Transcript Chapter 3 Antigens

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 “nonself”
• 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
B cell response
• 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
– T cells recog vs lipids of Mycobacterium
(resembles MHC I)
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:
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Persistence of Ag in tissue
Enhancement of co-stimulatory triggers (B7 molecules)
Increased local inflammation
Nonspecific increase of lymphocytes