Immunology Exam 2: Antibodies, B Cell Development, and Effector Functions

Comprehensive vocabulary review flashcards for Immunology Exam 2 covering antibody anatomy, somatic recombination, allelic exclusion, monoclonal/therapeutic antibodies, B cell development, germinal center reactions, and isotype-specific effector mechanisms.

Antigen

The pathogen or entity that causes disease.

Epitope

The specific portion of an antigen to which an antibody binds.

Linear Epitope

An epitope formed by sequential amino acids that lie next to each other in the primary sequence of a protein.

Discontinuous Epitope

An epitope formed by non-sequential amino acids that are brought together in close proximity within the tertiary structure of a protein (scattered in the primary structure).

Heavy Chain and Light Chain

The two types of polypeptide chains that compose an antibody molecule, featuring variable ($V$) and constant ($C$) regions.

Fab Fragment

The antigen-binding fragment of an antibody, consisting of both heavy and light chain segments containing both variable and constant regions.

Fc Fragment

The crystallizable fragment of an antibody that mediates effector functions, composed exclusively of heavy chain constant regions.

Hypervariable Region

A highly variable amino acid sequence within the variable ($V$) regions of heavy and light chains that directly forms the antigen-binding site.

Hinge Region

The flexible domain of an antibody molecule situated between the Fab arms and the Fc stem, allowing independent movement of the antigen-binding sites.

Immunoglobulin Isotypes (Classes)

The five classes of antibodies—IgG ($\gamma$), IgM ($\mu$), IgD ($\delta$), IgA ($\alpha$), and IgE ($\epsilon$)—which are defined by differences in their heavy chain constant regions.

RAG (Recombination-Activating Genes)

The enzyme complex responsible for somatic recombination; it recognizes recombination signal sequences, forms DNA hairpin loops between gene segments, cuts out the loop for nucleotide recycling, and splices the ends together.

12/23 Rule

The rule dictating that a gene segment flanked by a "one turn" ($12\text{ bp}$) spacer can only recombine with a segment flanked by a "two turn" ($23\text{ bp}$) spacer, enforcing the sequential $V$-to-$D$-to-$J$ rearrangement in heavy chains.

Pro-B Cell Stage

The stage of B cell development in which somatic recombination joins the $D$ and $J$ segments of the heavy chain.

Pre-B Cell Stage

The stage of B cell development occurring after the pro-B cell stage in which the $V$ segment is joined to the rearranged $DJ$ segment of the heavy chain.

Allelic Exclusion

The mechanism ensuring that diploid B cells express heavy and light chain genes from only one chromosome; once productive rearrangements are achieved, the recombination machinery shuts off so homologous chromosome genes are not expressed.

Productive vs. Nonproductive Rearrangements

Productive rearrangements preserve the correct reading frame to yield a complete, functional Ig chain; nonproductive rearrangements contain frameshifts that fail to produce a functional protein and lead to apoptosis if chromosome attempts fail.

Light Chain Rearrangement Order

The sequential process where a B cell attempts $kappa$ ($\kappa$) light chain rearrangement first; if both alleles fail, it attempts $lambda$ ($\lambda$) chain rearrangement, dying by apoptosis if both chromosomes fail.

Polyclonal Antibodies

A mixture of antibodies derived from multiple B cell clones that recognize different epitopes on the same antigen; obtained by collecting and purifying serum from an immunized animal.

Monoclonal Antibodies

Homogeneous antibodies produced by a single B cell clone that all recognize a single specific epitope; generated by isolating B cells from an immunized animal and fusing them with immortalized tumor cells.

Hybridoma

An immortalized cell line created by fusing an antigen-specific B cell with an immortalized tumor cell to allow continuous, long-term production of monoclonal antibodies.

Chimeric Antibodies

Engineered therapeutic antibodies that combine mouse variable ($V$) regions with human constant ($C$) regions.

Humanized Antibodies

Therapeutic antibodies in which only the hypervariable loops (complementarity-determining regions) are of mouse origin, while the entire remainder of the molecule is human.

B Cell Education

The developmental selection process occurring in the bone marrow where immature B cells are tested against self-antigens on stromal and hematopoietic cells; self-reactive cells undergo clonal deletion (apoptosis) or anergy, while successful cells express surface IgM and IgD.

Follicular Dendritic Cells (FDCs)

Stromal cells located in primary lymphoid follicles that display intact antigens draining from the lymph on their surface for extended periods and produce survival signals for B cells.

CCL21 and CCR7

The chemokine secreted by lymph node cells ($CCL21$) and its corresponding chemokine receptor on circulating immature B cells ($CCR7$) that guide B cells across high endothelial venules (HEVs) into lymph nodes.

Plasma Cells

Terminally differentiated B cells that secrete soluble antibodies produced by alternative RNA splicing that removes the $3'$ sequence coding for hydrophobic membrane-anchoring amino acids.

Somatic Hypermutation

The targeted introduction of single-nucleotide substitutions into rearranged immunoglobulin $V$ domain DNA upon B cell activation.

Affinity Maturation

The evolutionary process during an infection whereby B cell clones acquiring higher affinity for the pathogen via somatic hypermutation outcompete lower-affinity clones, producing progressively higher-affinity antibodies.

Class Switching (Isotype Switching)

A DNA recombination process mediated by activation-induced cytidine deaminase (AID) that swaps the heavy-chain constant ($C$) region gene while preserving the antigen-specific $V$ region.

Activation-Induced Cytidine Deaminase (AID)

The key enzyme responsible for initiating both somatic hypermutation and isotype class switching by targeting switch sequences at the $5'$ end of heavy chain $C$ genes.

Cognate Pair

The specific physical complex formed between an activated B cell and a follicular helper T ($T_{FH}$) cell that recognize epitopes of the exact same antigen.

CD40 and CD40L

The costimulatory receptor on B cells ($CD40$) and its ligand on follicular helper T cells ($CD40\text{L}$) that trigger cytoskeletal reorientation, targeted cytokine secretion by the $T_{FH}$ cell, and full B cell activation.

Germinal Center

The secondary focus within a primary follicle where activated B cells undergo rapid division into centroblasts/centrocytes, somatic hypermutation, and class switching, causing lymph node swelling.

FcRn (Neonatal Fc Receptor)

An endothelial cell receptor that binds the Fc region of IgG, protecting it from lysosomal degradation and mediating its transcytosis across blood vessel endothelium into extracellular spaces of tissues.

Poly-Ig Receptor

A receptor on the basolateral surface of mucosal epithelial cells that binds dimeric IgA, mediates its transcytosis, and is cleaved at the apical surface to leave the protective secretory component.

FcεR1

A high-affinity Fc receptor on mast cells, basophils, and activated eosinophils that binds monomeric IgE; crosslinking by antigen triggers immediate degranulation and histamine release to expel parasites.

Passive Immunity (Antibodies)

Protection conferred by maternal IgG transferred across the placenta to the fetus (persisting for about $6\text{ months}$) and dimeric IgA supplied through breast milk to protect the infant gut.

Neutralization

An effector function carried out by high-affinity IgG and IgA antibodies that bind directly to surface attachment proteins on pathogens or toxins (e.g., hemagglutinin on influenza or $F$ protein on Streptococcus pyogenes), preventing infection of host cells.

Agglutination

The crosslinking and clumping together of particulate antigens or cells (e.g., ABO antigens on RBCs during mismatched blood transfusions) primarily driven by multivalent pentameric IgM antibodies.

Classical C3 Convertase (C4bC2a)

An enzymatic complex formed when IgM or multiple IgG molecules activate the C1 complex, leading to C1s cleavage of C4 and C2; it cleaves C3 into anaphylatoxin C3a and opsonin C3b.

Opsonization (by IgG)

The coating of pathogen surfaces by IgG antibodies, which are recognized by $Fc\text{\textbackslash}gamma R1$ ($Fc\text{\textbackslash}gamma\text{RI}$) on phagocytes (monocytes, macrophages, dendritic cells) to promote engulfment, phagolysosomal destruction, and antigen presentation.

Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC)

A cytotoxic mechanism in which natural killer (NK) cells express $Fc\text{\textbackslash}gamma R3$ ($CD16$) to bind IgG-coated target host cells, triggering intracellular signals that direct the killing of infected or cancerous cells.

Complement Receptor 1 (CR1)

A receptor on red blood cells (RBCs) that binds to C3b within circulating immune complexes, allowing RBCs to transport complexes to macrophages in the liver and spleen for degradation.