Immunoglobulins and Antibody Generation Study Guide

Immunoglobulins

Five classes of antibodies in the immune system.

IgM

First antibody produced during an immune response.

IgD

Functions mainly as a B cell receptor on a newly mature B cell.

IgG

Most abundant antibody in serum, provides immunity.

IgA

Found in mucosal areas, protects body surfaces.

IgE

Involved in allergic reactions and parasite defense.

Variable region

Part of antibody that binds to antigens.

Complementarity-determining region (CDR)

Area within the variable region that is used specifically for antigen binding.

Constant region

Part of antibody that determines its class and function.

Hinge region

Provides flexibility to the antibody structure.

Disulfide bonds

Covalent bonds that stabilize antibody structure.

Fc region

Part of antibody that interacts with Fc receptors.

Fab fragment

Antigen-binding fragment of an antibody that is generated by cleavage with papain.

Fc fragment

Part of the antibody that mediates effector functions like binding C1q and Fc receptors.

F(ab)2 fragment

Two Fab fragments linked by disulfide bonds that is generated by cleave with pepsin.

Fc receptors

Proteins found on various white blood cells that bind to the Fc region of antibodies.

Continuous epitopes

Epitopes formed by a linear sequence of amino acids.

Discontinuous epitopes

Epitopes formed by non-contiguous amino acid sequences.

Cytokines

Signaling molecules that influence immunoglobulin secretion.

IL-4

Cytokine that promotes IgE and IgG1 production. Drives B cell class switching.

IFN-g

Cytokine that enhances IgG2 production and promotes macrophage activation.

TGF-beta

Cytokine that promotes IgA production.

IL-21

Cytokine that enhances B cell proliferation/differentiation.

IL-5

Cytokine that promotes eosinophil growth and IgA production.

A-B toxins

Toxins with two parts; the A part is responsible for toxicity and the B part binds to a receptor in the body.

Transcytosis

Process of transporting antibodies across epithelial cells in mucosal tissues.

Light chain rearrangement

Process of V-J recombination in B cells.

Heavy chain rearrangement

Process of V-D-J recombination in B cells.

Recombination Signal Sequence (RSS)

12 bp or 23 bp spacers guiding gene rearrangement in the variable region of light and heavy chain genes.

RAG-1/RAG-2

Enzymes essential for V(D)J recombination.

Artemis:DNA-PK

Endonuclease involved in DNA double-strand break repair.

TdT

Enzyme adding nucleotides to the 3' ends of DNA during heavy and light chain rearrangement.

DNA ligase

Enzyme that joins DNA fragments together during variable region rearrangement.

B cell development

Process of B cell maturation in bone marrow.

Class switching

Process of changing antibody class during immune response.

AID protein complex

Enzyme complex involved in class switch recombination and in somatic hypermutation of B cell receptors

Switch regions

DNA sequences guiding class switching in B cells.

FLT-3

cytokine that

stimulates proliferation of early hematopoietic stem cells

IL-7 receptor

On B cells,

-is essential for binding IL-7 secreted by thymic stromal cells - helps tell the B-cell what to do next in its maturation.

Receptor editing

B cells which interact too strongly with self-antigens undergo receptor editing which changes the light chain used in the antibody

Immature B cell

Stage of B cell with IgM expressed on surface

Mature B cell

Stage of B cell with IgM and IgD expressed on surface

Effector B cells

plasma cells secrete antibodies

Transitional B cells

Cells that survive negative selection and migrate to spleen for further selection

Signal 1 (B cell)

B cell presents antigen on MHC Class II to a T helper cell

Signal 2 (B cells)

CD40 on B cell binds CD40L on T helper cell, turns on NF-kB

Signal 3 (B cell)

T helper cell secretes cytokines to signal B cell or proliferate and differentiate

Somatic hypermutation and affinity maturation

B cell has high rate of point mutation in CDR regions which produces antibodies with higher affinity to the antigen

Activation-induced cytidine deaminase (AID)

Enzyme that contributes to somatic hypermutation of immunoglobulin gene variable regions by deaminating DNA directly at cytosine. It can lead to a permanent base change at the deaminated site. The enzyme is also involved in isotype switching.

uracil-DNA glycosylase (UNG)

Enzyme that removes uracil bases from DNA (formed by deaminating cytosine) in a DNA repair pathway that can lead to somatic hypermutation, class switch recombination.

Primary immune response

Immune response the first time the body is exposed to a particular antigen. Does not peak until 10-17 days after exposure.

secondary immune response

Immune response after the body has already been exposed to a specific antigen. Response is faster, of greater magnitude, and more prolonged.

Innate Lymphoid Cells (ILCs)

Lymphocytes that lack antigen-specific B- and T-cell receptors and contribute to both innate and adaptive immune responses. Three subsets of ILCs (ILC1, ILC2, ILC3) are recognized.

Memory B cells

circulate the body, proliferate, and response quickly (via antibody synthesis) to eliminate subsequent invasion by same antigen. (2ndary response - takes less time, ~5 days)

Original antigenic sin

A bias seen in successive immune responses to structurally related antigens such as those on different strains of influenza virus where secondary infection sees the antibody response is restricted to epitopes that the second strain shares with the first strain.