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Immunogens, Antigens, and Haptens

Immunogens, Antigens, and Haptens. Initiation of immune response. Interaction between receptor and ligand Affinity Avidity . Affinity: high. low. low. strong binding. strong binding. weak binding. Introduction. Immune responses arise as a result of exposure to foreign stimuli

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Immunogens, Antigens, and Haptens

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  1. Immunogens, Antigens, and Haptens

  2. Initiation of immune response • Interaction between receptor and ligand • Affinity • Avidity Affinity: high low low strong binding strong binding weak binding

  3. Introduction • Immune responses arise as a result of exposure to foreign stimuli • The compound that evokes an immune response is referred to as “antigen” or “immunogen.” • The distinction between the two is functional but they are commonly used as synonyms.

  4. Definitions • An immunogen is any substance capable of inducing an immune response • An antigen is any substance capable of binding specifically to the products of the immune response • All immunogens are antigens but not all antigens need be immunogens

  5. Special Types of Antigens • Allergen • Mitogen • Super antigen • Tolerogen • According to source of antigen: - Xenoantigen - Heteroantigen - Alloantigen - Autoantigen

  6. Haptens are low molecular weight compounds (antibiotics and drugs) that by themselves are incapable of inducing an immune response, but they can react with its products • When haptens are coupled with large molecules such as proteins (carriers), the resultant conjugate induces an immune response directed against the hapten and the carrier

  7. Factors influencing immunogenicity

  8. Contribution of the immunogen • Foreignness • High Molecular Weight - <1000 Daltons : nonimmunogenic - 1000-6000 Daltons: may be immunogenic - > 6000 immunogenic • Chemical Nature and Complexity -Homopolymers Vs Heteropolymers - Primary, secondary, tertiary, and quaternary structures

  9. Antigenic Determinants or Epitopes - Linear - Discontinuous • Paratope: “The site in the variable (V) domain of an antibody or T-cell receptor that binds to an epitope on an antigen • Physical Form • Particulate > Soluble • Denatured > Native • Degradability • Ag processing by Ag Presenting Cells (APC)

  10. Factors Influencing ImmunogenicityContribution of the Biological System • Genetics • Species • Individual • Responders vs. Non-responders • Age

  11. Factors Influencing ImmunogenicityMethod of Administration • Dose • Route • Subcutaneous > Intravenous > Intragastric • Rate of elimination • Adjuvant • Substances that enhance an immune response to an Ag

  12. Adjuvants • Substances which when mixed with an immunogen enhance the immune response against the immunogen • They differ from carriers as they do not enhance immunity to haptens • Release immunogens slowly but continuously • Types: Freund’s incomplete or complete adjuvants, BCG, Corynebacterium parvum, Bordetella pertussis, LPS, and Alum precipitate (most widely used )

  13. Major Classes of Immunogens • Proteins: Best immunogens • Carbohydrates: Usually but not always good immunogens • Nucleic Acids: Poor immunogens by themselves unless coupled to carriers • Lipids: Non immunogens unless coupled to carriers

  14. Cross Reactivity • Modification of a molecule; toxins and toxoids • Sharing epitopes between unrelated macromolecules • Structural resemblance (molecular mimicry) • Significance in - tolerance and autoimmunity - Isohemagglutinins

  15. Antigens: T-independent • Activate B cells without MHC class II T help • Polysaccharides • Properties • Polymeric structure • Polyclonal B cell activation, but poor memory • Resistance to degradation • Examples • Pneumococcal polysaccharide, LPS • Flagella

  16. Antigens: T-dependent • Require T help to activate B cells • Proteins • Structure • Examples • Microbial proteins • Non-self or altered-self proteins

  17. Hapten-carrier conjugates • Definition • Ag only if bound to carrier protein • Structure • Native determinants • Haptenic determinants

  18. Sequential (or linear) determinants • Epitopes formed by several adjacent amino acid residues are called linear determinants. • They exist on the surface of antigen molecules or inside of antigen molecules. • They are mainly recognized by T cells, but some can also be recognized by B cells.

  19. Conformationaldeterminants • Conformational determinants are formed by amino acid residues that are not in a sequence but become spatially juxtaposed in the folded protein. • They normally exist on the surface of antigen molecules. • They are recognized by B cells or antibody.

  20. Antigenic Determinants Recognized by B cells and Ab • Composition • Proteins, polysaccharides, nucleic acids • Sequence (linear) determinants • Conformational determinants • Size • 4-8 residues

  21. Antigenic Determinants Recognized by B cells and Ab • Composition • Size • Number • Limited (immunodominant epitopes) • Located on the external surfaces of the Ag

  22. Antigenic DeterminantsRecognized by T cells • Composition • Proteins (some lipids) • Sequence determinants • Processed • MHC presentation (lipid presentation by MHC-like CD1) • Size • 8 -15 residues • Number • Limited to those that can bind to MHC

  23. Superantigens Ag T cell T cell • Definition • Polyclonal T cell response • Examples • Staphylococcal enterotoxins • Toxic shock toxin TCR TCR Super Ag MHC MHC APC APC

  24. Superantigen Conventional Antigen Polyclonal T cell response 1:4 - 1:10 Superantigens • Definition Monoclonal/ Oligoclonal T cell response 1:104 - 1:105

  25. Most Important Human Antigens

  26. Membrane molecules of immune cells • Receptors: TCR, BCR, CR, CKR, FcR • Class Iand class Ⅱ MHC molecules • CD molecules: CD1~339 • Cell Adhesion Molecules • Cytokine Receptors • Blood Group Antigens

  27. Pathogen recognition by adaptive immunity: great variety, selectivity

  28. Distinguishing cell-surface markers include TCR, CD3, CD2, CD4 or CD8, CD28, and CD45 • Similarities between T and B cells: • Antigen receptor on surface • (TCR) • Recognize single, specific antigen • Expand through clonal selection • Some T cells exist as long-lived memory cells T Lymphocytes

  29. Bursa of fabricius B Lymphocytes • Recognize antigen by • means of surface-expressed • antigen receptor • Distinguishing cell-surface • markers include: B220 (CD45), • MHC Class II, CD80 (B7-1) and • CD86 (B7-2), CD40, CD19, • CD21, etc.

  30. Figure 3-13 part 1 of 2

  31. Figure 3-15 The peptide-binding groove of MHC molecules

  32. Present Ag to CD8 T cells Present Ag to CD4 T cells

  33. Polymorphism: presence of multiple alternative forms (alleles) of a gene. Help peptide loading Present antigen peptides to CD4+ T cells Polymorphism allows the population to handle a variety of pathogens.

  34. Figure 3-22 Different cell distribution of MHC class I and II • Almost all cells express MHC I for comprehensive surveillance by CD8 T cells • Only some cells express high levels of MHC II and MHC I • These are B cells, macrophages, dendritic cells and thymic epithelial cells. • B cells, macrophages and dendritic cells are called professional antigen- presentingcells (APC). • IFN-g increases the expression of MHC II in APC and induces the expression in non-APC cells at sites of infection

  35. Leukocyte Differentiation Antigens and CD • Leukocyte differentiation antigen: Cell surface molecules expressed (or disappeared) during different developmental and differential phases, activation or inactivation process of blood cells.

  36. Identifying Cell Using the CD Nomenclature • CD Cluster Of Differentiation • Over 300 CD Markers • T cells, CD4 or CD8 and CD3 • B cells, CD19 • NK cells, CD56 • Monocytes /Macrophages CD14 • Dendritic Cells, CD1c

  37. CD - Cluster of Differentiation Table 2-4

  38. CDs which take part in T cell recognition, adhesion and activation

  39. CDs which take part in B cell recognition, adhesion and activation

  40. Adhesion Molecules • Cell adhesion molecules (CAMs) are cell surface proteins involved in the interaction of cell-cell or cell-extracellular matrix. • CAMs take effect by the binding of receptor and ligand.

  41. Ⅱ. Classification • Integrin family • Selectin family • Immunoglobulin (Ig) superfamily • Cadherin family • Mucin - like family • Other adhesion molecules

  42. 1. Integrin family • Integrins consist of α and β chains. • According to β subunits, Integrins are divided into eight groups: β1- β8 • VLA-4(Very Late Antigen-4)------VCAM-1 LFA-1(Lymphocyte Function-associated Antigen-1) ICAM-1,2,3 • MAdCAM-1 (Mucosal Addressin Cell Adhesion Molecule-1) • TSP-1 ((Thrombospondin一1)

  43. 2. Selectin family • Selectins consist of one peptide chain. • The three family members include: E- selectin, L-selectin, and P-selectin.

  44. 3. Ig superfamily(IgSF) • The structure of these adhesion molecules resemble that of Ig. • CD4, CD8, CD2(LFA-2), CD58(LFA-3), VCAM-1, ICAM-1,2,3

  45. 4. Cadherin family • E- cadherin------ Epithelia cell • N- cadherin------ Nerve cell • P- cadherin-------Placenta

  46. 5. Mucin -like familyCD34, GlyCAM-1(glycosylation dependent cell adhesion molecule-1) PSGL-1(P-selectin glycoprotein ligand-1) 6. Other adhesion moleculesCD44

  47. Ⅲ. Functions • Participate in development and differentiation of immune cells • CD2----LFA-3 • LFA-1----ICAM-1 Participate in development and maturation of thymocytes. • 2.Participate in immune response and regulation

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