Chapter 3 Antigens

1. Chapter 3 Antigens • Substances which can be recognized by Ig of B cells (at Fab sites) and TCR’s of T cells (when accompanied by MHC) • B and T cells also differ in the way they recognize Ag Complementarity of Ag binding (Ab on left; Ag on right)

2. Terminology: • Immunogenicity vs. Antigenicity • Immunogenicity = ability to induce a humoral or cell-mediated IR • Ex: B cells + Ag*  Effector and Memory B cells • T cells + Ag*  Effector and Memory T cells • *these substances more appropriately called immunogens. • Antigenicity = ability to combine specifically w/ products of the above responses • All substances which are immunogenic are also antigenic; not the reverse • Some small molecules (Haptens) are antigenic but not capable of inducing a specific IR; they lack immunogenicity

3. Factors influencing immunogenicity • Our IS recognizes only small parts of parasites • Particular macromolecules such as proteins (#1) and polysaccharides (#2) • Lipids and nucleic acids do NOT, by themselves, stim IR unless they’re attached to proteins or polysacch’s • Immunogenicity is not an intrinsic property of the Ag, but depends on certain biological factors relative to the organism in which it is located

4. The Nature of Immunogens • Determined by 4 properties: • Degree of Foreignness • Molecular size • Chemical structure + heterogeneity • Ability to be processed and presented by an APC

5. 1) Degree of Foreignness • The body must be able to distinguish “self” from “non-self” • the greater the phylogenetic distance between 2 organisms, the greater the structural differences, hence foreignness (Ex: BSA ->rabbits; chicks vs goats) • Some macromolecules show conservancy of structure across phyla (e.g., collagen and cytochrome C) • Other macromolecules “outside” an organism’s system can be immunogenic! (e.g., cornea and sperm cells)

6. 2) Molecular size • Most immunogens are  100,000 daltons (Da) • Most molecules < 5-10,000 are poor ones

8. 3) Chemical structure/heterogeneity • All 4 levels of protein structure contrib to structural complexity…1°, 2°, 3°, 4° • Lipids can induce IR if presented properly • Lipids are typically ‘haptens’ carried by proteins (Ab’s are produced vs the lipid portion) • Ab’s can form vs steroids & fatty acid derivatives… • Several clinical assays use Ab’s to check for these subst • Ab’s vs leukotrienes  for evaluation of asthma • Ab’s vs steroids -> to measure amts in patient’s circulation • TCR recog lipid Ag assoc w/ CD1(resembles MHC I) • T cells recog vs lipids of Mycobacterium B cell response

9. 4) Ability to be processed/presented *Development of both Humoral and Cell-mediated IR requires T cell recognition of processed/ presented Ag *large, insoluble macromolecules and polymers are better immunogens than small and soluble *those molecules resistant to enzyme degradation (esp. D-amino acids) are poor immunogens

10. The bio system contributes to immunogenicity • Genotype of recipient– genetic makeup of person is important -there is a strong genetic link to immune response -e.g., MHC gene products, genes encoding B/T receptors 2)Dosage and route of Ag admin – exp’tl evidence indicates a dose-response curve to every immunogen -insufficient doses  nonresponse or tolerance -single doses  insignificant response (excessive too!) -“booster” shots are required for many immunizations -route affects which immune organ/cells involved…

11. Adjuvants (L. adjuvare = “to help”) • Substance which, when added to Ag, enhances its immunogenicity; used for immunizations how this works is not entirely understood, but they appear to help by: • Persistence of Ag in tissue • Enhancement of co-stimulatory triggers (B7 molecules) • Increased local inflammation • Nonspecific increase of lymphocytes