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Chapter 3- Antigens. Where we’re going- Immunogenicity vs antigenicity What makes for a good immunogen (aka antigen) Haptens Pattern recognition receptors. Some definitions:. Immunogenicity Immunogen, for practical purposes= antigen
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Chapter 3- Antigens Where we’re going- Immunogenicity vs antigenicity What makes for a good immunogen (aka antigen) Haptens Pattern recognition receptors
Some definitions: • Immunogenicity • Immunogen, for practical purposes= antigen • Antigenicity- ability to react with antibodies or Tcells; all immunogens are antigens, but haptens have antigenicity but not immunogenicity. (if this sounds confusing…)
So how do we tell a good antigen from a poor one? Inject with antigen- isolate serum, and react with antigen to produce, say, precipitation; the more dilute the serum can be, and still ppt the Ag, the better the response. Discuss more in Chapter 6
Immunogen’s contribution- usually think “protein” • Foreignness- cow vs chimp serum albumin; “shielded” parts from us- mitochondrial proteins, sperm. • Size- > 100K better, < 10K worse, especially for proteins • Complexity- homopolymers poor, heteropolymers better • Easily processed better than poorly processed; adding L-amino acids to a D-polymer increases its immunogenicity.
“Our” Contribution- both the animal and how immunization is done • Genetics- mouse studies- responders and non-responder mice. • Dosage and route of administration- the pneumococcal polysaccharide story. • Route determines which lymph tissues meet the antigen- e.g., spleen vs local lymph nodes. (know the terms)
Our contribution- adjuvants • Something that stimulates the immune response to the antigen. • Alum- ppt’s, prolongs persistence • Inflammatory- dead Mycobacterium • Non-specific proliferation of cells- LPS,
Epitopes, or Ag determinants • Our cells don’t react to the whole molecule, but to parts- epitopes • B cells react to differently to epitopes than do T cells. • Remember- interaction is specific!
How B cells do it An epitope can be non-sequential- 56-62 and 15-21 can be brought together spatially, producing a single epitope. B cell eptitopes tend to be on the surface,.
How T cells do it The binding is ternary- three components- MHCII, TCR, antigen. Only parts are displayed. No MHC binding= no antigenicity B cell eptitopes tend to be on the surface, but T cells can be from the interior of the molecule.
Haptens • Loved by some immunologists-esp. old ones! Haptens aren’t immunogenic alone. BUT- when bound to a carrier, Ab’s are produced that DO bind to the unbound hapten
Pattern Recognition receptors- innate immunity • The “patterns” are typical compounds found in pathogens • Some are soluble- we’ll meet these later • Some are membrane-bound- Toll-like receptors-
Toll-like Receptors • Recognize bacterial patterns. • The response: • Attraction of phagocytic and Antigen-presenting cells- better at stimulating T cells • Activation of macrophages • Induction of interferon- antiviral protein • Induces secretion of several cytokines
Wrap-up • Terms: Immunogen(icity), antigen(icity), hapten • What makes a good antigen? • Adjuvants and what they might do • B-cell epitopes and T cell epitopes- differences and why • The mystery of Table 3-5 • Haptens, and practical applications • Toll-like receptors- examples of what they recognize, types of response.
