Immunology - Antigens

What are antigens?

What are antigens?

Antigens are any molecule that can interact (specifically) with the immunoglobulin receptors of B-cells (or T-cells complexed with MHC)

What are immunogens?

immunogens are molecules that induce a specific immune response when they're recognized

Are all antigens immunogens?

no

(All immunogens are antigens, but not all antigens are immunogens) (something can interact with a lymphocyte without inducing an immune response)

Humoral Immunogens are recognized by...

B-cells

What are the chemical natures of the epitopes B-cells tend to recognize?

Proteins>>>Polysaccharides>>>Lipids&Nucleic Acids

What is the chemical nature of the epitopes T-cells tend to recognize?

Proteins

How do T-cells see epitopes?

In association with MHC after being processed from protein

What are the 4 properties that determine immunogenicity?

Foreignness, Molecular Size, Chemical Heterogeneity, Degradability

What are some exceptions to the link between foreignness and immunogenicity?

Some self cells will raise an immune response and are normally sequestered from the immune system. Also, sometimes highly conserved molecules may not be immunogenic, even in distant species

How does molecular size affect immunogenicity?

Best immunogens are around ~100,000 Da. Molecules must be large enough to be processed, but small enough to drain to the lymph nodes. Very small molecules are generally poor immunogens

How does chemical heterogeneity affect immunogenicity?

Proteins with more complexity in primary structure, and those who show secondary, tertiarty, and quaternary structures are more immunogenic

Are large homopolymers immunogenic?

No. Regardless of size, synthetic homopolymers are not immunogenic

How does degradability affect immunogenicity?

Proteins must be degraded in order to be presented by MHC molecules to activate T-cells --- so factors that affect this process affect immunogenicity.

What factors make a molecule more degradable?

Insoluble > soluble (more likely to be phagoctyosed and processed)

Large > small

L-amino acids > D-amino acids (because D-amino acids cannot be processed by processing enzymes)

What are epitopes

Also known as antigenic determinants, these are small, discrete sites on macromolecules that are what a lymphocyte actually recognizes on an antigen.

In order for B-cells to bind to an antigen in solution...

the epitopes must be hydrophilic and topographically accessible on the native molecular surface

Epitopes must be flexible and mobile for agglutination

Epitopes can be sequential or non-sequential

How are nonsequential (conformational) epitopes formed?

These epitopes are formed when amino acids are brought close by the tertiary conformation of a protein

What is immunodominance

It is where the immune system prefers a specific epitope -- that epitope most influences the specificity of the induced antibody.

True or false: after processing, conformational epitopes are still recognizable

False. Conformational epitopes are based entirely on 3D shape. Denaturation or digestion of a protein will get rid of this kind of epitope.

Can T-cells recognize solutble native antigen?

No. Native antigens are those that have not been processed by an antigen presenting cell.

T-cells only recognize antigens that have been processed and whose peptide fragments are presented in association with MHC molecules

How many amino acids in MHC I binding cleft? Which T-cells bind to this type of molecule?

Binding cleft of MHC I is 9-11 amino acids long -- binds to CD8+ "killer" T-cells

How many amino acids long is the binding cleft of MHC II? What kind of T-cell binds to this type of MHC molecule?

The binding cleft of MHC II is 11-17 amino acids long. CD4+ "helper" T-cells bind to MHC II molecules.

Why must peptides be amphipathic in order to be recognized by a T-cell?

One side must be hydrophilic in order to bind to the T-cell receptor. One side must be hydrophobic to bind to MHC.

Ag is seen as a trimolecular complex TCR-Ag-MHC

Are antigen-antibody interactions reversible?

Yes. Ag-Ab interactions involve highly specific and reversible binding between molecules

List (4) low-affinity non-covalent bonds that require a specific fit between the antibody and the antigen

• Van der Waals

• Hydrogen bonding

• Ionic Bonding

• Hydrophobic bonds These bonds determine specificity The better the fit, the stronger the association

What is the difference between affinity vs avidity?

Affinity is the strength of the interaction between one arm of an antibody and a single epitope

Avidity is the strength of multiple interactions between multivalent anitbodies and antigens. Avidity is the function of the combined strength of binding affinity and the Ab-Ag valency.

What is the association constant?

Ka is the fraction of bound [Ab-Ag]/[Ag][Ab]

What dictates avidity?

The affinity and the number of Ab-Ag bindinds

What dictates affinity?

The Ag-Ab fit

How to calculate avidity

Avidity = (strength of site) x (# of sites binded)

Can high avidity compensate for low affinity?

Yes. IgM has lower affinity than IgG, but the higher avidity of IgM, resulting from its multivalency, enables it to bind to the antigen effectively

Exposure to what causes Anti-A and B antibodies to form?

Anti-A antibodies form after exposure to the dlue. Anti-B antibodies form after exposure to gram-negative bacteria. (Only in individuals that do not produce that glycoprotein)

What is Antigen Precipitation?

Precipitation is the formation of a lattice structure as a result of antigen-antibody interactions at optimal conditions.

Define: Precipitin

an antibody that can precipitate out of a solution upon binding to an antigen

What is the Zone of Equivalence?

It is the optimal Antigen to antibody concentration where maximal precipitation is achieved

Why does less precipitate form when there is an excess of antigen?

Because there are enough antigens present, that each antibody can bind to separate antigens with no need to share

How can precipitin reactions be measured?

By adding an increasing amount of antigen to a constant concentration of antibodies