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| A foreign substance that elicits an immune response (specific) |
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| Soluble and cell bound protein (mostly), also polysaccharides, lipids, nucleic acids, etc. (often associated with proteins- glycoproteins/lipoproteins) |
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| induce specific immune responses, react with products of those responses (Abs), have distinct chemical groups that can bind specifically to the Ag binding site of an Ab or T cell receptor called antigenic determinants or epitopes. |
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| Most complete Ags are multideterminant, meaning have more than one type of epitope and multiple copies of each epitope |
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| an incomplete Ag is called a hapten (substance with low MW and can't induce an immune response on its own). Haptens contain a single epitope |
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| Hapten + large macromolecule (protein) that serves as a carrier = |
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| can bind to hapten whether or not it is bound to the carrier |
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| factors influencing antigenicity |
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| foreigness, molecular size, complexity, degradability |
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| Ag must be recognized as non-self/foreign by the host. Some self components which are effectively sequestered from the immune system are immunogenic |
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Usually the bigger = the better Molecules with MW of 5000-10000 D are poor immunogens with the best immunogens being about >100,000 D MW. However some substances with MW of 1000 D can be immunogenic. |
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| a polymer of a single amino acid or sugar = tends to lack immunogenicity. addition of aromatic amino acids increase immunogenicity. all four levels of protein organization contribute to the structural complexity of a protein. |
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| Development of humoral (Ab) and cell mediated (T) immune responses both require T-helper activation for robust immune responses (gives cytokines/cell to cell interactions).Therefore macromolecules that cannot be degraded and processed by Ag presenting cells will not be present by MHC molecules yielding no T-helper activation = very weak specific immune response (low degradbility = poor Ag) |
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| Factor of the host contributing to immunogenicity |
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Definition
| Genotype of the host (genes coding for BCR, TCR, and MHC) |
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| Dosage affecting immunogenicity |
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Definition
| dosage (too low a dose of Ag = fail to activate enough lymphocytes for a response, too high a dose of Ag = overwhelm the system and lymphocytes enter a non-responsive state (tolerance). One dose of Ag will not induce a stron response because the Ag has to persist (repeated doses to make memory cells). |
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| Administration effecting immunogenicity |
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Definition
| Ag injected IV is carried by the blood to the spleen, Ag injected subQ into the tissues is processed by the lymph nodes, Ag inhaled/injested is processed by MALT. |
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| substances that when mixed with an Ag serve to make that Ag persist and increase the immunogenicity of that Ag. Typically water in oil (emulsion) mixtures with various bacterial components added. |
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| Aluminum potassium sulfate (alum) |
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Definition
| only approved adjuvant for human use |
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| How does an adjuvant cause Ag persistance? |
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Definition
| Forms an Ag depot, allows slow release of Ag over time. Provides a protected reservoir of Ag for slow release, promotes the formation of memory cells and prolonged Ab responses without the need for repeated Ag injections. |
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| How does an adjuvant induce the formation of granulomas (a site for additional Ab production)? |
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| Sits of chronic inflammation with activated macrophages and lymphocytes (plus other accessory cells) is a site with all the cells needed for an optimum immune response. |
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| How does an adjuvant enhance costimulatory signals? |
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Definition
| Various cell wall components of bacteria in adjuvants activate macrophages to increase MHC expression (to increase Ag presentation) and to increase monokine production (IL1/IL6(increase Ab production)/TNF >> increase activation of B/T cells) |
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| How does an adjuvant augment the immune response? |
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Definition
| Increase B/T cell activation/proliferation/differentiation. Can activate C' components which are also immunostimulatory to macrophages and some c' components can interact with the B cell co-receptor (C3bi, C3dg, C3d, CR2) |
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| B-Cell Epitope Characteristics |
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Definition
| recognize Ag shape/conformation, free or bound Ags, nature of the Ag = protein/polysacc/lipid/NA/etc., lock&key fit |
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Definition
| Abs bind Ag non-covalently (h-bond, van der waals, ionic, electrostatic, hydrophobic) |
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| relatively small (4 to 6 amino acids or sugar residues) |
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| epitope fits into the Ab binding site called the paratope. A concave pocket shaped to complementarily match the convexity of the epitope (epitope and paratope have short range binding) |
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Definition
| hydrophilic regions of a protein surface are most likely to be antigenic, b-cell epitopes must be accessible (increase protrusion = increase chance to be b-cell epitope) |
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