DOCSLIB.ORG

Carrier-Specific Induction of Hapten-Specific Suppression Leonore A

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Carrier-Specific Induction of Hapten-Specific Suppression Leonore A 40 immunology today, March 1981 ) Carrier-specific induction of hapten-specific suppression Leonore A. Herzenberg, Takeshi Tokuhisa and Leonard A. Herzenberg Department of Genetics, Stanford University School of Medicine, Stanford, California, 94305, USA Two functionally opposing, regulatory T cell popula- regulation of hapten-carrier responses. Therefore, our tions are found in carrier-primed mice. Both popula- data throw a substantially new perspective on the tions are raised by essentially the same immunization regulatory interactions involved in the response to protocol, both control antibody production to deter- common antigens. minants on typical carrier proteins, both are 'carrier- specific' in that they control responses to haptens The mechanism of carrier-specific suppression is added to the initial priming (carrier), and both are indeterminate commonly studied as regulators of such anti-hapten Carrier-specific suppressor populations were generally responses in adoptive or in-vitro assays. However, one presumed to regulate antibody production by control- population helps the antibody response while the ling the supply of carrier-specific help because they other substantially suppresses it. suppress in-vitro or adoptive in-vivo responses to 2, 4- These two populations have captured the limelight as regulators of heterogeneous antibody responses to T-dependent antigens. The helper T cells, because 150~ they are required for a successful response to these antigens, are generally thought to stimulate and thereby to directly control the expression of anti- hapten memory B cells. In contrast, the suppressor cells are thought to regulate B-cell expression indirectly by reducing the size or activity of the avail- I O0 able helper population. In addition, helper cells are DNP-KLH DNP-KLH thought to regulate suppressor activity through 1 O0 ug 1 ug homeostatic 'feedback loops' that can prevent exces- IgG2a on alum aqueous sive suppression. Thus, over the last few years, a anti complex but fairly consistent picture of response DNP regulation has evolved which places carrier-specific regulation at the center of the immunological uni- 5(2~ verse 1. Nevertheless, as we shall show, this picture is based on data which can (and probably should) be interpreted quite differently. Our recent studies 2 on KLH first the regulation of it~-situ responses to hapten-carrier conjugates reveal assumptions that mar previous con- clusions about the role of the carrier-specific -1 0 1 2 3 4 5 6 7 8 suppressor population and suggest a novel alternative Weeks for the contribution these cells make towards regulat- ing antibody production. Furthermore, the charac- Figure l. Carrier-priming prevents hapten-carrier stimula- tion of anti-hapten antibody responses. teristics of response regulation revealed by our studies (BALB/c x SJL) FI responses shown are representative of suggest that mechanisms akin to idiotype-specific and responses in BALB/c, BAB/14 and G3H. SW mice. Protocol and allotype-specific regulation may be central to "the assay details are described in the legend to Fig. 2. Elsevier / Non h-Ilolland Biomedical Press 1981 immunology today, March 1981 41 dinitrophenyl (DNP) on the priming carrier but are Anti-DNP responses are suppressed in ineffective in controlling antibody production by the KLH-primed mice exposed to DNP-KLH same B-cell population to DNP on an unrelated carrier. This interpretation of the suppression specifi- K ~ I 3 city data is consistent with the demonstration that allotype suppressor T cells remove allotype-specific K,DK -I f,o.31 i help and is reinforced by evidence that idiotype K,DK,DK 00"3) I suppressor T cells remove idiotype-specific help. These data have been taken as evidence that carrier- DK --i (5.) specific suppressor T cells interfere with the carrier- DK,DK l(too? i specific help interactions necessary for the production i I I I I I of antibody to determinants on the carrier molecule. 50 100 150 100 200 300 We suggest, however, that the logic underlying this Igh-la Anti DNP Igh-la Anti KLH analysis is flawed. The suppression of adoptive and in- (ug/ml) (units) vilro responses to DNP on the priming carrier, but not *K = KLH; DK = DNP-KLH on an unrelated carrier molecule, clearly demonstrates Fig. 2. Hapten-specific suppression selectively reduces the that the suppressor population is carrier-specific magnitude and affinity of anti-hapten responses. (since its function depends on being confronted with Animals were exposed to 100pg of the indicated antigens (on hapten on the appropriate carrier). But this specificity alum) at 6 week intervals. Responses were measured two weeks is consistent with a variety of mechanisms and does after the last indicated exposure. Units of ariti-carrier antibody are measured in radioimmunoassays (RIA) and calculated relative to not necessarily indicate that the suppressor cells a standard adoptive secondary response serum (to DNP-KLH). interfere with carrier-specific help for antibody Anti-DNP responses were measured in an RIA modified to responses to determinants on the carrier molecule. measure magnitude and affinitylL Data in parentheses after anti- Theoretically the suppressor population could DNP response 'bars' show the average K a M -~ x 106 for that establish a carrier-specific induction mechanism using response. the hapten-carrier conjugate to induce a second indicated, that carrier-primed animals produce a (hapten-specific) mechanism to specifically suppress minimal anti-hapten response when stimulated with the production of anti-hapten antibodies. This hapten on the priming carrier (Figs. 1 and 2). By the hapten-specific mechanism could operate ana- time we discovered the original papers which sug- logously to idiotype-suppression mechanisms by gested that the minimal responses were due to inter- specifically preventing the production of antibodies ference with anti-hapten memory development 5, we that have combining sites for the hapten and could had shown that anti-DNP memory development therefore suppress anti-hapten responses without occurs normally in keyhole limpet hemocyanin interfering with carrier-specific help or with the (KLH)-primed animals exposed to DNP-KLH (Table response to other determinants on the hapten-carrier 1) and that the anti-hapten responses fail because ex- conjugate. Consequently, carrier-specific help could posure to the hapten-carrier conjugate induces a be present and functioning normally in the presence of specific and persistent suppression of antibody p'ro- the suppressor population even though anti-hapten duction to the (new) DNP hapten on the carrier mole- antibody production is suppressed. cule (Fig. 3). This theory seems complex when compared with the relative simplicity of the hypothesis that carrier- The suppression-effector mechanism is hapten- specific help is depleted but the immune system, being specific more concerned with function than with appearance, The specificity of this suppression for responses to the may have a different idea of what constitutes a work- DNP hapten was established conclusively by the able set of regulatory interactions. In any event, as we observation that anti-DNP responses were suppressed shall show, a hapten-specific mechanism such as the in KLH-primed mice exposed first to DNP-KLH and one we have just described regulates antibody produc- then to DNP on an unrelated carrier molecule (i.e., to tion to hapten-carrier conjugates; and a carrier- DNP-CGG (chicken gamma globulin) ). These specific mechanism suppressing induction such as the animals produce normal primary responses to the one described operates in carrier-primed animals to CGG determinants on the DNP-CGG molecule and induce the hapten-specific system to suppress the thus have normal carrier-specific helper populations. response to DNP on the priming carrier. Furthermore, as indicated above, they have normal Our studies are rooted in a set of observations well anti-DNP memory populations. Therefore, if their known in the early 1970s but largely forgotten since anti-DNP responses were not specifically suppressed, then. We inadvertently repeated some in-situ studies they should have produced secondary level anti-DNP reported in the first papers on hapten-carrier help responses comparable with those in the control mice interactions 3,4 and found, as these papers had exposed to DNP-KLH and then to DNP-CGG. 42 immunology today, March 1981 TABLE I. Hapten-carrier stimulation of anti-hapten memory B minants on these antigens suggests that the hapten- cells is normal in carrier-primed mice~ specific mechanism normally operates to selectively control responses to each of the determinants on an immunizing molecule, regardless of whether the Memory B cell donors' form Adoptive IgG (haptenic)determinants are added chemically or are of antigenic stimulation anti-DNP response defined by the natural structure of the molecule. However, understanding this mechanism of action in Mean K a 'ordinary' immunizations (to haptens on the priming Group KLH DNP-KLH Units (x 10 6) carrier) first requires consideration of how it suppresses responses and makes animals persistently l * Alum 73 10 responsive or non-responsive to individual deter- II Alum Alum 73 8 minants on an antigen. III * Aqueous 18 0.7 The induction of hapten-specific suppression by the IV Alum Aqueous 50 8 KLH/DNP-KLH immunization sequence does not appear to be due to anything unique in the KLH carrier molecule or DNP hapten. Exposure to a GGG/DNP-CGG sequence induces similar suppres- Donors (BALB/c x SJL) were killed 3 weeks after the first indicated stimulation with DNP-KLH. Splenic B cells were prepared by sion for anti-DNP responses 6, and exposure to a eytotoxic depletionof T cells using monoclonalanti-Thy-1.2 (30-H12, KLH/PC-KLH sequence induces suppression of anti- J Ledbetter). Cells obtained from 107 spleen cells were co-transferred PC (phosphoryl choline) responses (J. Kenny, with 2 x 106 nylon-passedsyngeneic T cells from KLH-primed donors personal communication). Therefore, suppression (100 gg on alum plus 109 Bordetella pertussis at least 6 weeks before induction must represent the animal's response to ex- transfer).
Load more

Recommended publications
  • Involvement of Haptens in Allergic and Non-Allergic Hypersensitivity
    Polish J. of Environ. Stud. Vol. 18, No 3 (2009), 325-330 Review Involvement of Haptens in Allergic and Non-Allergic Hypersensitivity E. Kucharska1*, J. Bober2**, L. Jędrychowski3*** 1Department of Human Nutrition, Faculty of Food Sciences and Fisheries, West-Pomeranian University of Technology, Papieża Pawła VI no. 3, 71-459 Szczecin, Poland 2Department of Medical Chemistry, Pomeranian Medical University, Powstańców Wlkp. 72, 70-111 Szczecin, Poland 3Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences in Olsztyn, Tuwima 10, 10-747 Olsztyn, Poland Received: 7 July 2008 Accepted: 11 December 2008 Abstract The environment is used as a broad umbrella term for all sources of allergens which may cause allergic hypersensitive reaction of the immune system of humans. Westernization of life leads to increased average consumption of food additives (natural and xenobiotics) – starting from over 5kg (10lbs) annually with a strong tendency to intensify. Modern technologies of food production often employ substances improving quality, texture, colour, taste, acidity or alkalinity. Haptens present in food or drugs, penetrating organism via gastrointestinal tract, may be responsible for symptoms not only in the gastrointestinal tract itself, but also in peripheral organs. Mechanisms of hapten action within human body are different – they include reactions when the immune system is involved (allergic hypersensitivity) and not involved (food intolerance also known as non-allergic hypersensitivity). Food intolerance is a more frequent phenomenon diagnosed in 20-50% of cases; food allergy affecting 6-8% children and 1-2% adults. Our work elucidates mechanisms of hypersensi- tivity responses to haptens, and characterizes major haptens applied as food additives.
    [Show full text]
  • Immunostimulatory Activity of Haptenated Proteins
    Immunostimulatory activity of haptenated proteins Noah W. Palm and Ruslan Medzhitov1 Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510 Communicated by Richard A. Flavell, Yale University School of Medicine, New Haven, CT, September 30, 2008 (received for review July 15, 2008) Antigen recognition alone is insufficient for the activation of In previous studies, we investigated the role of the TLR adaptive immune responses mediated by conventional lympho- signaling pathway in the induction of adaptive immune re- cytes. Additional signals that indicate the origin of the antigen are sponses, using mice deficient in the critical TLR signaling also required. These signals are generally provided by the innate adaptor Myeloid Differentiation primary response gene 88 immune system upon recognition of conserved microbial struc- (MyD88) (9, 10). To isolate the contribution of TLRs we used a tures by a variety of pattern recognition receptors (PRRs). The single defined TLR ligand, Lipopolysaccharide (LPS), as an Toll-like receptors (TLRs) are the best-characterized family of PRRs adjuvant, and the native proteins ovalbumin (OVA) or human and control the activation of adaptive immune responses to a serum albumin (HSA), as model antigens. incomplete Freund’s variety of immunizations and infections. However, recent studies adjuvant (IFA) and aluminum hydroxide, which contain low have questioned the role of TLRs in the induction of antibody levels of contaminating
    [Show full text]
  • Monoclonal Antibodies Specific for Mercuric Ions (Hybridomas/Metals) DWANE E
    Proc. Natl. Acad. Sci. USA Vol. 89, pp. 4104-4108, May 1992 Immunology Monoclonal antibodies specific for mercuric ions (hybridomas/metals) DWANE E. WYLIE*tt, Di Lut, LARRY D. CARLSON*, RANDY CARLSONt, K. FUNDA BABACAN§, SHELDON M. SCHUSTERt¶, AND FRED W. WAGNER*II tSchool of Biological Sciences, University of Nebraska, Lincoln, NE 68588; tBioNebraska, Inc., 3940 Cornhusker Highway, Lincoln, NE 68504; §Department of Microbiology, University of Marmara, Istanbul, Turkey; IDepartment of Biochemistry and Molecular Biology, J. Hillis Miller Health Center, University of Florida, Gainesville, FL 32610; and I'Department of Biochemistry, University of Nebraska, Lincoln, NE 68583 Communicated by Clarence A. Ryan, February 6, 1992 (received for review August 8, 1991) ABSTRACT Monoclonal antibodies (mAbs) that react These observations indicate that metals can at least influ- with soluble mercuric ions have been produced by i 'ection of ence antibody specificity and, rarely, in immunopathological BALB/c mice with a hapten-carrier complex designed to conditions, can serve as haptens toward which an antibody maximize exposure of the metal to the immune system. Three response can be directed. This report describes the produc- hybridomas producing antibodies that reacted with bovine tion of monoclonal antibodies (mAbs) specific for soluble serum albumin (BSA)-glutathione-HgCI, but not with BSA- mercuric ions by immunization of BALB/c mice with a glutathione, were isolated from the spleen of a mouse given complex consisting of mercuric chloride-glutathione- multiple iqjections with glutathione-HgCl conjugated to key- keyhole limpet hemocyanin (KLH). hole limpet hemocyanin. Stable subclones were established from two of these antibodies, designated mAb 4A10 and mAb MATERIALS AND METHODS IF10.
    [Show full text]
  • I M M U N O L O G Y
    I M M U N O L O G Y B T Immunology 2 Career Avenues GATE Coaching by IITians Table of Contents Introduction to Immune System ....................................................................................................... 4 Primary and Secondary Lymphoid Organs ...................................................................................... 12 Antigen ..................................................................... 26 Cells of Immune System .................................................................................................................. 33 Major Histocompatibility Complex ................................................................................................. 48 Antigen Processing and Presentation ............................................................................................. 51 Immunoglobulins ............................................................................................................................ 53 Origin of Antibody Diversity ........................................................................................................... 64 Polyclonal and Monolclonal Antibodies .......................................................................................... 66 Complement ............................................................. 70 Antigen-Antibody Reaction ............................................................................................................. 77 Regulation of Immune Response ...................................................................................................
    [Show full text]
  • The Fate of a Hapten
    www.nature.com/scientificreports OPEN The Fate of a Hapten - From the Skin to Modifcation of Macrophage Migration Inhibitory Factor (MIF) in Received: 14 September 2017 Accepted: 31 January 2018 Lymph Nodes Published: xx xx xxxx Isabella Karlsson 1, Kristin Samuelsson2, Carl Simonsson2, Anna-Lena Stenfeldt2, Ulrika Nilsson1, Leopold L. Ilag1, Charlotte Jonsson2 & Ann-Therese Karlberg2 Skin (contact) allergy, the most prevalent form of immunotoxicity in humans, is caused by low molecular weight chemicals (haptens) that penetrate stratum corneum and modify endogenous proteins. The fate of haptens after cutaneous absorption, especially what protein(s) they react with, is largely unknown. In this study the fuorescent hapten tetramethylrhodamine isothiocyanate (TRITC) was used to identify hapten-protein conjugates in the local lymph nodes after topical application, as they play a key role in activation of the adaptive immune system. TRITC interacted with dendritic cells but also with T and B cells in the lymph nodes as shown by fow cytometry. Identifcation of the most abundant TRITC-modifed protein in lymph nodes by tandem mass spectrometry revealed TRITC-modifcation of the N-terminal proline of macrophage migration inhibitory factor (MIF) – an evolutionary well-conserved protein involved in cell-mediated immunity and infammation. This is the frst time a hapten-modifed protein has been identifed in lymph nodes after topical administration of the hapten. Most haptens are electrophiles and can therefore modify the N-terminal proline of MIF, which has an unusually reactive amino group under physiological conditions; thus, modifcation of MIF by haptens may have an immunomodulating role in contact allergy as well as in other immunotoxicity reactions.
    [Show full text]
  • Monovalent and Divalent Haptens with Dual Specificity Monoclonal Antibody Conjugates: Enhanced Divalent Hapten Affinity for Cell Bound Antibody Conjugate
    In Vitro and In Vivo Targeting of Radiolabeled Monovalent and Divalent Haptens with Dual Specificity Monoclonal Antibody Conjugates: Enhanced Divalent Hapten Affinity for Cell Bound Antibody Conjugate Jean-Marc Le Doussal, Marie Martin, Emmanuel Gautherot, Michel Delaage, and Jacques Barbet Immunotech S.A., Campus de Luminy, Marseilles, France A method of pretargeted immunolocalizationof a mouse cell subset, using dual specificity monoclonalantibody conjugates and labeled divalent haptens, is described. Conjugates were prepared by coupling F(ab')@fragments of an antibody specificfor the allelicmouse B cell antigen Lyb8.2, to Fab' fragments of an anti-2,4-dinitrophenyl antibody. Divalent and monovalent haptens were obtained by coupling dinitrophenylto peptides or to diethylene tnamine-pentaacetic acid. In vitro, divalent haptens bind with higher affinityto mouse spleen lymphocyte-bound than to excess soluble conjugate (affinityenhancement). Invivo, localizationof 1251or 111ln-labeleddivalent haptens in mouse spleen is much higher than that ofthemonovalentanalogs.Thus,usingdivalenthaptens,a newkindofspecificitytotarget cells was achieved, suggesting that affinity enhancement may improve target to background ratios in radioimmunoscintigraphy. J Nucl Med30: 1358—1366,1989 ecently, the use of low molecular weight tracers, affinity of the DSC towards the hapten. Indeed, when such as indium chelates, associated with dual specificity the affinity is too strong, the tracer is effectively trapped antibody conjugates (DSC), combining antibodies (or by excess circulating DSC: its specific localization and fragments) to the target cells with high affinity antibod its clearance are impaired (3). Ifthis affinity is too low, ies (or fragments) to the indium chelate (dissociation no specificlocalizationwould be obtained.To take constant in the nM range), has been proposed for in advantage of the theoretical potential of the method, vivo radioimmunolocalization and radioimmunother excess DSC should be removed from the circulation apy ( 1).
    [Show full text]
  • Allotype Suppression and Epitope-Specific Regulation Leonore A
    Immunology Today, vol. 4, No. 4, 1983 113 Allotype suppression and epitope-specific regulation Leonore A. Herzenberg In neonatal (A x B) F1 mice, injections of maternal (A strain) antibody tothe Ig allotype of the paternal (B) strain chronically suppress the production of antibodies with the B-strain aUotype. Here Leonore Herzenberg describes how, in such animals, thisform of suppression influences the control of antibody responses to a thymus-dependent antigen that is subsequently encountered. The 'chronic allotype-suppression' system* occupies a As we have now shown, an 'epitope-specific' regu- peculiar niche in immunoregulatory history. Although latory system* operative in all mouse strains selectively often considered esoteric, this system (see Tables I and II) controls antibody responses to individual epitopes on has actually been one of the major contributorsto the complex antigens such as DNP-KLH (2,4-dinitrophenyl development of current concepts of how antibody hapten on keyhole limpet hemocyanin). This system responses are regulated in normal animals. The initial regulates the expression (rather than the development) of acceptance of suppressor T cells as functional regulatory memory B cells; it can be induced to either persistently agents, for example, was based to a considerable extent suppress or persistently support antibody production; on the strong and specific suppression demonstrable with and it consists of a series ofIgh-restricted, epitope-specific allotype suppressor T cells in adoptive 'co-transfer' elements individually dedicated to regulating the produc- assays I 4. Furthermore, many of the commonly known tion of antibody molecules that have the same combining- properties of suppressor T cells were first identified in site specifcity and Igh constant-region structure 1218.
    [Show full text]
  • NK Cell Memory: Discovery of a Mystery
    SERIES | COMMENT SERIES | comment NK cell memory: discovery of a mystery Ulrich von Andrian recounts how an unexpected experimental result called into question a well-established concept in immunology: the mechanism of immune memory. Follow-up experiments revealed that NK cells can mediate antigen-specifc adaptive immune responses. Ulrich H. von Andrian here must have been a mistake!” As expected, instillation of DNBS into the This was my first reaction when bladder of DNFB-sensitized animals resulted “TMahmood Goodarzi showed in a vigorous CHS response — a pronounced me a most unexpected set of experimental influx of diverse lymphoid and myeloid results. It was the summer of 2003, and we leukocytes that were readily detectable in were investigating the traffic signals that histologic sections of the bladder and could mediate the recruitment of effector T cells be quantified in single-cell suspensions to peripheral sites of antigen (Ag) challenge. of dissociated bladder tissue using flow Mahmood, a postdoctoral fellow, had set out cytometry10. The appearance of this to explore this phenomenon in the murine DNBS-induced inflammatory infiltrate bladder and was finalizing experiments for required prior sensitization with DNFB, our first manuscript on this topic. Our initial indicating that it was a learned response rationale for choosing the bladder for our driven by adaptive immune cells. Indeed, studies was that the default clinical therapy Ulrich von Andrian in 2005. the leukocyte infiltrate in DNBS-challenged for non-muscle invasive bladder cancer had bladders was dominated by CD8+ T cells been the intravesical instillation of Bacillus bearing activation markers, consistent Calmette–Guerin (BCG), which results in epidermis6.
    [Show full text]
  • Characterization of Primary T Helper Cell Activation and T Helper Cell Lines Stimulated by Hapten-Modified, Cultured Langerhans Cells
    characterization of Primary T Helper Cell Activation and T Helper Cell Lines Stimulated by Hapten-modified, Cultured Langerhans Cells Conrad H auser, M .D.! Wayne M . Yokoyama, M.D., and Stephen 1. Katz, M .D ., Ph.D. Derm.atolog-y Branch. National Cancer Insritute (CH. SIK). and ubor2tory of Immunology. National Institute of Allergic and Infectious Dise.ases (WY), Nation.allnstitutes of Health, Bethesda. Maryl.and . U .S.A. It has recentl y been shown that hapten-modified cultured ation induced by cultured Langerhans cells. Restimulation of Langerhans cells are "ble to activate SInaB resting syngeneic in vitro primed T helper cells with hapten-modified cultured L3T4+ T helper cells from nonsensitized animals. Repeated Langerhans cells revealed the prese nce. within the primed T stimulation of these T cells with hapten-modified cultured helper ce ll population. of activated cells with specificiry to an Langerhans ce lls leads to the establishment of L3T4+ hap­ unrelated hapten, suggesting that, in hapten-dependent T ten-specific interleukin-4-producing T-cell Jjnes. Here we helper cell activation, hapten-nonspecific cells are activated report on further characteristics oflrimary hapten-depen­ along with those that are hapten specilic. Restimulation of a dent activ",ion of L3T4+ T cells an ofT-ceil lines derived hapten-specifi c long-term T helper cell subline using differ­ from rhem. Dendritic cell-enriched spleen cells were as able ent antigen-presenting cell types demonstrates that factors as Langerhans cells to activate nonsensitized T helper cells other than major histocompatibil ity complex class II density after hapten modification. However, M12e, a major hisco­ or ti ssue derivation of (he antigen-presenting cell playa role compatibility complex class U-positive B-ce11 line that was in tbe acti va tion of T cells in vitro.
    [Show full text]
  • New Insights Into Drug Reaction with Eosinophilia and Systemic Symptoms Pathophysiology
    REVIEW published: 04 December 2017 doi: 10.3389/fmed.2017.00179 New Insights into Drug Reaction with Eosinophilia and Systemic Symptoms Pathophysiology Philippe Musette1* and Baptiste Janela2 1 Dermatology Department, Rouen University Hospital, Rouen, France, 2 Singapore Immunology Network, Singapore, Singapore Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome, is a severe type of cutaneous drug-induced eruption. DRESS may be a difficult disease to diagnose since the symptoms mimic those of cutaneous and systemic infectious pathologies and can appear up to 3 months after the initial culprit drug exposure. The symptoms of DRESS syndrome include rash development after a minimum of 3 weeks after the onset of a new medication, associated with facial edema, lymphadenopathy, and fever. Biological findings include liver abnormalities, leukocytosis, eosinophilia, atypical lymphocytosis, and reactivation of certain human herpes viruses. In DRESS, liver, kidneys, and lungs are frequently Edited by: Florence Emmanuelle involved in disease evolution. Patients with serious systemic involvement are treated Roufosse, with oral corticosteroids, and full recovery is achieved in the majority of cases. DRESS Free University of Brussels, is a rare disease, and little is known about factors that predict its occurrence. The key Belgium features of this reaction are eosinophil involvement, the role of the culprit drug, and Reviewed by: Dagmar Simon, virus reactivation that trigger an inappropriate systemic immune response in DRESS University Hospital Bern, patients. Interestingly, it was evidenced that at-risk individuals within a genetically Switzerland Ronan Desmond, restricted population shared a particular HLA loci. In this respect, a limited number of Tallaght Hospital, Ireland well-known drugs were able to induce DRESS.
    [Show full text]
  • The Nature of the Antigen Determine the Type of Immune Response
    LECTURE: 18 Title ANTIGENS AND IMMUNOGENS LEARNING OBJECTIVES: The student should be able to: • Define the antigenicity & immunogenecity. • Define the immunogen, antigen, hapten, epitope (antigenic determinant), and adjuvant. • Identify the factors that affect the antigenicity (characters of the substances which make it antigenic), such as; foreignness, chemical complexity, molecular size, dose of the antigen (high & low dose), and adjuvants (Freund’s adjuvants & Aluminum hydroxide). • Define the relation between the epitope & the antibody specificity. Also the valence of an antigen. • Explain the cross reactivity and define the antibody affinity and the avidity. • Describe the types of antigens for example; bacterial, viral, and isoantigens such as; blood grouping, MHC antigens. • Explain the organization & structure of MHC Genes & Products (MHC class II, III molecules, & I). • Identify the role of the MHC in controlling the T-Cell response. + • Explain the activation of CD8 cytotoxic T cells, & what determines that whether an antigen elicits a class II or class I restricted response. LECTURE REFRENCE: 1. TEXTBOOK: NATIONAL MEDICAL SERIES FOR INDEPENDENT STUDY. RICHARD M. HYDE. 3RD EDITION. Chapter 2. pg 23-30. 2. TEXTBOOK: JONATHAN M. AUSTYN AND KATHRYN J. WOOD Principles of Cellular and Molecular Immunology . Chapter 2. pg 63-84. 3. TEXTBOOK: ABUL K. ABBAS. ANDREW H. LICHTMAN. CELLULAR AND MOLECULAR IMMUNOLOGY. 5TH EDITION. pg 58, 216, 489. 4. TEXTBOOK: NATIONAL MEDICAL SERIES FOR INDEPENDENT STUDY. RICHARD M. HYDE. Chapter 2. pg 23-30. 1 ANTIGENS AND IMMUNOGENS I. DEFINITIONS A. Antigens. The immune response is characterized by the production of either proteins, called antibodies, or specifically reactive lymphocytes, called T cells, when an animal encounters a foreign macromolecule or cell.
    [Show full text]
  • Chapter 3. Antigens Terminology: Hapten - a Small Molecule That Is Antigenic but Not (By Itself) Immunogenic
    Chapter 3. Antigens Terminology: Hapten - a small molecule that is antigenic but not (by itself) immunogenic. Antigen : Substances that can be recognized by the surface antibody (B cells) or by the TCR when associated with MHC molecules Antibodies can be made to haptens only after the Immunogenicity VS Antigenicity: hapten is covalently conjugated to a large protein Immunogenicity – ability to induce an antibody and/or “carrier”. cell-mediated immune response Antigenicity – ability to combine with the final products of the response (antibodies and/or T cell receptor) NOTE: Most immunogenic molecules are also antigenic Figure 5.1 1 Factors that influence immunogenicity: - Foreign-ness – non-self (far apart evolutionary) 2 - Type of molecule (chemical nature) - protein > polysaccharide > lipid > nucleic acid - Size - larger molecules tend to be more immunogenic 3 -Composition - heterogeneity increases immunogenicity. - 4ry > 3ry > 2ry > 1ry structure -Degradability - protein antigens must be degraded (phagocytosis) in order to be presented to helper T cells . - Physical Form - Denatured > Native Additional factors that influence the immune response: - Genetics of the recipient (genotype - MHC) - Dosage of the antigen (optimal dose - tolerance) - Number of doses of the antigen (boosters) - Route of administration of the antigen - intravenous (spleen) - subcutaneous (lymph nodes) - intraperitoneal (lymph nodes) - oral (mucosal) - inhaled (mucosal) - Use of adjuvant 1 Commonly used adjuvants: (Table 3.3) Adjuvant : a substance that, when mixed with an antigen Alum - aluminum potassium sulfate - precipitates the antigen, and injected with it, serves to enhance the immune resulting in increased persistence of the antigen. Mild response to the antigen. granuloma. Possible mechanisms of action of adjuvants : Incomplete Freund’s adjuvant - mineral oil-based - increases - Prolong the persistence of the antigen , thus giving the persistence of the antigen, mild granuloma, and induces co- immune system more time to respond stimulatory signals.
    [Show full text]