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)

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

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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