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  2. 2. 12/14/2012 2
  3. 3. 12/14/2012 3
  4. 4. ANTIGEN Molecules that can be recognized by  Immunoglobulin receptors of B cells or  T cell receptors (when complexed with MHC) are called as ANTIGENS
  5. 5. DEFINITION.. ANTI - GEN Contd..  ‘ANTI’body ‘GEN’erator  Substances that react with antibodies IMMUNO - GEN  ‘IMMUN’E response ‘GEN’erator
  6. 6. DEFINITION..contd. IMMUNOGENICITY .  – ability of an Ag to elicit an immune reaction in the form of a B cell or T cell response ANTIGENICITY  – just the ability to combine with the products of the above responses
  7. 7. DEFINITION..contd.. All molecules that are immunogenic are antigenic All molecules that are antigenic are not immunogenic Antigens that are not immunogenic, but can take part in immune response
  9. 9. Determinants Of Antigenicity The importantdeterminants….  Molecular size  Foreignness  Chemical & Structural Complexity  Stability
  10. 10. MOLECULAR SIZE Protein molecules with large molecular weight - Highly Antigenic  Substances with mol wt > 1,00,000 Da  highly immunogenic  Substances with mol wt <
  11. 11. MOLECULAR This property is used in some SIZE..contd.. of the experimental studies  High molecular wt proteins like BOVINE GAMMA GLOBULIN (MW 1,50,000 da) - used to induce immune reaction  Substances with Low Mol Wt can be made antigenic by adsorbing these LMW molecules on
  12. 12. FOREIGNNESS A molecule should be recognized as non-self (foreign) to be more immunogenic Self or nonself  decided by the immune system,  Depending on whether or not
  13. 13. FOREIGNNESS Body has the ability to tolerate the self antigens Tolerance to self-antigens develops by contact with them in the initial phases of the development of the immune system, - particularly during the
  14. 14. Foreignness Immunogenicity of a molecule in a contd… a species species is greater when is distantly related to another species Immunogenicity of a molecule in a species is lesser when a species is closely related to another species Severity of immunogenicity of a molecule is dependent on the
  15. 15. Foreignness For example- a graft from a Human contd… to Human will be rejected within two weeks, if immunosuppressive drugs are not used, but a graft from a Chimpanzee to Human is rejected, even if immunosuppressive drugs are used Bovine Serum Albumin - more
  16. 16. Chemical & Structural Complexity Proteins – most potent immunogens Polysaccharides – Immunogenicity less than proteins Nucleic acids & Lipids – not efficient in eliciting an good immune reaction
  17. 17. Chemical & Structural Complexity In Proteins, the immunogenicity is dependent on its structural complexity – i.e  if the structure is simple (like chains of single amino acid or simple sugar,) it is less immunogenic.  if the structure is complex (like a
  18. 18. Chemical & Structural Complexity Contd.. In CMI, response of T cells to proteins, depends on how peptide is recognised & presented by MHC cells The structure of protein, plays an impt role in its immunogenicity, especially in CMI Since lipids are not efficient in eliciting a good immune response,
  19. 19. Chemical & Structural Complexity. Contd.. However these Lipid-specific Antibodies (LSAb) have a role in measurement of certain lipid- based molecules & drugs LSAb are produced by following process  First treat the lipid with hapten  Then conjugate the lipid-hapten with suitable carrier molecule such as
  20. 20. STABILITY Highly stable and non- degradable substances are not immunogenic. example:- some platics, metals, or chains of D- aminoacids  B’se Internalization,
  21. 21. STABILITY Very stable substances such as silicone have been successfully used as non- immunogenic substances for implants in breast reconstructive surgery. On the other hand, if a substance is very unstable,
  22. 22. Other factors of Antigenic Determinant Biological systems Dosage Route Adjuvants
  23. 23. BIOLOGICAL SYSTEMS Play an important role in determining the Immunological Efficiency of an Ag Some substances - immunogenic in one species
  24. 24. BIOLOGICAL SYSTEMS Some substances contd.  immunogenic in one individual ,  but not in others individual Species or individuals may lack or have altered genes that code for receptors for Ag on B&T cells. They may not have appropriate genes needed to code for APC to
  25. 25. Other Factors – Dosage & Dose of Route of Ag by Ag & the route which Ag comes into contact with the immune system also influences immunogenicity of Ag Very low dose of Ag – do not stimulate immune response  B’se too few lymphocytes are contacted
  26. 26. Other Factors – Dosage & Route of Ag Repeated administration of Ag – Booster dose  Required to enhance immune response of host to certain Ags  Particularly important in case of vaccines – to get the needed prerequisite immune level. Hence the Booster doses of vaccines such as DPT, DT, etc.
  27. 27. Other Factors – Dosage & Route of Ag Generally Ags are administered by parenteral route to produce good level of Antibodies Can be given by  Intravenous - IV,  Subcutaneous - SC,  Intradermal - ID,  Intramuscular - IM,  Intraperitoneal - IP, &  Mucosal routes SC route – better than IV route at
  28. 28. Other Factors – Adjuvants Substances that boost / increase the immunogenicity of the Ag, when mixed with that Ag & injected. Increase both the strength & duration of immune
  29. 29. ADJUVANTS CONTD… Boosts immunogenicity in several ways, eg:- by forming depot at injection site & prolongs persistence of Ag at the site  ALUM (aluminum potassium sulfate) precipitates Ag, releases
  30. 30. ADJUVANTS CONTD… Freund’s complete adjuvant  in addition to emulsifying factors, contains heat killed mycobacteria  Bacterial component activates macrophages & increases production of IL-1 & B7 membrane molecules  enhance immune response
  31. 31. ADJUVANTS.. B7 molecules on APC binds to contd.. CD28, a cell-surface protein on TH cells  triggers co- stimulation  an enhancement of T cell immune response Some adjuvants like synthetic polyribo-nucleotides & bacterial lipo-polysaccarides stimulate
  32. 32. ANTIGENIC SPECIFICITYAntigenicspecificity of anantigen dependsonEPITOPES or
  33. 33. EPITOPE Immunologically active region of an Immunogen Binds to Ag specific membrane receptors on lymphocytes or secreted antibodies Determines the complexity of any antigen 2 types & each have different properties
  34. 34. EPITOPE
  35. 35. EPITOPES
  36. 36. Antigenic Specificity – B Cell Epitopes Antigenic determinant recognized by B cell Can combine with its receptor only if the antigen molecule is in its native state Complementary surfaces of the Ab & Ag molecules appear to be relatively flat
  37. 37. Antigen Binding site
  38. 38. Antigenic Specificity – B Cell Epitopes About 6 or 7 sugar residues or AA long Hydrophilic Located at bends in protein structure Found in regions of protein that have a higher mobility
  39. 39. Antigenic Protein
  40. 40. Antigenic Specificity – T Cell Epitopes T cells recognize AA in proteins  T dependent Ags T cells do not recognize Polysaccharide Ag or Nucleic Acid Ag  T independent Ags Primary sequence of AA in proteins determines antigenic determinants recognized by T
  41. 41. Antigenic Specificity – T Cell Epitopes Free peptides are not recognised by the T cells, but they recognize peptides complexed with MHC molecules Thus for a T cell response, it should recognize both
  42. 42. Antigenic specificity – T cell epitopes T cell epitopes - small & only 8-15 AA Epitopes are restricted to those parts of Ag that can bind to MHC molecules There can be difference among individuals in their T cell response to same
  43. 43. Antigenic specificity – T cell epitopes Each MHC molecule can bind several peptides, but not all peptides. Therefore for a peptide to be immunogenic, in a particular individual, that individual must have the required MHC molecule that can bind to that peptide
  44. 44. Antigenic specificity – T cell epitopesprepares a 2 types of processing protein Ag for Ag presentation. They are  ‘Externally derived antigens’ processing  Phagocytosed bacteria are killed & lysed by phagocytic cells (macrophages). Pieces of bacteria are processed & presented by class II MHC mol
  45. 45. Species specificity Tissues of all individuals in a species possess certain species specific Ag. Some degree of cross-reaction occurs between Ag from related species Species Specificity shows phylogenetic relationship – useful in tracing evolutionary relationship
  46. 46. Speciesspecificity
  47. 47. Isospecificity Determined by the presence of ISOANTIGENS  Ag found in some members of species, but not all. A species can be grouped depending on the presence of different isoantigens in its members These are genetically determined Two examples of isoantigens are
  48. 48. Isoantigens- Blood Group Ag Based on human erythrocyte antigens, the individuals are classified into different blood group – best example of isoAntigen Blood groups are of primary importance in transfusion of blood & blood products and in isoimmunization during pregnancy Blood groups provide valuable
  49. 49. Isoantigens - The Histocompatibility Ag cellular determinants specific for each individual of a species Associated with plasma membrane of tissue cells HLA – Human Leukocyte Antigen – the major histocompatibility Ag that determines homograft rejection HLA typing - absolutely essential before carrying out transplantation
  50. 50. Auto-specificity Self-antigens are generally non- antigenic Sequestrated Ag are not recognised as selfAg  Eye lens protein  sperm B’se corneal tissue & sperm are never encountered by the immune system during development of
  51. 51. Organ specificity Ag characteristics of an organ/tissue – organ specific Ag Found in brain, kidney & lens tissues Even different animal species share same Ag  Brain specific Ag - shared by human brain & sheep
  52. 52. Heterophile specificity Determined by the presence of heterophile Ag Same Ag or closely related Ag present in tissues of different species, classes, or kingdom are known as Heterophile Ag Antibodies against the heterophile Ag produced by one of the species cross-react with the Ag of other
  53. 53. Heterophile specificity..contd.. Ex: of serological tests that use heterophile Ag  Weil-felix reaction  Paul-bunnell test  Cold agglutination tests Weil –Felix Reaction  diag of Rickettsial Inf  The strains of Proteus species such as OX-19, OX-2, OX-K are used to
  54. 54. Heterophile specificity.. contd.. diag of IM- Paul-Bunnell test  Infectious Mononucleosis - caused by Epstein-Barr virus – demonstration of heterophile antibodies that agglutinate sheep RBCs. Cold Agglutinin Test  diag of Primary Atypical Pneumonia
  55. 55. HAPTENS Small organic mol that are Antigenic Not immunogenic, b’se they cannot activate helper T cells Failure to activate helper T cells is due to their inability to bind to MHC proteins – b’se they are not proteins &
  56. 56. HAPTENS Haptens are univalent, hence cannot activate B cells by themselves – can activate when covalently bound to a ‘carrier protein’ – form an immunogenic hapten-carrier-conj Haptens (in hapten-carrier complex) combine with an IgM
  57. 57. HAPTENS A peptide of the carrier protein is presented in asso with class II MHC protein to the helper T cells. The activated helper T cells then produce interleukins, which stimulates the B cells
  58. 58. HAPTENS Animals immunized with such a conjugate produce antibodies specific for  The hapten determinant  Unaltered epitopes on the carrier protein, &  New epitopes formed by combined parts of both the hapten & carrier
  59. 59. HAPTENS Hapten – carrier molecule is then taken in, processed, & pieces of the carrier are presented by these B cells & helper T cells In our body, the formation of hapten-carrier conjugates is the basis for development of
  60. 60. SUPERANTIGEN Class of molecules that can S interact with APCs & T cells in a nonspecific way Act differently by interacting with MHC class II mol of the APC & the Vb domain of the T cell receptor  results in activation of a large number of T
  61. 61. SUPERANTIGENS Examples Staphylococcal enterotoxins, TSS toxin, Efoliative toxins & some viral proteins.
  62. 62. ANTIGEN SUPERANTIGEN Antigen presenting cell CHO α2 β2 CHO α2 β2 MHC Class II CHO α1 β1 CHO CHO α1 β1 CHO SuperAntigen antigen CHO CHO CHO CHO αV βV αV βV T cell receptor CHO CHO CHO CHO αC βC αC βC T lymphocyte