Question 1

Immunology — Which class of human immunoglobulin (antibody) can cross the placenta to provide passive immunity to the fetus?

Accepted Answer

Introduction / Context: Maternal antibodies protect the developing fetus and newborn before their own immune system fully matures. Understanding which immunoglobulin is transported across the placenta is vital in clinical immunology, vaccinology, and perinatal medicine. Given Data / Assumptions: Placental transfer occurs via receptor-mediated transport. Different immunoglobulin classes vary in structure and transport properties. The focus is on normal human pregnancy. Concept / Approach: IgG is the only immunoglobulin class that efficiently crosses the human placenta. This occurs through neonatal Fc receptors (FcRn) on placental syncytiotrophoblasts, which bind the Fc region of IgG and transport it to the fetal circulation. IgM, being pentameric and large, does not cross the placenta. IgA (mostly dimeric in secretions) is important for mucosal immunity and is transferred in breast milk, not across the placenta. IgD has limited known roles in serum and does not undergo significant placental transfer. Step-by-Step Solution: Identify the transport mechanism: FcRn-mediated transcytosis favors IgG.Exclude large pentameric IgM due to size and lack of FcRn-mediated transfer.Exclude IgA and IgD due to their roles and lack of significant placental transport. Verification / Alternative check: Cord blood serology demonstrates IgG specificities reflecting maternal exposure or vaccination, supporting placental transfer of IgG. Why Other Options Are Wrong: IgM: too large; does not cross the placenta. IgA: transferred mainly via breast milk (secretory IgA), not placentally. IgD: not known for placental transfer. Common Pitfalls: Assuming all antibodies cross equally; structure and Fc receptor interactions determine transfer efficiency. Final Answer: IgG

Question 2

Immunology recall – heat sensitivity of antibody classes: Among the major human immunoglobulin (antibody) classes, which one is characteristically heat-labile (readily inactivated by moderate heating such as 56 °C for standard laboratory treatment)?

Accepted Answer

Introduction / Context: Understanding the thermal stability of antibody classes is important in immunodiagnostics and allergy testing. Laboratories routinely heat sera (for example, at 56 °C) to inactivate complement; however, different immunoglobulin isotypes tolerate heat differently. This question tests recognition of the antibody class that is notably heat-labile. Given Data / Assumptions: Sera may be heated during sample preparation (e.g., complement inactivation). Antibody isotypes have distinct structures (monomeric vs polymeric) influencing stability. We compare common human isotypes: IgG, IgA, IgM, and IgE. Concept / Approach: IgE is structurally similar in basic domain architecture to IgG but is markedly more labile to heat and storage, which matters for assays that measure IgE (e.g., total IgE or allergen-specific IgE). In contrast, IgG is relatively heat-stable under complement-inactivation conditions; polymeric IgM is large and can lose activity with heat but is not classically labeled the most heat-labile; secretory IgA is protected by the secretory component in mucosa but serum IgA overall tolerates routine handling better than IgE. Step-by-Step Solution: Identify which isotype is classically described as heat-labile in clinical immunology. Recall that IgE levels can drop with routine heat treatment, affecting allergy assays. Therefore, select IgE as the best answer. Verification / Alternative check: Laboratory guidelines caution against heating samples for IgE assays because activity and epitope recognition decline after moderate heating, confirming practical heat lability. Why Other Options Are Wrong: IgG is comparatively heat-stable at 56 °C for short periods; IgA and IgM can be affected but are not the most labile in routine workflows. Common Pitfalls: Confusing heat inactivation of complement (a serum component) with heat sensitivity of the antibodies themselves; not all isotypes respond the same. Final Answer: IgE.

Question 3

Fc region functions of IgG – clinical significance: Which listed functions are mediated by the Fc fragment of human IgG antibodies during immune effector responses and in vivo handling?

Accepted Answer

Introduction / Context: The Fc (fragment crystallizable) portion of IgG governs interactions with host receptors and complement, shaping antibody persistence, placental transfer, and downstream effector functions such as opsonization and cell-mediated cytotoxicity. Recognizing Fc-mediated roles is essential for interpreting vaccine efficacy, monoclonal antibody engineering, and serology results. Given Data / Assumptions: IgG contains Fab (antigen binding) and Fc (effector) regions. Fc engages Fc receptors (e.g., FcRn, FcγR) and complement component C1q under defined geometries. Transplacental transfer relies on specialized Fc receptor pathways. Concept / Approach: The neonatal Fc receptor (FcRn) binds IgG Fc in acidic endosomes, recycling it to extend serum half-life, thereby influencing catabolic rate. Complement activation by IgG requires Fc-mediated C1q binding when multiple IgG molecules are arrayed on antigen. Placental transfer of maternal IgG to the fetus occurs through FcRn-dependent transport, a classic Fc function ensuring neonatal passive immunity. Step-by-Step Solution: Match each listed function to a known Fc-dependent mechanism. Confirm all three are well-established Fc roles. Select the inclusive option “All of these.” Verification / Alternative check: Therapeutic antibodies with engineered Fc domains alter half-life and effector functions, illustrating clinical control via Fc design. Why Other Options Are Wrong: Single statements (a–c) are true individually, so “None of these” is false; the correct comprehensive choice is “All of these.” Common Pitfalls: Attributing antigen specificity (a Fab property) to Fc; here the question focuses on downstream and transport roles. Final Answer: All of these.

Question 4

Polymerization of antibodies – the J chain: In human immunology, the joining (J) chain polypeptide is associated with which immunoglobulin classes in their polymeric forms?

Accepted Answer

Introduction / Context: The J (joining) chain is a small polypeptide critical for the assembly and secretion of polymeric antibodies. It influences mucosal immunity and complement activation by controlling antibody valency and transport. This question checks recognition of which isotypes carry J chain in their typical multimeric states. Given Data / Assumptions: IgA is secreted predominantly as a dimer across mucosal surfaces. IgM is secreted as a pentamer in serum during early responses. The J chain links monomers to form stable polymers and enables transcytosis of IgA. Concept / Approach: Dimeric secretory IgA incorporates one J chain to connect two IgA monomers and to bind the polymeric immunoglobulin receptor for epithelial transcytosis. Pentameric IgM contains one J chain that stabilizes the pentamer and contributes to its distinctive star-shaped structure and strong avidity. IgE and IgD are predominantly monomeric and do not normally include J chain. Step-by-Step Solution: Identify polymeric isotypes: IgA (dimer) and IgM (pentamer). Recall that J chain is required for their assembly and transport. Select “Both IgA and IgM.” Verification / Alternative check: Secretory IgA includes the secretory component in addition to the J chain; IgM’s high complement-fixing efficiency reflects its pentameric architecture supported by J chain. Why Other Options Are Wrong: IgA only or IgM only are incomplete; IgE and IgD do not typically associate with J chain. Common Pitfalls: Confusing the J chain with light-chain “J segments” (gene segments) or with the secretory component of IgA; they are distinct entities. Final Answer: Both IgA and IgM.

Question 5

Complement activation potency: Which antibody class is the most efficient at fixing complement via the classical pathway during early humoral immune responses?

Accepted Answer

Introduction / Context: Complement fixation is a key effector function that promotes opsonization, inflammation, and lysis of pathogens. Antibody isotypes differ in how strongly they activate the classical complement pathway, largely due to their quaternary structures and Fc properties. Given Data / Assumptions: IgM circulates as a pentamer; IgG is monomeric; IgA is usually monomeric in serum and dimeric at mucosa; IgE and IgD are monomeric. Complement component C1q binds clustered Fc domains. Higher local Fc density improves complement activation efficiency. Concept / Approach: IgM’s pentameric form presents multiple Fc regions in close proximity, allowing a single bound IgM pentamer on an antigen surface to efficiently recruit and activate C1q. IgG can also fix complement but typically requires multiple IgG molecules closely spaced on the antigen. IgA does not efficiently activate the classical pathway; IgE and IgD are ineffective at complement fixation in the classical route. Step-by-Step Solution: Compare structural valency of isotypes. Relate valency to C1q engagement thresholds. Identify IgM pentamer as the strongest activator. Select IgM. Verification / Alternative check: Complement fixation tests historically use IgM for high sensitivity; a single IgM can trigger robust classical pathway activation when properly bound. Why Other Options Are Wrong: IgG requires clustering; IgA functions mainly in mucosal immunity without strong classical pathway activation; IgE and IgD do not fix complement classically. Common Pitfalls: Assuming serum abundance equals complement potency; IgG is abundant but less efficient per molecule than pentameric IgM. Final Answer: IgM.

Question 6

Functions of IgG – identify the exception: Which of the following is NOT a characteristic function or property of human IgG antibodies in systemic immunity?

Accepted Answer

Introduction / Context: IgG is the dominant serum antibody in adults and mediates multiple effector functions. However, it is not typically the very first isotype produced upon initial exposure to a new antigen. This question asks you to identify the exception among otherwise true IgG statements. Given Data / Assumptions: Primary immune responses begin with IgM production, followed by class switching to IgG (and others). IgG is the most abundant serum antibody, crosses the placenta, fixes complement, and opsonizes pathogens. Statements refer to standard human systemic immunity. Concept / Approach: Naive B cells initially secrete IgM due to default heavy chain constant region usage. After T cell help and cytokine signals, class-switch recombination generates IgG subclasses with enhanced effector functions and longevity. Therefore, the statement that IgG is the first antibody made in primary responses is incorrect; that role belongs to IgM. Step-by-Step Solution: List established IgG functions: serum dominance, placental transfer, complement activation, opsonization. Contrast with primary response kinetics where IgM appears first. Identify the incorrect statement as the “first produced” claim. Choose option describing early primary response incorrectly. Verification / Alternative check: Serological time-course: IgM peaks early and declines; IgG rises later and persists, forming the basis of acute vs convalescent titer interpretation. Why Other Options Are Wrong: All other options are correct roles of IgG in humans. Common Pitfalls: Confusing rapid secondary response (memory) where IgG dominates early, with the initial primary encounter where IgM comes first. Final Answer: First antibody produced during the primary response to a new antigen.

Question 7

B-cell tolerance – absence of self-reactive antibodies in normal serum: Why are self-reactive antibodies generally not present at significant levels in healthy individuals under baseline conditions?

Accepted Answer

Introduction / Context: Immunological tolerance prevents damaging autoimmunity by deleting or silencing self-reactive lymphocytes. The B-cell arm employs both central and peripheral mechanisms to keep autoantibody levels low in healthy serum. Given Data / Assumptions: B-cell receptor (BCR) engagement without proper co-stimulation promotes tolerance. T-cell help (e.g., CD40–CD40L, cytokines) is usually required for robust class switching and persistence. Self antigens are frequently present and can be encountered during development and peripherally. Concept / Approach: Central tolerance in bone marrow edits or deletes strongly self-reactive clones. Peripherally, BCR signaling in the absence of T-cell help (signal 1 without signal 2) induces anergy or apoptosis. This “lack of help” is a key checkpoint: even if a self-reactive BCR engages antigen, without cognate T-helper signals the cell fails to mature into a high-affinity, class-switched plasma cell. Thus, self-reactive antibodies do not accumulate to significant concentrations in normal serum. Step-by-Step Solution: Recognize that generation of self-reactive receptors is possible (random recombination). Apply central tolerance (deletion/editing) and peripheral anergy/apoptosis. Note the requirement of T-cell help for sustained antibody responses. Conclude that absence of help drives anergy/apoptosis of self-reactive B cells. Verification / Alternative check: Experimental models show that providing inappropriate T-cell help to self-reactive B cells breaks tolerance and induces autoantibodies, underscoring the role of helper signals. Why Other Options Are Wrong: It is possible to generate self-reactive receptors (a is false); CD8 T cells are not the main tolerance mechanism for B cells (b); class switching to IgA does not “remove” autoreactivity (d); self antigens do circulate or are displayed (e). Common Pitfalls: Assuming tolerance equals complete absence of self-reactive clones; low-affinity or silenced clones can exist without pathogenic autoantibody levels. Final Answer: B cells stimulated via their B-cell receptor without appropriate T-cell help undergo anergy or apoptosis (functional deletion).

Question 8

Anatomy of an antibody – where antigen binds: In a complete immunoglobulin molecule, the antigen-binding sites are located specifically within which structural regions?

Accepted Answer

Introduction / Context: Antibodies bind antigens through highly variable regions formed by both heavy and light chains. Knowing exactly where binding occurs is essential for understanding specificity, affinity maturation, monoclonal antibody engineering, and diagnostic assay design. Given Data / Assumptions: An antibody has two antigen-binding arms (Fab) and one Fc stalk (effector region). Complementarity-determining regions (CDRs) lie within variable domains of heavy (VH) and light (VL) chains. Fc mediates effector functions rather than antigen recognition. Concept / Approach: Each Fab contains paired VH and VL domains. Six CDR loops (three from VH, three from VL) create the paratope that contacts the antigen’s epitope. The Fc portion is composed of constant domains of heavy chains and does not contribute to antigen specificity; instead, it binds Fc receptors and complement once antigen is bound. Step-by-Step Solution: Identify structural regions: Fab vs Fc. Locate CDRs within VH/VL of Fab arms. Conclude that antigen binding occurs in Fab variable domains of both chains. Select the option naming Fab regions. Verification / Alternative check: Papain digestion yields two Fab fragments that retain antigen binding and one Fc fragment without binding activity, confirming location. Why Other Options Are Wrong: Light or heavy constant regions alone do not bind antigen; Fc and hinge regions are not responsible for specificity. Common Pitfalls: Confusing Fc-mediated effector functions with antigen recognition; they are separable structurally and functionally. Final Answer: Fab regions (variable domains of both heavy and light chains).

Question 9

How the immune system chooses antibodies – core paradigm: Among classic theories of antibody production, which one is the most widely accepted to explain specificity and expansion of antigen-reactive lymphocytes?

Accepted Answer

Introduction / Context: The immune system’s ability to recognize an enormous diversity of antigens rests on how lymphocyte receptors are generated and selected. Competing historical theories attempted to explain this phenomenon, but one framework remains the modern cornerstone of immunology. Given Data / Assumptions: Lymphocytes bear unique receptors generated before antigen exposure. Antigen selects preexisting clones to proliferate and differentiate. Memory and specificity arise from expansion of selected clones. Concept / Approach: Clonal selection theory posits that each lymphocyte has a single specificity. Upon encountering its cognate antigen, that clone proliferates and differentiates into effector and memory cells. This model explains primary and secondary responses, self-tolerance mechanisms (deletion of self-reactive clones), and affinity maturation when coupled with somatic hypermutation and selection in germinal centers. Step-by-Step Solution: List candidate theories and assess against modern data. Recognize that template/side-chain ideas conflict with pre-formed receptor diversity. Choose the model consistent with V(D)J recombination and clonal expansion. Select clonal selection theory. Verification / Alternative check: Molecular findings (V(D)J recombination, junctional diversity, somatic hypermutation) validate preexisting receptor diversity and antigen-driven clone expansion, aligning with clonal selection. Why Other Options Are Wrong: Side-chain and template theories propose antigen instructs receptor shape, which is inconsistent with genetic generation of receptor repertoires. Common Pitfalls: Assuming affinity maturation contradicts clonal selection; in reality, selection acts on mutations generated during germinal center reactions. Final Answer: Clonal selection theory.

Question 10

Functions of IgA – identify the exception: Which statement below is NOT a recognized function of immunoglobulin A (IgA), especially in mucosal immunity?

Accepted Answer

Introduction / Context: IgA is the dominant antibody in secretions and is central to mucosal defense. Its functions emphasize neutralization and immune exclusion rather than vigorous complement-mediated inflammation, which could damage delicate epithelial barriers. Given Data / Assumptions: Secretory IgA is dimeric with a J chain and secretory component. Mucosal immunity prioritizes neutralization and agglutination over inflammatory lysis. Classical complement activation requires strong Fc clustering that IgA does not typically provide. Concept / Approach: IgA neutralizes pathogens and toxins, blocks adherence, and agglutinates particles for removal by mucus and peristalsis. It does not efficiently trigger the classical complement cascade in humans; excessive complement activation at mucosal surfaces would be harmful. Hence, “fix complement efficiently” is not a standard IgA function in the classical pathway sense. Step-by-Step Solution: List common IgA roles: neutralization, immune exclusion, agglutination, mucosal protection. Contrast with classical complement fixation, which is weak for IgA. Identify the exception statement. Select “Fixes complement efficiently via the classical pathway.” Verification / Alternative check: Clinical observations show selective IgA deficiency predisposes to mucosal infections, consistent with its protective, non-inflammatory roles rather than complement-driven lysis. Why Other Options Are Wrong: They accurately describe IgA’s protective roles at mucosa and in secretions (including tears). Common Pitfalls: Generalizing complement properties of IgM/IgG to IgA; isotype-specific Fc biology matters. Final Answer: Fixes complement efficiently via the classical pathway.

Question 11

Type I (immediate) hypersensitivity mediator: Which immunoglobulin class is the principal mediator of Type I hypersensitivity reactions such as anaphylaxis, allergic rhinitis, and many food allergies?

Accepted Answer

Introduction / Context: Type I hypersensitivity reactions are rapid, IgE-dependent responses to allergens, involving mast cells and basophils. Correctly identifying the antibody class at the core of this mechanism is essential for understanding allergy diagnostics and therapies (e.g., anti-IgE treatment). Given Data / Assumptions: Allergen exposure leads to class-switching to IgE in susceptible individuals. IgE binds FcεRI on mast cells and basophils with high affinity. Cross-linking of receptor-bound IgE by allergen triggers degranulation. Concept / Approach: IgE-coated effector cells release histamine, leukotrienes, prostaglandins, and cytokines upon allergen-induced cross-linking, producing immediate symptoms such as wheal-and-flare, bronchospasm, and anaphylaxis. Other isotypes (IgG, IgM, IgA, IgD) are not primary mediators of this immediate, mast cell–dependent pathway. Step-by-Step Solution: Identify the hypersensitivity type: Type I (immediate). Recall the effector mechanism: IgE bound to FcεRI on mast cells. Select IgE as the central immunoglobulin mediator. Confirm that other isotypes do not trigger this pathway. Verification / Alternative check: Clinical desensitization protocols and anti-IgE monoclonal antibodies reduce free IgE and FcεRI occupancy, alleviating allergic manifestations—evidence for IgE centrality. Why Other Options Are Wrong: IgG mediates other hypersensitivity types (e.g., II, III); IgM is early humoral responder; IgD is mainly a B-cell receptor; IgA protects mucosa rather than mediating immediate hypersensitivity. Common Pitfalls: Confusing IgE with IgG-mediated late-phase or complement-related reactions; timing and cellular players distinguish these categories. Final Answer: IgE.

Question 12

Immunology fundamentals: In humans, which immunoglobulin (antibody) class is the most abundant overall in blood serum and extracellular fluid, providing the majority of humoral immunity?

Accepted Answer

Introduction / Context: Understanding the relative abundance of immunoglobulin classes helps learners predict which antibody predominates in circulation, which tissues it protects, and how it contributes to diagnostic testing. Among the five major classes (IgG, IgA, IgM, IgD, IgE), one dominates quantitatively in human serum and interstitial fluid. Given Data / Assumptions: The question asks for the most abundant immunoglobulin in the body's extracellular compartments (serum and tissues). Immunoglobulins differ in structure, distribution, and function. Normal adult physiology is assumed; special states like selective Ig deficiencies are not considered. Concept / Approach: IgG is the predominant immunoglobulin in serum, typically accounting for about three-quarters of total serum antibodies. It diffuses efficiently into tissues, opsonizes pathogens, activates complement (classically IgG1 and IgG3), and crosses the placenta to provide passive neonatal immunity. By contrast, IgA is most abundant at mucosal surfaces and in secretions, IgM is the first produced in primary responses but remains mainly intravascular, IgE is present at very low concentrations, and IgD is primarily a B-cell receptor. Step-by-Step Solution: List antibody classes and their typical quantitative distribution in serum. Identify that IgG constitutes the majority of circulating antibody mass. Confirm that tissue distribution favors IgG because of its smaller size and longer half-life. Select IgG as the correct answer. Verification / Alternative check: Clinical laboratory ranges consistently show IgG concentration higher than IgA, IgM, IgD, or IgE in healthy adults. Neonatal passive immunity further underscores IgG's dominance due to placental transfer. Why Other Options Are Wrong: IgA: Most abundant in secretions (mucosal immunity), not in serum overall. IgM: First produced in primary response but less abundant than IgG in steady state. IgE: Lowest serum levels; specialized for allergy and helminths. IgD: Primarily membrane-bound on naive B cells; minimal in serum. Common Pitfalls: Confusing “most abundant in serum” (IgG) with “most abundant in secretions” (IgA). Also, equating early appearance (IgM) with long-term abundance is incorrect. Final Answer: IgG.

Question 13

Clinical immunohematology: Anti-Rh (anti-D) antibodies produced after exposure to Rh-positive red blood cells primarily belong to which immunoglobulin class?

Accepted Answer

Introduction / Context: In transfusion medicine and maternal–fetal medicine, the class of antibodies directed against Rh (D) antigen determines their ability to cross the placenta and cause hemolytic disease of the fetus and newborn. Correctly identifying anti-Rh as predominantly IgG has major clinical implications. Given Data / Assumptions: Anti-Rh (anti-D) antibodies arise after sensitization to Rh-positive erythrocytes. Placental transfer occurs via Fc receptors specific for IgG. We are focusing on the clinically significant, high-affinity response. Concept / Approach: Anti-Rh antibodies are class-switched, affinity-matured IgG, typically IgG1 and IgG3 subclasses. These efficiently cross the placenta, opsonize fetal red cells, and can activate complement or mediate Fc receptor–dependent destruction. While early responses to many antigens may include IgM, the clinically important anti-D antibodies that cause hemolysis are IgG. Step-by-Step Solution: Recognize that Rh antigens are proteinaceous and provoke T cell–dependent responses. Recall class switching to IgG in secondary responses with memory B cells. Note placental transfer of IgG explains fetal risk. Select IgG as the predominant class. Verification / Alternative check: Antiglobulin (Coombs) testing detects bound IgG on fetal or maternal red cells. Rho(D) immune globulin prophylaxis uses IgG anti-D to prevent maternal sensitization. Why Other Options Are Wrong: IgM: Does not cross placenta; initial low-affinity responses are less clinically significant here. IgA: Mucosal; not a driver of hemolysis in Rh disease. IgE / IgD: Involved in allergy or B-cell receptor, not hemolytic disease. Common Pitfalls: Assuming all first antibodies are IgM; anti-D of clinical concern is IgG after class switching. Also, conflating ABO hemolysis (often IgM) with Rh disease (IgG). Final Answer: IgG type.

Question 14

Primary immune response kinetics: Following the first stimulation by a novel antigen, which immunoglobulin class is the earliest to appear in detectable amounts in serum?

Accepted Answer

Introduction / Context: During a primary immune response, B cells initially secrete one antibody class before undergoing class switching. Recognizing the temporal pattern of antibody appearance is essential for interpreting serology (e.g., acute vs. past infection) and understanding vaccine responses. Given Data / Assumptions: This is a first exposure (primary response), not a secondary (anamnestic) response. We consider serum detection with standard clinical assays. Normal immunocompetence is assumed. Concept / Approach: Naive B cells express membrane IgM and IgD. Upon activation, they first secrete IgM. With T cell help and cytokines, B cells undergo class switching to produce other isotypes (e.g., IgG, IgA, or IgE) while improving affinity via somatic hypermutation. Therefore, IgM is the first class detectable after primary antigen exposure. Step-by-Step Solution: Identify the phase: initial antigen encounter. Recall that secreted antibody before class switching is IgM. Recognize that IgG typically rises later and persists longer. Choose IgM as the earliest detectable isotype. Verification / Alternative check: Serologic panels often interpret IgM positivity as recent or acute infection, whereas isolated IgG implies past exposure or immunity. Vaccine studies show early IgM peaks followed by class-switched IgG. Why Other Options Are Wrong: IgG: Dominates secondary responses; appears later in primary responses. IgA: Important in mucosa; generally follows class switching. IgE: Specialized; requires Th2 cytokines and class switching. IgD: Mostly membrane-bound; not a major secreted early isotype. Common Pitfalls: Confusing “most abundant overall” (IgG) with “first to appear” (IgM). Timing and abundance address different aspects of humoral immunity. Final Answer: IgM.

Question 15

Evolutionary immunology: Which immunoglobulin class is considered the phylogenetically oldest (earliest to appear in vertebrate evolution)?

Accepted Answer

Introduction / Context: Antibody classes evolved over time, with some isotypes appearing earlier in vertebrate evolution. Knowing which class is phylogenetically ancient helps explain why it plays foundational roles in primary responses across species. Given Data / Assumptions: Comparison across vertebrates (e.g., fish, amphibians, mammals). Focus on earliest-emerging class in evolutionary history. General immunology consensus on isotype evolution. Concept / Approach: IgM is widely recognized as the earliest immunoglobulin class to appear in vertebrates. It exists as a pentamer in serum (in mammals) and serves as the initial secreted antibody in primary responses. Other classes like IgG, IgA, and IgE are evolutionarily later, with specialized roles in systemic, mucosal, and allergic immunity respectively. Step-by-Step Solution: Identify isotype present across the broadest range of early vertebrates: IgM. Connect evolutionary antiquity with its role as first-line humoral responder. Rule out IgG, IgA, IgE as later specializations. Select IgM. Verification / Alternative check: Comparative immunology texts document IgM-like molecules in cartilaginous and bony fish, preceding the emergence of class-switched isotypes typical of mammals. Why Other Options Are Wrong: IgG / IgA / IgE: Appeared later with specialized functions. All are similar: Evolutionary timelines differ; they are not simultaneous. Common Pitfalls: Equating “most abundant in serum” (IgG) with “oldest.” Abundance today does not imply earliest evolutionary origin. Final Answer: IgM.

Question 16

Secretory IgA (sIgA) biology: The secretory component associated with dimeric IgA in mucosal secretions is derived from which source/mechanism?

Accepted Answer

Introduction / Context: Secretory IgA is the dominant immunoglobulin in mucosal secretions such as saliva, tears, and intestinal fluid. Its resistance to proteolysis and effective mucosal transport depend on a specialized secretory component attached to dimeric IgA. Given Data / Assumptions: Plasma cells in lamina propria produce dimeric IgA linked by J chain. Epithelial cells express a polymeric immunoglobulin receptor (pIgR). Secretory component originates from epithelial cells, not lymphocytes. Concept / Approach: Dimeric IgA binds to pIgR on the basolateral surface of epithelial cells. The complex undergoes transcytosis to the apical surface. There, a proteolytic cleavage releases IgA into the lumen with a residual portion of pIgR still attached—this remnant is the secretory component, which stabilizes IgA and protects it from proteases. Step-by-Step Solution: Identify producer of IgA: plasma cells create dimeric IgA with J chain. Recognize epithelial transport via pIgR. Note apical cleavage of pIgR yields the secretory component. Select the option describing pIgR cleavage during transcytosis. Verification / Alternative check: Immunohistochemical studies show pIgR expression on mucosal epithelia and colocalization with sIgA at the apical surface, confirming epithelial origin of the secretory component. Why Other Options Are Wrong: Plasma cells / T cells / Dendritic cells: Do not produce secretory component; they produce IgA or regulate responses. M cells: Specialized for antigen sampling, not for adding secretory component. Common Pitfalls: Assuming all parts of sIgA are lymphocyte-derived; in fact, secretory component is epithelial in origin via pIgR processing. Final Answer: Formed by cleavage of an epithelial polymeric Ig receptor during transcytosis.

Antibody Questions