Immunology: Lymphocyte Development, Immunoglobulins, Complement, and Serology

Vocabulary practice flashcards covering NK and B-cell differentiation, immunoglobulin structure and subclasses, the classical, lectin, and alternative complement pathways, complement regulation and assays, and serological laboratory math.

Bursa of Fabricius

The primary lymphoid organ in birds where B-cell maturation was originally discovered; functionally analogous to the human appendix and bone marrow.

Natural Killer (NK) Cell

A $CD56^+$ innate lymphoid cell that mediates cytolytic activity against tumor cells and virus-infected host cells without prior antigen exposure or memory.

Missing-Self Recognition

The mechanism whereby NK cells survey and lyse target cells that have downregulated or lost surface MHC Class I expression during viral infection or malignant transformation.

Antibody-Dependent Cellular Cytotoxicity (ADCC)

A cytotoxic process where the Fc receptor on effector cells (such as NK cells) recognizes and binds to antibody-coated target cells, triggering targeted cell lysis.

Killer Immunoglobulin-Like Receptors (KIR)

Receptors expressed on NK cells that bind MHC Class I molecules, transmitting balanced activating or inhibitory signals that regulate NK-cell cytolytic function.

Pro-B Cell

The earliest B-cell developmental stage characterized by $CD10$ and $CD19$ expression, EBF production, and immunoglobulin heavy-chain rearrangement ($D$ to $J$, then $V$ to $DJ$) on chromosome $14$.

Pre-BCR

A transient developmental receptor complex on pre-B cells consisting of a newly formed $\mu$ heavy chain ($\mu\text{HC}$), a surrogate light chain (VpreB and $\lambda 5$), and signaling molecules $\text{Ig}\alpha$ and $\text{Ig}\beta$.

Central Tolerance (B cells)

The negative selection process in the bone marrow where immature B cells recognizing self-antigen via membrane IgM undergo apoptosis, eliminating approximately $90\%$ of developing B cells.

Follicular B Cells

Mature recirculating B cells residing in lymphoid follicles that interact with follicular helper T ($\text{Tfh}$) cells via $CD40/CD40L$ to undergo isotype switching, affinity maturation, and memory cell generation.

Marginal-Zone B Cells

Mature non-circulating B cells localized to the splenic marginal zone that mount T-independent antibody responses against bacterial polysaccharides, producing primarily IgM without memory cell generation.

Plasma Cell

A terminally differentiated $CD138^+$ B cell specialized for high-level antibody secretion into blood and body fluids, characterized by an eccentric oval nucleus, condensed chromatin, and abundant endoplasmic reticulum.

Serum Protein Electrophoresis (SPEP) Gamma ($\gamma$) Band

The slow-moving electrophoretic fraction containing circulating immunoglobulins, which normally comprise approximately $20\%$ of total plasma proteins.

Hinge Region

A flexible, proline-rich segment located between the $C_H1$ and $C_H2$ domains of $\gamma$, $\delta$, and $\alpha$ heavy chains (absent in $\mu$ and $\varepsilon$) that allows independent movement of the antigen-binding Fab arms.

Papain Digestion

Enzymatic cleavage of an immunoglobulin above the hinge region disulfide bonds, yielding three distinct fragments: two separate monovalent Fab fragments and one intact Fc fragment.

Pepsin Digestion

Enzymatic cleavage of an immunoglobulin below the hinge region disulfide bonds, producing a single bivalent $F(ab')_2$ fragment and degrading the Fc region into multiple inactive fragments.

Isotype

Heavy-chain or light-chain constant region determinant sequences shared by all healthy individuals of the same species, defining immunoglobulin classes and subclasses.

Allotype

Minor genetically determined amino acid sequence variations in immunoglobulin constant regions present in some individuals of a species but not others.

Idiotype

The unique structural configuration of the hypervariable variable region (paratope) of an immunoglobulin molecule that dictates its specific target epitope binding.

Immunoglobulin G (IgG)

The most abundant serum antibody ($70\text{–}75\%$ of total Ig) with a $23$-day half-life; possesses four subclasses, mediates opsonization and ADCC, fixes complement, and is the only immunoglobulin capable of crossing the placenta.

Immunoglobulin M (IgM)

A pentameric macroglobulin ($\text{MW } 900{,}000$, $19\text{ S}$) joined by a J chain with $10$ antigen-binding sites; acts as the primary response antibody and the most efficient activator of the classical complement pathway and agglutination.

Secretory IgA

A dimeric immunoglobulin complex linked by a J chain and a secretory component derived from epithelial poly-Ig receptors that protects mucosal surfaces and is abundant in breast milk, tears, and saliva.

Immunoglobulin D (IgD)

A monomeric immunoglobulin with a long hinge region and short half-life ($1\text{–}3$ days) that is co-expressed with IgM on mature naive B cells and participates in B-cell activation.

Immunoglobulin E (IgE)

A monomeric immunoglobulin present in trace serum concentrations ($0.005\text{ mg/dL}$, $0.02\%$) whose $C_H3$ domains bind high-affinity $Fc\varepsilon R$ on mast cells and basophils, mediating Type I hypersensitivity and antiparasitic responses.

Class Switch Recombination (CSR)

A somatic DNA recombination event where repetitive switch-region sequences undergo excision to swap the constant heavy ($C_H$) gene segment while preserving antigen specificity.

Affinity Maturation

The process occurring in germinal centers where somatic hypermutation of rearranged V(D)J genes during rapid B-cell division leads to the selection of B cells possessing higher antigen-binding strength.

Hybridoma

An immortalized hybrid cell line created by polyethylene glycol (PEG)-mediated fusion of an antigen-primed spleen B cell with a non-secreting myeloma cell, selected in HAT medium to produce monoclonal antibodies.

Classical Pathway C3 Convertase

An enzymatic complex composed of $C4b2a$ (or $C4b2b$ in newer nomenclature) formed after active $C1s$ cleaves $C4$ and $C2$, responsible for cleaving intact $C3$ into $C3a$ and $C3b$.

Lectin Pathway

An antibody-independent complement cascade initiated when mannose-binding lectin (MBL) binds to carbohydrate residues on pathogens, activating MASP-1 and MASP-2 to cleave $C4$ and $C2$.

Alternative Pathway C3 Convertase

An enzymatic complex ($C3bBb$) generated by spontaneous $C3$ tickover or microbial surface binding, cleavage of Factor B by Factor D, and stabilization by properdin (P).

Membrane Attack Complex (MAC)

The terminal multi-protein pore ($C5b\text{–}9$) assembled when $C5b$ recruits $C6$, $C7$, $C8$, and multiple polymerized $C9$ molecules to insert into lipid bilayers and cause osmotic lysis.

Anaphylatoxins

Complement split fragments ($C5a > C3a \gg C4a$) that bind receptors on mast cells and basophils, stimulating histamine release, smooth muscle contraction, and increased vascular permeability.

C1 Inhibitor (C1-INH)

A serine protease regulator that irreversibly binds and dissociates $C1r$ and $C1s$ from $C1q$; deficiency results in uncontrolled complement and bradykinin activation known as Hereditary Angioedema (HAE).

Decay-Accelerating Factor (DAF / CD55)

A regulatory protein on host cells that dissociates $C2a$ (or $C2b$) from $C4b$ and $Bb$ from $C3b$, halting C3 convertase activity; absence on erythrocytes leads to Paroxysmal Nocturnal Hemoglobinuria (PNH).

Membrane Inhibitor of Reactive Lysis (MIRL / CD59)

A GPI-anchored membrane protein that prevents the incorporation and polymerization of $C9$ into the nascent $C5b\text{–}8$ complex, blocking MAC completion.

Complement Receptor 1 (CR1 / CD35)

A cell-surface glycoprotein on erythrocytes, leukocytes, and phagocytes that binds $C3b$ and $C4b$, serving as a Factor I cofactor and mediating the clearance of circulating immune complexes.

CH50 Assay

A functional hemolytic assay measuring total classical complement pathway activity ($C1\text{–}C9$), reported as the reciprocal of the serum dilution required to lyse $50\%$ of antibody-sensitized sheep red blood cells.

AH50 Assay

A hemolytic screening assay evaluating alternative complement pathway function using rabbit erythrocytes suspended in a $Ca^{2+}$-free buffer with $Mg^{2+}\text{-EGTA}$ to inhibit classical pathway activation.

Serology

The clinical laboratory science focused on examining serum components and measuring in-vitro antigen-antibody interactions.

Volumetric Pipette

A laboratory pipette calibrated 'To Deliver' (TD) a single, highly accurate, specific volume of fluid.

Graduated (Serological) Pipette

A versatile pipette featuring graduated volume markings extending down to the tip; blowout varieties have a frosted band at the top requiring fluid expulsion with a bulb.

Dilution Factor

The mathematical reciprocal of the dilution fraction ($V_{\text{total}} / V_{\text{solute}}$), used as a multiplier with the dilute concentration to calculate the final undiluted concentration.

Compound Dilution

A process where multiple serial or successive dilution steps are combined to achieve an extreme final dilution when a single-step dilution would require an impractically small volume of solute.

Serial Dilution

A sequential series of dilutions performed across consecutive tubes maintaining an identical dilution factor and diluent volume at each stage, used in titers.

Titer

The reciprocal of the highest serum dilution (lowest concentration) at which an observable antigen-antibody reaction (such as agglutination or precipitation) is detected.