Antibody Structure, T-Cell Antigen Recognition, and B-Cell Development

Vocabulary practice flashcards covering antibody structure, genetic recombination mechanisms, T-cell receptor interaction, MHC processing pathways, and B-cell developmental stages based on the lecture slides.

Antibodies

Soluble protein immunoglobulins secreted by activated B cells (plasma cells) that circulate in blood, lymph, and tissue fluids to bind foreign antigens and mark them for destruction.

Fab segment

The flexible antigen-binding arms of an antibody molecule, composed of complete light chains paired with the variable and first constant domains of heavy chains.

Fc segment

The stem region of an antibody molecule formed by the constant domains of the heavy chains, containing binding sites for phagocytes and complement proteins.

Heavy chain isotypes

Five functional classes of antibody heavy chains (\alpha, \n\delta, \epsilon, \gamma, \mu) that determine the antibody's class (IgA, IgD, IgE, IgG, IgM) and specific effector functions.

Light chain classes

Two classes of immunoglobulin light chains, kappa ($\kappa$) and lambda ($\lambda$); an individual antibody contains two identical chains of one type, with approximately $2/3$ of human antibodies expressing $\kappa$ chains.

Complementarity determining regions (CDRs)

Hypervariable loops (CDR1, CDR2, CDR3) located at the tips of antibody and T-cell receptor variable domains that form the antigen-binding site.

Multivalent antigen

An antigen that contains more than one epitope, which may consist of multiple identical epitopes or several different epitopes.

Discontinuous epitope

An antigenic determinant (conformational epitope) composed of non-adjacent amino acids in a protein sequence that are brought into close spatial proximity by 3-D protein folding.

Somatic recombination

The enzymatic cutting and random splicing of Variable (V), Diversity (D), and Joining (J) gene segments in developing B and T cells to form functional variable region genes.

Junctional diversity

Variation introduced at gene segment junctions by RAG enzymes and terminal deoxynucleotidyl transferase (TdT) adding palindromic P-nucleotides and non-templated N-nucleotides, creating roughly $3 \times 10^7$ additional sequence variations.

Ig$\alpha$ and Ig$\beta$

Invariant transmembrane proteins associated with membrane immunoglobulins that transport B-cell receptors to the cell surface and transduce intracellular signals upon antigen binding.

Allelic exclusion

The process ensuring that only one allele of a heavy-chain or light-chain gene is expressed in a single B cell, guaranteeing monoclonal specificity for a single antigen.

Somatic hypermutation

The targeted introduction of single nucleotide mutations into immunoglobulin V region genes of activated B cells, leading to affinity maturation.

Isotype switching

A DNA recombination process in activated B cells that replaces the constant region gene of an antibody heavy chain with a different C gene, altering effector function while preserving antigen specificity.

Neutralization

An antibody effector mechanism in which antibodies bind directly to pathogens or toxins to inhibit their entry into host cells.

Opsonization

An antibody effector mechanism where antibodies coat the surface of a pathogen to promote recognition and phagocytosis by immune cells.

T-cell receptor complex

A membrane-bound complex comprising the antigen-binding $\alpha:\beta$ or $\gamma:\delta$ T-cell receptor heterodimer non-covalently linked to invariant CD3 signaling proteins (CD3$\gamma, \delta, \epsilon$) and a $\zeta$ chain homodimer.

CD8

A glycoprotein co-receptor expressed on cytotoxic T cells that binds directly to the $\alpha_3$ domain of MHC Class I molecules.

CD4

A glycoprotein co-receptor expressed on helper T cells that binds directly to the $\beta_2$ domain of MHC Class II molecules.

Th1 cell

A CD4 helper T cell subset that activates macrophages to engulf and destroy pathogens and secretes inflammatory cytokines.

Th2 cell

A CD4 helper T cell subset that stimulates B cells to proliferate, produce antibodies, and undergo isotype switching.

MHC Class I

A surface molecule composed of a transmembrane $\alpha$ chain ($\alpha_1, \alpha_2, \alpha_3$) non-covalently bound to $\beta_2$-microglobulin, presenting intracellular peptides ($8\text{--}10$ amino acids) to CD8 T cells.

Degenerate binding specificity

The property of an MHC molecule allowing its single peptide-binding groove to accommodate many different peptide sequences (also termed promiscuous binding specificity).

Invariant chain

A chaperone protein that blocks the peptide-binding site of MHC Class II molecules in the endoplasmic reticulum and directs their transport to endosomal vesicles.

HLA-DM

An endosomal glycoprotein that promotes the release of the CLIP fragment from MHC Class II molecules, enabling antigenic peptides to bind.

Human Leukocyte Antigen (HLA)

The human major histocompatibility complex (MHC) gene locus located on chromosome 6, encoding Class I and Class II antigen-presenting proteins.

MHC restriction

The requirement that a specific T-cell receptor recognize its peptide antigen only when displayed in complex with a specific self-MHC molecule.

Pro-B cell

An early bone marrow stage of B-cell development characterized by heavy-chain gene recombination ($D\text{--}J$ in early pro-B cells, $V\text{--}DJ$ in late pro-B cells).

Surrogate light chain

A temporary protein complex composed of $V_{\text{preB}}$ and $\lambda 5$ that pairs with the $\mu$ heavy chain in pre-B cells to form the pre-B cell receptor.

Immature B cell

A developing B cell in the bone marrow that has successfully re-arranged its light chain genes and expresses functional IgM on its cell surface.

Mature naive B cell

A fully developed B cell that expresses surface IgM and IgD via alternative RNA splicing and recirculates in peripheral lymphoid tissues without having bound antigen.

Anergy

A state of metabolic unresponsiveness induced in immature B cells upon binding soluble self-antigen, resulting in down-regulation of surface IgM.

Clonal deletion

The elimination of self-reactive immature lymphocytes by apoptosis upon binding multivalent self-antigens in primary lymphoid tissues.

Receptor editing

The process by which self-reactive immature B cells reactivate RAG genes to perform secondary light-chain rearrangements, swapping out self-reactive specificity.

Follicular Dendritic Cells (FDCs)

Non-hematopoietic stromal cells located in primary lymphoid follicles that display intact antigen to recirculating B cells and promote B-cell survival.

B-1 cells

A minority population of self-renewing, innate-like B cells that develop in the fetal liver, reside in peritoneal and pleural cavities, and produce low-affinity polyreactive IgM antibodies.