Humoral immunity: B cells and antibodies

What is an antigen?

Any substance that reacts specifically with an antibody molecule (e.g., proteins, polysaccharides, lipids, nucleic acids, or hormones).

What is an epitope?

The specific portion of an antigen recognized by an antibody.

Differentiate between linear and conformational epitopes.

Linear epitopes are formed by adjacent amino acids; conformational epitopes arise from amino acids brought together upon protein folding.

Describe the basic structure of an antibody.

Y-shaped molecule composed of two identical heavy chains and two identical light chains connected by disulfide bonds.

What regions make up an antibody molecule?

Variable (antigen-binding) and constant regions.

What holds the antigen-antibody complex together?

Non-covalent forces: electrostatic forces, hydrogen bonds, van der Waals forces, and hydrophobic interactions.

What are hypervariable regions (CDRs)?

Highly variable loops in the variable domains of antibodies that form the antigen-binding site.

Where are the hypervariable regions located?

In both heavy and light chain variable regions.

How does proteolytic digestion by papain affect antibodies?

It cleaves above the disulfide bond, producing two Fab fragments and one Fc fragment.

How does proteolytic digestion by pepsin affect antibodies?

It cleaves below the disulfide bond, producing an F(ab')₂ fragment and degraded Fc fragments.

What chromosome encodes the λ light chain locus?

Chromosome 22.

What chromosome encodes the κ light chain locus?

Chromosome 2.

What chromosome encodes the heavy chain locus?

Chromosome 14.

What gene segments compose the light chain variable region?

V (variable), J (joining), and C (constant) segments.

What gene segments compose the heavy chain variable region?

V (variable), D (diversity), J (joining), and C (constant) segments.

What process creates antibody diversity?

Somatic recombination (gene rearrangement) of V, D, and J segments.

What is isotype switching?

A DNA recombination process that replaces one constant region gene with another (except δ), changing the antibody isotype while preserving antigen specificity.

What triggers isotype switching?

Signals from helper T cells (cytokines and CD40-CD40L interactions).

List the main immunoglobulin isotypes.

IgG, IgM, IgA, IgE, and IgD.

Which immunoglobulins are monomers?

IgG, IgD, IgE (and monomeric IgA).

Which immunoglobulins are polymeric?

IgM (pentamer) and IgA (dimer).

What connects the monomers in polymeric antibodies?

The J (joining) chain.

What are the heavy chain types associated with each isotype?

γ (IgG), μ (IgM), α (IgA), ε (IgE), δ (IgD).

Which antibody can cross the placenta?

IgG.

Which antibody is found mainly in secretions like milk and saliva?

Dimeric IgA.

Which antibody is most effective in complement activation?

IgM.

Which antibody mediates allergic reactions and binds mast cells?

IgE.

Which antibody is the first produced in a primary immune response?

IgM.

Which antibody is most abundant in serum?

IgG.

What ensures that each B cell expresses only one antibody specificity?

Allelic exclusion.

What are the three key processes in antigen-independent B-cell development?

DNA rearrangement, allelic exclusion, and deletion of self-reactive clones (tolerance).

Where does antigen-independent B cell development occur?

In the bone marrow.

Where does antigen-dependent B cell development occur?

In the periphery (spleen and lymph nodes).

What happens when a mature B cell encounters its specific antigen?

It proliferates and differentiates into plasma cells and memory B cells.

What are plasma cells responsible for?

Secretion of large amounts of antibodies.

What are memory B cells responsible for?

Rapid and strong antibody responses upon antigen re-exposure.

Compare antigen recognition by B and T cells.

B cells recognize free antigens; T cells recognize peptide antigens bound to MHC molecules.

Which antibodies are primarily found in the blood?

IgM and IgG.

Which antibody is associated with mucosal immunity?

IgA.

What is the half-life of IgG in serum?

Approximately 21 days.

What is the half-life of IgM in serum?

About 10 days.

What are the main functions of antibodies?

Neutralization, opsonization, complement activation, antibody-dependent cell cytotoxicity (ADCC), and agglutination.

Summarize the stages of B cell development.

(1) Rearrangement of immunoglobulin genes in bone marrow, (2) removal of self-reactive B cells, (3) migration to lymphoid organs, (4) activation by antigen, (5) differentiation into plasma and memory cells.

What is the main takeaway about immunoglobulin structure and function?

The structure of antibodies determines their function, distribution, and effector mechanisms.