of and complement Jules J. B. V. Bordet activity as the active factors in bacteriolysis 1896 Discovery of specific Herbert E. Durham and Max von Gruber 1896 Agglutination test for the diagnosis of Georges F. I. Widal and typhoid (Widal test) Arthur Sicard 1900 Formulation of side-chain theory of anti- Paul Ehrlich body formation 1900 Discovery of A, B, 0 blood groups Karl Landsteiner 1900 Development of complement fixation Jules J. B. V. Bordet and reaction Octave Gengou 1902 Discovery of anaphylaxis Charles R. Richet and Paul Portier 1903 Local anaphylaxis due to antibody- Nicholas M. Arthus antigen complex: Arthus reaction 1903 Discovery of opsonization Almroth E. Wright and Steward R.Douglas 412 Brief History of Important Immunologic Discoveries and Developments

Year Event Author(s)

1905 Description of serum sickness Clemens von Pirquet and Bela Schick 1910 Introduction of salvarsan, later neo- Paul Ehrlich and Sahachiro Hata salvarsan, foundation of chemotherapy of infections 1910 Development of anaphylaxis test William Schultz (Schultz-Dale) 1914 Formulation of genetic theory of tumor Clarence C. Little transplantation 1921 Experimental trial with BCG vaccine Albert L. C. Calmette and Camille Guerin 1921 Development of cutaneous anaphylactic Carl W. Prausnitz and Heinz reaction Kiistner 1923 Production of anatoxin (toxoid) by Ramon Gaston formaldehyde treatment 1928 Discovery of penicillin, the first anti• Alexander Fleming biotic 1935 Discovery of sulfonamides for chemo• Gerhard Domagk therapy of infections 1935 Discovery of local immunity; oral Alexandre Besredka vaccination 1935-36 Purification of , quantitative Michael Heidelberger and precipitation reaction Forrest E. Kendall 1937 Evidence for identity of the gene for Peter A. Gorer blood group antigen II with one gene for tumor resistance in the mouse (H-2) 1938 Evidence that antibodies are y-globulins Arne Tiselius and Elvin A. Kabat 1942 Discovery of cellular transfer of delayed Karl Landsteiner and Merrill type hypersensitivity in guinea pigs W.Chase 1942 Fluorescence labeling of antibodies and Albert H. Coons antigens 1942 Introduction of adjuvants Jules T. Freund 1943-44 Establishment of immunologic basis of Peter B. Medawar rejection of normal tissue transplants 1944 Theory of acquired immunologic Peter B. Medawar and Frank tolerance M.Burnet 1946-48 Theory of congenic mouse lines formu• George D. Snell lated, first congenic lines initiated, and the term histocompatibility introduced Brief History of Important Immunologic Discoveries and Developments 413

Year Event Author(s)

1945 Development of antiglobulin test for Robin R. A. Coombs, R. R. Race, incomplete Rh antibodies and A. E. Mourant 1945 Description of tolerance (chimerism) in R.D.Owen dizygotic cattle twins 1946 Development of precipitin test in gels Jaques Oudin 1947 Immunoglobulins as "transporteurs" Pierre Grabar 1948 Development of double Orjan Ouchterlony and Stephen test in gels D. Elek 1948 Discovery of plasma cells as antibody Astrid E. Fagraeus producing cells 1949 Elucidation of the structure of A, B, 0 Elvin A. Kabat, W. T. J. Morgan, blood group antigens and W. M. Watkins 1952 Description of agammaglobulinemia in Ogdon Carr Bruton human 1952 Discovery of histamine in mast cells James F. Riley and Geoffrey B. West 1953 Development of Pierre Grabar 1953 Experimental evidence of acquired Milan Hasek immunologic tolerance 1956 Major histocompatibility (H-2) complex George D. Snell in the mouse defined 1956 Discovery of human leukocyte antigen, Jean Dal.J.sset later be shown to belong to the major histocompatibility complex of man (HLA) 1956 Experimental induction of autoimmunity Ernest Witebsky and Noel R. Rose 1956 Discovery of allotypes Rune Grubb and Jaques Oudin 1957 Discovery of interferon Jean Lindemann and Alick Isaacs 1957 Discovery of macroglobulins with anti• H. Hugh Fudenberg and Henry body activity G.Kunkel 1957 Discovery of Australia antigen, later Baruch Blumberg shown to be Hepatitis B antigen 1957 Discovery of human slow virus infection Carleton Gajdusek (Kuru) 1959 Introduction of the radioimmune assay Rosalyn Yalow and Solomon A. Berson 1960 Antibody structure Alfred Nisonoff, Gerald Edel• man, Rodney P. Porter, Henry G. Kunkel 414 Brief History of Important Immunologic Discoveries and Developments

Year Event Author(s)

1961 Discovery of the as part of the Jaques F. A. P. Miller, Robert A.Good 1963 Development of the plaque formation Nils K. Jerne, Richard J. Henry, test Albert A. Nordin 1963 Ss Locus in the H-2 complex discovered Donald C. Shreffler coding for the C4-complement component 1964 Development of rosette-test G. Biozzi 1965 Discovery of the variable region of anti- Norbert Hilschmann body molecules 1965 Linkage of MLR reactivity to the HLA Fritz Bach, Kurt Hirschhorn complex discovered 1965 Immune response-l (Ir-l) locus in the Hugh O. McDevitt and Michael mouse discovered Sela 1966 Enzyme labeling of antibodies and S.Avremeas antigens 1966 Discovery of IgE as reaginic antibody Kimishige Ishizaka 1969 Thymus function defined, dichotomy of Jaques F. A. P. Miller and the immune system discovered Graham Mitchell 1969 H-2 antigen isolated Stanley G. Nathenson and Akira Shimada 1969 T helper function in antibody formation N. Avrion Mitchison described (T -B Collaboration) 1969 B lymphocytes as cells with surface- Benvenuto Pernis bound Ig discovered 1969 Discovery of idiotypes Jaques Oudin 1971-72 Cytotoxic T cells described Jean-Charles Cerrotini, K. Theodor Brunner, Peter Perl- mann, Hermann Wagner 1971 Discovery of MLR locus linked to HLA Edmond J. Yunis and Bernhard mman Amos 1971 Two-locus model of the mouse MBC George D. Snell, Jan Klein, (B-2) formulated Donald C. Shreffler, Jack Stimpfling 1971 T and B cell tolerance dermed Jaques Chiller 1972 T suppressor cells described Richard K. Gershon 1972 Discovery of MHC-restriction of Berenice Kindred and Donald dependent immune responses C. Shreffler 1973 Discovery of Ia antigens Chella S. David, Donald C. Shreffler, Jan Klein, Dietrich Gotze, David H. Sachs Brief History of Important Immunologic Discoveries and Developments 415

Year Event Author(s)

1973 T-B cell collaboration I region restricted David H. Katz and Baruch Benacerraf 1974 Idiotypic network theory formulated Nils K. Jerne 1974 K,D-restriction of cytotoxic T cells Peter Doherty and Rolf Zinker• discovered nagel 1975 Fusion of myeloma cells with normal, George Kohler and Cesar specific antibody-producing plasma Milstein cells (hybridoma) 1978 Structure of MHC (H-2 and HLA) Stanley G. Nathenson, Jack antigens defined Strominger 1978 Macrophage-T cell collaboration Jonathan Sprent I-region restricted 1978-80 Elucidation of immunoglobulin genes; Suzuma Tonegawa generation of diversity is (almost) solved 1980 Smallpox worldwide eradicated World Health Organization (WHO) Glossary of Immunologic Terms

Accessory cells. Lymphoid cells predominantly of cells by cytotropic antibodies following ex• the monocyte and macrophage lineage which posure to antigen cooperate with T and B lymphocytes in im• Anergy. The inability to react to an antigen (mi• mune reactions croorganism) Acquired immunity. Immunity that develops as a Antibody. A protein that is produced as a result result of exposure to a foreigne substrate of the introduction of an antigen and which Activated lymphocytes. Lymphocytes that have has the ability to combine with the antigen that been stimulated by specific antigen or nonspe• stimulated its production cific mitogen Antibody combining site. That configuration pre• Adoptive transfer. Transfer of immunity by im• sent on an antibody molecule which links with munocompetent cells from one animal to an• a corresponding antigenic determinant other Antibody-dependent cell-mediated cytotoxicity Affiuity. Binding strength between antibody and (ADCC). A form of lymphocyte-mediated cy• antigen in an antibody-antigen reaction totoxicity in which an effector cell kills an anti• Agglutination. An antibody-antigen reaction in body-coated target cell which a solid or particulate antigen forms a Anticomplementarity. Unspecific complement ac• lattice with a soluble antibody tivation, i.e., not due to antibody-antigen reac• Allelic exclusion. The phenotypic expression of a tion single allele in cells containing 2 different al• Antigen. A substance which can induce a detect• leles for that genetic locus able immune response when introduced into Allergens. Antigens which give rise to allergic sen• an animal sitization by IgE antibodies Antigenic determinant (epitope). That area of an Allergy. An overshouting hypersensitivity reac• antigen which determines the specificity of the tion antigen-antibody reaction Allogeneic. Denotes the relationship which exists Antigenicity. Property of a substance to react between genetically dissimilar members of the with an antibody, but not necessarily to induce same species its formation Allograft. A tissue or organ between two Antigen processing. The series of events which oc• genetically dissimilar members of the same curs following antigen administration until species antibody production Allotype. The genetically determined antigenic Antiglobulin test (Coombs' test). A technic to de• difference on molecules, varying in different tect cell-bound immunoglobulin. In the direct members of the same species Coombs' test, red blood cells taken directly Anamnesis (immunologic memory). A heightened from a sensitized individual are agglutinated responsiveness to the second or subsequent ad• by antigammaglobulin antibodies. In the in• ministration of antigen to an immune animal direct Coombs' test, a patient's serum is incu• Anaphylatoxin. A substance produced by com• bated with test red blood cells and the sensi• plement activation which causes an increased tized cells are then agglutinated with an anti• vascular permeability through the release of immunoglobulin or with Coombs reagent pharmacologically active mediators from mast Antitoxins. Protective antibodies which inacti• cells vate soluble toxic proteins of bacteria Anaphylaxis. A reaction of immediate hypersen• Atopy. A genetically determined abnormal state sitivity present in nearly all vertebrates which of hypersensitivity as distinguished from hy• results from sensitization of tissue-fixed mast persensitivity responses in normal individuals 418 Glossary of Immunologic Terms Attenuated. Rendered less virulent Bursal equivalent. Hypothetical organ or organs Autoantibody. Antibody to self antigen analogous to the bursa of Fabricius in Autoantigens. Self antigens nonavian species Autograft. A tissue graft between genetically identical members of the same species Avidity. Refers broadly to the ability of antibod• C. The abbreviation for serum complement ies to bind to antigens. (Affinity is a more pre• Capping. The movement of cell surface antigens cisely used term referring to activity per anti• toward one pole of a cell after the antigens are body-combining site) cross-linked by specific antibody Cardiolipin. A substance derived from beef heart, probably a component of mitochondrial mem• Basement membrane. A sheet of material up to branes, which serves as an antigenic substrate 0.2 ~ thick lying immediately below epithelial for reagin or antitreponemal antibody (and endothelial) cells and supporting them. Carrier. An immunogenic substance which, when Contains glycoproteins and collagen and to coupled to a hapten, renders the hapten im• some extent acts as a diffusion barrier for munogenic microorganisms. Thickness and structure Cell-mediated immunity. Immunity in which the varies in different parts of the body participation of lymphocytes and macro• B cell (B lymphocyte). Strictly a bursa-derived cell phages is predominant in avian species and, by analogy, bursa-equiv• Cell-mediated lymphocytolysis. An in vitro assay alent derived cells in nonavian species. B cells for cellular immunity in which a standard mix• are the precursors of plasma cells that produce ed lymphocyte reaction is followed by destruc• antibody tion of target cells which are used to sensitize BCG (bacillus Calmette-Guerin). A viable attenu• allogeneic cells during the MLC ated strain of Mycobacterium bovis which has CHso unit. The quantity or dilution of serum been obtained by progressive reduction of vir• required to lyse 50% of the red blood cells in ulence and which confers immunitiy to myco• a standard hemolytic complement assay bacterial infection and possibly possesses anti• Chemotaxis. A process whereby phagocytic cells cancer activity in selected diseases are attracted to the vicinity of invading patho• Bence-Jones proteins. Monoclonal light chains gens present in the urine of patients with parapro• aassical complement pathway. A series of en• teinemic disorders zyme-substrate and protein-protein inter• Blast cell. A large lymphocyte or other immature actions which ultimately leads to biologically cell containing a nucleus with loosely packed active complement enzymes. It proceeds se• chromatin, a large nucleolus, and a large quentially C 1,423, 567, 89 amount of cytoplasm with numerous polyribo• aonal selection theory. The theory of antibody somes synthesis proposed by Burnet which predicts Blocking factors (antibody). Substances that are that the individual carries a complement of present in the serum of tumor-bearing animals clones of lymphoid cells which are capable of and are capable of blocking the ability of im• reacting with all possible antigenic deter• mune lymphocytes to kill tumor cells minants. The antigens which actually come in Blood groups. Antigens present at the surface of contact with the organism select "their" red blood cells which may vary between indi• clones; these clones differentiate and expand viduals of the same species. The most impor• aone. A group of cells all of which are the prog• tant blood groups in man are the ABO and the eny of a single cell Rh blood groups Cold agglutinins. Antibodies which agglutinate . Soft connective tissue located in bacteria or erythrocytes more efficiently at the cavities of the bones temperatures below 37°C than at 37 °C Bone marrow-derived cell. A lymphoid cell pre• Committed cell. Antigen-specifically sensitized sent in one of the lymphoid organs which orig• lymphocytes inated in the bone marrow and escaped the in• Complement. A system of serum proteins which is fluence of the thymus the primary humoral mediator of antigen-anti• Bursa of Fabricins. The hindgut organ located in body reactions the cloaca of birds which controls the onto• Complement fixation. A standard serologic assay geny of B lymphocytes used for the detection of an antigen-antibody Glossary of Immunologic Terms 419

reaction in which complement is fixed as a re• Domains. Segments of H or L chains that are sult of the formation of an immune complex. folded 3-dimensionallY and stabilized with di• The subsequent failure of lysis of sensitized red sulfide bonds blood cells by complement which has been fixed indicates the degree of antigen-antibody reaction EAC rosette. Formation of a cluster of red cells Concanavalin A (ConA). A lectin which is derived (erythrocytes) sensitized with antibody and from the jack bean and which stimulates pre• complement around human B lymphocytes dominantly T lymphocytes Eczema. A skin eruption common to atopic per• Congenic. (originally called congenic resistant) sons, with characteristic itching, inflammation Denotes a line of mice identical or nearly iden• and swelling tical with other inbred strains except for the Effector cells. Usually denotes T cells capable of substitution at one locus of a foreign allele in• mediating cytotoxicity, suppression, or helper troduced by appropriate crosses with a second function inbred strain Encapsulation. A quasi-immunologic phenome• Coombs' test. See antiglobulin test non in which foreign material is walled off C region (constant region). The carboxyl terminal within the tissues of invertebrates portion of the H or L chain which is identical Endocytosis. The process whereby material exter• in immunoglobulin molecules of a given class nal to a cell is internalized within a particular and subclass apart from genetic polymor• cell. It consists of pinocytosis and phagocyto• phisms sis Cross-reaction. The reaction of an antibody with Endotoxins. Lipopolysaccharides which are de• an antigen other than the one which induced rived from the cell walls of gram-negative its formation microorganisms and have toxic and pyrogenic Cytotoxic antibody. Antibody which reacts with effects when injected in vivo antigens present on a cell surface and which Enhancement. Improved survival of tumor cells produces damage to that cell or its surface in animals which have been previously immun• Cytotoxic T lymphocytes (CTL). Thymus-derived ized to the antigens of a given tumor lymphocytes with the ability to lyse comple• Epitope. The simplest form of an antigenic deter• ment-independently target cells against which minant present on a complex antigenic mole• they have been specifically sensitized cule Cytotropic antibodies. Antibodies of the IgG and Equivalence. A ratio of antigen-antibody concen• IgE classes which sensitize cells for subsequent tration where maximal precipitation occurs anaphylaxis E rosette. Formation of a cluster (rosette) of cells consisting of sheep erythrocytes surrounded by bound human T lymphocytes Defective virus replication. Incomplete virus repli• Erythroblastosis fetalis. The medical term for Rh cation, with production only of viral nucleic incompatibility disease of the newborn acid, proteins or non-infectious virus particles Euglobulin. Class of globulins which are insoluble Degranulation. A process whereby cytoplasmic in water, but soluble in salt solution granules of phagocytic cells fuse with ph ago• Exotoxins. Diffusible toxins produced by certain somes and discharge their contents into the gram-positive and gram-negative microor• phagolysosome thus formed ganisms Delayed hypersensitivity. A cell-mediated im• mune reaction which can be elicited by sub• cutaneous injection of antigen, with a sub• Fab. Antigen-binding fragment produced by en• sequent cellular infiltrate and edema which are zymatic digestion of an IgG molecule with pa• maximal between 24 and 28 h after antigen pain challenge F(ab'h. Fragment obtained by pepsin digestion Diapedesis. The outward passage of cells through of immunoglobulin molecules containing the intact vessel walls 2 Hand 2 L chains linked by disulfide bonds. Direct . The detection of anti• It contains antigen-binding activity. An gens by fluorescently labeled antibody F(ab')2 fragment and an Fc fragment comprise Diversity. Multitude of different antigen-specific an entire monomeric immunoglobulin mole•

combining sites (VH and V L regions) cule 420 Glossary of Immunologic Terms

Fc fragment. Crystallizable fragment obtained by destruction and ultimate rejection of the trans• papain digestion of IgG molecules. Fc frag• planted tissue ment consists of the C-terminal half of 2 H Graft-versus-host (GVH reaction). The clinical chains linked by disulfide bonds. Contains no and phatologic sequelae of the reactions of im• antigen-binding capability but determines im• munocompetent cells in a graft against the cells portant biologic characteristics of the intact of the histoincompatible and immunodeficient molecule recipient Fc receptor. A receptor present on various sub• Gram-negative. Losing the primary violet or blue classes of lymphocytes for the Fc fragment of during decolorization in Gram's staining immunoglo bulins method F 1 generation. The first generation of offspring Gram-positive. Retaining the primary violet or after a designated mating blue stain in Gram's method F 2 generation. The second generation of offspring Granuloma. A local accumulation of densely after a designated mating packed macrophages, often fusing to form gi• Fluorescence. The emission of light of one color ant cells and sometimes together with lympho• while a substance is irradiated with a light of a cytes and plasma cells. Seen in chronic infec• different color tions such as tuberculosis and syphilis Forssman-antigen, -antibody. So-called hetero• Granulopoietin (Colony-stimulating factor). A phil antigen that can be demonstrated on tis• glycoprotein with a molecular weight of 45,000 sue cells of different species, e.g., horse, sheep, derived from monocytes which controls the mouse a.o., but is absent from tissue of human production of granulocytes by the bone mar• and rabbit. Forssman-antibodies are present row as "natural antibodies" in the serum of man, and agglutinate red blood cells, e.g., of sheep Freund's complete adjuvant (FCA). An oil-water H-2Iocus. The major histocompatibility complex emulsion which contains killed mycobacteria (MHC) in the mouse and enhances immune responses when mixed Haplotype. That portion of the phenotype deter• in an emulsion with antigen mined by closely linked genes of a single Freund's incomplete adjuvant. Contains all of the chromosome inherited from one parent elements of Freund's complete adjuvant with Hapten. A substance which is not immunogenic the exception of killed mycobacteria but can react with an antibody of appropriate specificity Gamma globulins. Serum proteins with gamma Hassall's corpuscles. Whorls of thymic epithelial mobility in electrophoresis which comprise the cells whose function is unknown majority of immunoglobulins HB antigen. Hepatitis B virus antigen detectable Gammopathy. Paraprotein disorder involving ab• in serum of infected though not necessarily normalities of immunoglobulins sick individuals Genetic switch hypothesis. A hypothesis which Hay fever. A seasonal allergic disease causing in• postulates that there is a switch in the gene flammation of the eyes and nasal passages controlling heavy chain synthesis in plasma H chain (heavy chain). One pair of identical poly• cells during the development of an immune re• peptide chains making up an immunoglobulin sponse molecule. The heavy chain contains approxi• Germinal centers. A collection of metabolically mately twice the number of amino acids and is active lymphoblasts, macrophages, and plas• twice the molecular weight of the light chain ma cells which appears within the primary fol• Heavy chain diseases. A heterogeneous group of licle of lymphoid tissues following antigenic paraprotein disorders characterized by the stimulation presence of monoclonal but incomplete heavy Glomerulonephritis. An autoimmune disease in chains without light chains in serum or urine which the major damage is to the glomeruli of Helper T cells. A subtype ofT lymphocytes which the kidney cooperate with B cells in antibody formation Gm marker. Allotypic determinant on the heavy inhibition. A technic for detect• chain of human IgG ing small amounts of antigen in which homol• Graft rejection. A cell-mediated immune reaction ogous antigen inhibits the agglutination of red elicited by the grafting of genetically dissimilar cells or other particles coated with antigen by tissue onto a recipient. The reaction leads to specific antibody Glossary of Immunologic Terms 421

Hematopoietic system. All tissues responsible for mine the antibody combining site of an anti• production of the cellular elements of periph• body molecule eral blood Hypogammaglobulinemia (agammaglobulinemia). Hemolysin. Antibody or other substance capable Deficiency of all major classes of serum immu• of lysing red blood cells noglobulins Heterocytotropic antibodies. Antibody which can passively sensitize tissues of species other than Ia antigens (I region-associated antigens). Anti• those in which the antibody is present gens which are controlled by Ir genes and are present on lymphocytes and macrophages Heterologous antigen. An antigen which partici• Idiotope. An epitope of the antigen-binding site pates in a cross-reaction of an antibody High dose (high zone) tolerance. Classical immuno• Idiotype. Unique antigenic determinants present logic unresponsiveness produced by repeated on homogeneous antibody or myeloma pro• injections of large amounts of antigen tein. The idiotype appears to represent the Hinge region. The area of the H chains in the C antigenicity of the antigen-binding site of an region between the first and second C region antibody and is therefore located in the V re• domains. It is the site of enzymatic cleavage in• gion to F(ab)2 and Fc fragments IgA. Predominant immunoglobulin class present Histocompatible. Sharing transplantation anti• in secretions gens IgD. Predominant immunoglobulin class present HLA (human leukocyte antigen). The major on human B lymphocytes histocompatibility complex in man IgE. Reaginic antibody involved in immediate Homocytotropic antibody. Antibody which at• hypersensitivity reactions taches to cells of animals of the same species IgG. Predominant immunoglobulin class present Homologous antigen. An antigen which induces in human serum an antibody and reacts specifically with it IgM. A pentameric immunoglobulin comprising Homozygous typing cells (HTC). Cells that carry approximately lO% of normal human serum the same allele at their two HLA-D loci (ho• immunoglobulins, with a molecular weight of mozygous) which are used as stimulating cells 900,000 and a sedimentation coefficient of 19 S in mixed lymphocyte cultures for the typing of 7 S IgM. A monomeric IgM consisting of one HLA-D phenotypes monomer of 5 identical subunits Horizontal transmission. The transmission of in• Immediate hypersensitivity. An immunologic sen• fection from individual to individual in a pop• sitivity to antigens that manifests itself by tis• ulation rather than from parent to offspring sue reactions occurring within minutes after Hot antigen suicide. A technic in which an antigen the antigen combines with its appropriate anti• is labeled with high-specific-activity body radioisotope e31 I). Used either in vivo or in vi• Immune complexes. Antigen-antibody complexes tro to inhibit specific lymphocyte function by Immune elimination. The enhanced clearance of attachment to an antigen-binding lymphocyte, an injected antigen from the circulation as a re• subsequently killing it by radiolysis sult of immunity to that antigen brought about Humoral. Pertaining to molecules in solution in a by enhanced phagocytosis of the re• body fluid, particularly antibody and comple• ticuloendothelial system ment Immune response genes (Ir genes). Genes which Hybridoma. Specific antibodies secreting hybrid control immune responses to specific antigens cells obtained by fusion of plasma cells with Immune surveillance. A theory which holds that myeloma cells the immune system destroys tumor cells, which Hypersensitivity. The state, existing in a previ• are constantly arising during the life of the in• ously immunized individual, in which tissue dividual damage results from the immune reaction to a Immunodominant. That antigenic determinant of further dose of antigen. If tissue damage is se• an antigen which is dominant in eliciting anti• vere, the condition may be referred to as one body formation form of allergy Immunoelectrophoresis. A technic combining an Hypervariable regions. At least 4 regions of ex• initial electrophoretic separation of proteins treme variability which occur throughout the followed by immunodiffusion with resultant V region of Hand L chains and which deter- precipitation arcs 422 Glossary of Immunologic Terms Immunofluorescence. A histo- or cytochemical Kappa (K) chains. One of 2 major types of L technic for the detection and localization of chains antigens in which specific antibody is conju• K cell. Killer cell responsible for antibody-depen• gated with fluorescent compounds, resulting in dent cell-mediated cytotoxicity a sensitive tracer which can be detected by K and D regions. Genetic loci in the major fluorometric measurements histocompatibility complex of the mouse, cod• Immunogen. A substance which, when introduced ing for H-2 molecules which are the restricting into an animal, stimulates the immune re• elements of cytotoxic T cells sponse Kinin. A peptide that increases vascular perme• Immunogenicity. Property of a substance making ability and is formed by the action of esterases it capable of inducing a detectable immune re• on kallikreins, which then act as vasodilators sponse Km marker (also called Inv). Allotypic marker on Immunoglobulin. A glycoprotein composed of H the K L chain of human immunoglobulins and L chains which functions as antibody. All Koch phenomenon. Delayed hypersensitivity reac• antibodies are immunoglobulins, but it is not tion by tuberculin in the skin of a guinea pig certain that all immunoglobulins have anti• following infection with Mycobacterium tuber• body function culosis Imunoglobulin class. A subdivision of immuno• Kupffer cells. Fixed mononuclear phagocytes of globulin molecules based on structural and the reticuloendothelial system that are present unique antigenic differences in the C regions of within the sinusoids of the liver the H chains. In man there are 5 classes of im• munoglobulins designated IgG, IgA, IgM, IgD, and IgE Lambda (II.) chain. One of 2 major types of L Immunoglobulin subclass. A subdivision of the chains classes of immunoglobulins based on struc• Latency. Stage of persistent infection in which tural and antigenic differences in the H chains. microorganism causes no disease, but remains For human IgG there are 4 subclasses: IgG I, capable of activation and disease production IgG2, IgG3, and IgG4 . An agglutination reaction in Immunopathology. Pathological changes partly which latex particles are used to passively ad• or completely caused by the immune response sorb soluble protein and polysaccharide anti• Immunosuppression. Suppression of immune re• gens sponsiveness by irradiation, drugs, or micro• LATS (long-acting thyroid stimulator). An anti• bial toxins body reacting with the thyroid stimulating Immune tolerance. An immunologically specific hormone (TSH) receptor in the thyroid gland; reduction in immune responsiveness to a given this antibody is present in about 45% of antigen patients with hyperthyroidism and causes de• Interferon. A heterogeneous group oflow-molec• layed uptake of iodine in an animal assay sys• ular-weight proteins elaborated by infected tem host cells which protect noninfected cells from LE cell phenomenon. Phagocytic leukocytes that viral infection have engulfed DNA, immunoglobulin, and Iov marker. See Km marker complement and are present as a large homo• I region. That portion of the major histocompati• geneous mass which is extruded from a dam• bility complex which contains genes that con• aged lymphocyte in systemic lupus erythe• trol immune responses matosus and other rheumatoid diseases Ir genes. See Immune response genes Lectin. A substance that is derived from a plant and has panagglutinating activity for red blood cells. Lectins are commonly mitogens as well J chain. A glycopeptide chain which is normally Leishmaniasis. Disease caused by protozoa of ge• found in polymeric immunoglobulins, particu• nus Leishmania, e.g. cutaneous leishmaniasis larly IgA and IgM (oriental sore) or generalized leishmaniasis Joining. Linking together DNA segments (in• (kala-azar) trons) of genes in somatic cells which are sepa• Leukocyte inhibitory factor (LIF). A lymphokine rated by non-translated DNA sequences (ex• which inhibits the migration of polymorpho• ons) in the germ line nuclear leukocytes Glossary of Immunologic Terms 423 Leukocyte mitogenic factor (LMF). A lym• Lysostrip. Removal of one kind of surface anti• phokine that will induce normal lymphocytes gen by capping with subsequent reaction of the to undergo blast transformation and DNA same cells with antibodies and complement to synthesis another kind of surface antigen. Employed for Leucocytes. Circulating white blood cells. There the demonstration of antigenic determinants are about 9,000jmm3 in human blood, divided on the same or different molecules into granulocytes (polymorphs 68%-70% Lysozyme. An enzyme present in the granules of eosinophils 3% basophils 0.5%) and mononu• polymorphs, in macrophages, in tears, mucus clear cells (monocytes 4% lymphocytes 23- and saliva. It lyses certain bacteria, especially 25%) gram-positive cocci, splitting the muramic Light chain (L chain). Polypeptide chain present acid-f3 (1-4)-N-acetylglucosamine linkage in in all immunoglobulin molecules. Two types the bacterial cell wall. It potentiates the action exist in most species and are termed kappa (K) of complement on these bacteria and lambda (1) Macrophage activation factor (MAF). A lym• Linkage diseqnilibrium. When alleles of two phokine which will activate macro phages to closely linked loci are found together more fre• become avid phagocytic cells quently than predicted by their individual gene Macrophage chemotactic factor (MCF). A lym• frequencies phokine which selectively attracts monocytes Lipopolysaccharide (also called endotoxin). A or macrophages to the area of its release compound derived from a variety of gram-ne• Macrophages. Phagocytic mononuclear cells that gative enteric bacteria which have various bio• derive from bone marrow monocytes and sub• logic functions including mitogenic activity for serve accessory roles in cellular immunity B lymphocytes Macrophage processing. Uptake of antigens by Low dose (low zone) tolerance. A state of toler• macrophages, especially in the form of large ance induced with small subimmunogenic particles or microorganisms, and preparation doses of soluble antigen of antigen or antigens for delivery to adjacent Lupus erythematosus. A fatal autoimmune dis• immunocompetent lymphoytes ease, characterized by certain antinuclear anti• Major histocompatibility complex (MHC). An as bodies yet undetermined number of genes located in Ly antigens. Differentiation antigens present on close proximity which determine histocom• and peripheral T cells patibility antigens of members of a species Lymph nodes. Small pea-sized organs distributed Mast cell. A tissue cell which resembles a periph• widely throughout the body which are com• eral blood basophil and contains granules with posed mostly of lymphoid cells serotonin and histamine present Lymphocyte. A mononuclear cell 7-12 flm in di• Memory cells. Sensitized cells generated during ameter containing a nucleus with densely an immune response, and surviving in large packed chromatin and a small rim of cyto• enough numbers to give an accelerated im• plasm mune response on challenge Lymphocyte activation (lymphocyte stimulation, 132 Microglobulin. A protein (MW 11,600) that is lymphocyte transformation, or blastogenesis). associated with the outer membrane of many An in vitro technic in which lymphocytes are cells, including lymphocytes, and which may stimulatedto become metabolically active by function as a structural part of the histocom• antigen or mitogen patibility antigens on cells Lymphocyte defined (LD) antigens. A series of Migration inhibitory factor (MIF). A lymphokine histocompatibility antigens that are present on which is capable of inhibiting the migration of the majority of mammalian cells and detect• macrophages able primarily by reactivity in the mixed lym• Mitogens (also called phytomitogens). Substances phocyte reaction (MLR) which cause DNA synthesis, blast transforma• Lymphokine. Soluble factor released by primed tion, and ultimately division of lymphocytes lymphocyte on contact with specific antigen Mixed lymphocyte culture (mixed leukocyte cul• Lysosome. Cytoplasmic sac present in many cells, ture) (MLC). An in vitro test for cellular im• bounded by a lipoprotein membrane and con• munity in which lymphocytes or leukocytes taining various enzymes. Plays an important from different individuals are mixed and mu• part in intracellular digestion tually stimulate DNA synthesis 424 Glossary of Immunologic Terms Mixed lymphocyte reaction (MLR). See Mixed Paraproteinemia. A heterogeneous group of dis• lymphocyte culture eases characterized by the presence in serum or Monoclonal immunoglobulin molecules. Identical urine of a monoclonal immunoglobulin copies of antibody which consist of one H Paratope. An antibody combining site for epito• chain class and one L chain type pe, the simplest form of an antigenic deter• Monoclonal protein. A protein produced from the minant progeny of a single cell called a clone Passive cutaneous anaphylaxis (peA). An in vivo Monokines. Soluble factors released by activated passive transfer test for recognizing cytotropic macrophages/monocytes antibody responsible for immediate hypersen• Multiple myeloma. A paraproteinemic disorder sitivity reactions consisting typically of the presence of serum Passive immunity. Transfer of preformed anti• paraprotein, anemia, and lytic bone lesions bodies to non-immune individual by means of Myeloma protein. Either an intact monoclonal blood, serum components, etc. e.g. maternal immunoglobulin molecule or a portion of one antibodies transferred to fetus via placenta or produced by malignant plasma cells milk, or immunoglobulins injected to prevent Myeloperoxidase. An enzyme that is present or modify infections within granules of phagocytic cells and Patching. The reorganization of a cell surface catalyzes peroxidation of a variety of microor• membrane component into discrete patches ganisms over the entire cell surface Pathogenic. Producing disease or pathological changes Natural antibody. Antibody present in the serum Persistent infection. An infection in which the mi• produced against unknown antigens, primarily croorganism persists in the body, not necessar• antigenic structures of the intestinal microor• ily in a fully infectious form, but often for long ganism flora periods or throughout life Neutralization. The process by which antibody or Peyer's patches. Collections oflymphoid tissue in antibody and complement neutralizes the in• the submucosa of the small intestine which fectivity of microorganisms, particularly contain lymphocytes, plasma cells, germinal viruses centers, and T cell-dependent areas NK cells (natural killer cells). Cytotoxic cells of Pfeiffer phenomenon. Demonstration that chol• undefined lineage, responsible for cellular cy• era vibrios introduced into the peritoneal cav• totoxicity without prior sensitization ity of an immune guinea pig lose their mobility Nonresponder. An animal unable to respond to and are lysed regardless of the presence of cells an antigen, usually because of genetic factors Phagocytes. Cells which are capable of ingesting Nude mouse. A hairless mouse which congenitally particulate matter lacks a thymus and has a marked deficiency of Phagocytosis. The engulfment of microorganisms thymus-derived lymphocytes or other particles by leukocytes Null cells. Cells lacking the specific identifying Phagolysosome. A cellular organelle which is the surface markers for either T or B lymphocytes product of the fusion of a phagosome and a NZB mouse. A genetically inbred strain of mice in lysosome which autoimmune disease resembling sys• Phagosome. A phagocytic vesicle bounded by in• temic lupus erythematosus develops spontane• verted plasma membrane ously Phylogeny. The developmental and evolutionary history of a group of animals Ontogeny. The developmental history of an indi• Phytohemagglutinin (PHA). A lectin which is de• vidual organism within a group of animals rived from the red kidney bean (Phaseolus vul• Opsonin. A substance capable of enhancing garis) and which stimulates predominantly T phagocytosis. Antibodies and complement are lymphocytes the 2 main opsonins Pinocytosis. The ingestion of soluble materials by cells Plaque-forming cells (PFC). Antibody producing Paralysis. The pseudo tolerant condition in which cell capable of forming a hemolytic plaque in an ongoing immune response is masked by the the presence of complement and antigenic ery• presence of overwhelming amounts of antigen throcytes Glossary of Immunologic Terms 425 Plasma cells. Fully differentiated antibody-syn• Reagin. Synonymous with IgE antibody. Also de• thesizing cells which are derived from B lym• notes a complement-fixing antibody which phocytes reacts in the Wassermann reaction with car• Pokeweed mitogen (PWM). A lectin that is de• diolipin rived from pokeweed (Phytolacca americana) Receptor. A chemical structure on the surface of and stimulates both Band T lymphocytes any immunologically competent cell Polyclonal mitogens. Mitogens which activate Recombinant. An animal which has experienced a large subpopulations of lymphocytes recombinational event during meiosis, consist• Polyetbylenglycol (pEG). Substance used as fu• ing of cross-over and recombination of parts sion reagent for the production of somatic cell of 2 chromosomes hybrids Rejection response. Immune response with both Pre-B cells. Large immature lymphoid cells with humoral and cellular components directed diffuse cytoplasmic IgM which eventually de• against transplanted tissue velop into cells Reservoir. Animal (bird, mammal, mosquito, Precipitation. A reaction between a soluble anti• etc.) or animals in which microorganism main• gen and soluble antibody in which a complex tains itself independently of human infection lattice of interlocking aggregates forms Restriction. Stimulation and activation of coop• Primary follicles. Tightly packed aggregates of erating cells in the immune response occurs on• lymphocytes found in the cortex of the lymph ly if the reacting cells share either K, D mole• node or in the white pulp of the after cules (cytotoxic T cells) or la molecules (help• antigenic stimulation. Primary follicles devel• er/suppressor T cells), i.e. the recognition of op into germinal centers antigens is restricted to the concomitant pres• Primary lymphoid organs. Lymphoid organs that ence of antigen and the own MHC molecules are essential to the development of the immune Reticuloendothelial system. A system of cells that response, i.e., the thymus and the bursa of take up particles and certain dyes injected into Fabricius the body. Comprises Kupffer cells of liver, tis• Private antigen. A composition of antigenic de• sue, histocytes, monocytes, and the lymph terminants on MHC molecules characteristic node, splenic, alveolar, peritoneal, and pleural of an allele macrophages Properdin system (or alternate pathway of comple• Rh incompatibility. Incompatibility between cer• ment activation). A group of proteins which af• tain blood group antigens of a mother and her ter activation by microbial substances (e.g. zy• baby or between donor and recipient in blood mosan, complex polysaccharides a. 0.) activate transfusions C 3 of the classical complement pathway inde• Rheumatoid factor (RF). An anti-immunoglobu• pendently of antibody-antigen reactions lin antibody directed against denatured IgG Prostaglandins. A variety of naturally occurring present in the serum of patients with rheu• aliphatic acids with various biologic activities, matoid arthritis and other rheumatoid diseases including increased vascular permeability, Rocket electrophoresis (Laurell technic). An elec• smooth muscle contraction, bronchial con• troimmunodiffusion technic in which antigen striction, and alteration in the pain threshold is electrophoresed into agar containing specific Prothymocytes. Immature precursors of mature antibody and precipitates in a tapered rocket• thymocytes which develop within the thymus shaped pattern. This technic is used for quanti• gland tation of antigens Prozone phenomenon. Suboptimal immune reac• Rose-Waaler test. A type of passive hemaggluti• tion in vitro (precipitation, cytolysis, ag• nation test for the detection of rheumatoid fac• glutination) which occurs in the region of anti• tor which employs tanned red blood cells body excess during immune reactions coated with rabbit 7 S IgG antibodies specific Pyogenicmicroorganisms. Microorganisms whose for sheep red blood cells presence in tissues stimulates an outpouring of polymorphonuclear leukocytes Pyrogens. Substances released either endoge• Schistosomiasis (= bilharzia). Disease with uri• nously from leukocytes or administered exoge• nary symptoms common in many parts of nously, usually from bacteria, and which pro• Africa. Caused by the fluke (trematode) duce fever in susceptible hosts Schistosoma haematobium; larvae from in- 426 Glossary of Immunologic Terms

fected snails enter water and penetrate human belong to Group A (= Streptococcus pyo• skin genes), which is divided into 47 types according Secondary lymphoid organs. Lymphoid organs to antigenic properties of M protein present on not essential to the ontogeny of immune re• outermost surface of bacteria sponses, i.e., the spleen, lymph nodes, , Streptolysin O. Exotoxin produced by Strep• and Peyer's patches tococcus pyogenes. Oxygen-labile, haemolytic, Secretory 19A. A dimer of IgA molecules with a and a powerful antigen sedimentation coefficient of 11 S, linked by J Streptolysin S. Exotoxin produced by Streptococ• chain and secretory component cus pyogenes. Oxygen-stable, causing fJ hae• Secretory immune system. A distinct immune sys• molysis on blood agar plates, but not demon• tem that is common to external secretions and strably antigenic consists predominantly of IgA Suppressor T cells. A subset of T lymphocytes Secretory piece (T piece). A molecule of MW which suppress antibody synthesis by B cells or 70,000 produced in epithelial cells and associ• inhibit other cellular immune reactions by ef• ated with secretory immunoglobulins, particu• fector T cells larly IgA and IgM Surveillance. The process by which an intact im• Self-recognition. Recognition of self-antigens by mune system monitors both self and foreign one's own immunologic system antigens Sensitized. Synonymous with immunized S value. Svedberg unit. Denotes the sedimenta• Serologically defined (SD) antigens. Antigens that tion coefficient of a protein, determined are present on membranes of nearly all mam• usually by analytic ultracentrifugation malian cells and are controlled by genes pre• Syngeneic. Denotes the relationship which exists sent in the major histocompatibility complex. between genetically identical members of the They can be easily detected with antibodies same species Serology. Literally, the study of serum. Refers to Systemic infection. Infection that spreads the determination of antibodies to infectious throughout the body agents important in clinical medicine Serum (pI. sera). The liquid part of the blood re• maining after cells and fibrin have been re• T cell (T lymphocyte). A thymus-derived cell moved which participates in a variety of cell-mediated Serum sickness. An adverse immunologic re• immune reactions sponse to a foreign antigen, usually a T cell rosette. See E rosette heterologous protein Teleology. Doctrine that biological phenomena Shedding. The liberation of microorganisms from generally have a purpose, serving some func• the infected host tion Side chain theory. Theory of antibody synthesis Thy-l antigen (theta antigen). An alloantigen pre• proposed by Ehrlich in 1900 suggesting that sent on the surface of most thymocytes and pe• specific side chains which form antigen recep• ripheral T lymphocytes tors are present on the surface membranes of Thymopoietin (originally termed thymin). A pro• antibody-producing cells tein of MW 7,000 that is dervied originally Slow virus. A virus which produces disease with from the thymus of animals with autoimmune a greatly delayed onset and protracted course thymitis and myasthenia gravis and which can Specificity. A term referring to the selective reac• impair neuromuscular transmission tion which occurs between an antigen and its 'Thymosin. A thymic hormone protein of MW corresponding antibody or lymphocyte 12,000 which can restore T cell immunity in Spleen. An organ in the abdominal cavity, com• rhymectomized animals posed largely of lymphocytes and macro• Thymus. The central lymphoid organ which is phages. It is an important site of antibody pro• present in the thorax and controls the onto• duction geny of T lymphocytes S region. The chromosomal region in the H-2 Thymus-dependent antigen. Antigen which de• complex containing the gene for a serum fJ• pends on T cell interaction with B cells for anti• globulin (C4 complement component) body synthesis, e.g., erythrocytes, serum pro• Streptococci. Classified into groups A-H by anti• teins, and hapten-carrier complexes genic properties of carbohydrate extracted Thymus-derived lymphocytes (T lymphocyte). from cell wall. Important human pathogens Small lymphocytes which on (or after) resi- Glossary of Immunologic Terms 427 dence in the thymus attain new immunologic Vaccination. Immunization with antigens admin• capabilities istered for the prevention of infectious diseases Thymus-independent antigen. Antigen which can (term originally coined to denote immuniza• induce an immune response without the appar• tion against vaccinia or cowpox virus) ent participation of T lymphocytes V antigens. Virally induced antigens which are ex• Tissue typing. The processes of identifying and pressed on viruses and virus-infected cells matching antigens on prospective donor and Vertical transmission. The transmission of infec• recipient tissues tion directly from parent to offspring. This can Titre (1). A measure of units of antibody per unit take place in utero via egg, sperm, placenta, or volume of serum, usually quoted as reciprocal postnatally via milk, blood, contact, etc. of last serum dilution giving antibody-medi• Viremia. Presence of virus in blood stream. Virus ated reaction e.g. 120. (2) Measure of units of may be associated with leucocytes (leucocyte virus per unit volume of fluid or tissue. Usually viraemia), or free in the plasma (plasma given in log 10 units per ml or G e.g. 10 5 .5 pfuj viraemia), or occasionally associated with ery• m1 throcytes or platelets TL antigen. A membrane antigen that is present Virion. The complete virus particle on prothymocytes in mice with a TL + gene, V (variable) region. The amino terminal portion but which is lost during thymic maturation of the H or L chain of an immunoglobulin Tolerance. Traditionally denotes that condition molecule, containing considerable heterogene• in which responsive cell clones have been in• ity in the amino acid residues compared to the activated by prior contact with antigen, with constant region the result that no immune response occurs on V region subgroups. Subdivisions of V regions of administration of antigen kappa chains based on substantial homology Toxoids. Antigenic but nontoxic derivatives of in sequences of amino acids toxins T piece. See Secretory piece Wasting disease (runt disease). A chronic, ulti• Transfer factor. A dialyzable extract of immune mately fatal illness associated with lymphoid lymphocytes that is capable of transferring atrophy in mice who are neonatally thymec• cell-mediated immunity in humans and possi• tomized bly in other animal species Translocon. Stretch of chromosome containing Xenogeneic. Denotes the relationship which gene sequences coding for heavy, kappa or exists between members of genetically different lambda polypeptide chains of immunoglobu• species lins Xenograft. A tissue or organ graft between mem• Transplantation antigens. Those antigens which bers of 2 distinct or different species are expressed on the surface of virtually all cells and which induce rejection of tissues transplanted from one individual to a geneti• References cally disparate individual Tuberculin test. A skin test for delayed hypersen• Fudenberg HH, Stites DP, Caldwell JL, Wells JV sitivity to antigens from Mycobacterium tuber• (1980) Basic and clinical , 4th ed. Lange Medical Publications, Los Altos/Calif. culosis. In man the antigen is introduced into Mims CA (1977) The pathogenesis of infectious dis• the skin by intradermal injection (Mantoux eases. Academic Press, New York test) Amos DB (ed) (1976) Immunology: Its role in disease Tuftsin. A y-globulin which is capable of stimu• and health. US DHEW publication No. (NIH) 75- lating endocytosis by neutrophils 940 Subject and Author Index

Page numbers in italics refer to the principle discussion of each subject.

AAME (N-acetyl-arginine-methyl on T cells 9,39,50,149,341 platelets 271 ester) 117 on thymocytes 9,149 prostaglandins 267 ABO blood group 219,249 alloantiserum 69 protracted shock 260 alloantibody 221 allogeneic 131, 235 sensitization period 260 genetics of 221 allotype 93, 94, 394 serotonin 266 genotypes of 221 Gm factors 94 slow-reacting substance 267 typing of the 220 Inv factors 94 systemic 259 abortion theory 365 method for detecting 96 valence of the antigen 264 acanthosis nigricans 381 allylisopropylacetylurea 192 Ancylostoma duodenale 325 ACTH (adrenocorticotrope alpha chain disease 350 anemia hormone) 8 alum 66 aplastic 252 actin polymerization deficiency aluminium hydroxide 66 autoimmune hemolytic 230, 360 aluminium phosphate 66 381 actinomycin 409 Amebia 319 pernicious 385 Addison's disease 380 amebiasis 323 spontaneous autoimmune of adenosine-deaminase deficiency amino acid antagonists 400,409 the NZB mouse 383 (ADA) 352 aminopterin 74,408 anergy 370 adherence 303,343 anaphylatoxin 112,123 Anguilla anguilla 220 adjuvant 66, 69 biologic properties 124 ankylosing spondylitis 147 Freund's 70 anaphylatoxin-induced shock Annelids 30 mechanism of 67 273 antibacterial sera adjuvanticity 66 anaphylaxis 258 protective action of 203 adoptive transfer 334 acute 274 antibiotics 409 adrenergic receptor 280 antibody fixation 263 antibody 69 affinity-labeling technique 87 antibody involved in 272 affinity-labeling technique 87 agglutinating antigen-induced liberation anti-D 248 titration of sera 177 272 anti-idiotope 106 agglutination 176,312 atopy 274 anti-nuclear (ANA) 371 cross reaction 180 basophils 270 antilymphocytic (ALA) 392 passive 181 Bradykinin 267 blocking 281 agglutinin 177 cells involved in 268 chains 80 Agnates 30 cellular receptor 263 characteristics of the homo- agranUlocytosis, infantile genetic characteristic of different cytotropic 263 359 species 259 combining site 210 akute leukemias 356 eosinophilotactic factor of constant region 85 alexin 111 267 detection 169 alkaloids 408 eosinophils 272 domain 85 alkylating agents 405 heparin 267 Donath-Landsteiner 382 allelic exclusion 49, 99 histamine 265 dynamics of formation 70 alloantibody in man 274 electron microscopic studies to ABO antigens 221 in the guinea pig 259 of the 95 to HLA antigens 141 local 259,274 enzymatic digestion 79,82 to H-2 antigens 135 mastocytes 268 evaluation of function 339 ,to Rh antigens 225 mechanism of 259,265 Fab fragments 83 alloantigen 131 mediator of 266 Fc fragment 83 on B cells 11,49,50,149, passive 260 formation at the cellular level 341 passive cutaneous 261 72 430 Subject and Author Index antibody regulatory cell circuits 106 antibiotics 400 formation at the gene level 96 antibody fragments antitoxins formation at the level of the functions of 84 avidity of 201 organism 69 antibody idiotopic network 105 horse type 201 formation at the protein level antibody-antigen interaction 169 rabbit type 201 75 antibody-dependent cell-mediated aplasia framework (FR) segments 87 cytotoxicity (ADCC) 43,240, bone marrow 252 heavy chains 80 244, 282,294 thymus 252,344,351 heterocytotropic 262 antibody-forming cells arthritis 165,371 heterogeneity and structure of differentiation of 74 rheumatoid 393 the chains 84 antibody-hapten reaction 212 Arthus reaction 185,282,284 homocytotropic 262 thermodynamics 214 pathogenesis of 285 host resistance to viral infec- antibody-producing cell 4,47 arylsulphatase 7 tions 316 antigen 59,100 Ascaris lumbricoides 325 hypervariable regions 86, 87 determinants 63 Aschoff 195 incomplete 178 epitope 62,104 Ascoli's reaction 207 kappa chain 85 group specific 180 asparaginase 409 lambda chain 85 homologous reactions 62 ataxia telangiectasia 354 length of different chains 86 molecular weight of protein ATEE (N-acetyl-L-tyrosine-ethyl light chains 80 101 ester) 117 monoclonal 74 polar groups 61 atopy 274 natural or preformed 300 polysaccharide determinants mechanism of immunotherapy nature and heterogeneity of 79 of 62 in 277 precipitation 79, 170 private 135 atrophy, gastric 385 production of monoclonal 75 public 135 auto-anti-idiotype antibody 245 purification by nonspecific spatial configuration 61 autoantibodies 59 methods 77 specific determinants of 61 autogenic 132 purification by specific specificity 64 autoimmune disease 368, 373 methods 79 type specific 180 acanthosis nigricans 381 purification of 76 antigen chart of acute disseminated encephalo• reaginic 91 class 1 molecules 137 myelitis 377 sedimentation constant 80 D molecules 137 Addison's disease 380 size of 210 I-A specificities 138 autoimmune hemolytic structural model of 81 1-E specificities 139 anemia 381 structure 80 K molecules 137 autoimmune leukopenias 385 to auto antigens 366,379, antigen E 147 classification of the 375 382,391 antigen II (H-2) 132 criteria of 373 variable region 85 antigen recognition Crohn's disease 385 antibody blocking 235 control of T cell 155 endocrine glands 378 antibody combining site antigen seclusion 368 experimental allergic encepha- chemical structure of 86 antigen-antibody complex 282, lomyelitis 374 antibody formation 373 experimental autoimmune clonal selection theory 96 Arthus reaction 282 thyroiditis 378 instructive theory 96 methods for detection of 282 gastric atrophy 385 side-chain theory 96 pathogenesis of inflammatory glomerulonephritis 287, 386 antibody formation, regulation of lesions due to 282 Goodpasture's syndrom 388 by antigens 100 serum sickness 282 Graves disease 380 by factors inherent to the antigen-antibody interaction 169 hematologic 381 immune system 104 antigenic drift 318 infection agents of 372 by factors ofthe organism 103 antigenic shift 318 insulin-dependent diabetes by feedback control 104 antigenic variation mellitus 380 by idiotypic network interac• of parasites 329 mechanism oftissue lesion 374 tion 104 antigenicity multiple sclerosis (MS) 376 influence of age 103 chemical basis of 60 of the central nervous system influence of genetic factors antiglobulin test 178 374 103 antithymocyte serum 252 of the eye 389 influence of nutritional state antilymphocytic sera 402 of the gastrointestinal tract 103 antimetabolites 400,406 and liver 385 Subject and Author Index 431

of the heart 389 B complex 132,148 class II molecules 15 3 of the kidney 386 B lymphocyte 11, 44 class III molecules 155 of the lung 388 activation of 45 complement components of the skin 390 alloantigens 50 117 pemphigus vulgaris 390 cooperation with T lympho- immunoglobulins 79 pernicious anemia 385 cytes 50 Biozzi 72,193 progressive systemic sclerosis C3b-receptor 50 Bittner virus 164 (PPS) 395 differences to T lymphocytes blanks 142 rheumatoid arthritis 393 49 blastogenic factor 313 scleroderma 395 differentiation 12,74 blood 254 sympathetic ophthalmia 390 disorders 345,354 blood group 219 systemic 390 evaluation of function of 340 and autoimmune hemolytic systemic lupus erythematosus Fc-receptor 11, 50 anemia 230 (SLE) 390 life span 11 and maternal-fetal incompati- tissue lesion 373 localization of the immuno• bility 229 thrombocytopenias 384 globulin 46 and transfusion 229 ulcerative colitis 385 membrane immunoglobulin biosynthesis of 222 vasculitis in 394 50 chemistry of 222 autoimmunity 368 mitogen activation 50 Diego 228 antigen seclusion 368 pre-B-Cell 11 Duffy 228 autoimmune diseases 368 receptor for 11 forensic medicine 231 autorecognition 368 receptor for T helper factor Kell 228 factor influencing 371 11 Kell-Cellano 228 genetic factor in 372 specific characteristics of 340 Kidd 228 immunodeficiency associated Bacillus anthracis 315 Lewis 228 with 372 backcross system (NX) Lutheran 228 induction 368 for the production of congenic MN 228 autorecognition 365, 366 strains of mice 133 P 228 auxiliary regulatory circuits bactericidal deficiency structure of 223 (ARC) 107 chronic granulomatous system I 229 azaserine 409 disease (CGD) 360 system Xg 229 azathioprine 407 glucose-6-phosphate dehydro• ~ 228 genase deficiency 361 blood transfusion 229,253 B cell 3,11,44 lipochrome histiocytosis 361 Bloom's syndrome 357 B cell deficiency 345 myeloperoxidase (MPO) Blundell 219 alpha chain disease 350 deficiency 361 BoLA 148 aquired hypogammaglobulin- bacteriolysis 112,123,190,303 Bombay type 220 emias 346 of Gram-negative 123 bone marrow 4 Bruton-type congenital 345 Baroni 249 bone marrow transplantation Franklin's disease 349 basement membrane (BM) 192, 252 gammopathies monoclonal 386 graft -versus-host reaction 253 347 basophil activity 324 booster 104 heavy chain disease 349 metazoan infection 324 Bordatella pertussis 315 hypergammaglobulinemia 347 basophils 5,8,270,324 Bordet 111,112,177,185,189 IgA and IgM deficiency selec- BDB (bis-diazobenzidine) 116 Borneboe 47 tive 347 Behring 199 botulism 315 IgA deficiency selective 346 Benacerraf 93,103,156 Boyden's chamber 313, 342 IgG and IgA deficiency selec- Bence-Jones protein 85, 347 Boyden's technique 181 tive 347 bentonite 177 Bradykinin 267,301 IgM deficiency selective 346 Bert 249 Bruton-type congenital light chain abnormalities 350 beryllium sulfate 66 hypogammaglobulinemia 345 macroglobulinemia betalysins 191, 300 Burkitt's lymphoma 354 Waldenstrom's 349 betarmicroglobulin 153 Burnet 96, 246, 365 myeloma multiple 347 bidiazotized benzidine (BDB) bursa of Fabricius 2, 20 paraproteinemia Deutsch's 181 bursectomy 4,400 350 biochemistry of butterfly-shaped rash 390 poly clonal gammopathy 350 blood group substances 222 bypass selective IgG deficiency 346 class I molecules 152 T cell 369 432 Subject and Author Index

C1 116 actin polymerization defi• classical complement pathway chromatographic resolution ciency 360 163 117' Chediak-Higashi syndrome clonal expansion 100 esterolytic activities of 117 (CHS) 359 clonal selection theory 96 C1q solid phase radioimmune Jobs'syndrome 360 Oostridium botulinum 315 assay 283 lazy leukocyte syndrome 360 Clostridium tetani 315 C2 119 chemotactic factors 112, 125, Oostrldium welchii 315 C3 119, 127,139,163 267,301 cobra factor (CoF) 128 receptors of 11 for eosinophils 292 cobra venom 114,129 C3 b incactivator for lymphocytes 292 coeliac disease (CD) 147 conglutinin activating factor for macrophages 292,310 Cohn 78,365 120 for neutrophils 292 colitis, ulcerative 385 C3 b-INA 128 chemotaxin collagen-producing factor 310 C3 b-inactivator (KAF) 128 bradykinin 301 collagenase 6 C3 (factor A) 127 eosinophi1s chemotactic factor Collins 354 C3-convertase 119 (ECF-A) 302 colony-stimulating factor (CSF) P-dependent 129 fibrin peptides 301 6,307,310 C4 118 Hagemann factor 302 complement 111, 123 C5 120 HETE (12-L-hydroxy-5,8,10, alternative pathway or proper- C5-convertase 120 14-eicosatetraenoic acid) din system 127 C6 120 301 biosynthesis of 129 C7 120 HHT (12-L-hydroxy-5,8,10- cascade reaction 115 C8 121 heptadecatrienoic acid) effect of the solUbilization of C9 121 301 immune complexes by 129 C-esterase inhibitor 118 chemotaxis 301,313 hereditary deficiencies of 129 C-reactive protein (CRP) 300 Chido immunobiologic activities of carbodiimide (CDI) 181 C4-allotypes 147 122 Campbell 79 chimerism 246 immunocytotoxic reactions candidiasis mucocutaneous 351 ChLA 148 122 Cantor 106 chloramphenicol 409 nomenclature 114 capping 46, 149 cholchicine 408 polymorphism 129 capsular swelling 312 cholera 315 properties of 114 cardiolipin 370 chemotactic movement 342 quantitative determination of Carrell 249 chronic granulomatous disease 122 Carrier 60 (GCD) 360 separation of the classic cartwheel picture 11 CHso unit 112 components of 114 Casoni test 312 Cinader structure genes linkes to the Castellani's test 180 index 201 major histocompatibility cathepsin 7 class I gene complex 130 cationic-chymase 8 control of the cellular immune complement deficiency 361 cell-mediated cytotoxicity 243, response by 156 complement fixation 185, 312 313 class I genes 136 effects of, on cell membranes antibody-dependent 144 molecules 136 190 genetics of 243 class I molecules mechanism 189 specificity of 243 antigen chart of 137 complement-dependent Ceppellini 222 biochemistry of 152 liberation of histamine 125 Cestodes 320 complexity of 136 congeneity Chagas disease 323 class II gene (Ir gene) degree of 134 chain, antibody control of the immune response congenic strains relation between, and frag• by 158 of mice 133 ments 83 class II genes 136 production of 133 separation of the 80 class II molecules 137 conglutination 193 separation of the H and L 82 biochemistry of 153 conglutinin activating factor 120 Chang liver cell 244 class III genes conglutinin radioimmune assay Chediak-Higashi syndrome 357 function of, in the immune 283 chemotactic activity response 163 constant region 85 eosinophil 8 class III molecule contact chemotactic deficiencies 359 biochemistry of 155 sensitivity 288 Subject and Author Index 433

2 x 2 contingency table 141 Diphyllobothrium latum 325 Escherichia coli 315 Coombs antiglobulin test 227 disease susceptibility genes 147 espundia leishmaniasis 323 Coomb's test 178,382 diversity 100 ethanol Coons 48,71 DLA complex 132,148 serum fractionation with 78 copolymers 65 Doherty 156 250 core regulatory circuits (CRC) 107 domain 85 exotoxins Corynebacterium diphteriae 315 functions of the 86 bacterial 315 correlation coefficient test 141 Donath 230 properties of 315 corticosteroids 403 Donath-Landsteiner 382 Cosenza 105 dopamine 8 Fab fragments 83 Coulomb forces 215 Down's syndrome 357 factor B 128,147 counterimmunoelectrophoresis DR antigen 143 glycine-glycoprotein (GGG) 176 Drancunculus medinensis 325 128 C-reactive protein 300 DTH skin test 313 glycine-rich {}-glycoprotein Creutzfeld-Jacob disease 319 dual recognition 161 (GBG) 128 Crohn's disease 385 Duffy 228 factor D 128 cross-absorption 135 Durham 177 Fagraeus 47 cross-reaction dysentery 315 Fanconi's anaemia 357 microbial agglutination 180 dysregulation Farr 208 cutaneous basophil hypersen• T cell 370 Fasciola hepatica 325 sitivity (CBH) 324 Fc fragment 83 cutaneous T cell lymphomas 356 EB virus 354 Fc receptor 11 mycosis fungoides 356 Echinococcus granulosis 325 Fenner 246 Sezary syndrome (SS) 356 eczema, allergic 288 Ferrata 113 cyclophosphamide 252,406 Edelman 81, 85 fibrin peptides 301 cyclosporine A 253 Ehrlich 96,189,200,245,365 Ficks'law 172 cytolysis 112 encephalomyelitis Fisher 225 cytotoxic reaction (Type II) 281 acute disseminated 377 Fleischman 81 complement-independent encephalomyelitis flocculation 202,312 antibody reaction 281 experimental allergic (EAE) fluid mosaic membrane model cytotoxic T lymphocytes 42, 374 151 155 endotoxin 67 fluorescence quenching 214 enhancement 235,245 5-fluorouracil (5FU) 407 D gene 136 afferent 245 folic acid antagonists 408 D molecules 136 efferent 245 food poisoning 315 antigen chart of 137 enzyme-linked immunosorbent forbidden clones 365 D segments 99 assay (ELISA) 212 Ford 237 Dale 260 enzymes, hydrolytic 306 Forssman shock 273 Dausset 139 eosinophilia 272,326 framework (FR) segments 87 Dean 171 eosinophil chemotactic factor of Franklin's disease 349 degranulation 303,343 anaphylaxis, ECF-A 267, 302, Frei test 312 determinant (epitope) 62 326 Freund's adjuvant 67,70 minimum size of 62 eosinophil stimulation promoter Friedberger 273 determinants (ESP) 310,326 Friedburger 123 cross-reactions 63 eosinophil-IgE-mediated cyto• Friend virus 164 Deutsch 79 toxicity 326 Fudenberg 345 DFP, diisopropyl fluorophos• eosinophil-IgG-mediated immunity Fulthrope 173 phate 117 327 diabetes mellitus, inSUlin-depen- eosinophilia 326 gametic association 145 dent 380 eosinophils 5, 7, 272 gammopathy, monoclonal 347 Dick test 312 helminthic infections 8 gammopathy, poly clonal 350 Diego 228 role in allergies 8 gas gangrene 315 diethylaminoethyl (DEAE) epitope 62,73,104 gastric atrophy 385 cellulose chromatography 77 internal image of 106 GAT (glutamine-alanine-tyrosine) diethylcarbazamine citrate Epstein-Barr (EB) virus 318 41 (Hetrazan) 278 equilibrium dialysis 213 gel diffusion 312 DiGeorge's syndrome 4,252,351 erythroblastosis gel nItration 78 diphtheria 315 fetalis 230,248,333 gel precipitation 171 434 Subject and Author Index gene map 141,147 H chain translocon 99 genotypes 145 oflg 96 D segments 99 haplotypes 145 ofMHC 141,147 H-2 148 phenotypes 145 genetics of restriction 157 HLA complex 139 ABO blood groups 221 H-2 antigen 9,132 linkage analysis of 147 antibody diversity 97 H-2 complex 132 HLA-A 141 cell-mediated lympholysis genetic map of the 141 HLA-B 141 243 linkage analysis of 138 HLA-C 141 graft-versus-host reaction 238 linked genes 139 HLA-D 141 histocompatibility 138,145 H-2 K,D genes HLA-DR 141 host-versus-graft reaction 237 molecules 136 Hodgkin's disease 351 immune response 158 H-2 recombinant strains 140 homologous disease 383 mixed lymphocyte reaction H-2 recombinants 136 homologous reactions 62 242 Hagemann factor 302 homopolymers 65 Rh-system 226 hagfish 30 Honjo 99 Gengou 185 Haldane 131 host-versus-graft reaction 235 Gershon 41,106 haplotypes genetics of 237 Glo (glyoxalase) 139 H-2 136 HTC homozygous typing cells glomerulonephritis 287,386, Hardy-Weinberg theorem 145 144 388 lWek 246 Hu (Hunter) 224 glucose-6-phosphate dehydro- Hashimoto's thyroiditis 378 Hudack 47 genase deficiency 361 antibody in 379 hybridomas 74 glutaraldehyde (GA) 181 Hassal's corpuscles 14, 352 hydrazine 114 glycine"ilycoprotein (GGG) 128 HAT-medium 74 hydrolases glycine-rich {J-glycoprotein (GBG) HBs antigen (Australia antigen) acid 6 128 176,385 hydrophobic bonds 216 glycuronidase 7 He (Henshaw factor) 224 5-hydroxytryptamine 13 glyoxalase (GLo) 147 heavy chain disease 349 hypergammaglobulinemias 347 Gm factors 94 heavy chain switches 99 hypersensitivity 257 gnotobiotic unit 253 heavy chains 80 anaphylaxis (Type I) 258 GOD Heidelberger 79, 80, 204 antigen-antibody complex generation of diversity 96 helper T cells 39,50,155,341 (Type III) 282 Good 253 hemagglutination 312 Arthus reaction 282 Goodpasture's syndrome 388 passive 181 classification 258 Gorer 131,249 hemagglutination inhibition 312 complement-dependent anti- GPLA complex 132,148 hemodialysis 250 body reaction 281 Gr (Graydon) 224 hemolysis 123,312 cutaneous basophil 324 Grabar 80, 174, 368 immune 112 cytotoxic reaction 258 graft-versus-host reaction 20, heparin 267 cytotoxic reaction (Type II) 235 hepatitis 165, 385 281 genetics of 238 Heremans 80 delayed (Type N) 287 graft-versus-host disease 383 Herzenberg 107 immediate 258 granules HETE (12-L-hydroxy-5,8,10,14- serum sickness 282 azuropbilic 6 eicosatetraenoic acid) 301 hypersensitivity, delayed eosine 7 heterotopic graft 235 (Type N) 287 metachromatic 8,270 hexosemonophosphate shunt 304 antibody-dependent, cell- specific 6 HHT (12-L-hydroxy-5,8,1 O-hepta- mediated cytotoxicity 294 granulocytes 4 decatrienoic acid) 301 effector cell of 290 granulocytopoesis 5 histamine 8, 265 Jones-Mote reaction 294 granulocytopoietin 6 histamine-sensitizing factor (HSF) lymphotoxin-mediated Graves disease 380 68 destruction 294 Green 95 histocompatibility 131 mechanism of target-cell Gross virus 164 antigens 132 destruction 292 Grubb 94 histogenetics transfer factor 290 Gruber 177 terminology of 132 transfer of 289 guanidine silica 66 HLA 148 hypervariable regions 86 Guthrie 249 antigen specificities 143 hypogammaglobulinemia 345 genetics 145 acquired 346 Subject and Author Index 435 hypogammaglobulinemias macrophages 53 eosinophil-lgG mediated 327 selective variable 346 plasma cells 47 escape from 318 hypoxanthine-guanine-phospho• T lymphocytes 38 in agnates 30 ribosyl-transferase (HGPRT) immune complex in annelids 30 74 disease associated with 273, 283 macrophage-IgE mediated 327 pathogenesis of inflammatory maternal-fetal transfer 331 I restriction 160 lesions due to 282 mechanisms of 297 la molecules 137 immune defense mechanisms natural 297 I-A locus escape due to nonsterilizing 320 mapping of 158 antigenic variation 329 ontogenic development of I-A specificities immunosuppression 329 332 antigen chart 138 inaccessibility 328 ontogeny 30 I-E locus loss of MHC antigens 329 passive 331 mapping of 158 molecular masking 329 phylogeny of 30 I-E specificities seclusion inside host cells immunity cell-mediated test antigen chart 139 328 system 313 I-Jlocus 139 soluble antigen 330 immunity, parasite idiotope 105 escape from 328 escape from 328 idiotype 105 immune response immunization 104 immunoglobulin 94 cooperationin 51,107,158 booster 104 idiotype network 162 maturation of the 103 immune complex idiotypic network interaction primary 70 methods for detection 282 104 secondary 71 immunoadherence 193 19A 88 to infections 311 immunoadsorbants 79 secretion piece or transport immune response region genes immuno-competent cell 3 piece 90 136 immunocytoadherence 193 synthesis and transport of immune response to immunocytoiysis 190 secretory 91 immunoglobulin allotype immunocytotoxicity 191 IgA and IgM deficiency, selective (IgG) 159 immunodeficiency 339 347 lactate dehydrogenase-B antibody 339 IgA deficiency, selective 346 (LDHB) 159 associated with autoimmune IgD 91 ribonuclease (RNase) 159 symptoms 372 IgE 91 suppression 159 classification of 343 biologic activity of 275 immune sera immune system functions, control of, production 280 preparation of 69 evaluation of 339 leukocyte sensitization 275 immune system immunoglobulin 339 liberation of histamine 275 antibody-producing cells 4 immunodeficiency syndrome, radioallergosorbent 275 cell of 4 severe combined (SCID) 351 radioimmunodiffusion 275 control of the, by the H-2 immunodiagnosis 312,313 structure of 92 complex 164 immunodiffusion 171 test for detecting 275 dichotomy of 4 immunoelectrophoresis 174,312 IgE response 322 sensitized cells 4 counter 176 metazoan infection 322 immune system, evaluation of rocket 176 IgG 88 functions of two-dimensional 175 Fc-receptor 11 B lymphocytes 340 immunofluorescence 184 IgG and 19A deficiency, selective immunoglobulins 339 immunofluorescence antibody 347 Mancini test 340 test 312 IgM 88 pokeweed mitogen stimulation immunogenicity 60,64 cytoplasmic 11 340 chemical basis of 64 junction (j) chain 88 radioimmune assay 340 importance of the external monomeric 11 T lymphocytes 341 groupings of the antigen in slgM (secrete IgM) 11 immunity 66 IgM deficiency, selective 346 acquisition of 330 immunoglobulin 94 immobilization 312 active 331 allotype 93 immune cells actively acquired 335 classes and subclasses of animal activity of 33 adaptive 310 93 B lymphocytes 44 cellular 4 classes and subclasses of human lymphocytes 33 concomitant 320 88 436 Subject and Author Index immunoglobulin immunotherapy 332 Jerne Plaque technique 72 genetic markers of 93 accidents of 333 Job's syndrome 360 horse 93 adoptive transfer 334 joining (J) region 98 IgA 88 allogeneic 333 Jones-Mote reaction 294 IgD 91 material used for 334 junction (j) chain 88 IgE 91 xenogeneic 333 IgG 88 inaccessibility 328 K cell (killer cell) 43, 245 IgM 88 anatomical 328 K gene 136 nomenclature of animal 93 inbred strains of mice 133 K molecules 136 physicochemical and biologic infection 319 antigen chart of 137 properties of 89 autoimmune symptomes asso- Kabat 63,79,87 properties of 90 ciated with 371 kala-azar leishmaniasis 323 rodent 93 immune responses to 311 kallikreins 8 structure of 80 metazoal 319 Kapp 41 immunoglobulin genes protozoal 319 kappa chain 85 D segments 99 slow virus 319 kappa chain translocon 98 deletion model 99 special aspects of bacterial Kataoka 99 diversity 99,100 313 Katz 160 formation of active 97 tests for detection of anti• K,D, restriction 157 H chain translocon 99 bodies in 312 Kell 228 heavy chain switches 99 infections, viral Kendall 79,204 intron 98 special aspects of 314 Kendrew 64 joining (J) region 98 infection, parasite 324 kerato-conjunctivitis sicca 390 kappa chain translocon 98 basophil activity in 324 Kidd 228 lambda chain translocon 97 IgE response 322 kidney, transplantation 250 leader (L) sequences 97 mast cell activity in 324 Kiel classification of lymphomas organization of, and their influenza A virus 318 354 expression 97 pandemic strain of 318 killer cell 43 S (switching) sequences 99 ingestion 303,343 killer T cell translocons 97 ingestion deficiency 360 antigen recognition by 294 V-C joining 98 tuftsin deficiency 360 Kindred 160 immunologic techniques initiating factor (IF) 128 King 223 relative sensitivity of 215 inner volume Vi 78 kinins 126 immunoneutropenias 359 instructive theory 96 Kitasato 199 immunosuppression 397,402 insulin-dependent diabetes mellitus Kline 181 alkylating agents 405 380 Koch 287 amino acid antagonists 409 insulitis 380 Kohler 74, 105 aminopterin 408 interactions antigen 161 Konigsberg 162 antibiotic 409 interferon 307,310,313,316 Korngold 85 antimetabolites 406 effector mechanism of 317 Kostmann 359 azathioprine 407 interleukin 1 160,307 Kuru 319 by parasites 329 properties of 161 Kiistner 275 corticosteroids 403 interleukin 2 160,310 Kwashiokor 103 5-fluorouracil (5FU) 407 properties of 161 inhibition of biosynthesis of intercellular killing 34 lactoferrin 6, 306 nuclei acids and protein intrinsic factor 385 lambda chain 85 404 intron 98 lambda chain translocon 97 irradiation 401 Inv factors 94 laminar flow 253 6-mercaptopurine (6-MP) Ir-gene 103,137,158 lamprey 30 407 irradiation 401 Landsteiner 60,96,219 methotrexate 408 total-body 252 Landsteiner's rule 220 plant alkaloids 408 Ishizaka 91, 189 Lapresle 62 rules for 410 isoelectric focusing (IEF) 75 latex 177 6-thioguanine (6-TG) 407 isofixation curve 188 latex test 312 immunosuppressive agents 68 Issaeff 111 LATS, long-acting thyroid immunosuppressives stimulator 380 classification of 400 Jenner 335 Laurell 176 mechanisms of 389 Jerne 72,96,105 lazy leukocyte syndrome 360 Subject and Author Index 437

LD2 392 cartwheel picture 11 Peyer's patches 2 LE cell 392 cooperation between B and T postcapillary venules 22 LE-factor, anti-NP 393 50 primary 2 leader (L) sequence 97 cytotoxic T lymphocytes 42 secondary 2 leishmania 319 differences between B and T thymus 14 leishmaniasis 323 49 lymphoid tissue 1 Lennert 354 differentiation 9, 12 histogenesis of 1 lepromin 313 ecotaxis 34 histology of 1 le~emias 356,358 evaluation of function of B lymphokines 310 acute leukemias 356 340 properties of 292 chroniclymphaticleukemias 357 evaluation of function of T lymphoma, childhood lympho• chronic myelomonocytic 341 blastic 354 leukemia (CMML) 359 immunocompetence of 36 lymphoma, mediterranean 350 leukemogenesis 164 killer cell 43 lymphomas 354 leukocidin 309 long-lived 35 Burkitt's lymphoma 354 leukocyte inhibitor factor (LIF) maturation 9 childhood lymphoblastic 310 memory cells 36 lymphoma 354 leukocyte proliferative disorder migration of 33 classification of non-Hodgkin chronic myelomonocytic natural killer cell 44 355 leukemia (CMML) 359 origin 2 Sezary syndrome 356 leukocyte transfusion 254 plasma cells 47 T cell lymphomas, cutaneous leukopenias, autoimmune 384 receptor for T helper factor 11 356 Levine 219 short-lived 35 lymphotoxin (Ln 292,310,313 Lewis system 222 suppressor T-cell 41 lysozyme 6,191,199,306 light chain abnormality 350 T helper cells 39 light chains 80 T lymphocytes 9, 38 M locus 243 linkage equilibrium 145 T, specific characteristics of M protein 309 Lipari 85 341 macrophage 8,53, 306 lipochrome histiocytosis 361 thymus-dependent 37 activation factor 55 lipopolysaccharide (LPS) 67 thymus-independent 37 activation of 307 Little 131,249 lymphocyte proliferative disorder interaction of microorganisms liver surface protein (LPS) 386 354,358 with 309 Loa loa 325 acute leukemias 356 locomotion of 307 local weight test 237 Burkitt's lymphoma 354 microorganisms that multiply Loeb 131,249 childhood lymphoblastic in 308 Lonai 158 lymphoma 354 phagocytosis by 53 long-acting thyroid stimulator chronic lymphatic leukemias precursor 53 (LATS) 281 357 receptors of 53 Lotus tetragonolobus 220 leukemias 356 role in cellular immunity 54 low zone tolerance 106 lymphomas 354 role in the humoral response Lukes 354 mycosis fungoides 356 55 lupus erythematosus, systemic Sezary syndrome 356 macrophage activating factor (SLE) T cell lymphomas, cutaneous (MAF) 292, 310 association with HLA 165 356 macrophage aggregation factor autoantibodies 391 lymphocyte stimulation 313 292 etiology 391 lymphocyte-activating deter• macrophage inhibition test 291 experimental 393 minants (LAD) 142 macrophage inhibitory factor -like syndromes 362 lymphoid follicles 23 (MIF) 292 Lutheran system 222 lymphoid organs macrophage-lgE lymph functional properties of 3 mediated immunity 327 nodes 2,21 immunologic activity of the macrophage-T cell cooperation vessels 1 primary 14 241 lymphatic leukemias, chronic 357 immunologic activity of the major histocompatibility complex lymphoblast 9 secondary 21 131 lymphochoriomeningitis virus 164 localization of the antigen in malaria 323 lymphocyte 4,9,33 the 29 Malphighian body 26 B lymphocyte 11, 44 lymph nodes 2, 21 Mancini 275 B, specific characteristics 341 origin of primary 2 Mancini test 173, 340 438 Subject and Author Index

Mantoux test 288 iJ2-microglobulin @rMg) 153 NA system 254 Marx 47 microphage 4 NADPH-oxidase 6,303 mast cell 8,268, 324 migration inhibition 313 respiratory burst 304 connective tissue 324 migration inhibition factor Nathenson 151 mucosal 324 (MIF) 310 natural killer cell 44 origin 8 Milstein 74 Necator americanus 325 mast cell-eosinophil cooperation mineral oil emulsion 66 Nematodes 320 326 minimum lethal doses (MLD) 200 nephrotoxic sera (NS) 386 Masugi's nephritis 192, 386 Mitchison 40 network theory 105 maternal-fetal transfer of immuno- mitogenic factor 292 neutralization globulin 331 mixed lymphocyte culture (MLC) complement -dependent 316 Mayer 112,187 cells involved in 241 complement-independent 316 McDevitt 103,156,158 geneticsof 147,242 mechanism of 202 McMaster 47 number of reactive cells 240 of toxins 199 Medawar 132,246, 249 responder 144,240 of virus 312 mediator, antigen-induced libera- stimulator 144,240 virus 316 tion of 272 typing by 144,249 neutropenias 359 megakaryocytes 12 MLC, mixed lymphocyte culture 142 cyclic 359 memory, immunologic 104 MLR, mixed lymphocyte reaction familial severe neutropenia memory cells 36 143 359 6-mercaptopurine (6-MP) 407 specificity of 241 immunoneutropenias 359 Merril 249 MNSs system 224 infantile genetic agranulo• merthiolate 70 molecular masking of parasites 329 cytosis 359 metazoa infections 319,325 molecular mimicry 167 neutrophil 6 basophil activity in 324 monocyte 8 half-life of 7 eosinophilia in 326 life span of 9 Nezelof's syndrome 353 IgE response to 322 locomotion 9 Nicholson 151 mast cell activity in 324 precursor of 8 Nippostrongylus basiliensis prepatency of 325 receptors 9 324 Metchnikoff 4 turnover 9 Nisonoff 83,105 methotrexate 74,253,408 monokines 307 nitroblue tetrazolium dye (NBT) Meyer 122 colony stimulating factor 307 304,343 MHC interferon 307 nomenclature of B complex 132,148 interleukin 1 307 complement 114 BoLA 148 prostaglandins 307 congenic strains 133 ChLA 148 mononucleosis, infectious 181, Ia molecules 137 congenic strains 133 312,371 H-2 K,D specificities 136 DLA complex 132, 148 Morgan 223 Nossal 73,366 gene structure of 147 motility 342 NP 40 151 GPLA complex 132,148 mu chain disease 350 nude mice 321 H-2 complex 132, 148 mucopolysaccharid 8 HLA 148 Miiller-Eberhard 120 Oakley 173 restriction 157 multipe sclerosis (MS) 147,376 Onchocerca volvulus 325 RhLA complex 132,148 Murray 249 ontogeny of the immune system RLA 148 myasthenia gravis 377 30 RTI complex 132,148 mycobacterium tuberculosis 310 ophthalmia, sympathetic 390 SLA 148 mycoplasma pneumoniae 309 opossum 31 MHC antigen (molecule) mycosis fungoides 356 opsonization 112,125,197,302, solubiliZation 151 myeloid leukemia, chronic (CML) 343 MHC gene, function of 155 358 opsonization index 198 MHC molecules myeloma 85 oriental sore, leishmaniasis 323 biochemistry of 151 myeloma, multiple 347 orthotopic graft 235 tissue distribution of 148 myelomonocytic leukemia, chronic osteoclast activating factor (OAF) MHC-disease association 164 (CMML) 359 310 MiiJ Miltenberger) 224 myeloperoxidase 6, 305 Ouchterlony 173 micro complement consumption myeloperoxidase (MPO) Oudin 93,95, 171 test 283 deficiency 361 Owen 246 microdrop technique 73 myoglobin 65 Subject and Author Index 439

P blood group 249 actin polymerization defiency H-2 136 P system 224 360 I-A locus 137 PI A system 254 bactericidal deficiency 360 I-E locus 137 PAF, platelet activating factor 271 Chediak-Higashi syndrome Ia molecules 137 Pain 81 359 polymorphonuclear leukocytes pancreatitis, autoimmune 380 chronic granulomatous disease 4,300 paragonimus 325 (CGD) 360 adherence 303 paraproteinemia, Deutsch's 350 familial severe neutropenia bactericidal activity 303 parasite infection 324 359 basophils 5,270,324 basophil activity 324 glucose-6-phosphate dehydro• chemotaxis 301 eosinophilia 326 genase 361 eosinophils 5,272,326 escape from immune response immunoneutropenias 359 ingestion 303 328 infantile genetic, agranulo- interaction of microorganisms IgE response 322 cytosis 359 with 309 mast cell activity 324 ingestion deficiency 360 microbicidal mechanisms 304 metazoal infections 322 Job's syndrome 360 neutrophils 5,300,342,359 protozoal infections 320 lazy leukocyte syndrome 360 platelets 12, 271,281 paratopes 105 lipochrome histiocytosis 361 Pope 79 Parfentjev 79 myeloperoxidase (MPO) defi- Porter 81,82 PAS reaction (periodic acid Schiff ciency 361 Portier 258 .reaction) 344 neutropenias 359 postcapillary venules 22 passive cutaneous anaphylaxis tuftin deficiency 360 PPD 313 261 phagocytic index 195 Prausnitz-Kiistner reaction inverse Pasteur 336 phagocytosis 194,302 276 288 adherence 303 Prausnitz-Kiistner test 275 Paul-Bunnell reaction 181 degranulation 303 precipitation Pedersen 80 ingestion 303 gel 171 pemphigus foliaceus 390 respiratory burst 304 qualitative 207 pemphigus vulgaris 390 phagolysosome, formation of quantitative 204, 208 precipitation 312 303 ABC-33 methods 209 mechanisms of 170 phagosome 197, 303 assay 208 permeability, vascular 259,282, phosphatase 7 Farr 208 300 alkaline 6 inhibition of 209 peroxidase 7, 305 phosphoglucomutase-3 (PGM-3) P-80 method 208 Peyer's patches 2 147 Preer 173 Pfeiffer 47, 111 phospholipids 7 premunition 321 Pfeiffer's phenomenon 111, picryl chloride 289 prepatency 323 190,203 PK test 91 primary response 70 Pg-5 urinary pepsinogen-5 139 plant alkaloids 400,408 private antigens 135 Pgk (phosphoglycerate kinase) plaque-forming cells (PFC) 72 proactivator (factor B) 127 139 plasma cell 11 , 47 procoagulant (tissue factor) 310 phagocyte 195,302, 342 plasmodia 319 progressive systemic sclerosis adherence 343 platelet 12,271 (PSS) 395 Boyden's chambers 342 release reaction 13 properdin system 127,163,191 chemotactic movement 342 platelet activating factor (pAF) 8 activation of the, by solid degranulation 343 structure of 271 particles 128 disorders 359 platelet aggregation test 284 physico-chemical properties of evaluation of function 342 platelet factor 4 13 components of 127 interaction of microorganisms platelet-specific antigens 254 prostaglandins 8,267,307 with 309 PLLgene 103 protamine sulfate 8 intracellular killing 343 PLT, primary lymphocyte typing protease, neutral 6 motility 342 250 protein A, staphylococcus aureus opsonization 5,194,303,343 pokeweed mitogen stimulation 309 PAS reaction (periodic acid 340 proteins, cationic 6,306 Schiff reaction) 344 polyethylenglycol (PEG) 74 protopod 7 Rebuck skin window test 344 polylysine (PPL) 65 protozoal infection 319 phagocyte deficiency diseases polymorphism of immunologic features of 323 359 complement components 129 protozoan, parasites of mice 321 440 Subject and Author Index prozone 178 RLA 148 lymphoid stem cell defect 352 psoriasis vulgaris 165 rocket immunoelectrophoresis Nezelof's syndrom 353 public antigens l35 176 purine nucleoside phosphory- pulmonate fish 31 Rodgers, C4-allotypes 147 lase (PNP) deficiency 352 purin nucleoside phosphorylase Romer 200 reticular dysgenesia 353 (pNP) deficiency 352 Rose 365,378 transcobalamin II deficiency puromycin 409 Rose-Waaler hemagglutination 352 test 394 Sezary syndrome (SS) 356 quinidine 192 Rosette technique 72 sharks 30 Qyloci 139 RTI complex 132, 148 Shigella dysenteria 315 ruut disease 20,383 side-chain theory 96 Race 226 Simonson 237 radiation-induced leukemia virus S region l38 Singer 151 164 S (switching) sequence 99 skin reactive factor 292,313 (RAST) Sabin, vaccination 336 SLA 148 212,275 Sabin-Feldmann test 312 slow viruses infection 319 radioimmune assay (IgE) 340 salting out 77 slow-reacting substances of 211, 312 sandwich technique 185 anaphylaxis (SRS-A) 8,267 radioimmunodiffusion 275 sapoain 66 slow-virus infection 371 Raff 41 scalded skin syndrome 315 SIp (sex-limited protein) gene Raji cell assay 284 scar let fever 315 l38 Ramon 66,201 Scatohard's equation 212 Smith 104 flocculation 171 scavenger cells 194 Snell l32, 136,249 Rappaport's classification of Schick test 312 soluble antigen, by parasite 330 lymphomas 354 schistosoma 325 spleen 2,26 Raynaud's syndrome 390 Schultz-Dale reaction 276 histology 26 reaginic antibody 91 scleroderma 395 spleen index (ST) 237 Rebuck skin window test 344 scrapie 319 splenomegaly test 237 recombinants for the H-2 com- seclusion inside host cells 328 splitting of serologic HLA plex l36 secondary disease 237, 383 specificities 142 recombination frequency 134 secondary response 71 Sprent 160 regulatory cell circuits 10 6 secretion piece 90 Staphylococcus aureus 309,315 Reisfeld 151 secretory system 222 protein A 309 release reaction 13 Sela 65 stem cell 5 restriction selection stem cell defect, lymphoid 352 I region 160 negativ 241 Still's disease 393 K,D 157 positiv 241 stimulation index 237 reticular cells 57 selective IgG deficiency 346 Stokes law 183 dendritic 57 self-recognition 366 Streptococcus pyogens 315 reticular dysgenesia 353 sensitivity, contact 288 streptolysines 309 reticuloendothelial system (RES) sensitized cells 4 Strominger 153 195 sepharose, activated 78 strongyloides stercorali 325 Rh system Sercarz 71 superantigen 57 agglutinogen 224 serodiagnostic test 187 suppressor gene l39,158 allonantibody 226 serology 169 supressor T-cell 41 factor 224 of the HIA complex 139 Swiss-type agammaglobulin 252 genetics 226 of the mouse MHC 135 Swiss-type deficiency 352 rheumatic fever 389 serotonin- (5-hydroxytryptamine) switch from IgM to IgG 49 rheumatoid arthritis 165,393 8,266 synergeneic 235 rheumatoid factor (RF) 94,370, serum, electrophoretic profile of syngeneic l32 394 80 syphilis 181 RhLA l32, 148 serum sickness 282,285 system I 229 ribonuclease 7,159 pathogenesis of 286 system Xg 229 Richards 162 serum thymic factor (STF) 19 Richet 258 severe, combined immunodefi• T cell 3,9,38 Rieckenberg reaction 193 ciency disease 351 T cell bypass 368, 369 ring test 170 adenosine-deaminase deficiency T ~ll deficiency 350 Rivers 374 (ADA) 352 .candidiasis mucocutaneous 351 Subject and Author Index 441

DiGeorge's syndrome 351 thrombopoesis 13 transplantation 235,252 Hodgkins's disease 351 thrombopoietin 12 blood 229,253 T cell receptor 162 Thy-1 (theta, 8) antigen 9,39 bone marrow 252 T helper cells 39 4,400 kidneys 250 T lymphocyte 9,39,156,341, effect of 15 organ 249 370 thymic humoral factor (THF) 19 terminology 235 antigen (human) 356 thymidine-kinase (TK) 74 thymus 252 cooperation with B lympho- thymopoietine I 19 typing for 141, 249 cytes 50,241 thymosine fraction 19 transplantation reaction cytotoxic 42,50,156,243 thymosine at 19 graft -versus-host reaction differences to B lymphocytes thymus 2,14 235,238 49,341 active substances produced 19 host-versus-graft reaction 236 helper cells 39,50,158 dependent 15 mechanism 239 killer cells 43, 244 dependent system 4 stimulation index 237 marker 50,341 destiny of lymphocytes of the transport piece 90 origin 9 15 transporter theory of immuno- specific characteristics 341 functions of the adult 17 globulin 368 suppressor 41,50,158,370 graft 17 transfer factor 290 tolerance 248 Hassal's corpuscles 14,352 trematodes 320 T ,B cell deficiencies, combined hormonal activity, of the 19 Trichinella spiralis 325 351 importance of, in the produc- Trichuris trichiura 325 adenosine-daminase deficiency tion of antibody 16 Trypanosoma 319 ADA) 352 independent 16 trytophol 330 ataxia telangiectasia 354 mitotic activity of lymphocytes TSH receptor 379 lymphoid stem cell defect of the thymus 14 tuberculin, reaction to 287 352 origin lymphocytes, of the 18 tuftsin 303 Nezelof's syndrome 353 thymus hormone 19,252 tuftsin deficiency 360 purine nucleoside phosphory• thymus transplantation 252 tumor growth, susceptibility 131 lase (PNP) deficiency 352 thyroglobulin 379 typing reticular dysgenesia 353 thyroiditis cellular 143,249 severe-combined immunodefi• experimental autoimmune primary lymphocyte (PL T) ciency syndrome (SCID) 378 250 351 Hashimoto's chronic lympho- serologic 249 trans cobalamin II deficiency cytic 378 Tyzzer 131 352 Tiselius 79, 80 Wiscott-Aldrich syndrome 353 TL antigen 9,18 U factor 224 T-B-cell interaction 241 Tla locus 139 ubiquitine 20 T-cell defect 252 tolerance 245, 366, 409 ulcerative colitis 385 T-helper factor 11 tolerance, immunologic 235 ulex europeus 220 T-T cell interaction 241 Tomasi 90 urine-pepsinogen-5 (Pg-5) 147 Taenia saginata 325 Tonegawa 96 uropod 7 Taenia solium 325 total-body irradiation (TBI) 252 Tagliacozzi 249 toxins, neutralization of 199 V genes 97 Takatsy microtitrator 182 Toxocarna canis 325 V-C joining 98 TAME (N-p-toluenesulfony- toxoids, bacterial 335 vaccination 335 methyl ester) 117 toxoplasma 319 vaccine 336 Tennant virus 164 toxoplasmosis 323 Vaccinia virus 164 Terasaki 165 TPI test 192 Valentine 95 ~-test 141 transcobalamin II deficiency 352 van Bekkum 253 tetanus 315,334 transfer factor 292 van der Waals forces 215 6-thioguanine (t-TG) 407 transfusion 229, 254 van Krogh equation 112 Thomas 253 translocon 97 van Rood 141 thoracic ducts 1 heavy chain translocon 98 variable region 85 thrombocyte transfusion 254 kappa chain translocon 98 vasculitis 185, 394 thrombocytes 12 lambda chain translocon 97 VDRL tests 181 maturation of 12 transmission, viral velocity sedimentation 241 thrombocytopenias 384 horizontal 314 V genes 99 thrombocytopenic purpura 192 vertical 314 Vibrio cholerae 315 442 Subject and Author Index vicia graminea 224 Waaler 394 Williams 174 virus Waldenstrom's macroglobulinemia Wiskott-Aldrich syndrome 353 complement-dependent neutrali• 349 Witebsky 365,378 zation 316 Wassermann 370 Witebsky substances 221 complement-independent Wassermann reaction 185 Wucheria banchrofti 325 316 wasting disease 20 virus infection 314 wasting syndrome 237 xenoantisera 69 cell mediated immunity 316 Webb 171 xenogeneic 132,235 vitamin B12-biriding glycoprotein' Weckerle 365 Xg3 228 385 Well-Felix reaction 312 V L chains, histogram of the White-Kaufmann table 180 Yoffey's fourth circulation 34 variability of 87 whooping cough 315 void volume, Vo 78 Widal's test 180 Zinkernagel 156 Vw (Verweyrt) 224 Wiener 224 zymosan 114, 127 J. C. Cawley, G.P. Burns, F. G. J. Hayhoe Hairy-Cell Leukaemia 1980.64 figures, 4 tables. IX, 123 pages (Recent Results in Cancer Research, Vol. 72) ISBN 3-540-09920-4

Current Topics in Microbiology and Immunology Editors: W.Arber, S.Falkow, W.Henle, P.H.Hofschneider, J. H. Humphrey, J. Klein, P. Koldovsky, H. Koprowski, O. Maal0e, P. Melchers, R Rott, H. G. Schweiger, L. Syrucek, P.K Vogt Volume 86 1979.29 figures, 22 tables. III, 168 pages ISBN 3-540-09432-6 Contents: Genetic Potential ofBunyaviruses. - Defective Interfering Particles of Togaviruses. - The Fv-l Gene of Mouse and its Control of Murine Leukemia Virus Repli• cation. - Defective Interfering Particles ofRhabdoviruses.

Immune Deficiency Editors: M.D.Cooper, ARLawton, P.AMiescher, R J. Mueller-Eberhard 1979. 10 figures, 22 tables. IV, 184 pages ISBN 3-540-09490-3

Immunodiagnosis and Immunotherapy of Malignant Tumors Relevance to Surgery Editors: H.-D. Flad, C.Herfarth, M.Betzler 1979. 101 figures, 109 tables. X, 329 pages ISBN 3-540-09161-0

Immunological Diagnosis of Leukemias Springer-Verlag and Lymphomas International Symposium of the Institut flir Hiimatologie, Berlin GSF, October 28-30, 1976, Neuherberg/Mtinchen Editors: S. Thierfelder, H. Rodt, E. Thiel Heidelberg 1977.98 figures, 2 in color, 101 tables. X, 387 pages New York ISBN 3-540-08216-6 Immunostimulation Editors: L. Chedid, P. A Miescher, H.l Mueller-Eberhard 1980. 44 figures, 39 tables. VIII, 236 pages ISBN 3-540-10354-6

1 Klein Biology of the Mouse Histo• compatibility-2 Complex Principles ofImmunogenetics Applied to a Single System 1975.58 figures, 90 tables. XII, 620 pages ISBN 3-540-06733-7

Lymphocyte Hybridomas Second Workshop on "Functional Properties of Tumors ofT and B Lymphocytes" Sponsored by the National Cancer Institute (NIH) April 3-5, 1978 Bethesda, Maryland, USA Editors: F. Melchers, M. Potter, N. L. Warner Reprint. 1979.85 figures, 86 tables. XXI, 246 pages ISBN 3-540-09670-1

The Major Histocompatibility System in Man and Animals Editor: D. G6tze With contributions by numerous experts 1977. 23 figures. X, 404 pages ISBN 3-540-08097-X

RE.Mancini Immunologic Aspects of Testicular Function 1976.36 figures, 8 tables. Ix, 114 pages (Monographs on Endocrinology, Vol. 9) ISBN 3-540-07496-1

Springer-Verlag W. E. Stewart II Berlin The Interferon System Heidelberg Second, enlarged edition. 1981. 23 figures. Approx. 500 pages Wien-New York: Springer-Verlag New York ISBN 3-211-81634-8