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22 Cards in this Set

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What Determines whether or not a substance will be immunogenic?
1. Nature of the host (genetic make-up influences magnitude of response. Controlled by MHC)
2. Mode of immunization: route, dose, and form of the administered material (adjuvants)
3. Sensitivity of assays used to measure the response.
3. Sensitivity of assay
Properties of Immunogens
1. Foreignness
2. Molecular size
3. Chemical composition
4. Structural organization
5. Solubility & Accessibility
6. Charge
7. Ability to be degraded.
What is the correlation between molecular size & immunogenicity?
•High MW substances (solids like steel): not immunogenic.

•Intermediate MW substances (microbes, proteins, etc.): most are immunogenic (large range)

•Low MW substances (drugs, chemicals): most are immunogenic.
HAPTEN: Define & describe immune reaction to carrier-hapten complex.
•substance that reacts specifically with an antibody but cannot induce an immune respons itself.
•Incomplete or Partial Ag.
•When coupled to a carrier (usually a protein), the hapten-carrier complex can elicit a population of Ab:
Ab to the carrier. (minor)
Ab to conjugate-hapten carrier. (minor)
Ab to the hapten. (most Ab produced**)
e.g. Food allergies are based on the hapten-carrier system.
e.g PENICILLIN: The penicillin metabolite can act as a hapten. The penicillin metabolite can couple to a serum protein carrier. IgE Ab form in response to teh penicillin albumin & remain in the immune system. If penicillin is administered again, you can suffer a massive histamine response against the medicine, causing an anaphalactic response. (Type I Immediate Hypersensitivity).
Epitopes / Antigenic Determinants
•A reactive chemical component on the Antigen that can elicit antibody formation.
Valence
# of epitopes found on an antigenic molecule.

Multivalent = multiple epitopes

Functional valence can decrease because of steric hindrance.
Determinance
Refers to type of epitope.

Multideterminant: an Ag displays structurally different epitopes

**Haptens are usually unideterminant & univalent.
**To bind an Antibody, an Ag must be at least BIVALENT.
Immunodominant
the most potent epitope on an antigen (multideterminant)

e.g. ABO on a RBC
Polyclonal Response
A single multideterminant Ag reacts with many different B cells to create a population of Ab.

Note: different B cells are predetermined to react with different epitopes on an antigen.
Monoclonal Response
Ab response made against a single epitope by the progeny of a single B cell clone.
**Ab produced react with only one epitope.
What type of molecules tend to be more potent antigens: particulate antigens or soluble antigens?
A molecule must be able to get to anybody forming cells & therefore must be able to form colloidal suspensions so that it can be transported through the lymphoid organs for process & presentation.
Particulate antigens are usually more potent as immunogens than soluble substances.
How does charge influence immunogenicity?
Charge can influence teh specificity of the Ab produced. It is not a requirement for immunogenicity.
Which forms of proteins are immunogenic?
L-amino acids are natural, metabolized, & immunogenic.
D-amino acids are unnatural, not degraded and poor immunogens.
Describe the immunogenicity & associated properties of proteins.
•most potent immunogens.
•Structurally Complex: display several types of determinants:
(1) LINEAR DETERMINANTS: continuous sequence of amino acids
(2) CONFORMATIONAL DETERMINANTS: formed by amino acids found in teh same area of a protein by not adjacent in the peptide chain (but adj. in tertiary & quaternary structure). These conformational determinants can either be:
(a) TOPOGRAPHIC (on the surface of a protein)
or
(b) INTERNAL (exposed after the protein has been denatured/unfolded).

•B cells recognize native unaltered antigen only.
•T cells recognize processed (denatured) antigen in association with self-MHC.
What type of Ag do B cells recognize?
B cells recognize CONFORMATIONAL determinants: areas on native proteins or bacteria that are either on the outside or exposed after some action. These are usually hydrophilic or reside on the surface of a molecule.
B cells reocgnize native, unaltered (not denatured) Ag.
What type of Ag do T cells recognize?
T cells can only recognize pieces of immunogen in the context of class I or II MHC molecules.
T cells recognized processed/denatured antigen in association with self-MHC found on APC.

•T cell epitopes are usually amphipathic peptides:
Hydrophobic residues bind to MHC.
Hydrophilic Residues bind to TCR.

*Rules of 8:
•CD4+ cells reocognize Ag in association with Class II MHC --> function as T Helper Cells.
•CD8+ T cells recognize Ag in association w/ Class I MHC --> Cytotoxic effector cells.
Describe Immunogenic properties of Polysaccharides.
•potentially,but not always, immunogenic. Most function w/ haptens.

* T-INDEPENDENT ANTIGENS. Are not presented vis MHC to C cells. Instead, tehy usually react w/ B cells to produce IgM against polysaccharides. They cannot induce Ig class switch because a B cell must have cytokines provided to T cells to do this and the polysaccharides do not stimulate T cells).

•lack molecular complexity/chemical diversity to be potent immunogens.

•Are poorly degraded (not accessible to immune cells to induce a response).

•May be immunogenic in several forms:
(1) Lipopolysaccharide: endotoxin of Gram-negative bacteria.
(2) Glycoprotein: blood group substance, MHC molecules.
Describe the immunogenic properties of Lipids
•Poorly immunogenic when administered alone.

•Function as haptens/incomplete antigens.

•Can be coupled to protein or polysaccharide.

•Lack of immunogenicity attributed to:
(1) poor solubility & accessibility
(2) lack of structural organization and rigidity.

•are not processed by APCs and therefore do not associate with MHC molecules.

•T INDEPENDANT ANTIGENS.
Describe the immunogenic properties of Nucleic acids.
•Not immunogenic in native form.

•You can elicit an Ab reactive with nucleic acid if you immunize with the whole nuclei, ribosomes, ribonucleoprotein, or single-stranded material coupled to a protein carrier.

•Function as incomplete antigens/partial (can be haptens).

•Lack of immunogenicity attributed to:
(1) Rapidly degraded by high levels of serum nucleases.
(2) The nucleic acids are structurally the same in all individuals and are recognized as self. The unique part (bases) ae buried inside and not seen.
Describe the cellular immunogens of prokaryotes & eukaryotes.
•prokaryotic immunogens include both viruses & bacteria.

VIRUSES: composed of 3 antigenic determinents.
•nucleic acid (DNA/RNA) = protein
•Capsid (usually protein)
•Envelope (usually lipoprotein in structure)

BACTERIA: more diverse & can have many different components on the surface that are immunogenic. They are multideterminant.


EUKARYOTES: more structurally complex as immunogens than prokaryotes. E.g. RBC contains 30-40 different epitopes.
Mitogen
agents which can induce cell division in a large number of B & T cells WITHOUT regard to Ag specificity.

•Function as polyclonal activators.

•Lectins/plant proteins:
Phytohemagglutinin (PHA) --> preferential for T cells
Concanvalin (ConA): preferential for T cells
Pokeweed Mitogen (PWM): preferential for T & B cells
•Bacterial Mitogens:
Lipopolysaccharide (LPS): preferential for B cells.
Superantigens
very potent POLYCLONAL ACTIVATORS OF T CELLS.

•Activate large #s of T cells w/o regard to specificity for antigen/MHC.

•Can result in release of cytokines that cause inflammation, leading to tissue injury, shock, & death.

•E.g. staphylococcyl Toxic Shock Syndrome Toxin.