Antigens Lecture 3 PDF

Antigens 5.1. Definitions Antigen (Ag) : is substance which when introduced parentally into the body stimulates the production of an antibody with which it reacts specifically and in an observable manner. The word originated from the notion that they can stimulate ant...

Antigens 5.1. Definitions Antigen (Ag) : is substance which when introduced parentally into the body stimulates the production of an antibody with which it reacts specifically and in an observable manner. The word originated from the notion that they can stimulate antibody generation. Immunogen: A substance that induces a specific immune response. Epitope or Antigenic Determinant: That portion of an antigen that combines with the products of a specific immune response. 5.1. Definitions Tolerogen: antigen that induce Immunologic tolerance Immunological tolerance: is a complex series of mechanisms that impair the immune system to mount responses against self antigens. Allergen: antigen that induce Anaphylaxis (severe immediate hypersensitivity reaction occurring as a result of rapid generalized mast-cell granulation) Allergen: some medicine, flower powder, seafood 5.1. Definitions Tumor antigens - are those antigens that are presented by the MHC I molecules on the surface of tumor cells. These antigens can sometimes be presented only by tumor cells and never by the normal ones. In this case, they are called tumor-specific antigens (TSAs) and typically result from a tumor specific mutation.  5.1. Definitions Autoantigens - is usually a normal protein or complex of proteins (and sometimes DNA or RNA) that is recognized by the immune system of patients suffering from a specific autoimmune disease. These antigens should under normal conditions not be the target of the immune system, but due to mainly genetic and environmental factors the normal immunological tolerance for such an antigen has been lost in these patients. 5.1. Definitions Vaccines: are antigen preparations that induce a protective immune response against microbes and are used to prevent diseases. The preparations could be : Killed vaccine: Rubella virus, Attenuated vaccine: Measles Toxoid :Tetanus 5.1. Definitions Antibody (Ab): A specific protein which is produced in response to an immunogen and which reacts with an antigen 5.2 Immunogenicity Versus Antigenicity Immunogenicity is the ability of a molecule/microbe or cell to be recognized by hosts immune cells and elicit an immune response. While The ability of a molecule to bind/react with the products of an immune response (antibodies or lymphocytes) is called antigenicity Not all antigens are immunogens while all immunogens are antigens. 5.3. Classification of Antigen (Ag) Basis for classification: Complete and Incomplete According to source/origin of Ag According to whether need the help of T cells when B cells produce Ab Based on chemical nature  5.3. Classification of Antigen (Ag) Incomplete antigens (hapten): A substance that is non-immunogenic but which can react with the products of a specific immune response. Haptens are small molecules which could never induce an immune response when administered by themselves but which can when coupled to a carrier molecule. Free haptens, however, can react with 2 products of the immune response after such products have been elicited. Haptens have the property of antigenicity but not immunogenicity. 5.3. Classification of Antigen (Ag) Complete antigens: Are usually proteins or porteinous in nature, large in molecular size and are capable of stimulating an immune response by them selves Majority human pathogens/microbes and their toxins are examples of complete antigens/ immunogens 5.3. Classification of Antigen (Ag) Exogenous antigens: Are antigens that have entered the body from the outside, for example by inhalation, ingestion, or injection. By endocytosis or phagocytosis, these antigens are taken into the antigen-presenting cells (APCs) and processed into fragments. 5.3. Classification of Antigen (Ag) Endogenous antigens: Are antigens that have been generated within the cell, as a result of normal cell metabolism, or because of viral or intracellular bacterial infection. Example Autoantigens - is usually a normal protein or complex of proteins (and sometimes DNA or RNA). Tumor antigens - are those antigens that are presented by the MHC I molecules on the surface of tumor cells. 5.3. Classification of Antigen (Ag) Based on chemical nature antigens classified into: Protein antigens:- The vast majority of immunogens are proteins. These may be pure proteins or they may be glycoproteins or lipoproteins. In general, proteins are usually very good immunogens Polysaccharide antigens:- Pure polysaccharides and lipopolysaccharides are good immunogens.  5.3. Classification of Antigen (Ag) Based on chemical nature antigens classified into: Nucleic acid antigens:- Nucleic acids are usually poorly immunogenic. However they may become immunogenic when single stranded or when complexed with proteins. Lipid antigens:- In general lipids are non-immunogenic, although they may be haptens. Some glycolipids and phospholipids can stimulate T cells and produce a cell- mediated immune response. 5.3. Classification of Antigen (Ag) T-dependent- antigens: Do not directly stimulate the production of antibody without the help of T cells. Proteins are T-dependent antigens. Structurally these antigens are characterized by a few copies of many different antigenic determinants Examples Microbial proteins Non-self or Altered- self proteins 5.3. Classification of Antigen (Ag) T-independent antigens: Can directly stimulate the B cells to produce antibody without the requirement for T cell help. Characterized by the production of almost exclusively IgM Ab and no secondary response. Properties Polysaccharides Polymeric/repetitive structure Resistance to degradation Monoclonal B cell activation Examples Pneumococcal polysaccharide, lipopolysaccharide, Flagella  5.3. Classification of Antigen (Ag) Superantigens: Are potent T lymphocyte mitogens and simultaneously bind to class II MHC molecules. Superantigen stimulate the production Polyclonal T cell response Conventional Antigen stimulate the production Monoclonal/ Oligoclonal T cell response Examples Staphylococcal enterotoxins Staphylococcal toxic shock toxin Staphylococcal exfoliating toxin Streptococcal pyrogenic exotoxins Conventional Ag th Source: Janeway Jr. et al immunobiology 2001, 5 ed  th Source: Janeway Jr. et al immunobiology 2001, 5 ed 5.4. Factors That influence Immunogenicity Factors that influence immunogenicity could be : Those related to the antigen/ foreign substance Those related to the host/ biologic system 5.4. Factors That influence Immunogenicity Factors related to the immunogen/antigen are: Foreignness-The immune system normally discriminates between self and non-self such that only foreign molecules are immunogenic. Size - There is not absolute size above which a substance will be immunogenic. However, in general, the larger the molecule the more immunogenic it is likely to be. Most potent immunogens have a molecular weight 3 greater than 50 10 Daltons (Da) Few immunogens have molecular weight between 3 3 10 10 -50 10 Da A few immunogens are known to have mole wt less than 10,000 Da 5.4. Factors That influence Immunogenicity Chemical Composition - In general, the more complex the substance is chemically the more immunogenic it will be. Complex proteins are potent immunogens Physical form - In general particulate antigens are more immunogenic than soluble ones and denatured antigens more immunogenic than the native form. Particulate > Soluble Denatured > Native 5.4. Factors That influence Immunogenicity Degradability - Antigens that are easily phagocytosed are generally more immunogenic. This is because for most antigens (T-dependant antigens) the development of an immune response requires that the antigen be phagocytosed, processed and presented to helper T cells by an antigen presenting cell (APC). 5.4. Factors That influence Immunogenicity Contribution of the host/biological System Genetic Factors - The species or individuals may lack or have altered genes that code for the receptors for antigen on B cells and T cells or they may not have the appropriate genes needed for the APC to present antigen to the helper T cells. Age - Age can also influence immunogenicity. Usually the very young and the very old have a diminished ability to mount an immune response in response to an immunogen. 5.4. Factors That influence Immunogenicity Method of Administration 1. Dose - The dose of administration of an immunogen can influence its immunogenicity. There is a dose of antigen above or below which the immune response will not be optimal. 2. Route - Generally the subcutaneous route is better than the intravenous or intra gastric routes. The route of antigen administration can also alter the nature of the respons 3. Adjuvants - Substances that can enhance the immune response to an immunogen are called adjuvants. 5.5. Determinants Recognized by the Innate Immune System The innate immune system functions by recognizing highly conserved sets of molecules PAMPs – Pathogen Associated Molecular Patterns: Are structural molecules on the surface of microbes or secreted; that are recognized by the host innate immune molecules. PRRs – Pattern Recognition Receptors: Are molecules on the cells and or molecules of the immune system that are capable of recognizing foreign substances 5.5. Determinants Recognized by the Innate Immune System These molecular structures are specific to the microbes (pathogen-associated molecular patterns, or PAMPs) through a limited set of germ line encoded receptors called pattern- recognition receptors (PRRs) There are several distinct classes of PRRs, each of which is involved in performing specific tasks These include opsonization, activation of complement cascade, phagocytosis, etc. 5.5. Determinants Recognized by the Innate Immune System First, PRRs recognize microbial components, known as pathogen-associated molecular patterns (PAMPs), that are essential for the survival of the microorganism and are therefore difficult for the microorganism to alter Second, PRRs are expressed constitutively in the host and detect the pathogens regardless of their life-cycle stage Third, PRRs are expressed on all cells of a given type, and independent of immunologic memory 5.5. Determinants Recognized by the Innate Immune System Different PRRs react with specific PAMPs, show distinct expression patterns, activate specific signaling pathways, and lead to distinct anti-pathogen responses. The basic machineries underlying innate immune recognition are highly conserved among species, from plants and fruit flies to mammals A class of PRRs called Toll-like receptors (TLRs) has the ability to recognize pathogens or pathogen-derived products and initiate signaling events leading to activation of innate host defenses 5.5. Determinants Recognized by the Innate Immune System Toll-like receptors (TLRs) are a family of pattern recognition receptors that are activated by specific components of microbes and certain host molecules. Signaling by TLRs initiates acute inflammatory responses by induction of anti-microbial genes and inflammatory cytokines and chemokines Subsequent events, such as recruitment of neutrophils and activation of macrophages, lead to direct killing of the microbes 5.5. Determinants Recognized by the Innate Immune System The notion of TLRs is primary sensors of pathogens and responsible for orchestrating the innate responses TLRs contribute significantly to activation of adaptive immune responses There are 10 TLRs, named TLRs 1–10, known in mammals These receptors recognizes molecules derived from a unique class of microbial agents See table below for examples of PAMPs, PRRs and their biologic effects 5.5. Determinants Recognized by the Innate Immune System Biological Consequence of PAMP PRR Interaction Microbial cell wall Complement Opsonization; Complement components activation Mannose-containing Mannose-binding Opsonization; Complement carbohydrates protein activation Polyanions Scavenger receptors Phagocytosis Lipoproteins of Gram+ TLR-2 (Toll-like Macrophage activation; bacteria Yeast cell wall receptor 2) Secretion of inflammatory components cytokines 5.5. Determinants Recognized by the Innate Immune System Biological Consequence PAMP PRR of Interaction Double stranded TLR-3 Production of interferon RNA (antiviral) LPS TLR-4 Macrophage activation; (lipopolysaccharid Secretion of inflammatory e of Gram-bacteria cytokines Flagellin (bacterial TLR-5 Macrophage activation; flagella) Secretion of inflammatory cytokines 5.5. Determinants Recognized by the Innate Immune System Biological PAMP PRR Consequence of Interaction U-rich single TLR-7 Production of stranded viral interferon (antiviral) RNA CpG containing TLR-9 Macrophage DNA activation; Secretion of inflammatory cytokines  Including phagocyte- Toll-Like Receptors attracting citokines. Danger, I’m infected! signal. TLR-2 TLR- 5 TLR- 9 TLR- 4 Source: Abbas - Cellular And Molecular Immunology (5Ed).  5.6. Antigen Processing and Presentation Antigen processing involves the interaction of PAMPs and PRRs followed by digestion of the foreign substance by host phagocytic cells. Antigen presentation is the process of displaying peptide antigens associated with MHC molecules to a T cell. The path leading to the association of protein fragments with MHC molecules differs for class I and class II MHC. MHC class I molecules present degradation products derived from intracellular (endogenous) proteins in the cytosol. MHC class II molecules present fragments derived from extracellular (exogenous) proteins that are located in an intracellular compartment.  5.6. Antigen Processing and Presentation Class I MHC Pathway: All nucleated cells express class I MHC. Proteins are fragmented in the cytosol by proteosomes (a complex of proteins having proteolytic activity) or by other proteases. The fragments are then transported across the membrane of the endoplasmic reticulum by transporter proteins. (The transporter proteins and some components of the proteosome are encoded by genes in the MHC complex). 5.6. Antigen Processing and Presentation Class II MHC pathway Only a limited group of cells express class II MHC, which includes the antigen presenting cells (APC). The principal APC are macrophages (MӨ) , dendritic cells (Langerhans cells) (DCs), and B cells. Often known as professional APCs The expression of class II MHC molecules is either constitutive or inducible, especially by interferon- gamma in the case of macrophages. exogenous proteins taken in by endocytosis are fragmented by proteases in an endosome. 5.6. Antigen Processing and Presentation The alpha and beta chains of MHC class II, along with an invariant chain, are synthesized and assembled in the endoplasmic reticulum The invariant chain prevents endogenous peptides from the cytosol from associating with class II MHC molecules. The class II MHC molecules with the associated invariant chain are finally transported to the cell surface for presentation to T cells Source: Abbas - Cellular And Molecular Immunology 2008 (5ed).  Summary Immunogenicity is the ability of a substance to induce an immune reaction. In contrast, antigenicity is the ability of a substance to react with a preformed antibody or receptor. Immunogen must be somewhat complex , with an appreciable molecular weight and must be considered foreign by the immune system. The relatively small area of antigen that reacts with an antibody or receptor is called the antigenic determinant or, epitope. A single epitope is called a hapten Hapten are too small to be immunogens in the their own right but may become immunogen when associated with a larger molecule. The penicillin's may act as haptens. Adaptive, Specific Immunity and Immunization Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education. 1  Specific Immunity: The Adaptive Line of Defense Third line of defense – acquired Dual System of B and T lymphocytes – Immunocompetence Antigen – Molecules that stimulate a response by T and B cells Two features that characterize specific immunity: – Specificity – antibodies produced, function only against the antigen that they were produced in response to – Memory – lymphocytes are programmed to “recall” their first encounter with an antigen and respond rapidly to subsequent encounters 2 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Overview of Specific Immune Responses Separate but related activities of the specific immune response: Development and differentiation of the immune system Lymphocytes and antigen processing The cooperation between lymphocytes during antigen presentation B lymphocytes and the production and actions of antibodies T lymphocyte responses 3 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Overview of Specific Immune Responses 4 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  5 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  6 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  7 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Development of the Immune Response System Cell receptors or markers confer specificity and identity of a cell Major functions of receptors are: – To perceive and attach to nonself or foreign molecules – To promote the recognition of self molecules – To receive and transmit chemical messages among other cells of the system – To aid in cellular development 8 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education. Major Histocompatibility Complex (MHC) Receptors found on all cells except RBCs Also known as human leukocyte antigen (HLA) Plays a role in recognition of self by the immune system and in rejection of foreign tissue Copyright © McGraw-Hill Education. Permission required for reproduction or display. Peptides Cell membrane Class I MHC molecule Class II MHC found on all nucleated found on some types 9 human cells of white blood cells Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Functions of MHC Genes for MHC clustered in a multigene complex: – Class I – markers that display unique characteristics of self molecules and regulation of immune reactions Required for T lymphocytes – Class II – regulatory receptors found on macrophages, dendritic cells, and B cells Involved in presenting antigen to T-cells 10 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Lymphocyte Receptors Lymphocyte’s role in surveillance and recognition is a function of their receptors B-cell receptors – bind free antigens T-cell receptors – bind processed antigens together with the MHC molecules on the cells that present antigens to them 11 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Clonal Selection Theory Lymphocytes use 500 genes to produce a tremendous variety of specific receptors Undifferentiated lymphocytes undergo a continuous series of divisions and genetic changes that generate millions of different cell types Each cell has a particular/unique receptor specificity 12 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  The Development of Lymphocytes Copyright © McGraw-Hill Education. Permission required for reproduction or display. B cells T cells In the bone marrow, Bone marrow lymphocytic stem cells differentiate into either T or Release of Immature B cells lymphocytes Bone marrow Differentiation B cells stay in the bone stromal cells and maturation Thymus In separate sites marrow while T cells migrate to the thymus Ig receptor Expression of cell receptors T-cell receptor Migration to specific compartments of lymphoid Both T and B cells migrate organs to secondary lymphoid B cell T cell tissue Lymph node 13 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Lymphocyte Development Lymphocyte specificity is preprogrammed, existing in the genetic makeup before an antigen has ever entered the system Each genetically different type of lymphocyte (clone) expresses a single specificity 14 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Clonal Selection First introduction of each type of antigen into the immune system selects a genetically distinct lymphocyte Causes it to expand into a clone of cells that can react to that antigen 15 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Concept Check: All lymphocytes have the same receptor specificity. True False 16 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Concept Check: All lymphocytes have the same receptor specificity. True False 17 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Specific B-Cell Receptor: Immunoglobulin Receptor genes of B cells govern immunoglobulin (Ig) synthesis – Immunoglobulins are large glycoproteins that serve as specific receptors of B cells Copyright © McGraw-Hill Education. Permission required for reproduction or display. Light chains Antigen binding sites V V V V C C S-S S-S C C -S-S- Disulfide bonds C C Heavy chains 18 (a) Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Specific B-Cell Receptor: Immunoglobulin Composed of 4 polypeptide Copyright © McGraw-Hill Education. Permission required for reproduction or display. chains: Light chains – 2 identical heavy chains (H) Antigen binding sites – 2 identical light chains (L) V V V V Y shaped arrangement – ends S-S C C S-S C C of the forks formed by light and heavy chains contain a wide range of variable antigen -S-S- binding sites Disulfide bonds C C Variable regions and Constant regions (a) Heavy chains 19 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Development of Receptors Copyright © McGraw-Hill Education. Permission required for reproduction or display. 1 The heavy-chain genes are composed off Immunoglobulin genes our separate segments (V, D, J, and C) that are 2 transcribed and translated lie on 3 different to form the heavy polypeptide chains. chromosomes V1 V2 3 The light-chain genes are put together like heavy ones, except that the final gene is spliced from three gene groups V3 (V, J, and C), making smaller V4 polypeptides. Undifferentiated V 79 V1 V2 lymphocyte has 150 Vn 1 2 V3 different genes for the D1 3 D2 X2 V 98 X2 V 99 Light-chain gene complex variable region of light Heavy-chain gene D12complex J1 V 100 chains and 250 for the J2 J1 J2 variable region and J4 C1 J5 diversity region of the C2 C3 Precisely shaped binding sites C heavy chain C4 4 During final assembly, first C5 the heavy and light chains are bound, and then the heavy-light combinations are connected to form the (b) immunoglobulin molecule. 20 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Development of Receptors Copyright © McGraw-Hill Education. Permission required for reproduction or display. 1 The heavy-chain genes are composed off our separate segments (V, D, J, and C) that are 2 transcribed and translated During development, to form the heavy polypeptide chains. recombination causes only V1 V2 3 The light-chain genes are put together like heavy ones, except that the final gene is spliced from three gene groups the selected V and D V3 V4 (V, J, and C), making smaller polypeptides. genes to be active in the V1 mature cell V 79 V2 Vn 2 V3 1 D1 3 D2 X2 V 98 X2 V 99 Once synthesized, Light-chain gene comple Heavy-chain gene D12complex V 100 J1 immunoglobulin is J2 J1 J2 transported to cell J4 C1 J5 membrane and inserted C2 C3 Precisely shaped binding sites C there to act as a receptor C4 4 During final assembly, first C5 the heavy and light chains are bound, and then the heavy-light combinations are connected to form the (b) immunoglobulin molecule. 21 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  T-Cell Receptors for Antigen Formed by genetic recombination, with variable and constant regions 2 parallel polypeptide chains Small, not secreted 22 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Lymphocyte Responses and Antigens B-cell maturation: – Directed by bone marrow sites that harbor stromal cells, which nurture the lymphocyte stem cells and provide hormonal signals – Millions of distinct B cells develop and “home” to specific sites in the lymph nodes, spleen, and GALT – Come into contact with antigens throughout life – Have immunoglobulin as surface receptors for antigens 23 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Lymphocyte Responses and Antigens T-cell maturation: – Maturation is directed by the thymus gland and its hormones – Different classes of T-cell receptors termed CD - Cluster of differentiation CD4 and CD8 – Mature T cells migrate to lymphoid organs 24 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  B Cells and T Cell 25 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Entrance and Processing of Antigens and Clonal Selection Antigen (Ag) is a substance that provokes an immune response in specific lymphocytes Property of behaving as an antigen is antigenicity – Foreignness, size, shape, and accessibility Copyright © McGraw-Hill Education. Permission required for reproduction or display. Microbial cells, Foreign human Plant molecules 26 viruses or animal cells (a) Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Characteristics of Antigens Perceived as foreign, not a normal constituent of the body Foreign cells and large complex molecules over 10,000 MW are most antigenic Antigenic determinant, epitope – small molecular group that is recognized by lymphocytes Antigen has many antigenic determinants 27 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Haptens Haptens – small foreign molecules that consist only of a determinant group – Not antigenic unless attached to a larger carrier Carrier group contributes to the size of the complex and enhances the orientation of the antigen Copyright © McGraw-Hill Education. Permission required for reproduction or display. (a) Hapten No antibody Insert Fig 15.8 (b) Hapten bound to Antibody carrier molecule formed in response to hapten 28 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education. Special Categories of Antigens Alloantigens – cell surface markers and molecules that occur in some members of the same species but not in others Superantigens – potent T cell stimulators; provoke an overwhelming response Allergen – antigen that evokes allergic reactions Autoantigens – molecules on self tissues for which tolerance is inadequate 29 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Concept Check: Which of the following would be LEAST likely to produce a large immune response? A complex antigen with multiple epitopes A simple antigen bound to a hapten An antigen exhibiting a repeated structure An allergen 30 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Concept Check: Which of the following would be LEAST likely to produce a large immune response? A complex antigen with multiple epitopes A simple antigen bound to a hapten An antigen exhibiting a repeated structure An allergen 31 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education. An antigen with a repeated structure might not stimulate a large immune response because it can induce immune tolerance. When the immune system encounters repeated structures, especially in high abundance, it might interpret them as "self" rather than foreign. This can lead to the suppression of immune responses against those structures to prevent the body from attacking its own tissues. This phenomenon is known as "tolerance induction." Therefore, while repeated structures might seem highly immunogenic at first glance, they can paradoxically lead to immune tolerance and dampened immune responses. 32 Antibody Learning objectives By the end of this session student should be able to know The structure of antibody Immunoglobulin classes Antigenic determinants of immunoglobulins Monoclonal antibodies Genetics of antibody production  Antibody or immunoglobulin Specialized glycoprotein, produced from activated B cells (plasma cells) in response to an antigen. Capable of combining with the antigen that triggered its production.  Antibody or immunoglobulin A.Tiselius in 1939 subjected the serum to electrophoresis, the serum proteins are separated into four fragments- albumin, globulin α, β and γ. Antibodies are located in the γ-globulin fraction; because they immunologically react with the antigen; they were given the name as immunoglobulin.  Antibody or immunoglobulin Both the terms, immunoglobulin (Ig) and antibody are used interchangeably; representing the physiological &functional properties of same molecule respectively. Immunoglobulin (Ig) constitutes 20-25 per cent of total serum proteins. There are five classes (or isotypes) of immunoglobulins recognised-IgG, IgA, IgM, IgD and IgE.  STRUCTURE OF ANTIBODY An antibody molecule is a ‘Y-shaped’ heterodimer; composed of four polypeptide chains. Two identical light (L) chains, of molecular weight 25,000 Da each Two identical heavy (H) chains each having molecular weight 50,000 Da or more.  STRUCTURE OF ANTIBODY (cont..) H and L chain: All four H and L chains are bound to each other by disulfide bonds, and by noncovalent interactions such as salt linkages, hydrogen bonds, and hydrophobic bonds. All the chains have two ends- an amino terminal end (NH3) and a carboxyl terminal end (COOH).  STRUCTURE OF ANTIBODY (cont..) There are five classes of H chains and two classes of light chains. Immunoglobulin class Heavy chain type IgG γ(gamma) IgA α (alpha) IgM µ(mu) IgD δ(delta) IgE ε(epsilon)  STRUCTURE OF ANTIBODY (cont..) L chains are of two types- kappa (κ) and lambda (λ), named after Korngold and Lapari who originally described them. Each H and L chain comprises of two regions- variable and constant region. Variable region: Represents the antigen binding site of the antibody.  Hyper variable region Within the variable region, there are some zones (hot spots) that show relatively higher variability in the amino acid sequences. Called as hypervariable regions or complementarity determining regions (CDRs). Form the antigen-binding site. There are three hot spots in the L and  Hyper variable region Paratope The site on the hypervariable regions that make actual contact with the epitope of an antigen is called as paratope.  Constant regions Constant region Constitutes the remaining part of an Ig molecule other than that of variable region. Length of the constant regions is approximately 104 amino acids for light chain, 330 amino acids for γ, α and δ heavy chains and 440 amino acids for µ and ε heavy chains. The amino acid sequence of constant region shows uniform pattern. A single antibody molecule has two identical heavy chains and two identical light chains; H2L2.  H & L chain domains Light chain contains one variable domain (VL) and one constant domain (CL). Heavy chains possess one variable domain (VH) and 3 or 4 numbers of constant domains (CH)- Heavy chains γ, α and δ have three constant domains- CH1, CH2 and CH3. Heavy chains µ and ε have four constant domains- CH1 to CH 4.  Hinge region Rich in proline and cysteine. Quite flexible, allowing the Ig molecule to assume different positions, thus helps the antibody in reaching towards the antigen. Hinge region is sensitive to various enzymatic digestions.  Enzymatic digestion When an immunoglobulin molecule is subjected to enzymatic digestion, it generates various fragments. Types: Papain digestion- Pepsin digestion Mercaptoethanol reduction  Papain digestion Result in three fragments each having a sedimentation coefficient of 3.5 S - Two Fab fragments Fc fragment  Pepsin digestion One F (ab')2 fragment Many smaller fragments  Mercaptoethanol reduction Mercaptoethanol reduction of Ig molecule- generates four fragments (two H and 2 L chains) as it cleaves only disulphide bonds sparing the peptide bonds.  FUNCTIONS OF IMMUNOGLOBULINS Antigen binding (by Fab region) Protection of the host. Interaction with the antigen. Valency of an antibody refers to the number of Fab regions it possesses. Thus, a simple monomeric antibody molecule has a valency of two.  FUNCTIONS OF IMMUNOGLOBULINS Effector functions (by Fc region) Fixation of complement: Antibody coating the target cell binds to complement through its Fc receptor which leads to complement mediated lysis of the target cell. Binding to various cell types Phagocytic cells, lymphocytes, platelets, mast cells, NK cell, eosinophils and basophils bear Fc receptors (FcR) that bind to Fc region of immunoglobulins. Binding can activate the cells to perform some biological functions. Some immunoglobulins (e.g. IgG) also bind to receptors on placental trophoblasts, which results in transfer of the immunoglobulin across the placenta.  IMMUNOGLOBULIN CLASSES Based on five types of heavy chains, there are five classes of immunoglobulins (lgG, IgA, IgM, IgD and IgE).  Immunoglobulin G (IgG) Constitutes about 70-80% of total Igs of the body. IgG has maximum daily production. Longest half-life of 23 days. Highest serum concentration.  Immunoglobulin G (IgG) IgG has four subclasses- IgG1, IgG2, IgG3 and IgG4; all differ from each other in the amino acid sequences of the constant region of their γ-heavy chain. Subclasses vary in their biological functions, length of hinge region and number of disulphide bridges. IgG3 has longest hinge region with 11 inter-chain disulphide bonds.  Functions of IgG IgG can cross placenta - hence provide immunity to the fetus and new born. Among subclasses, IgG2 has the poorest ability to cross placenta. Complement fixing: Complement fixing ability of subclasses varies - IgG3> IgG1> IgG2. IgG4 does not fix complements. Phagocytosis  Functions of IgG Mediates precipitation and neutralization reactions. IgG plays a major role in neutralization of toxins as it can easily diffuse into extravascular space. IgG is raised after long time following infection and represents chronic or past infection (recovery). Coagglutination  Immunoglobulin M (IgM) Among all Igs, IgM has highest molecular weight, and maximum sedimentation coefficient (19S). Present only in intravascular compartment, not in body fluids or secretions.  Immunoglobulin M (IgM) IgM exists in both monomeric and pentameric forms: When present as membrane-bound antibody on B cells, it exists in monomeric form. When present in secreted form, it is pentameric in nature  Functions of IgM Acute infection Complement fixing Antigen receptor. Acts as an opsonin Protection against intravascular organisms Mediate agglutination Immunoglobulin A (IgA) IgA is the second most abundant class of Ig next to IgG, constituting about 10-15% of total serum Ig. Exists in both monomeric and dimeric forms. IgA in serum is predominantly in monomeric form.  Secretory IgA Dimeric in nature; two IgA monomeric units joined by a J chain. Secretory component Location- Predominant antibody found in body secretions like milk, saliva, tears, intestinal & respiratory tract mucosal secretions. Secretory component is derived from poly Ig receptor present on the serosal  Function of secretory IgA Local or mucosal immunity Effective against bacteria like Salmonella, Vibrio, Neisseria, and viruses like polio and influenza. Breast milk is rich in secretory IgA and provides good protection to the immunologically immature infant gut.  Formation of secretory IgA Dimeric secretory IgA is synthesised by plasma cells situated near mucosal epithelium. J chain is also produced in the same cell. Secretory component protects IgA from denaturation by bacterial proteases produced by intestinal flora.  Formation of secretory IgA Dimeric secretory IgA binds to poly Ig receptor on the basolateral surface of mucosal epithelium Receptor- IgA complex is endocytosed into mucosal epithelial cells Receptor is partially cleaved leaving behind a part of it (secretory component) Subsequently secretory IgA (complex of dimeric IgA with J chain and secretory component) is released into the mucosal secretions.  Subclasses of IgA Depending upon the amino acid sequences in the constant region of heavy chain, IgA exists in two isotypes: IgA1 IgA2  Immunoglobulin E (IgE) Lowest serum concentration. Shortest half life. Minimum daily production. Only heat labile antibody (inactivated at 56º C in one hour). Has affinity for the surface of tissue cells (mainly mast cells) of the same species (homocytotropism). Extravascular in distribution.  Functions of IgE Mediator of type I hypersensitivity reactions IgE is elevated in helminthic infections.  Immunoglobulin D (IgD) IgD is found as membrane Ig on the surface of B cells and acts as a B cell receptor along with IgM. Has the highest carbohydrate content among all the Igs. No other function is known for IgD so far. Property IgG IgA IgM IgD IgE PropertiesMonomer Usual form of various immunoglobulins Monomer,dimer Monomer,Penta Monomer Monomer mer Valency 2 2 or 4 2 or 10 2 2 Other chains None J chain, J chain None None secretory component Subclasses G1, G2, G3, G4 A1, A2 None None None Molecular weight (kDa) 150 150-600 900 150 190 Serum level mg/mL 9.5–12.5 IgA1- 3.0 1.5 0.03 0.0003 IgA2 - 0.5 % of total serum Ig 75–85% 10–15% 5–10% 0.3% 0.019% Half-life, days 23* 6 5 3 2.5 Daily production mg/kg 34 24 3.3 0.4 0.0023  Properties of various immunoglobulins Property Intravascular IgG 45% IgA 42% IgM 80% IgD 75% IgE 50% distribution (%) Sedimentation 7 7 19 7 8 coefficient activation Complement Classical ++ (IgG3>1>2) – +++ – – Alternate - + - - - Binds to Fc receptors of ++ - ? ** - - phagocytes Placental transfer Yes (except IgG2) - - - - Mediates Yes (except IgG3) - - - - coagglutination Mucosal transport - Yes - - - Mast cell degranulation - - - - yes Marker for B cells - - + + - Heat stability + + + + -  Cooperation in Immune Reactions to Antigens Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education. 1  Cooperation in Immune Reactions to Antigens The basis for most immune responses is the encounter between antigens and white blood cells Lymph nodes and spleen concentrate the antigens and circulate them so they will come into contact with lymphocytes 2 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Antigen Processing and Presentation to Lymphocytes T-cell dependent antigens must be processed by phagocytes called antigen presenting cells (APC) APCs modify the antigen; then the Ag is moved to the APC surface and bound to MHC receptor Antigen presentation involves a direct collaboration among an APC, and a T helper cell – Interleukin-1 is secreted by APC to activate TH cells – Interleukin-2 is produced by TH to activate B and other T cells 3 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  T Helper Activation 4 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  B Cell Responses B-cell activation and antibody production – Once B cells process the Ag, interact with TH cells, and are stimulated by growth and differentiation factors, they enter the cell cycle in preparation for mitosis and clonal expansion – Divisions give rise to plasma cells that secrete antibodies and memory cells that can react to the same antigen later 5 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education. B Cell Activation and Differentiation 6 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Antibody Structure and Functions Copyright © McGraw-Hill Education. Permission required for reproduction or display. Immunoglobulins Antigen binding sites Large Y-shaped protein Consist of 4 V V V V polypeptide chains Fab Fab C Disulfide C bonds C S-S S-S C Contain 2 identical -S-S- fragments (Fab) with Hinge regions ends that bind to a Complemet C C specific antigen binding site Fc Fc binds to various cells and molecules of the immune system (a) Binding site for cells 7 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Antigen-Antibody Binding 8 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Antibody-Antigen Interactions Principle antibody activity is to unite with the Ag, to call attention to, or neutralize the Ag for which it was formed Opsonization – process of coating microorganisms or other particles with specific antibodies so they are more readily recognized by phagocytes Neutralization – Abs fill the surface receptors on a virus or the active site on a microbial enzyme to prevent it from attaching Copyright © McGraw-Hill Education. Permission required for reproduction or display. Bacterial cell “tagged” Opsonization Neutralization with Abs Antibodies block binding Macrophage Viruses Opsonized bacteria engulfed more readily Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education. 9  Antibody-Antigen Interactions Agglutination – Ab aggregation; cross-linking cells or particles into large clumps Complement fixation – Activation of the classical complement pathway can result in the specific rupturing of cells and some viruses Precipitation - Aggregation of particulate antigen Agglutination Cross-linked Complement fixation Precipitation bacterial cells Abs Antibodies aggregate antigen molecules Lysing bacterial cells 10 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Functions of the Fc Fragment Fc fragment binds to cells – macrophages, neutrophils, eosinophils, mast cells, basophils, and lymphocytes Certain antibodies have regions on the Fc portion for fixing complement – Binding of Fc may cause release of cytokines 11 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Classes of Immunoglobulins 5 classes of immunoglobulins (Ig): – IgG – monomer, produced by plasma cells (primary response) and memory cells (secondary), most prevalent – IgA – monomer circulates in blood, dimer in mucous and serous secretions – IgM – five monomers, first class synthesized following Ag encounter – IgD – monomer, serves as a receptor for antigen on B cells – IgE – Involved in allergic responses and parasitic worm infections 12 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Immunoglobulin Classes 13 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Concept Check: All antibodies in the IgA class Have identical Fc regions Have identical antigen binding sites Have identical variable regions Are all monomers 14 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Concept Check: All antibodies in the IgA class Have identical Fc regions Have identical antigen binding sites Have identical variable regions Are all monomers 15 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Primary Response to Antigen Primary response – after first exposure to an Ag immune system produces IgM and a gradual increase in Ab titer (concentration of antibodies) with the production of IgG 16 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Secondary Response to Antigen Secondary response – after second contact with the same Ag, immune system produces a more rapid, stronger response due to memory cells – Anamnestic response 17 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Monoclonal Antibodies Originate from a single clone and have a single specificity for antigen Pure preparation of antibody Single specificity antibodies formed by fusing a mouse B cell with a cancer cell Used in diagnosis of disease, identification of microbes and therapy 18 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Using Monoclonal Antibodies for Treatment 19 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  T Cells & Cell-Mediated Immunity Cell-mediated immunity requires the direct involvement of T lymphocytes T cells act directly against Ag and foreign cells when presented in association with an MHC carrier T cells secrete cytokines that act on other cells Sensitized T cells proliferate into long-lasting memory T cells 20 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Types of T Cells 21 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Types of T Cells T helper cells (CD4 or TH) most prevalent type of T cell; regulate immune reaction to antigens, including other T and B cells; also involved in activating macrophages and increasing phagocytosis; differentiate into T helper 1 (TH1) cells or T helper 2 (TH2) cells Cytotoxic T cells (CD8 or TC) destroy foreign or abnormal cells by secreting perforins that lyse cells Natural killer cells – lack specificity; circulate through the spleen, blood, and lungs 22 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education. T-Cell Activation and Differentiation 23 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Cytotoxic T Cell Activity 24 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  25 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  T Cells and Superantigens Reaction has drastic consequences Superantigens are a form of a virulence factor Provoke overwhelming immune responses by large numbers of T cells – Release of cytokines – Blood vessel damage – Toxic shock – Multiorgan damage 26 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Concept Check: The lymphocyte responsible for finding and destroying cancerous cells is the Antigen presenting cell B cell Cytotoxic T cell T helper cell 27 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Concept Check: The lymphocyte responsible for finding and destroying cancerous cells is the Antigen presenting cell B cell Cytotoxic T cell T helper cell 28 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Disorders in Immunity Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education. 1  The Immune Response Immunopathology: the study of disease states associated with underactivity and overactivity of the immune response – Allergy, hypersensitivity – an exaggerated, misdirected expression of immune responses to an allergen (antigen) – Autoimmunity – abnormal responses to self Ag – Immunodeficiency – deficiency or loss of immunity – Cancer – both a cause and effect of immune dysfunction 2 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Immune System Disorders 3 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  The Hypersensitivity Reactions 4 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Type I Allergic Reactions Two levels of severity: Atopy – any chronic local allergy such as hay fever or asthma Anaphylaxis – a systemic, often explosive reaction that involves airway obstruction and circulatory collapse 5 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Contact with Allergens Generalized predisposition to allergies is familial – not to a specific allergy Allergy can be affected by age, infection, and geographic area Atopic allergies may be lifelong or may be “outgrown”; may also develop later in life 6 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Nature of Allergens and Their Portals of Entry Allergens have immunogenic characteristics Typically enter through epithelial portals – respiratory, gastrointestinal, skin Organ of allergic expression may or may not be the same as the portal of entropy 7 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Mechanism of Type I Allergy Develop in stages: Sensitizing dose – on first contact with allergen, specific B cells form IgE which attaches to mast cells and basophils; generally no signs or symptoms Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education. 8  Mechanism of Type I Allergy Provocative dose – subsequent exposure with the same allergen binds to the IgE-mast cell complex Degranulation releases mediators with physiological effects such as vasodilation and bronchoconstriction 9 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Role of Mast Cells and Basophils Mast cells are located in the connective tissue of virtually all organs; high concentration in lungs, skin, GI, and genital tract Basophils circulate in blood and migrate into tissues Each cell can bind 10,000-40,000 IgE Cytoplasmic granules contain physiologically active cytokines, histamine, etc. Cells degranulate when stimulated by allergen 10 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Type 1 Mechanism Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education. 11  Concept Check: Type I reactions produce symptoms upon the second exposure to an allergen. A. True B. False 12 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Concept Check: Type I reactions produce symptoms upon the second exposure to an allergen. A. True B. False 13 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Cytokines, Target Organs, and Allergic Symptoms Act alone or in combination; account for scope of allergic symptoms – Histamine, serotonin, leukotriene, platelet-activating factor, prostaglandins, bradykinin General targets include: skin, upper respiratory tract, GI tract, and conjunctiva – Responses: rashes, itching, redness, rhinitis, sneezing, diarrhea, shedding tears Systemic targets: smooth muscles, mucous glands, and nervous tissue – Responses: vascular dilation and constriction resulting in change in blood pressure and respiration 14 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Main Chemical Mediators Histamine – most profuse and fastest acting; stimulator of smooth muscle, glands, and eosinophils Response to chemical depends on the muscle location: constricts smooth muscles of small bronchi, intestines; relaxes vascular smooth muscles Serotonin, leukotrienes, prostaglandins, bradykinin are additional allergic mediators 15 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education. Reactions to Inflammatory Cytokines Copyright © McGraw-Hill Education. Permission required for reproduction or display. Constricted Headache (pain) bronchioles Dilated blood vessel Wheal and flare reaction, itching Dilated blood vessel Increased blood flow Nerve cell Constricted Prostaglandin bronchiole Smooth muscle Wheezing, nulation Difficult breathing Bradykinin Histamine Serotonin coughing, D e g ra Increased peristalsis of intestine; diarrhea, vomiting Secretory Glands on epithelial tissues Leukotriene Typical Response in asthma Airway obstruction: Excessive mucus, tear formation, 16 mucus buildup glandular secretions Constriction of bronchioles Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Specific Diseases Atopic disease – hay fever, rhinitis; seasonal, inhaled plant pollen or mold – Asthma – severe bronchoconstriction; inhaled allergen – Eczema – dermatitis; ingestion, inhalation, skin contact 17 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Specific Diseases Food allergy – intestinal portal can affect skin and respiratory tract – Vomiting, diarrhea, abdominal pain; possibly severe – Eczema, hives, rhinitis, asthma, occasionally anaphylaxis Drug allergy – common side effect of treatment; any tissue can be affected; reaction from mild atopy to fatal anaphylaxis Copyright © McGraw-Hill Education. Permission required for reproduction or display. 18 © Kathy Park Talaro (b) Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Anaphylaxis Anaphylaxis – a reaction of animals injected with a foreign protein Systemic anaphylaxis – sudden respiratory and circulatory disruption that can be fatal in a few minutes – Allergen and route are variable Bee stings, antibiotics, or serum injection 19 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Diagnosis of Allergy Important to determine if a person is experiencing allergy or infection Skin testing 20 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Treatment and Prevention General methods include: 1. Avoiding allergen 2. Use drugs that block the action of the lymphocytes, mast cells, or chemical mediators (antihistamines) Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education. 21  Treatment and Prevention General methods include: 1. Avoiding allergen 2. Drugs 3. Desensitization therapy – injected allergens may stimulate the formation of