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Immunology lecture 4-1.pptx power point ppt
- 1. Antibodies, Antigens, and ImmuneResponses
- 2. Immunoglobulins • Generally assumeone of two roles May act as plasma membrane bound antigen receptors on the surface of a B cell May act as antibodies in cellular fluids functioning to capture and eliminate antigenic determinants
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- 5. Immunoglobulin Classes • Fivedifferent classes (isotypes) determined by the type of heavy chains - IgG – gamma heavy chains. Have 4 sub-classes being IgG1, 2, 3, and IgG4 - IgM – mu heavy chains - IgA – alpha heavy chains. Have 2 sub-classes being IgA1, and IgA2. - IgD – delta heavy chains - IgE – epsilon heavy chains
- 6. Ig types • Twotypes exist - Kappa light chains - Lambda light chains – has four subtypes (lambda 1, 2, 3, and 4)
- 7. Other classification ofIg • Allotypes – determined by the amino acid sequence and corresponding 3D structure of the heavy chain constant region just like the isotypes. However, the allotypes reflect genetic differences between members of the same species. • Idiotypes – determined by the amino acid sequence and 3D structure of the variable region. They reflect the antigen binding specificity of the antibody molecule.
- 9. • The mostversatile immunoglobulin since it is capable of carrying out most of the functions of Ig molecules. • The functions include: Opsonization and ADCC of microbes Opsonization and phagocytosis of microbes Complement fixation Opsonization and neutralization of toxins and microbes – this function is dependent on the binding capacity of the antibody
- 10. Protection of thegrowing fetus (IgG2 does not cross the placenta well so does not perform this function)
- 12. - First classproduced in a primary response - First class to be synthesized by the neonates - Serum IgM has a higher valency than other isotypes and so more efficient than others - Its J chain allows binding to secretory cells which transports it to the external secretions that bathe the mucosal surfaces - Cell surface IgM exists as a monomer
- 14. • Predominant Igclass in secretions existing as either a dimer or tetramer containing a J chain and polypetide chain called secretory component • In serum, IgA exists as a monomer but polymeric forms (dimers, trimers, and some tetramers) are sometimes seen all of which contain a J chain • The daily production of sIgA is greater than that of any other Ig class.
- 16. • Low levelsin serum with no known role • Together with IgM, IgD is the major membrane bound Ig expressed by mature B cells, and its role in the physiology of B cells is under investigation
- 18. • Binds verytightly to Fc receptors on basophils and mast cells so it is the least common serum Ig. • Involved in allergic reactions • IgE also plays a role in parasitic helminthes diseases. • Can be diagnostic marker for parasitic infections
- 19. Generation of AntibodyDiversity • Capacity to respond to 10^7 different antigens. Possible ways for generating such a huge diversity: Multiple genes in the germ line DNA - Up to 200 different variable (V) genes, 12 diversity (D) genes and 4 joining (J) genes exist in the germ line DNA that makes up the loci controlling heavy chain production - Up to 200 different V genes and 5 different J genes exist in the germ line DNA that makes up the loci controlling light chain production
- 20. Variable recombination duringthe differentiation of germ line cells into B cells - Several events of recombination take place that lead to changes in amino acid sequences and their diversity Mutations during the differentiation of germ line cells into B cells - Changes in DNA sequence take place leading to changes in the amino acid sequence changes. - This may explain in part the diversity observed in the CDRs.
- 21. Production of Ig •Rearrangement, recombination, and mutation take place during differentiation of the B cells thereby producing functional VJ light chain and VDJ heavy chain genes. This determines the antigen specificity of the mature B cell. • These are mostly IgD and some IgM which are expressed as receptors
- 22. • Upon stimulationby antigen, sIgM is produced. The B cells also undergo class-switching where rearrangement of DNA will occur and placing the VDJ gene next to the genes encoding IgG, IgE, or IgA constant regions • Upon secondary induction, these B cells will differentiate into plasma cells expressing the new isotype.
- 23. Antigens • Antigen –a substance that react with products of a specific immune response • Immunogen – a substance that induces a specific immune response • Hapten – non-immunogenic substance that can react with products of a specific immune response. When coupled to carrier molecules, haptens become immunogenic
- 24. • Hapten-carrier conjugates– Molecules to which haptens have been covalently attached to make the whole complex immunogenic • Epitope/antigenic determinant – a portion of an antigen that combines with the products of a specific immune response • Antibody – a protein produced in response to an immunogen and reacts with an antigen
- 25. Factors Influencing Immunogenicity •In relation to Immunogen - Foreignness – self molecules may not be immunogenic - Size – too small molecules are not immunogenic - Chemical composition – the more complex a substance is the more immunogenic it is - Physical forms – particulate more immunogenic than soluble, denatured form more immunogenic than native form - Degradability – those that can be phagocytosed and degraded and presented to T cells (T-dependent) are more immunogenic.
- 26. • In relationto biological system - Genetic factors – some antigen receptor genes may be turned on/off while some may be mutated leading to immunogenicity of some antigens in certain individuals but not in others - Age – the very young and very old have a diminished ability to mount an immune response to antigens
- 27. • In relationto Method of administration - Dose – some doses may not be optimal for inducing immune responses - Route – some routes may be better at inducing immune responses than others - Adjuvants – enhance immunogenicity of antigens
- 28. • In relationto nature of antigen - Proteins – most immunogens are proteins - Polysaccharides – pure polysaccharides and lipopolysaccharides are good immunogens - Nucleic acids – these are usually poor immunogens unless they are complexed with proteins or are single stranded - Lipids – generally, these are non-immunogenic but they can be haptens.
- 29. Types of Antigens T-independent– these directly stimulate B cells to produce antibodies without the need for T cell help. In general, polysaccharides are T-independent antigens • Properties of T-independent antigens - Polymeric structure – many antigenic determinants in one structure - Polyclonal activation of B cells – some T-indepent antigens (type 1) activate even B cells that are not specific them and so they are said to be polyclona activators while others are not polyclonal activators (type 2)
- 30. - Resistant todegradation – T-independent antigens are not processed (degraded) and as such they persist for long periods of time and continue to stimulate the immune system T-dependent antigens – processed and presented to T cells • Properties of T-dependent antigens - Opposite of those found in T-independent antigens
- 31. Superantigens - These areantigens that activate T cells polyclonally. - Up to 25% of T cells may be activated. - Examples of superantigens are: Staphylococcal entero-toxins (food poisoning) Staphylococcal toxic shock toxin (toxic shock syndrome) Staphylococcal exfoliating toxins (scalded skin syndrome) Staphylococcal pyrogenic exotoxins (shock) - The diseases caused are as a result of hyper-activation of the immune system and subsequent release of biologically active cytokines by activated T cells
- 32. Antigenic Determinants • Determinantsrecognized by B cells - Composition – created by the primary sequence of residues in a polymer (linear or sequence determinants) and/or by the secondary, tertiary, or quaternary structure of the molecule (conformational determinants) - Size – generally, antigenic determinants are small and limited to about 4 – 8 residues - Number – antigenic determinants are limited to those accessible to antibodies
- 33. • Determinants recognizedby T cells - Composition – created by the primary sequence of AA in proteins. Need not be located on the surface since processing takes place. - Size – generally small and limited to 8 – 30 amino-acids - Number – limited to those that can bind to MHC molecules
- 34. Determinants Recognized bythe Innate Immune System • There are broad molecular patterns called pathogen associated molecular patterns (PAMPs) recognized by pattern recognition receptors (PRRs) of the innate immune system • A particular PRR can recognize a molecular pattern that may be present on a number of different pathogens. • Examples of PAMPs and PRRs are shown in the table below.
- 35. Table 1 Examplesof pathogen associated molecular patterns and their receptors PAMP PRR Biological Consequence of Interaction Microbial cell wall components Complement Opsonization, Complement activation Mannose-containing carbohydrates Mannose-binding protein Opsonization Complement activation Polyanions Scavenger receptors Phagocytosis Lipoproteins of Gram + bacteria Yeast cell wall components TLR-2 (Toll-like receptor 2) Macrophage activation, secretion of inflammatory cytokines Double stranded RNA TLR-3 Production of interferon (antiviral) LPS (lipopolysaccharide of Gram negative bacteria) TLR-4 Macrophage activation, secretion of inflammatory cytokines Flagellin (bacterial flagella) TLR-5 Macrophage activation, secretion of inflammatory cytokines U-rich Single stranded viral RNA TLR-7 Production of interferon (antiviral) CpG containing DNA TLR-9 Macrophage activation, secretion of inflammatory cytokines