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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 bacteriology 1880 Discovery of attenuated vaccine by Louis Pasteur invitro passages 1883 , cellular theory Elie I. I. Metchnikoff 1888 Discovery of bacterial toxins P. P. Emile Roux and Alexandre E. J. Y ersin 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 1896 Agglutination test for the diagnosis of Georges F. I. Widal and typhoid (Widal test) Jean-Marie-Athanase Sicard 1900 Formulation of side-chain theory of anti- body formation 1900 Discovery of A, B, 0 groups 1900 Development of complement fixation Jules J.B. V. Bordet and reaction Octave Gengou 1902 Discovery of Charles R. Richet and Paul Portier 1903 Local anaphylaxis due to antibody- Nicholas M. Arthus complex: 1903 Discovery of opsonization Almroth E. Wright and Steward R. Douglas 440 Brief History of Important Immunologic Discoveries and Developments

Year Event Author(s)

1905 Description of Clemens von Pirquet and Bela Schick 1910 Introduction of salvarsan, later neo- Paul Ehrlich and Sahachiro Hata salvarsan, foundation of chemotherapy of 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• biotic 1935 Discovery of sulfonamides for chemo• therapy of infections 1935 Discovery of local immunity; oral Alexandre Besredka vaccination 1935-36 Purification of , quantitative and precipitation reaction Forrest E. Kendall 1937 Evidence for identity of the for Peter A. Gorer blood group antigen II with one gene for tumor resistance in the mouse (B-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 in guinea pigs W.Chase 1942 Fluorescence labeling of antibodies and Albert H. Coons 1942 Introduction of adjuvants Jules T. Freund 1943-44 Establishment of immunologic basis of Peter B. Medawar rejection of normal tissue transplants 1946--48 Theory of congenic mouse lines formu• George D. Snell lated, first congenic lines initiated, and the term introduced 1945 Development of antiglobulin test for Robin R.A. Coombs, R.R.Race, incomplete Rh antibodies and A. E. Mourant Brief History of Important Immunologic Discoveries and Developments 441

Year Event Author(s)

1945 Description of tolerance (chimerism) in Ray 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 , later be shown to belong to the major histocompatibility complex of man (HLA) 1956 Experimental induction of 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 Carleton Gajdusek (Kuru) 1959 Introduction of the radioimmune Rosalyn Yalow and Solomon A. Berson 1960 Antibody structure Alfred Nisonoff, Gerald Edel- man, Rodney P. Porter, Henry G.Kunkel 1961 Discovery of the thymus as part of the Jaques F. A. P. Miller, Robert A. Good 442 Brief History of Important Immunologic Discoveries and Developments

Year Event Author(s)

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 1963 (1953) Histamine release by mast cells in Ivan Mota anaphylaxis 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 -l (Ir-1) 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 as cells with surface• Benvenuto Pernis bound Ig discovered 1969 Discovery of 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 toHLA Edmond J. Yunis and Bernhard in man Amos 1971 Two-locus model of the mouse MHC George D. Snell, Jan Klein, (H-2) formulated Donald C. Shreffler, Jack Stimpfling 1971 T and tolerance defined 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 G6tze, David H. Sachs Brief History of Important Immunologic Discoveries and Developments 443

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. N athenson, Jack antigens defined Strominger 1978 -T cell collaboration Jonathan Sprent I-region restricted 1978-80 Elucidation of immunoglobulin ; Suzuma Tonegawa generation of diversity is (almost) solved 1980 worldwide eradicated World Health Organization (WHO) 1982 CD antigens defined by monoclonal Leukocyte antigen workshop, antibodies (Reinharz) 1983-85 T cell antigen receptor genes elucidated Marrack, Allison Glossary of Immunologic Terms

Accessory cells. Lymphoid cells predominantly of cells by cytotropic antibodies following ex• the 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 Affinity. Binding strength between antibody and (ADCC). A form of -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 . Antigens which give rise to allergic sen• an animal sitization by IgE antibodies Antigenic determinant (). That area of an . 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 graft between two Antigen processing. The series of events which oc• genetically dissimilar members of the same curs following antigen administration until species antibody production . 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• . 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 Anaphylaxis. A reaction of immediate hypersen• . 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 446 Glossary of Immunologic Terms

Attenuated. Rendered less virulent Bursal equivalent. Hypothetical organ or organs . 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 . 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 Il 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 coHagen and to coupled to a , 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• Classical 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 I, 423, 567, 89 amount of cytoplasm with numerous polyribo• 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• Clone. 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 Bone marrow. Soft 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 Fabricius. 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 447

reaction in which complement is fixed as a re• Domains. Segments of H or L chains that are sult of the formation of an . folded 3-dimensionally and stabilized with di• The subsequent failure oflysis 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, Denotes a line of mice identical or nearly iden• and swelling tical with other inbred strains except for the Effector ceUs. 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. 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 phago• 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 immunoftuorescence. The detection of anti• It contains antigen-binding activity. An gens by fluorescently labeled antibody F(ab12 fragment and an Fc fragment comprise Diversity. Multitude of different antigen-specific an entire monomeric immunoglobulin mole• combining sites (VH and VL regions) cule 448 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 . 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 immunoglobulins 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 , 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 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 which controls the mouse a.o., but is absent from tissue of human production of 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 . An 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 449

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 la 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• ldiotope. An epitope of the antigen-binding site pates in a cross-reaction of an antibody High dose (high zone) tolerance. Classical immuno• ldiotype. Unique antigenic determinants present logic unresponsiveness produced by repeated on homogeneous antibody or myeloma pro• injections of large amounts of antigen tein. The appears to represent the Hinge region. The area of the H chains between antigenicity of the antigen-binding site of an the first and second C region domains. It is antibody and is therefore located in the V re• the site of enzymatic cleavage into F(ab'h and gion 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 ceUs (HTC). Cells that carry approximately 10% 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 radio• body isotope e31I). Used either in vivo or in vitro Immune complexes. Antigen-antibody complexes 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 450 Glossary of Immunologic Terms

Immunoftuorescence. 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 ceO. 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• . 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 ceUs. Fixed mononuclear 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 (A) 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 1, capable of activation and disease production IgG2, IgG3, and IgG4 Latex fixation test. 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 . 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 ceO phenomenon. Phagocytic leukocytes that viral infection have engulfed DNA, immunoglobulin, and Inv 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 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 451

Leukocyte mitogenic factor (LMF). A lym• Lysostrip. Removal of one kind of surface anti• phokine that will induce normal lymphocytes gen by capping wi th 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 9,000/mm3 in human blood, divided on the same or different molecules into granulocytes (polymorphs 68%-70% Lysozyme. An enzyme present in the granules of 3% 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-p (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 disequilibrium. When alleles of two phokine which will activate macrophages 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 (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 Oow 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 (MIIC). 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 ceo. A tissue cell which resembles a periph• widely throughout the body which are com• eral blood and contains granules with posed mostly of lymphoid cells serotonin and histamine present Lymphocyte. A mononuclear cell 7-12 J..I.Ill in di• Memory ceUs. 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 Oymphocyte stimulation, P'1. 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• . 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 452 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 . 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 . Transfer of preformed anti• paraprotein, , 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 of lymphoid tissue in antibody and complement neutralizes the in• the submucosa of the small intestine which fectivity of microorganisms, particularly contain lymphocytes, plasma cells, germinal 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 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• . A substance capable of enhancing garis) and which stimulates predominantly T phagocytosis. Antibodies and complement are lymphocytes the 2 main Pinocytosis. The ingestion of soluble materials by cells Plaque-forming cells (PFC). Antibody producing Paralysis. The pseudotolerant 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 453

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• Polyethylenglycol (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 Ia 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 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• (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 Pyogenic microorganisms. Microorganisms for sheep red blood cells whose presence in tissues stimulates an out• pouring of polymorphonuclear leukocytes Pyrogens. Substances released either elldoge• 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- 454 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 ofM protein present on not essential to the ontogeny of immune re• outermost surface of bacteria sponses, i.e., the spleen, lymph nodes, tonsils, Streptolysin O. Exotoxin produced by Strep• and Peyer's patches tococcus pyogenes. Oxygen-labile, haemolytic, Secretory IgA. A dimer of IgA molecules with a and a powerful antigen sedimentation coefficient of II S, linked by J Streptolysin S. Exotoxin produced by Streptococ• chain and secretory component cus pyogenes. Oxygen-stable, causing P 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 . 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 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 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 (C 4 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 Small lymphocytes which on (or after) resi- Glossary of Immunologic Terms 455

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. lO s.s pful viraemia), or occasionally associated with ery• ml throcytes or 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 (1980) Basic and clinical , 4th ed. Lange sitivity to antigens from Mycobacterium tuber• 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 940 SUbject and Author Index

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

AAME (N-acetyl-arginine-methyl adriamycin, immunostimulation alternative complement pathway ester) 121 422 133,135 ABC (antigen binding capacity), affinity labeling technique 92 properties of components 134 inhibition of 219 agammaglobulinemia 365 alum 71 method 218 age, influence of immune re- aluminium hydroxide 70 ABO blood group sponse 108 aluminium phosphate 70 alloantibodies 229 agglutination 187,332 am, human Ig allotype 98 biochemistry 231 passive 191 amebiasis 343 genetics 229 amino acid antagonists 436 agnates 32 serology 227 aminopterine 79, 436 agranulocystosis, infantile genetic typing 311 amphibians 32 377 abortion, clonal 310, 350, 383 ANA, anti-nuclear-antibodies in Aldrich 271 acanthosis nigricans 399 LE 409 alexin 115 actin polymerization deficiency, anaphylactic shock, after sero• alginate of calcium 70 deficiencies 378 therapy 352 alkaloids 435 actinomycin 435 anaphylatoxin 116, 128 alkylating agents 432 acute leukemias 375-376 anaphylaxis alleles, MHC 144 B,T cell proliferative disorders acute 267 allelic exclusion 53, 101 375-376 atopy 268 alloantibodies basophils 259 bone marrow transplantation ABO blood groups 229 314 bradykinin 253 H-2 molecules 143-146 cAMP 265, 272 acute respiratory distress syn• HLA molecules 148-150 drome, ARDS 129 calcium influx 265 Rh antigens 234 cells involved 255-257 adaptive immunity 330 alloantigen 139 ADCC, antibody-dependent cell• chemotactic factor B cells 54, 55 252,254 mediated cytolysis 292, 346 erythrocytes 227,297 Addison's disease 398 eosinophils 260 Gv 41 Forssman shock 266 adenosine-deaminase, ADA, histocompatibility 45, 143, 148 deficiency 371 in guinea pigs 245-267 leukocytes 143, 148,297 heparin 255 adenosine-deaminase deficiency, Lyt antigens 11, 41, 45, 55, 59 leukotriens 254 T,B cell combined deficiencies Qa antigens 11 local 267 371 T cells 11,47, 55, 173 in man 267-278 adherence, white blood cells 323, TL antigen 12, 19,41 mechanism 244 362 Thy-l antigen 11, 19,39,41 mediators 244, 252 adherent cells 60 thymocytes 12, 19,20 chemotactic factor adjuvants 70, 417--420 alloantiserum 73 254 depot effect 7 I effect 61 passive 246 effect on cells 419 reactive cells 304 activating factor 252, immunostimulation 4 I 7 allogeneic 140, 297 255 mitogenicity 71 alloreactivity 170 platelets 259 tapioca 417 allotransplant 140 ancylosing spondylitis 176 target of action 4 I 8 allotypes 98, 99 ancylostoma duodenale 345 adoptive immunization 243 allotypic restriction 98 anemia adoptive transfer 355 alpha chain aplastic 315 adrenal 21-hydroxylase, 21-0H T cell receptor 172 autoimmune hemolytic 399 154 alpha chain disease 369 autoimmune in NZB mice 401 adrenogenitale syndrome, AGS alpha method of precipitation 18 I autoimmune in dogs 402 176 alpha-naphtyl acetate 363 pernicious 173, 403 458 Subject Index anergy 388 IgM 93 neutrophil specific 316 aneuploidy 376 J(unction) chain 94 particulate 75 animal kappa chain 90 phylogenic distance 106 Ig 97 kappa chain translocon 103 platelet specific 316 MHC 156 lambda chain 90 polar groups 65 annelids 32 mediated inhibition 384 polylysine, PLL 69 anti-idiotype antibody 271 monoclonal 79 polysaccharide 66,75 antibacterial sera nomenclature of animal Ig 97 protein 64, 68, 75 protective action of 212 physicochemical properties 93, protein, molecular weight 106 antibiotics 435 94 recall 361 antibodies see also immunoglobulin precipitation 83, 180, 332 recognition by antibodies 89 affinity labeling technique 92 preformed (natural) 318,320 recognition by T cells 162 agglutination 187, 332 primary response 74 seclusion 348, 386 allotypes 98 production 39 species-specific 67 anti-basement 404 purification 81 synthetic 64 antigen combining site 91 regulation offormation 105 T cell receptor 56 antigen complexes, type III hy- regulatory cell circuits of anti- thymus-independent 72 persensitivity 279 body formation 111 variation 348 binding site 67 secondary response 75 antigen-antibody complex reaction, blocking 270, 297 secretion piece of IgA 95 hypersensitivity type III 279 catabolism 89 sedimentation constant 84 antigenic determinants 1, 64 chromatography 82, 87 serologic reactions 179 antigenic drift, influenza virus classes human 92 structure 85, 94 338 classes of horse Ig 97 subclasses human 92 antigenic shift, influenza virus classes of rodent Ig 97 subclasses of rodent Ig 97 339 clonal selection theory 100, 105 synthesis of IgA 95 antilymphocyte serum (globulin) Cohn fractination 83 translocons 101 427 cold 399 transport piece of IgA 95 immunosuppressors 427 dependent cell-mediated Iym• variable region 90 mechanism of action 428 pholysis, ADCC 292, 302, warm 399 antimetabolites, immunosup• 305,306 antibody-antigen complexes 350 pressors 433 detection in infectious diseases antibody-dependent cell-mediated antitoxin, avidity 211 332 cytotoxicity, ADCC 45,292, antiviral effector molecules, differentiation of 78 302,305,306 AVEMs 337 differentiation of antibody form- antibody-mediated inhibition 384 aquafor 71 ing cells 78 antibody reactions arachidonic acid in anaphylaxis domains 89 agglutination 187,332 254 Donath-Landsteiner 400 complement fixation 196, 332 arlacel 71 dynamics of formation 74 conglutination 203 arthritis, rheumatoid 176 electronmicroscopy 100 immunoadherence 202 Arthus 131,283 enzymatic fragmentation 87 immunocytolysis 21 Arthus reaction 131,279,283 feedback control of synthesis immunocytotoxicity 201 ascaris lumbricoides 345 109 194,332 Aschoff 205 forming cells 78 neutralization, toxin 209 Askenase 294 Forssmann 74 opsonization 206 asparaginase 436 frame work region 91 precipitation 180, 332 ataxia teleangiectasia, T,B cell generation of diversity 101, 105 serologic reactions 179 combined deficiencies 372 H chain translocon 103 antigen 63 ATEE, n-acetyl-L-tyrosine-ethyl heavy chain, gene structure 102 antibody formation related to ester 121 heavy chain, protein structure 105 athymic mice 41 86 CD 361 atopy 109,268 heterocytotropic 248 cluster of differentiation 55 Austen 263 heterogeneity 84, 89 combining site, structure 91 Australia antigen 187 hinge region 88 competition 348 383, 384 homocytotropic 248 determinants 67 autogenic 140 hypervariable region 91 E271 autoimmune disease idiotypes 99 Forssman 67,74 acanthosis nigricans 399 IgA 94 leukocyte specific 315 Addison's disease 398 IgD 95 lipid 64 anemia, autoimmune IgE 96 loss 349 hemolytic 399 IgG 93 natural 65 blood 399 Subject Index 459

central nervous system 392 evaluation of function 360 Bombay type, erythrocyte blood classification 393 IgE producing, ontogeny 263 group 228 endocrine glands 396 marker 55 bone marrow transplantation erythrocytes 399 B,T cell, indications 314 experimental allergic encephalo- 371-373 prognosis 314 myelitis 392 B, T cell proliferative disorder booster 75, 109 eye 407 acute leukemias 375-376 Bordet 115, 116, 187, 196, 199 factors influencing 389 Burkitt's lymphoma 374 Boyden chamber 130, 362 gastrointestinal tract 403 childhood lymphoblastic lym- Boyden's technique 192 Graves disease 398 phoma 374 Boyse II, 303 Hashimoto thyreoiditis 396 chronic lymphatic leukemia bradykinin in anaphylaxis 253 heart 407 376 Bruton-type hypogammaglobu- induction 386 classification 374 linemia 365 infectious agents in 390 cutaneous lymphoma, mucosis Burkitt's lymphoma, B,T cell pro- insulin-dependant diabetes melli- fungoides 375 liferative disorders 374 tus 398 immunodeficiencies 373-377 Burnet 100, 163, 308, 383 kidney 404 leukemias 375 bursa of Fabricius 2, 22 liver 403 lymphomas 373-375 bursectomy in chicken 365 lung 406 Sezary syndrome 375 bursectomy, immunosuppressors lupus erythematosus, systemic T cell lymphoma 375 426 408 babesia 349 C genes 102 mechanisms 392 Bach 152 C reactive protein 320 394 backcross system 141 Cl 120 myasthenia gravis 395 bacterial infections 334 Cl-esterase 121,131 pancreatitis, autoimmune 398 bacterial toxins 335 C I-esterase deficiency 121, 380 progressive systemic sclerosis, bactericidal deficiencies 379 Clq solid phase radioimmune as- PSS 413 bactericidy say 282 411 oxygen-dependent 324 CIR, -receptor 134 skin 408 oxygen-independent 326 C2 123 specific 391-413 bacteriolysis, complement-medi• C3 123 systemic 408-413 ated 116, 127 C3-convertase 124, 164, 174 thyreoiditis, experimental Baroni 311 C3 gene, man 124 autoimmune 396 basophils 8, 344 C3 gene, mouse 147 tissue lesions 391 in anaphylaxis 259 C3b-inactivator 124 autoimmune symptoms, Basten 77 C3b receptor 54 associated with immunodeficien• Bayol F 71 C4 122 cies 391 BCG 355 C4 gene, man 154 associated with infections 389 vaccine 209 C4, man 154, 164 autoimmunity 384, 386 Becker 263 C4, mouse 146, 164 auto recognition 63, 383, 386 Behrendt 257 C5 124 autotransplant 140 Behring 209 C6 124 auxiliary regulatory circuits 113 Benaceraff 20,97, 109, 165 C7 124 avidity, antitoxin 211 Bence-Jones protein 89 C8 124 azathioprine (Imuran) 433 Bennich 262 C9 125 Bert 311 cAMP, in anaphylaxis 265, 272 B animals 303 beryllium sulfate 70 CD, see cluster of differentiation B cell bestatin, immunostimulation 421 CD antigens 361 alloantigen 54, 55 beta method of precipitation 181 on T cells 173 differentiation factor 49 Binz 56 CD8 antigen, structure 161 immunodeficiencies 364--370 Biozzi 76, 203 calcium alginate 70 tolerance 310 birds calcium influx, anaphylaxis 265 B complex, chicken major his- immune system 22, 23 Campbell 84 tocompatibility complex 140 Bittner virus 176 Cantor 11, 112,303 B factor B 134 Bjorneboe 52 capillary tube migration test 362 B factor, man 154 Black 253 capping 51, 157 B lymphocytes 12, 48 Blaser 271 Capron 259 activation 49 blast 39 caps 51 anti serum 39 transformation 49, 150 Carrel 311 clonal expansion 50 blocking antibodies 270, 297 carrier 64 differences from T 54 Bloom's syndrome 376 cartwheel picture 13 differentiation of 13 Blundell 227 Castellani's test 191 460 Subject Index

Catty 262 classes of human antibodies 92 solubilization of immune com• celiac disease 176 classification plexes 137 cell mediated hypersensitivity 284 autoimmune disease 393 tissue injuries 131 cell-mediated cytotoxicity 305, B, T cell proliferative disorders titration of hemolytic 116 333 374 concanavalin A, Con A 60 genetics 305 hypersensitivity 244 configuration, protein 192 cell-mediated immunity, assay sys• immunodeficiencies 364 spatial 65 tems 333 immunosuppressors 424 conformational determinants 68 cellular immunity, macro phages lymphomas 374 congenic mouse strains 142 61 clonal (T cell) abortion 373 nomenclature 142 cellular typing, human 150 3 \0 production 141 cestodes 339, 345 clonal expansion 50, 105 congenital (passive) immunity chagas disease 343 clonal inactivation 384 350 Chediak-Higashi syndrome, phago- clonal selection 78, \05 conglutinin activating factor 124, cyte deficiencies 376, 378 theory of antibody formation 203 chemiluminescence 324 100 conglutinin radioimmune assay chemotactic deficiencies 378 done, B lymphocyte 13 282 chemotactic factors 116, 129,322 cloning, monoclonal antibodies connective tissue mast cells 8 eosinophils 291 79 contingency table 149 lymphocytes 291 clonotypic determinant 171 Coombs 399 macrophages 291 cluster of differentiation, CD 47, Coomb's test 400 neutrophils 291 55 Coons 52,75, 195 chemotactic substances, Cobra venom factor 128, 136 cooperation between T and B lym- generation 321, 331 Cohn 83,383 phocyte 57-59 chemotaxis 320, 321, 333 Cohn fractionation of antibodies cord factor 418 Chen 277 83 core regulatory circuits 112 Chido, complement marker 137, Cohn's fractionation 352 correlation coefficient test 149 154 corticosteroids 428 childhood lymphoblastic lym• colchicine 435 colitis, ulcerative 403 effects on lymphocytes 430 phoma, B,T cell proliferative immunosuppressors 428-430 disorders 37 Collins 373 colony stimulating factor, CSF 5 mechanism of action 429 chimerism 314 Cosenza 1\0 chloramines 325 complement 118 alternative pathway 133 counter-immunoelectrophoresis chloramphenicol 435 186 cholera vaccine 356 biologic activities 127 Crohn's disease 403 Christiansen 197 biosynthesis 137 cross-absorption 143 chromoglycate 272 CI 123 cross-reaction 65 chromosomal location of Ig genes CI-esterase 121,131 agglutination 190 101 C2 123 precipitation 218 chronic granulomatous disease, C3 123 5lCr-release assay 165 CGO of childhood 379 C3-convertase 124, 164, 174 cutaneous basophil hypersensitiv• chronic lymphatic leukemia, B,T C4 122 ity 294,342 cell proliferative disorders C5 124 376 C6 124 cutaneous delayed chronic lymphatic leukemias, C7 124 hypersensitivity 61 CLL 376-377 C8 124 cutaneous lymphoma, mucosis fun• chronic myeloid leukemia, CML C9 125 goides, B,T cell proliferative 377 cascade 119 disorders 375 chronic mye1omonocytic deficiencies 177,380-382 cyclophosphamide, immunostimu• leukemia 377 dependent liberation of hista- lation 422 cimetidine, immunostimulation mine 130 cyclosporin A, 421 fixation 89, 196,332 immunostimulation 421 Cinader 211 fixation, mechanism 199 cysticercosis 345 Cinader index 211 formation of kinines 131 cytolysis, complement-mediated cistrons ofIg 101 hereditary deficiencies 137,380 116, 125 class I genes, mouse 143 in host defense against infec- cytoreductive treatment 314 class I molecules, structure 159 tion 132 cytotoxic lymphocyte 45 class II genes, mouse 144 MHC linked components 174 cytotoxic reaction, hypersensitivity class II molecules, structure 161 nomenclature \18 type II 278 class III molecules, structure 162 properties of human 118 cytotoxicity classes of animal Ig 97 quantitative determination 126 cell-mediated 333 Subject Index 461

eosinophil-IgG 347 Donath-Landsteiner antibodies Feldman 77 macrophage-IgE 347 400 Feldman and Basten chamber 77 cytotropy 89 DP antigens, HLA 152 Fenner 308 dracunculus medinensis 345 Ferrata 116 DTH skin test 333 fetal erythroblastosis 353 D, C3-proactivator convertase DTP, diphteria-tetanus-pertussis fibrinopeptide B 132 134 vaccine 355 Fick's law 181 Dale 246, 269 Durham 187 filopodia 350 Dausset 148 Fisher 234 Dean 181 E, antigen 154,271 Fisher-Race nomenclature 235 degranulation 362 ECF-A Fleischman 86 phagocytosis 323 eosinophil chemotactic factor-A, flocculation 211,332 delayed hypersensitivity 39,61, in anaphylaxis 252, 254 fluorescence microscopy 194 71,284 ff. metazoal infection 346 fluorescent quenching 222, 223 contact sensitivity 287 eosinophil chemotactic factor 5-fluorouracil 434 effector cells 289 133, 322 folic acid antagonists 434 mast cells 294 enhancing factor of allergy 277 Foreman 265 pathogenesis 285, 293 echinococcus granulosis 343,345 Forssman 266 protein 287 echinococcus multilocularis 342, Forssman antigen 67 transfer 288 345 F orssman shock 266 transfer factor 288 ecotaxis 36 Fragraeus 52 tuberculin 286 Edelman 85, 86 frame work, regions of, FR 91 ff deletion 383 Ehrlich 100, 199,210,256,307, Franklin's disease 368 depot effect 71 383 Freund's adjuvant 71 dermatitis, contact 287 ELISA, enzyme-linked immu• Friedburger 128 dermatitis herpetiformis 176 nosorbent assay 221,332 Friend virus 176 Deutsch 83 encephalomyelitis Fudenberg 98, 365 Deutsch's paraproteinemia 369 acute disseminated 395 Fulthrope 182 de Week 271 experimental allergic 392 DFP, diisoporyl fluorophosphate endophthalmitis phaco-anaphylac- GAT, glutamine-alanine-tyrosine 121 tica 407 42 diGeorge's syndrome 370 end-point dilution 189 gametic association, HLA 153 diabetes, juvenile 176 enhancement 297,307,385 gamma chain disease 368 dialysis, equilibrium 222 enzyme-linked immunosorbent as- gammopathies diazotization 65 say, ELISA 221,332 alpha chain disease 369 dichotomy of lymphatic system 4, eosinophil stimulation promotor, Deutsch's paraproteinemia 369 22 ESP 346 heavy chain disease 368 differences between T and B lym• eosinophilia 344, 346 light chain abnormalities 370 phocytes 54 eosinophils 8 mu chain disease 369 differentiation of antibody forming in anaphylaxis 260 polyclonal 370 cells 78 chemotactic factors 291 gastric atrophy 403 differentiation, antigen-depen- 1,64, 110 Gauss's function 222 dent 111 equilibrium dialysis 222 gel precipitation 181 cluster of, CD 47,55 erythroblastosis fetalis 110 genetics, HLA 152 human T lymphocytes 47 erythrocytes, alloantigen 297 complement 124 lymphoid cells 2 euglobulin 81,203 immune response 109 mouse T lymphocytes 10, 20, eurotransplant 312 Gengou 196 40 ff. exotoxins 334 germinal centers 26 plasma cells 53 external image of the idiotype 63 Gershon 42, 112 thymic cells 19 Giemsa staining 9 digestion, intracellular 208 fab, antigen-binding fragment 87 Glo gene diphyllobothrium latum 345 Falba 71 man 154 disease association, to MHC 176 Fanconi's anemia 376 mouse 147 diversity of antibodies, Farr 217 glomerulonephritis 131,279,283, generation 101, 105 fasciola hepatica 342, 345 404 diversity, D segment, Ig genes Fe, crystallizable fragment 87 experimental 202 104 Fe-receptor 46, 55 glucose-6-phosphate dehydroge• DLA, dog leukocyte antigen 140 feedback control of antibody syn• nase deficiency 381 Doherty 164 thesis 109 glutathion peroxidase deficiency domains of antibodies 89 feedback inhibition of antibody 381 Donath 399 synthesis 109 glyoxalase genes 147, 154 462 Subject Index

Gm, human Ig allotype 98 helper lymphocytes 41 serology, human 148 Good 315 hemagglutination 187,332 serology, mouse 13 131, 176, hemodialysis 312 tissue distribution of mole• 405,406 hemoglobinuria, paroxysmal noc- cules I Gorer 139,311 turnal 400 histogenesis of immun system 1 GPLA, guinea pig leukocyte hemolysis 179, 332 histology of immune system 1 antigen 140 immune 116, 127 thymus dependent region 17, Grabar 84,184,386 hemopoietic-inducing microen• 23 graft vironment, HIM I thymus independent regions 23 heterotopic 297 heparin in anaphylaxis 255 HLA disease association 176 orthotopic 297 hepatitis HBs antigen 187 DP genes 152 graft rejection chronic active 176,403 HLA-D gene(s) 151 genetics 299, 300, 304 Herzenberg 112 genetics 152 hyperacute 313 HETE, 12-L-hydroxy-5,8, 10, 14- human leukocyte antigen com• mechanism 301 eicosatetraenoic acid 133,321 plex 148 graft versus host reaction 297, heterocytotropic antibodies 248 HLA-A 149 299 heterotopic graft 297 HLA-A,B,C molecules, structure disease 401 hetrazan 272 159 genetics 300 hexosemonophosphate shunt 324 HLA-B 149 gran ulocytopoiesis 6 HHT,12-L-hydroxy-5,8,10-hep- HLA-C 149 granulopoietin 5 tadecatrienoic acid 133,321 HLA-D molecules, structure 161, Graves' disease 176, 398 HIM, see hemopoietic-inducing 162 Gross virus 176 microenvironment 1 HLA-DQ 149 growth factors, immunostimula- hinge region 88 HLA-DR 149 tion 416 histamine in anaphylaxis 252, 253 HLA-DZ 149 Grubb 98 complement-dependent release Hockley 349 Gruber 187 130 Hodgkin's disease 371 guanidine silica 70 receptors 253 homing receptor oflymphocytes Guthrie 311 released from mast cells 132 37 histamine-sensitizing factor, HSF homochromatosis, idiopathic 176 H agglutinogen 228 71 homocytotropic antibodies 248 H chain translocon 103 9 homologous disease 401 H-2 recombinant strains 147 histocompatibility, Honjo 104 linkage analysis 146 alloantigen 143, 148 horse Ig 97 mouse major histocompatibility antigens 45 host versus graft reaction 297, complex 140 major complex, 298 H-2A,E molecules, structure 161 allele frequency 144 genetics 299 H-2K,D molecules, structure 159 alloreactivity 170 Hozumi 102 Haber-Weiss cycle 326 cellular typing, HLA 150 HTC, homozygous typing cells, Hacek 308 cytogenetics of mouse 147 HLA 152 Hageman factor 322 disease association 176 Hudack 51 hagfish 32 genes 140 human alloantigens Haldane 139 genetic map, man 155 cluster of differentiation 47,55 haplotypes, HLA 153 genetic map, mouse MHC T lymphocytes 47 hapten 64 148 human gamma globulin, in sero- hapten-antibody reaction, thermo• H-2K,D genes mouse 143 therapy 352 dynamics 223 H-2K,D molecules 145 hybridoma 78 Hardy-Weinberg theorem 152 human (HLA) 148 hydrogen peroxide 61 Hashimoto thyreoiditis 396 Ia antigens 145, 146 hyperacute rejection, kidney 313 antibodies in 397 I-A locus 145 hypersensitivity 243-296 Hassal's corpuscule 15 I-E locus 146 anaphylaxis in guinea pigs 245 HAT medium 79 immune response genes, anaphylaxis in man 267-278 hay-fever 270,275 mouse 144 antibody-antigen complexes heat labile serum factor, HLF L locus 146 (type III) 279 204 linkage analysis, man 154 Arthus reaction 279,283 heavy chain disease 368 linkage analysis; mouse 148 cell-mediated 284 heavy chain of Ig 86 mouse 141 classification 244 heavy chain switch 104 mouse recombinant strains contact dermatitis 287 Heidelberger 84,214,217 147 cytotoxic reactions (type II) Heidelberger-Kendall method polymophism 144, 170 278 217 restriction 164, 168, 169 delayed type 284-294 Subject Index 463

immediate type 244-284 I-J antigen 43 sequence of events in 319 mediators of 252 image immunization, scheme 355, 356 serum sickness 285 external of antibody 63 immunoadherence 202 tuberculin reaction 286 internal of antibody IIO immunocompetence hypervariable region of an• immobilization (TPI) test 202 lymphocytes 38 tibodies 91 immune complexes ontogeny of 108 hypogammaglobulinemia diseases associated with 280 immunocytoadherence 76 aquired primary 365 hypersensitivity type III 279 immunocytolysis 201 aquired secondary 365 methods of detection 282 immunocytotoxicity 20 I Bruton-type 365 immune response immunodeficiencies in infants 364 bacterial infections 334 B cell 364-370 macroglobulinemia Walden- control by MHC 175 Band T cell 371-373 strom 367 escape from 348 Band T cell proliferative dis• monoclonal gammopathies 367 anatomical inaccessibility 347 orders 373-377 multiple myeloma 367 348 classification 364 polyclonal 370 immunosuppression 349 complement deficiencies 380- selective, variable 366-367 MHC antigen loss 349 382 hypoxanthin-guanine-phosphoryl• molecular masking 349 phagocytic dysfunctions 377- transferase, HGPRT 79 seclusion 348 381 hytatide cyst 345 soluble antigen 348 severe 315 evaluation of function 359 T cell 370-371 I, C3b-inactivator 134 genes (Ir-genes), mouse 144, immunodiffusion 180 ff., 332 I region, mouse, molecule struc- 145, 162, 166 immunoelectrophoresis 184, 186, ture 161 genetic factors 109 332 I-A locus, mouse MHC 146 in guinea pigs 107 immunofluorescence 194 Ia molecule 61 infections 331 immunogen idiotope 110 influence of age 108 polysaccharides 106 idiotype 42, 112 influence of antigen 106 immunogenicity 68 external image of 63 in LE patients 410 Immunoglobulin idiotype-anti-idiotype network macrophages in 59 allotypes 98 44,63 mapping 166 on B cell membrane 51 idiotypic determinants, T cell re- maturation 53 binding factor, IBF 331 ceptor 56 metazoal infections 342 catabolic elimination 360 idiotypic network 110 to parasites 340 evaluation of function 359 Ig genes 101 PLL gene 109 gene organisation 101 Ig superfamily 174 primary 53, 63, 74 genetic markers 97 IgA 94 protozoal infections 340, 343 idiotypes 99 and IgG selective deficiency 366 restnctlOn 164, 168 maternal-fetal transfer 351 and IgM selective deficiency 367 secondary 63, 75 secretion 53 selective deficiency 366 viral infections 334 serotherapy 352 synthesis 95 immune serum structure of IgE 96 IgD 95 with adjuvant 74 synthesis 53 IgE 96 monoclonal 79 immunologic memory 38 dependent mediator secretion polyclonal 78 immuno-osmophoresis 186 264 preparation 73 immunostimulants, thymic hor- macrophage cytotoxicity 347 immune system mones 420 ontogeny of producing lympho- dichotomy 4, 22 immunostimulation 416-424 cytes 263 histogenesis 1 adjuvants 417 reaginic antibody 249,262 histology 1 adriamycin 422 receptor, structure 250-277 homeostasis 385 bestatin 421 response, metazoal infections ontogeny 32 cimetidine 421 342 phylogeny 32 cyclophosphamide 422 IgG 93 immunity cyclosporin A 421 and IgA selective deficiency active 355 growth factors 416 366 adaptive 330 interferons 423 selective deficiency 366 aquisition 350 isoprinosine 421 IgM 93 concomitant 340 levamisol 421 and IgA selective deficiency escape 337 lymphokines 421 367 natural 317 monokines 421 secrete 12 nonsterilizing 340 thymic hormones 420 selective deficiency 366 passiv,e 350 tuftsin 421 464 Subject Index immunosuppression 349 irradiation lactoperoxidase 317 immunosuppressive agents 72 immunosuppressors 426 lambda chain 90 immunosuppressive therapy 314 lethal 19 lambda chain translocon 102 immunosuppressors Isaacs 336 lamprey 32 alkylating agents 432 ISF, human IG allotype 98 Landsteiner 64, 100,227,399 amino acid antagonists 436 Iskizaka 96, 199, 276 Landsteiner's rule 228 antibiotics 435 isofixation curve, antibody-antigen Langerhans cells 61 antilymphocytic serum 427 reaction 199 Lapresle 66 antimetabolites 433 isogenic 140 latency 328 bursectomy 426 isoprinosine, immunostimulation latex test 332 classification 424 421 Laurell 186 corticosteroids 428-430 isothiocyanate 194 Lawrence 288 folic acid antagonists 434 isotransplant 140 lazy leukocyte syndrome, phago- irridation 426 Issaeff 115 cyte deficiencies 378 mechanism 424 leader, L segment, Ig genes 103 niridazole 436 Jenner 355 leishmania 327, 340, 343 nucleic acid, inhibition of bio• Jerne 44,63, 100, 105, 110,417 Lennert 373 synthesis 431 Jerne plaque technique 76 leukemias, B,T cell proliferative plant alkaloids 435 Job's syndrome, phagocyte disorders 375 proteins, inhibition of biosynthe- deficiencies 378 leukin 208 sis 431 Johansson 262 leukoaggressin 132 rules 437 joining, J segment 103, 104 leukocidin 329 specific 436 Jones-Mota reaction 294 leukocytes, alloantigen 297 thymectomy 425 j(unction) chain of IgM 94 leukokininase 323 immunotherapy 352 leukopenia, autoimmune 402 mechanism in atopic diseases lCabat 67,84,92,105,219 leukotrienes in anaphylaxis 254 270 lCAF 134 Leung 290 inbred strains, mouse 141 lCala-Azar 343 levanisol, immunostimulation infections lCaposi sarkom 176 421 complement in 132 lCapp 42 levine 227,234,275 inflammatory lesions, kappa chain 90 Lewis, blood group system 230 pathogenesis 279 kappa chain translocon 103 life span influenza vaccine 356 lCataoka 104 lymphocytes 37, 109 influenza virus lCatz 271,277 monocytes 9 antigenic drift 338 lCen~all 217 polymorphnuclear cells 5 antigenic shift 339 lCendrew 68 light chain abnormalities 370 pandemic strains 339 lCern, of human lambda light chain of Ig 86 ingestion 323, 362 chain 98 Lindemann 336 ingestion deficiencies, phagocyte kidney transplantation 312 lingual tonsil 30 deficiencies 378-379 complications 313 linkage analysis inhibition of precipitation 219 pregnancy 313 animals 156 instructive theory of antibody for• survival 313 H-2 148 mation 100 lCiel classification of lymphomas HLA 154 insulin-dependent diabetes 374 linkage disequilibrium 152 mellitus 398 killer cells 45 Lipari 90 insulitis 398 lCindred 168 lipochrome histiocytosis 381 interferon 327, 330, 333, 336 lCishimoto 276 lipomodulin 276 interferons, immunostimulation lCitasato 209 Jipopolysaccharides 71 423 lCline test 191 Little 139, 311 interleukin-I,IL-I 49,327,330 ko, platelet specific antigen 316 liver surface protein, LSP 404 properties 170 lCoch 286 loa loa 345 interleukin-2, IL-2 49, 330 lCoch's phenomenon 286 local lymph node weight test 299 properties 170 lCiihler 78, 110 locomotion of polymorphnuclear internal image 110 lCorngold 90 cells 7 intraleukocyte killing test 379 lCostmann 377 Loeb 139,311 intrinsic factor 403 lCastner 247,268 Lukes 373 In V, human Ig allotype 98 lCupffer cells 9 Lukes and Collins classification of IPCA, inverse passive cutaneous lCwashiorkor 108 lymphomas 374 anaphylaxis 247 lupus erythematosus, Ir gene 109, 275 L locus, mouse MHC 146 experimental 411 mouse 144, 145, 162, 167 lactoferrin 326 systemic 408 Subject Index 465

Lutheran, blood group system Malpighian bodies 28 linked complement 230 Maltaner 197 components 174 lymph nodes 23 Mancini 181, 269 restriction 165, 169 auto radiograph of 31 Mancini test 181,360 MHC molecules lymph vessels 2 287 biochemistry 158 lymphatic cells 5,9, 35 Mantovani 280 class I, structure 159 B lymphocytes 12 Marbrook culture 77 class II, structure 161 differentiation 2 Marx 51 class III, structure 162 origin 2 8, 344 tissue distribution 156 stem cell 21 anaphylaxis 255 micro-dye exclusion test 202 subpopulations 42 delayed hypersensitivity 294 microcomplement consumption T lymphocytes 10,41 eosinophil cooperation 346 test 282 lymphatic system mastocytes in anaphylaxis 255 microdrop, technique 78 dichotomy 4 Masugi nephritis 404 microfilaria 349 primary organs 3 maternal-fetal transfer, immunity P2-microglobulin 160 secondary organs 23 340,350 microorganisms 328 Iymphochoriomeningitis virus, maturation, immune response 53, MIF 375 LCM 176 108 macrophage inhibition test 290 lymphocyte mitogenic factor, Maximow 35 migration LMF 331 Mayer 116, 197 current 36 stimulation 333 MBP, major basic protein 133 inhibition 333 typing, primary 149 McDevitt 165 inhibition factor 330,331 lymphocytes 9, 35 McLeod phenotype, Kell blood leukocytes 320, 321 chemotactic factors 291 group 381 lymphocytes 35 homing receptors 37 McMaster 51 Milstein 78 immunocompetence 38 measle vaccine 355 mineral oil emulsion 70 life-span 37 Medawar 140,308,311 minimum lethal dose, MLD 209, migration 35 mediator secretion, IgE depen- 210 mitotic activity 15 dent 264 minimum reactive dose, MRD 209 thymus-dependent 39 mediators, liberation 274 mitogenic factor 291 thymus-independent 39 mediterranean lymphoma 369 mitogenicity of adjuvants 71 trapping 30 megakaryocytes 14 mitogens 60 Iymphocytotoxicity 202 memory, cells 39, 75, 109 mixed lymphocyte culture, MLC lymphoid follicles 26 immunologic 38 45, 150, 302, 311 nodules 23 106 MNSs blood group system 232 stem cell defect, T,B cell com• 6-Mercaptopurine 433 mobility, white blood cells 362 bined deficiencies 371 Merril 311 molecular mimicry 177 Iymphokines 132,330,331 metazoa Mongar 265 immunostimulation 421 human pathogenic 345 monoclonal antibodies properties 291 vectors 345 cloning 79 lymphomas, B,T cell proliferative metazoal infections 342 to HLA 149 disorders 373-375 Metchnikoff 5, 204 production 79 Iymphotoxins 291,330,331,333 methotrexate 79,435 monocytes 9 Iysosomes 9 Meyer 126 monokines 327 lysozyme 201,208,317,324,326, MHC see major histocompatibility immunostimulation 421 327 complex Mota 256,262,276 Lyt antigens 11,41,55,59 antigen loss 349 mouse alloantigens genetic organisation, BoLA, T lymphocytes 11 M protein, streptococcal 177 cattle 156 mu chain disease 369 macrophage activating factor 291 ChLA, chimpanzee 156 mucocutaneous candidiasis 370 inhibition factor, MIF 302 DLA, dog 156 Miiller-Eberhard 124 inhibition test 282, 290 ELA, horse 156 multiple sclerosis 176, 394 macrophage-T cell cooperation GPLA, guinea pig 156 mumps vaccine 355 303 H-2, mouse 156 Murray 311 macrophages 9,59 H-B, chicken 156 myasthenia gravis 176, 395 chemotactic factors 291 HLA, man 156 myelin basic protein 393 in immunity 326 OLA, sheep 156 myeloperoxidase deficiency 381 marker 55 RhLA, rhesus monkey 156 myoglobin 68 major histocompatiblity complex, RLA, rabbit 156 MHC 20, 139 ff RTl, rat 156 NA, neutrophil antigen 316 343 SLA, swine 156 NADPH-oxidase deficiency 381 466 Subject Index

Nakagawa 271 ophthalmia, sympathetic 408 Job's syndrome 378 IX-Naphtyl acetate 363 oppossum 33 lazy leukocyte syndrome 378 narcolepsy 176 opsonization 116, 130,204,206, neutropenias 377-378 Nash 290 322,362 tuftsin deficiency 378 Nathenson 158 oriental sore 343 phagocyte dysfunctions, immuno- natural killer cells 46 orthotopic graft 297 deficiencies 377-381 NB, neutrophil antigen 316 osteoclasts 9 phagocytic index 205 NBT, nitroblue tetrazolium dye Ouchterlony 183 phagocytin 208 324 Ouchterlony test 183 phagocytosis 59,204 NBT test 381 Oudin 98, 181 complement-mediated 166,322 necator americanus 345 Oudin's test 181 evaluation offunction 362 nematodes 339, 345 Owen 308 stimulation 71 human pathogenic 345 oxygen, singlet 325 phagolysosome 324, 328 neutralization Oz, isotype of human lambda phagosome 207,323 mechanism 212 chain 98 pharyngeal tonsil 30 toxin 209,332 phylogenic distance of antigen 106 of virions 335 P, properdin 134 phylogenicy of immune system 30 neutropenia, cyclic 377 PAF, platelet activating factor, in physicochemical properties of hu- familial severe 377 anaphylaxis 252, 255 man Ig 93 immuno 378 structure 260 phythemaggiutinin, PHA 60 phagocyte deficiencies 377-378 Pain 86 Pick 65 neutrophil chemotactic factor in palatine tonsil 30 Pillemer 136 anaphylaxis 254 papain digestion of antibodies 88 PK reaction 247,268 neutrophils 5 parabiosis 308 inverse 270 chemotactic factors 291 paracortical region 24 PK test 96 Newhauser's space 365 paragonimus 342, 345 plaque forming cells, PFC 77 Nezelofs syndrome, T,B cell com- paratope 110 plaque technique, Jerne 76 bined deficiencies 372 Parfentjev 83 vaccine 356 Nicholson 157 PAS reaction 363 13,49, 51 niridazole 436 287 differentiation 54 Nisonoff 110 pathogenesis plasmocytosis 52 nitroblue tetrazolium dye 324 Arthus reaction 284 platelet aggregation test 282 nitrogen mustard 432 serum sickness 285 factor 4 15 nomenclature Paul-Bunnell reaction 191 lytic factor 347 animallg 97 PCA, passive cutaneous anaphy- specific antigen 316 congenic mouse strains 142 laxis 247 platelets 13 histocompatibility 140 Pedersen 84 in anaphylaxis 259 human Ig 97 pemphigus vulgaris 176, 408 Pie, platelet specific antigen 316 inbred strains 141 pepsin digestion of antibodies 88 PLL gene 109 transplantation 140 perfect fit, antibody-antigen reac- PLL, see polylysine Nossal 78, 384 tion 108, 113 PLT, primary lymphocyte typing NP40, non-ionic detergent 159 periarteriolar sheath 28 152,312 nucleic acids, inhibition of biosyn- Perini 262 pokeweed mitogen stimulation thesis 431 periodic acid Schiff reaction 363 360 Nussenzweig 281 permeability 320 poliomyelitis vaccine 355 Peyer's patches 3,30,318 polyclonal gammopathies 370 Oakley 182 Pfeiffer 51, 115 polyethylenglycol 79 Oakley's technique 183 Pfeiffer's phenomenon 115,201, polylysine, PLL 69 Obermayer 65 213 polymorphism, genetic of MHC onchocerca volvulus 345 Pg-5 gene, mouse 147 144 onchocercosis 345 urine-pepsinogen-5, man 154 polymorphnuclear cells oncogenic virus 176 Pgk gene, mouse 147 characteristics 5 one-hit-theory, complement 126 PGm, phosphoglucomutase-3, in immunity 320 one way reaction 151 man 154 locomotion 7 one way stimulation 151 phagocyte deficiencies polynucleic acids 70 ontogeny actin polymerization deficiency Pope 83 IgE producing B lymphocytes 378 Porter 85, 86 263 Chediak-Higashi syndrome Portier 244 immune system 30 378 . postcapillary venules 25 immunocompetent cells 108 chemotactic deficiencies 378 PPD, purified protein derivative immunologic capacity 351 ingestion deficiencies 378-379 286 Subject Index 467

Prausnitz 247,268 Qa antigens II Romer 210 Prausnitz-Kiistner (PK) reaction Qa loci 147 Ropartz 98 247,268 quenching, fluorescent 222, 223 Rose 383,396,412 precipitation, antibody reaction Rose-Waaler test 412 180 rabies vaccine 356 Rosenthal 168 precipitation reactions Race 234 rosette formation 203 ABC method 218 radiation-induced leukemia virus technique 77 Heidelberger-Kendall method 176 rosettes, erythrocytes 361 217 , RAST RTI, rat transplantation locus immunodiffusion, double 182 221,268 140 double radial (Ouchterlony) 220, 332, 360 rubella vaccine 355 183,332 radioimmunodiffusion (Mancini) runt disease 299 radial (Mancini) 181 269 simple (Oudin) 181 Raji cell assay 282 S region, mouse MHC 146,164 immunoelectrophoresis 184 Ramon 70, 181 Sabin 355 inhibition of 219 'Ramon flocculation 181 Saito 57 in liquid media 180 Rappaport 373 sandwich technique, immuno• neutralization, toxin 209 Rappaport classification of lym• fluorescence 195 P-80 method 217 phomas 374 SA-P, sialic acid rich polysac- quantitative 214 RAST, radioallergosorbent test charide 134 rocket i-e 186 221 saponin 70 two dimensional 186 Raynaud's syndrome 408 Scatchard's equation 221 Preer 183 Rays 32 Schick reaction 360 preformed antibodies 318,320 rearrangement of Ig genes 102 Schild 253,265 premunition 340 Rebuck skin test 363 schistosoma hematobium 328, prepatency 345 recognition of antigen 162 342,345,346 primary lymphocyte typing 149 red pulp, spleen 27 japonicum 345 pirmary lymphoid organs regulatory cell circuits III mansoni 345 activity 15 regulatory circuits 44 schlepper 64 function 4 Reisfeld 158 Schultz 269 origin 3 Reiter's disease 176 Schultz-Dale reaction 269 primordial cell, immune system 41 reptiles 32 Schulze venules 26 private antigen 143 respiratory burst 208, 323, 324 SCID, severe combined immuno• properdin 201 respiratory distress syndrom, deficiencies, T,B cell combined properdin syndrom, see alternative acute 129 deficiencies 371 complement pathway restriction, genetic of immune re• 413 prostaglandins 327 sponse 164, 168 sclerosis, progressive systemic 413 in anaphylaxis 252, 254 reticular cells 61 seclusion, of antigen 348 protective action of an tibacterial reticular dysgenesia, T,B cell com• secondary disease 299,401 sera 203 bined deficiencies 372 secondary lymphoid organs 23, , staphylococcus aureus reticuloendothelial system, RES 36 159 205 secretion piece of IgA 95 protein elimination 234 Sedormid 279,402 syngeneic 285 genetics 235 Sela 69 xenogeneic 285 nomenclature 235 selection proteins, inhibition ofbio- 407 negative 303 synthesis 431 rheumatoid agglutinins 98 positive 303 protopod 7 arthritis 411 self-recognition 384 protozoa 339 factor 412 self-tolerance 165,383 protozoal infections 340 RhLA, rhesus monkey leukocyte Sercarz 75 protracted shock 246 antigen 140 serine esterase 263 prozone 188 rhodmine B 194 serodiagnostic tests 197 pseudoglobulin 81 Richet 244 serotherapy 352 psoriasis vulgaris 176 Rieckenberg reaction 202 serotonin in anaphylaxis 252, 253 public antigen 143 Riley 256 serum sickness 280 pulmonary edema 131 ring test 180 Sezary cell 375 pulmonate fishes 32 Rivers 392 Sezary syndrome, B, T cell prolifer• purine nucleoside phosphorylase rocket immunoelectrophoresis 186 ative disorders 375 deficiency, T,B cell combined rodents, Ig 97 SFA, suppressive factor of deficiency 372 Rodgers, complement marker allergy 277 puromycin 435 137, 154 sharks 32 468 Subject Index

Shaw 152 marker 55 thymidinkinase 79 Shevach 168 T helper cells 11, 41 thymocytes, alloantigen 12, 19, shock organ, in hypersensitivity marker 55 20 246 T lymphocyte 10, 40 thymoma 395 Shreffler 168 activity in toads 32 thymopoietin 4,21,41 side-chain theory of antibodies clones 170 thymosine 21 100 cytotoxic 45,47 fraction 21 silica guanidine 70 differences from B 54 thymic hormones 420 Singer 157 differentiation 20, 47 thymus 2,5 Sip's function 221 evaluation of function 361 aplasia 315 skin reactive factor 291 helper 41,47 cells sleeping sickness 343 interaction with antigen 169 destiny 16 slow reacting substance, SRS marker 55 differentiation 19 252,254 regulatory 44 mitotic activity 15 slow virus 339 specificity 20 graft 18 infections 390 subpopulations 42 hormonal activity 21 Sip gene, mouse MHC 146,164 suppressor 42,47 thymus-dependent, lymphocytes Smithers 349 T,B cell combined deficiencies 39 Snell 140, 143,311 adenosine-deaminase regions in Iymphnodes 24,41 solubilization of immune com- deficiency 371 regions in spleen 28, 41 plexes by complement 137 ataxia telangiectasia 372 thymus-dependent regions 17 species-specific antigens 67 lymphoid stem cell defect 371 antigen 72 spectrophotometry 179 Nezelofs syndrome 372 lymphnodes 24 spermine 318 purine nucleoside phosphorylase spleen 28 spleen 27 deficiency 372 thymus-independent region spleen index 299 reticular dysgenesia 372 antigen 72 splenomegaly test 299 SCID, severe combined immu• Iymphnodes 24 SRS 347 nodeficiencies 371 spleen 28 Ss gene, mouse MHC 146 transco balamin II deficiency thyphoid vaccine 356 Stein 197 372 thyphus vaccine 356 stem cell 21,41 Wiskott-Aldrich syndrome 372 thyreoiditis, subacute Quervain Still's disease 411 tadpoles 33 176 stimulation index 299 taenia saginata 342, 345 Tiselius 84 Stokes'law 194 taenia solium 345 TL antigen 12,41 streptolysine 329 Tagliacozzi 311 TLa locus 147 strongyloides stercoralis 342, 345 Takatsy microtitrator 192 toads 32 subclasses of animal Ig 97 Talal 386 Todd 98 of human antibodies 92 TAME, N-p-toluenesulfonyl- Todd phenomenon 98 superoxide anion 61, 324 methyl ester 121 tolerance 297,303,307 dismutase 324 tanning 192 adaptive 340 suppressor lymphocytes 42 tapioca, adjuvant 417 low zone 111,387 susceptibility to tumors 139 teleosts 32 mechanism 310 syngenic 140,297 Tennant virus 176 self 165 syphilis 191, 196 Terry 349 Tomasi 95 thermodynamics of hapten-anti- Tonegawa 102 T cell antigen receptor 56, 171 body reaction 223 total body irradiation 314 genes 172 6-thioguanine 433 toxid infections structure 161 thoracic duct 3, 54 serotherapy 353 T cell thrombin 136 toxin neutralization by antibodies alloantigen 11,47,55, 173 thrombin-arachidonic acid path- 209 bypass 387 way 136 toxins, bacterial 335 deficiencies 370-371 thrombocytes 13 toxocarna canis 345 dysregulation 388 thrombocytopenia 202 343 immunodeficiencies 370-371 autoimmune 402 TPI, trepanoma pallidum immobil• lymphoma, B,T cell proliferative thrombopoiesis 14 isation test 202 disorders 375 thromboxane A2 255 transcobalamin II deficiency, T,B regulation, immunity 385 thy-l antigen 11,41 cell combined deficiencies 372 replacing factor 49 thymectomy 16,40 transfer factor 291 tolerance 310 immunosuppressors 425 delayed hypersensitivity 288 T component, IgG T horse 97 thymic hormones, immunostimu• transferrin gene 154 T cytolytic cells 11 lants 420 translocons ofIg 10 I Subject Index 469 transmission, virus 334 serologic, mouse 143 wax D 418 transplantation Tyzzer 139 Webb 181 315 Webster 338 bone marrow 314 uropod 7 Weckerle 383 kidney 312 West 256 nomenclature 140 V genes 102 , evaluation of organ 311-316 vaccines 354-357 function 363-363 thymus 315 vaCCInia ViruS 176 white graft rejection 299 tumor 139 van Bekkum 314 white pulp, spleen 27 transport piece of IgA 95 van Krogh's equation 116 White-Kaufman table 191 trematodes 339, 345 van Ngu 197 Widal's test 191 triad, antibody formation III van Rood 149 Wiener 234 trichinella spiralis 345 variable region 90 Wigzell 56 trichuris trichiura 342, 345 , hypersensitivity type Wilander 256 trypan blue 202 III 279 Williams 184 trypanosomiasis 343 vasectomy 280 Wi scott 271 tryptophol 349 Vaz 275 Wiscott-Aldrich syndrome 271 T-T lymphocyte cooperation 58 V-C joining 103 Witebsky 383, 396 tit complex 147 VDRL test 191 Wright staining 9 tuftsin 323 vinblastine 435 wucheria bancrofti 345 deficiency, phagocyte deficien• vincristine 435 cies 378 viral infections 334 x2-test 149 immunostimulation 421 serotherapy 353 xenoantiserum 73 tumor susceptibility 139 vitamin Bl2-binding protein 403 xenogenic 140,297 transplantation 139 xenotransplant 140 two-dimensional immunoelectro• Waaler 412 phoresis 186 Wagner 303 yellow fever vaccine 356 191 Waldeyer, ring of 318 Yodoi 277 typing, cellular, human 150, 311 Wassermann 196 Yoffey 36 homozygous cells 151 Wassermann reaction 196 primed lymphocyte 149,152 wasting disease 21 Zinkernagel 164 serologic, human 148,311 syndrome 299 Zw, platelet specific antigen 316