Exam 2 - Antigen Recognition (Lectures 9-10)

Define Antigen

Any molecule that is recognized by the immune response and triggers an immune response - usually proteins

Define Epitope

The part of the antigen that is recognized by an antibody

What are antigens typically composed of? What are they not?

Proteins, peptides, polysaccharides

NOT: lipids or nucleic acids

Define CD and their characteristics

Cluster of differentiation - refers to unique cell surface proteins

- functionally diverse

- not specific to a single cell type

CD3

signaling chains associated with T cell receptor - FOUND ON ALL T CELLS

CD4

Coreceptor for MHC2 on T cells

CD8

Coreceptor for MHC1 on T cells

What are the 4 types of Antigens?

1. Exogenous

2. Endogenous

3. Autoantigen

4. Neoantigen

Exogenous Antigen

- originates outside of the body

- introduced by inhalation, ingestion, or penetration

Endogenous Antigen

- Originates from inside the body

- generated by our body

Autoantigen

- a self protein recognized by the immune system

- immune mediated disease

Neoantigen

- mutated self protein

- cancer

Describe B cell Antibody Molecule Structure

- Y shaped antibody

- Variable region

- Constant Region

- Light Chain

- Heavy chain

- Soluble (Floating in cell)

Describe T cell Antigen Receptor Structure

- I shaped

- Variable region

- constant region

- Alpha and Beta chain

- attached to cell membrane

What do B cells (antibody) recognize and where?

- recognize native antigens

- antigens outside of the cell

What do T cells (T cell antigen receptors) recognize and where?

- recognize pieces of antigens that have been digested and presented by APCs

- antigens inside of cells

What is the N terminus on the Antibody?

What binds to the peptide (antigen)

- on the variable region

What is the C terminus on the Antibody?

- on the constant region

What are the two types of epitopes?

1. Linear epitope

2. Conformational epitope

Linear Epitope

A linear stretch of amino acids on the antigen that is recognized by the antibody

Conformational Epitope

2 different regions of amino acids that are only recognized by the antibody if they are in a certain conformation (in close proximity)

What is the Constant Region of the Antibody

- Bottom of the Y

- determines the important effector function

- constant region binds to the FC receptors

- 5 subtypes: all have different function

What are the 5 subtypes of the Constant Region

1. IgM

2. IgG

3. IgA

4. IgE

5. IgD

What is the FUNCTION of the Constant Region

- bind complement -> activates complement pathways

- binds to Fc Receptors on other cells (macrophages, mast cells, neutrophils, NK cells)

- Bind to molecules that transport antibodies

What specific "shape"/multimer does IgA have?

Dimeric IgA

- 2 antibodies together

What specific "shape"/multimer does IgM have?

Pentameric IgM

- 5 antibodies together

Where are the 2 places that antibodies are located?

1. secreted

2. expressed on B cell surface

What is the importance of B cell surface antibodies?

- when an antigen binds it causes B cell division cascade

- acts as a feedback mechanism that tell B cells to make less/more antibody

T-Cell Receptor (TCR) Definition and Characteristics

antigen receptor on the surface of a T cell that recognizes a peptide displayed by MHC after antigen has been digested

- alpha and beta chains (instead of heavy and light chains)

- variable region

- constant region

What do TCR always recognize?

A peptide presented by MHC on an APC

MHC1 Characteristics

- expressed on surfaces of all nucleated cells

- present endogenously derived antigens

- intracellular infections (viral)

MHC2 Characteristics

- expressed on surfaces of APCs

- present exogenously derived antigens

- extracellular infections (bacterial)

What CD is associated with MHC1 pathways?

CD8 recognizes MHC1

What CD is associated with MHC2 pathways?

CD4 recognizes MHC2

Graft vs Host disease

Graft: when donor bone marrow or stem cells attack the recipient

Host: When an organ is transplanted and the body recognizes MHCs as non self

Define VDJ

Variable Diversity and Joining Region

Describe the VDJ and how it functions

Sequence at the beginning of the genome that will connect to one sequence and determine the isotype Ig_

What is determines B cell maturation

1. Affinity maturation

2. Isotype switching

Affinity Maturation

Increase in affinity of the antigen-binding sites of antibodies for the antigen via AID and somatic hypermutation

Isotype Switching

Changes in the constant region of the same VDJ variable region that causes a switch to either IgG, IgA, or IgE

Describe the steps of Affinity Maturation

1. B cell recognizes its antigen

2. Stimulated to divide

3. Upregulates AID enzyme

4. AID mutates genetic code and changes VDJ

5. new B cell has higher affinity

6. increases the signaling to cells

7. new cell divides and becomes the dominant B cell with much higher affinity than before

How is the rest of the genome chain removed during affinity maturation?

AID selectively targets parts of the genome -> DNA is nicked -> DNA is looped and chopped off -> DNA chain loop is digested