Chapter 3 Antigens Substances which can be recognized by Ig of B cells (at F ab 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)

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

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

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

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)

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

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

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

The bio system contributes to immunogenicity 1)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…

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