Antibody structure, B cell diversity, B cell development Flashcards
B cell receptors are referred to as
Immunoglobulins
Soluble forms of B cell receptors are
Antibodies
BCR chains
Polypeptides are folded into separate domains, each with a separate function
- domain: compact and rigid structure held together by noncovalent bonds
Light chain
Single variable domain and a single constant domain
Heavy chain
Single variable domain and 3-4 constant domains
Variable region
Antigen recognition!!
- all antibodies differ in the number and types of amino acids encoded in the variable region
Constant region
Determines effector function of the antibody
- recognized by leukocytes and plasma proteins
The constant region is also known as the ____
Fc region
How many classes of antibodies are there and what are they defined as?
5 classes called isotopes. Defined by heavy chain constant region
- IgG, IgA, IgM, IgD, IgE
Isotope
Member of related gene family
- heavy chain with different effector functions
- differ in domains and amino acid contents (varies with affected body parts and how pathogen is to be eliminated)
Different effector functions of antibodies are directed by _____
Heavy chain constant region
____ is the first antibody produced in a primary immune response
IgM
Isotope switching
Later in the immune response different isotypes are produced
- heavy chain variable region of IgM along with original light chain is expressed with a different heavy chain isotype
B cell receptor recognizes the _____
Native form of an antigen
- important because the antibody will link the pathogen to the leukocytes and plasma proteins that will eliminate it
Epitope
Part of the antigen bound by the antibody
- antibodies recognize epitopes on a protein or carb antigen
- epitope can be a cluster of amino acids or portion of a polysaccharide
The ____ of the antigen-binding site must be ____ to the shape of the epitope
Shape; complementary
- heavy and light chains pair to form a variety of shapes that can accommodate a variety of different antigen epitopes (1 specific shape per antibody)
Cross reactivity
An antibody generated against one antigen that binds to an unrelated antigen
- shared
- similar
Shared epitope
Different antigens share the same epitope (basis for vaccines)
Similar epitope
Some pathogens express protein or carbohydrate epitopes that resemble host epitopes
Monoclonal antibodies
Antibody originating from a single B cell
- the antibody is specific for one epitope
- used frequently for diagnostics (ex: heartworm test)
Polyclonal antibodies
A mixture of antibodies, each specific for a different epitope from the same antigen
Somatic recombination
DNA recombination that occurs between gene segments in the immunoglobulin genes
- takes place during B cell development in the bone marrow
How does the process of somatic recombination contribute to the diversity of antigen-binding sites?
There are multiple copies of gene segments in the light chain gene and the heavy chain gene = amplification of diversity
Construction of the antigen-binding site by somatic recombination
- Gene segments are used to construct variable region of light and heavy chain gene
- Gene segments differ from one another in short regions (hypervariable regions)
- Process of somatic recombination results in random addition of nucleotides at the joints between gene segments –> responsible for diversity of HV3
Somatic recombination variable region
Antigen binding site differs from one antibody to the next because of differences in the number and kinds of amino acids encoded in the 3 HV regions
Control tolerance
Removal of immature B cells with specificity for self-proteins (autoreactivity)
- only B cells tolerant to self proteins present in the bone marrow will be exported into the blood
Surveillance
Naive B cells exported to the periphery circulate through secondary lymphoid tissues
Mature naive B cells
The same variable region domain is expressed with 2 different heavy chains (IgM and IgD)
- both isotypes served as an antigen receptor
Primary immune response
- Recognition of antigen
- Activation by helper T cells
- Differentiation to short-lived plasma cells producing IgM
- Surface expression of IgM and IgD is downregulated as activated B cells differentiate to short lived plasma cells
Why is IgM secreted as a pentamer in a primary immune response?
IgM generally possesses low affinity for the antigen epitope –> pentameric structure increases the valence from 2 antigen binding sites to 10 antigen binding sites
- increases affinity, less likely to dissociate, and provides a binding site for C1q
