Question 1

T-cell development — If MHC class II is not expressed in the thymus, which function would NOT be reduced (i.e., is the exception)?

Accepted Answer

Introduction: T-cell positive selection in the thymus depends on cortical epithelial cell expression of MHC molecules. Class II MHC is required to select CD4 T cells, while class I MHC is needed for CD8 T cells. This question asks which immune function would NOT be reduced if thymic MHC class II were absent. Given Data / Assumptions: MHC class II expression in thymus is essential for generating CD4 T cells. CD4 T cells provide help to B cells (class switching to IgG) and activate macrophages (Th1) for intracellular/vesicular pathogens. CD8 T cells are selected on MHC class I, not class II. Alternative complement activation is innate and MHC-independent. Concept / Approach: Predict consequences of lacking CD4 T cells: decreased Th-dependent macrophage activation and impaired T-dependent antibody responses (e.g., IgG). Identify which listed function relies on CD8 or innate pathways and therefore would not necessarily be reduced. Step-by-Step Solution: 1) Remove MHC II in thymus → no positive selection for CD4 → severe CD4 lymphopenia.2) With low CD4, expect reduced Th1-mediated macrophage activation and reduced T-dependent isotype switching (IgG).3) CD8 cytotoxicity depends on MHC I selection → remains relatively intact.4) Complement alternative pathway is innate → not directly affected by thymic MHC II absence. Verification / Alternative check: Patients with bare lymphocyte syndrome type II (MHC II deficiency) show markedly decreased CD4 counts and impaired humoral responses, while CD8 T cells can be near normal since MHC I is preserved. Why Other Options Are Wrong: a) Typically not reduced by lack of MHC II; however, among adaptive options, CD8 function most clearly persists.c) Requires Th1 CD4 help; reduced.d) Requires T-cell help for class switching; reduced.e) A CD4-mediated response; reduced. Common Pitfalls: Assuming all T-cell functions decline; failing to separate CD4-dependent functions from CD8-dependent or innate pathways. Final Answer: CD8 T cell-mediated cytotoxicity would NOT be reduced.

Question 2

HIV tropism — The HIV virus primarily infects which cell population in humans?

Accepted Answer

Introduction: Human immunodeficiency virus (HIV) causes progressive immune deficiency by targeting key immune cells. Recognizing the primary cellular targets explains both pathogenesis and clinical vulnerability to opportunistic infections. Given Data / Assumptions: HIV entry requires CD4 along with coreceptors such as CCR5 or CXCR4. CD4 is expressed on helper T cells and subsets of macrophages and dendritic cells. RBCs lack nuclei and CD4, making them non-permissive for HIV infection. Concept / Approach: Match viral receptor usage (CD4 plus coreceptors) to host cell types to identify the primary infected populations that drive immunodeficiency. Step-by-Step Solution: 1) Identify cells expressing CD4: helper T cells, macrophages, dendritic cells.2) Recognize that coreceptor usage determines tissue tropism (CCR5, CXCR4).3) Conclude immune cells are the main targets, explaining CD4 T-cell depletion. Verification / Alternative check: Clinical monitoring of HIV focuses on CD4 T-cell counts and viral load; antiretroviral therapy restores CD4 levels by suppressing replication in these cell types. Why Other Options Are Wrong: a,d,e) While HIV can affect other tissues indirectly, the primary replication sites are immune cells.c) RBCs lack nuclei and CD4; they are not infected. Common Pitfalls: Assuming any cell can be infected; overlooking receptor/coreceptor requirements for viral entry. Final Answer: Cells of the immune system (CD4 T cells, macrophages, dendritic cells).

Question 3

Antibody cross-reactivity — A monoclonal antibody specific for the aromatic hapten 2,4-dinitrophenyl (DNP) might also bind which amino acid side chains most plausibly?

Accepted Answer

Introduction: Haptens like 2,4-dinitrophenyl (DNP) are small aromatic molecules that elicit specific antibodies when coupled to carriers. Antibody paratopes recognize shape, charge, and hydrophobic features; cross-reactivity often occurs with structurally similar epitopes. This question probes recognition of aromaticity as a key determinant. Given Data / Assumptions: DNP contains a substituted benzene ring (planar, aromatic, hydrophobic). Some amino acids have aromatic side chains (Phe, Tyr, Trp). Cross-reactivity is more likely when shape/chemistry resembles the hapten. Concept / Approach: Pair the DNP aromatic ring with amino acids that also present aromatic ring systems. Tyrosine and phenylalanine provide phenyl rings; tyrosine adds a phenolic OH, enabling potential π-stacking and hydrophobic interactions reminiscent of DNP’s ring. Step-by-Step Solution: 1) Identify the salient chemical feature of DNP: an aromatic ring.2) List amino acids with aromatic rings: phenylalanine, tyrosine, tryptophan.3) Select options containing aromatic side chains → Tyr or Phe fits best among the choices. Verification / Alternative check: Experimental binding assays often reveal weak binding of DNP-specific mAbs to other aromatic moieties compared with strong binding to DNP-conjugates, consistent with partial shape/chemistry overlap. Why Other Options Are Wrong: a) Aliphatic chains lack aromatic rings.b) Histidine’s imidazole differs; proline is non-aromatic.d) Ser/Thr are polar, non-aromatic.e) Basic aliphatic chains are non-aromatic. Common Pitfalls: Confusing hydrophobicity in general with aromatic ring recognition; not all hydrophobic residues mimic aromatic epitopes. Final Answer: Tyrosine or phenylalanine.

Question 4

Pathogenesis of AIDS — What is the primary reason AIDS is a deadly disease?

Accepted Answer

Introduction: Acquired immunodeficiency syndrome (AIDS) arises from chronic HIV infection culminating in profound immune dysfunction. The lethality of AIDS is linked to opportunistic infections and malignancies that flourish when adaptive immunity is compromised, not merely to the fact that a virus is present. Given Data / Assumptions: HIV targets CD4 T cells and myeloid lineage cells. Loss of CD4 help cripples both cellular and humoral arms. Opportunistic infections and certain cancers define AIDS. Concept / Approach: Identify the mechanistic cause of mortality: immune collapse. The disease’s severity stems from the destruction of immune coordination, leaving patients vulnerable to pathogens and tumors normally controlled by intact immunity. Step-by-Step Solution: 1) HIV infection reduces CD4 T-cell counts over time.2) With diminished CD4 help, B-cell class switching and CD8 responses are impaired.3) The host fails to contain opportunists (e.g., Pneumocystis, CMV) and oncogenic processes (e.g., Kaposi sarcoma). Verification / Alternative check: Effective antiretroviral therapy halts CD4 decline, reduces opportunistic disease, and lowers mortality, directly tying immune restoration to improved outcomes. Why Other Options Are Wrong: a) Viral causation alone does not explain lethality without immune destruction.b) AIDS is not bacterial.d,e) Oversimplify or misstate the spectrum of immune defects in AIDS. Common Pitfalls: Believing AIDS kills by direct viral cytolysis alone; the critical factor is systemic immune failure. Final Answer: Destruction of key immune components, especially CD4 T cells, causing immunodeficiency.

Question 5

Allergy mediators — Which chemical is typically released by the body during an acute allergic (type I hypersensitivity) reaction?

Accepted Answer

Introduction: Type I hypersensitivity (immediate allergy) involves IgE-sensitized mast cells and basophils that rapidly degranulate upon allergen cross-linking. Understanding the key mediators helps explain clinical signs such as itching, wheal-and-flare, bronchospasm, and hypotension. Given Data / Assumptions: Mast cells/basophils carry surface-bound IgE via FcεRI. Cross-linking by allergen triggers degranulation. Granules and lipid mediators cause vasodilation, increased permeability, and smooth muscle effects. Concept / Approach: Identify the canonical mediator stored preformed in granules: histamine. Distinguish histamine from external allergens, therapeutic antihistamines, cytotoxic proteins like perforin, and complement enzymes, which are not the immediate mast-cell mediator in classic allergy. Step-by-Step Solution: 1) Allergen binds IgE on mast cells → cross-linking.2) Degranulation releases histamine (and tryptase, heparin).3) Histamine acts on H1 receptors → vasodilation, permeability, pruritus, bronchoconstriction. Verification / Alternative check: Clinical efficacy of H1 antihistamines in urticaria and allergic rhinitis confirms histamine’s pivotal role in early-phase symptoms. Why Other Options Are Wrong: b) Allergens trigger the response; they are not released by the body as mediators.c) Antihistamines are drugs that block receptors, not endogenous mediators.d) Perforin is a cytotoxic granule protein from CD8/NK cells, not mast cells.e) Complement enzymes contribute to inflammation but are not the hallmark mast-cell mediator. Common Pitfalls: Confusing triggers with mediators; attributing cytotoxic granule proteins to allergic mast-cell responses. Final Answer: Histamine.

Question 6

Immunodeficiency vs autoimmunity — Which of the following is an example of an immunodeficiency disorder?

Accepted Answer

Introduction: Immune disorders can be broadly classified as excessive/misdirected (allergy, autoimmunity) or insufficient (immunodeficiency). This question checks your ability to distinguish examples of each category and identify a true immunodeficiency state. Given Data / Assumptions: AIDS results from acquired immune deficiency due to HIV. Autoimmune diseases feature immune attack on self tissues. Hypersensitivity reactions may be antibody-mediated or T-cell-mediated but are not deficiencies. Concept / Approach: Match each option to its category: immunodeficiency (lack of function) vs autoimmunity/hypersensitivity (misdirected/exaggerated function). Select the one that reflects deficient immunity. Step-by-Step Solution: 1) Evaluate AIDS → hallmark immunodeficiency with opportunistic infections.2) Thyroiditis and SLE → autoimmune diseases.3) Rheumatic fever → post-streptococcal autoimmune/hypersensitivity phenomenon.4) Contact dermatitis → T-cell-mediated hypersensitivity (type IV). Verification / Alternative check: Diagnostic criteria for AIDS rely on low CD4 counts and indicator infections, directly evidencing deficient immunity. Why Other Options Are Wrong: a,c) Autoimmune conditions with self-reactivity.b) Immune-mediated sequela, not deficiency.e) Hypersensitivity reaction, not deficiency. Common Pitfalls: Labeling any immune-related disease as “immunodeficiency” without considering whether function is excessive/misdirected vs absent. Final Answer: AIDS.

Question 7

HIV therapy challenge — What is a major reason antiretroviral drug treatment for HIV can fail over time without combination therapy and adherence?

Accepted Answer

Introduction: HIV has a high mutation rate due to error-prone reverse transcriptase and large population sizes, enabling rapid selection of resistant variants. Understanding resistance explains why combination antiretroviral therapy and adherence are critical to long-term viral suppression. Given Data / Assumptions: Reverse transcription lacks proofreading, generating diversity. Selective pressure from single-agent therapy favors resistant mutants. Protease, reverse transcriptase, and integrase inhibitors target essential viral enzymes. Concept / Approach: Connect viral mutability with target-based drugs: mutations in protease (or other targets) reduce inhibitor binding, conferring resistance. Combination therapy lowers the probability that a single variant is resistant to all drugs simultaneously. Step-by-Step Solution: 1) Consider HIV replication dynamics → frequent mutations.2) Apply drug pressure → resistant variants gain fitness advantage.3) Clinical outcome → virologic failure unless using potent combinations with good adherence. Verification / Alternative check: Genotypic resistance testing detects mutations in protease/RT/integrase correlating with reduced drug susceptibility; regimen changes based on these tests often restore suppression. Why Other Options Are Wrong: a) Potent inhibitors exist and are widely used.b) Adverse effects vary; disruption of digestion is not universal nor the primary barrier.d) Many agents have adequate half-lives; rapid universal degradation is false.e) HIV expresses proteins; enzyme inhibitors are effective until resistance emerges. Common Pitfalls: Underestimating adherence; assuming monotherapy suffices; overlooking the role of viral reservoirs but misattributing failure solely to drug instability. Final Answer: Resistance due to mutant viral enzymes, particularly protease, arising under drug pressure.

Question 8

Selective IgA deficiency — Which class of pathogens/problems would most likely increase in a patient lacking IgA?

Accepted Answer

Introduction: IgA is the dominant immunoglobulin at mucosal surfaces, where it neutralizes pathogens and toxins without inducing intense inflammation. Selective IgA deficiency is among the most common primary immunodeficiencies and predisposes patients to mucosal infections and some allergic/autoimmune phenomena. Given Data / Assumptions: Secretory IgA (sIgA) is transported across epithelia via the poly-Ig receptor. sIgA neutralizes microbes and toxins in the lumen at mucosal surfaces. Other isotypes (e.g., IgG, IgM) may partially compensate systemically but not fully at mucosa. Concept / Approach: Predict the clinical vulnerability based on the anatomic niche where IgA dominates. Loss of IgA mainly impairs first-line defense at respiratory, GI, and GU mucosa, leading to recurrent otitis media, sinusitis, bronchitis, diarrhea, and related infections. Step-by-Step Solution: 1) Identify IgA’s location and function → mucosal neutralization.2) Map likely pathogens → mucosal bacteria, viruses, and parasites that colonize these surfaces.3) Choose the option emphasizing mucosal risk across systems. Verification / Alternative check: Clinical cohorts show increased respiratory and GI infections and sometimes Giardia in IgA deficiency; serum IgG often remains normal, explaining relatively preserved systemic responses. Why Other Options Are Wrong: a) Deep tissue extracellular infections are less specifically linked to IgA loss.b) Transient bacteremia after procedures is more related to barrier disruption than IgA alone.d) Control of strictly intracellular pathogens relies on cell-mediated immunity.e) Eosinophils/IgE address helminths; IgA loss does not uniquely point to this. Common Pitfalls: Assuming serum antibody levels predict mucosal protection; overlooking the specialized transport and polymeric form (dimer) of sIgA. Final Answer: Mucosal pathogens at respiratory, gastrointestinal, and genitourinary surfaces.

Question 9

Clinical Immunology—Bone Marrow Transplant in SCID (Severe Combined Immunodeficiency) For an infant diagnosed with SCID who is receiving a bone marrow (hematopoietic stem cell) transplant, which condition is essential for the donor graft to minimize…

Accepted Answer

Introduction / Context: Severe Combined Immunodeficiency (SCID) is a life-threatening condition characterized by profound defects in T-cell function with variable B- and NK-cell impairment. Curative therapy often involves hematopoietic stem cell transplantation (HSCT). A central principle for HSCT success is appropriate donor–recipient MHC (HLA) matching to promote engraftment and reduce the risk of graft-versus-host disease (GVHD). This question tests understanding of which requirement is essential (“must”) for bone marrow given to an infant with SCID. Given Data / Assumptions: Recipient: infant with SCID requiring HSCT. Outcome goals: successful engraftment, immune reconstitution, low GVHD risk. Clinical practice emphasizes HLA compatibility and careful management of mature donor T cells. Concept / Approach: HSCT success hinges on matching histocompatibility antigens (MHC/HLA). T-cell allorecognition of mismatched HLA is a primary driver of GVHD. While partial (haploidentical) related donors can be used with T-cell depletion, some level of HLA matching remains indispensable to balance engraftment and GVHD risk. Irradiating the graft itself would destroy stem cells; instead, selective T-cell depletion or careful donor selection is used to manage GVHD risk. Step-by-Step Solution: Step 1: Identify the non-negotiable factor for engraftment and GVHD mitigation: compatibility at key HLA loci.Step 2: Evaluate “irradiated graft”: irradiation would ablate stem cell viability, so this is not standard practice for the graft (blood products for SCID may be irradiated to prevent transfusion-associated GVHD, but not the stem-cell graft).Step 3: Evaluate “mature T cells must be present”: mature donor T cells increase GVHD risk; many protocols purposefully deplete them.Step 4: Evaluate “must come from a parent”: parents are convenient haploidentical donors but a matched sibling or unrelated HLA-matched donor is often preferable; thus “parent” is not mandatory. Verification / Alternative check: Clinical HSCT protocols prioritize highest feasible HLA match; where full match is impossible, graft manipulation (e.g., T-cell depletion) is performed, underscoring that HLA matching is the indispensable requirement. Why Other Options Are Wrong: Irradiating the graft would inactivate stem cells. Including many mature T cells heightens GVHD risk. Requiring a parent donor is unnecessary; matched sibling/unrelated donors are acceptable. B-cell depletion alone does not address GVHD risk; T cells are the main concern. Common Pitfalls: Confusing irradiated blood products with irradiating the stem-cell graft; assuming kinship guarantees better outcomes regardless of HLA matching. Final Answer: Come from a donor who shares key MHC (HLA) alleles with the recipient

Question 10

Immunodeficiency—Combined Cellular and Humoral Defects Combined T- and B-cell immune deficiencies can result from the absence of several components. Which of the following is the EXCEPTION (least likely to cause a combined deficiency)?

Accepted Answer

Introduction / Context: Combined immunodeficiencies involve impaired cellular (T-cell) and humoral (B-cell) arms because B-cell responses depend on T-cell help for effective isotype switching, affinity maturation, and memory formation. This question asks you to identify which listed defect would NOT typically produce a combined deficiency pattern. Given Data / Assumptions: Thymus absence → few/absent mature T cells → poor T-dependent antibody responses. Class II MHC deficiency → defective positive selection/activation of CD4+ T cells → profound help deficiency for B cells. HIV infection of CD4+ T cells → loss of T-cell help → impaired humoral immunity. TAP deficiency → low class I surface expression and poor CD8+ T-cell selection. Concept / Approach: Pick the defect that is primarily restricted to CD8+ T-cell development and cytotoxic responses (class I pathway) but leaves CD4+ T-cell help and B-cell function relatively intact. TAP deficiency fits this description, often presenting with recurrent infections but not a classic “combined” humoral defect pattern like class II deficiency or thymic aplasia. Step-by-Step Solution: Step 1: Recognize that lack of thymus and class II MHC cripple CD4+ T-cell function, leading to combined deficiencies.Step 2: Recognize that HIV destroys CD4+ T cells, again yielding combined defects.Step 3: Identify TAP deficiency as primarily affecting CD8+ T-cell maturation and antigen presentation on class I, with less direct impact on T-dependent B-cell responses.Step 4: Therefore, TAP deficiency is the exception. Verification / Alternative check: Clinical immunology texts describe class II deficiency and thymic aplasia as causing severe combined defects; TAP deficiency is categorized as a type of MHC class I deficiency with characteristic CD8 lymphopenia but often near-normal immunoglobulins. Why Other Options Are Wrong: Thymus absence: eliminates T-cell education → combined defect. Class II absence: eliminates CD4+ T help → combined defect. HIV of CD4+ T cells: hallmark combined deficiency. Common γ chain absence (listed as E): causes X-linked SCID → classic combined defect. Common Pitfalls: Assuming any antigen-presentation defect automatically causes combined humoral failure; it is specifically lack of CD4+ T-cell help that collapses B-cell function. Final Answer: Transporter associated with antigen processing (TAP) is absent

Question 11

Oncogenes—Rous Sarcoma Virus (RSV) and Cellular Homologs Which entry names the NORMAL cellular homolog that corresponds to the RSV oncogene src?

Accepted Answer

Introduction / Context: Retroviral oncogenes (v-onc) often derive from captured cellular proto-oncogenes (c-onc) that regulate normal growth signaling. Rous sarcoma virus (RSV) carries the viral oncogene v-src, a constitutively active tyrosine kinase. The question tests recognition of the naming relationship between viral oncogenes and their cellular homologs. Given Data / Assumptions: RSV oncogene: v-src. Normal cellular counterpart: c-src (proto-oncogene encoding a regulated tyrosine kinase). Other viral tags (e.g., v-ras) correspond to different cellular genes (c-ras), not src. Concept / Approach: Match “v-src” (viral) with “c-src” (cellular). The “v-” prefix denotes a viral oncogene usually mutated/truncated; “c-” denotes the proto-oncogene in normal cells. Therefore the correct answer is the cellular homolog c-src, not the viral forms listed. Step-by-Step Solution: Step 1: Identify the RSV gene: v-src.Step 2: Recall that normal cellular homologs bear the “c-” prefix.Step 3: Select c-src as the cellular homolog. Verification / Alternative check: Classic molecular oncology texts map v-src back to c-src, with transformation arising from mutations that disrupt normal regulation. Why Other Options Are Wrong: v-src and v-ha-src: viral, not cellular homologs. v-ha-ras and c-ras concern ras, not src. Common Pitfalls: Confusing viral vs cellular prefixes; mixing src and ras families. Final Answer: c-src

Question 12

Gene Therapy—Barriers to Somatic Gene Transfer Somatic gene therapy faces multiple technical and biological hurdles. Which of the following is the EXCEPTION (least relevant difficulty for gene therapy itself)?

Accepted Answer

Introduction / Context: Somatic gene therapy aims to correct genetic defects by delivering functional genes into a patient’s cells. Success depends on safe, stable gene delivery and expression in appropriate target cells—often hematopoietic stem cells for systemic disorders. The question asks you to identify which listed issue is not a core difficulty of gene therapy itself. Given Data / Assumptions: Gene addition strategies use viral/nonviral vectors. Long-term correction generally requires stem-cell targeting. Transduction efficiency, insertional safety, and expression control are central problems. GVHD is primarily a complication of allogeneic cellular grafts (e.g., HSCT), not of autologous gene-corrected cells. Concept / Approach: Differentiate challenges specific to gene transfer/expression from complications of allogeneic transplantation. Autologous gene therapy typically uses the patient’s own cells after ex vivo modification, thereby largely avoiding GVHD. In contrast, issues such as site-specific integration, promoter choice, vector tropism, and stem-cell transduction efficiency are intrinsic hurdles for gene therapy. Step-by-Step Solution: Step 1: Recognize that proper gene insertion and regulated expression (B, E) are fundamental.Step 2: Recognize that mature cell short lifespan (C) motivates stem-cell targeting.Step 3: Efficient stem-cell transduction (D) is a notorious bottleneck.Step 4: GVHD (A) is not inherent to autologous somatic gene therapy; hence it is the exception. Verification / Alternative check: Clinical gene therapy protocols overwhelmingly use autologous cells to avoid allo-immune reactions; GVHD belongs to allogeneic HSCT risk profiles. Why Other Options Are Wrong: B/D/E are classic gene therapy challenges. C explains why stem-cell targeting is preferred for durable benefit. Common Pitfalls: Conflating HSCT complications with autologous gene-modified cell therapies. Final Answer: GVHD caused by mature T cells present in transplanted cells

Question 13

Immunology—X-Linked Hyper-IgM (CD40L Deficiency) In X-linked hyper IgM syndrome caused by defective CD40L on T helper cells, which specific immune interaction is PREVENTED?

Accepted Answer

Introduction / Context: X-linked hyper IgM syndrome (HIGM) is classically due to mutations in CD40 ligand (CD40L, CD154) on activated CD4+ T cells. CD40L is essential for cognate T–B interactions that drive isotype (class) switching and germinal center formation. Patients have high/normal IgM but very low IgG, IgA, and IgE, with susceptibility to opportunistic infections. This item asks which precise immune event is blocked when CD40L is defective. Given Data / Assumptions: CD40L on Th cells binds CD40 on B cells and dendritic cells. CD40 signaling in B cells is necessary for class switching and germinal center reactions. T-independent antigens can activate B cells without T-cell help. Concept / Approach: Identify the CD40L-dependent step: T-cell help to B cells for isotype switching. Without CD40L–CD40 engagement, activation-induced cytidine deaminase (AID)–dependent class switching fails, trapping responses in the IgM isotype and impairing affinity maturation. Step-by-Step Solution: Step 1: Map the interaction: Th cell CD40L ↔ B-cell CD40 → signals for switching.Step 2: Determine outcomes: absent switching → low IgG/IgA/IgE; often normal/high IgM.Step 3: Select the option that directly names the missing co-stimulatory help for isotype switching. Verification / Alternative check: Clinical phenotypes and in vitro studies of CD40L deficiency show failure to form germinal centers and to switch isotypes despite presence of B cells. Why Other Options Are Wrong: A: T-independent activation does not require CD40L. B: Inverting the direction of co-stimulation; B → Th co-stimulation is not the central defect in HIGM. D: B-cell proliferation can occur via other signals (e.g., TLRs, BCR with cytokines), though germinal center proliferation is impaired. E: IgM assembly is intact; the problem is switching away from IgM. Common Pitfalls: Assuming all B-cell activation requires T-cell help; confusing general proliferation with the specific requirement for CD40L in class switching. Final Answer: Provision of CD40L-dependent co-stimulation by Th cells that is required for B-cell isotype switching

Question 14

Autoimmunity—Identify the Disease Which of the following is an autoimmune disease characterized by multisystem involvement and autoantibodies (e.g., anti-dsDNA, anti-Sm)?

Accepted Answer

Introduction / Context: Autoimmune diseases arise when immune tolerance fails and self-reactive lymphocytes cause tissue damage. Systemic lupus erythematosus (SLE) is a prototypical systemic autoimmune disease with diverse clinical features and hallmark autoantibodies. This item differentiates autoimmune disease from infectious diseases and immunodeficiency syndromes. Given Data / Assumptions: SLE involves immune complex deposition and complement activation. AIDS results from HIV infection and progressive immunodeficiency, not autoimmunity. Measles, mumps, influenza are viral infections, not autoimmune disorders. Concept / Approach: Identify which option depicts an autoimmune pathology rather than an infection or immunodeficiency. SLE uniquely fits, with chronic relapsing disease, multi-organ involvement (skin, kidneys, joints, CNS), and serologies such as ANA, anti-dsDNA, and anti-Sm antibodies. Step-by-Step Solution: Step 1: Exclude infections (measles, mumps, influenza).Step 2: Exclude AIDS (immunodeficiency secondary to HIV rather than autoimmunity).Step 3: Select lupus as the autoimmune disease. Verification / Alternative check: Diagnostic criteria include clinical and immunologic domains; serologic testing often reveals anti-dsDNA with low complement levels during flares. Why Other Options Are Wrong: AIDS: acquired immunodeficiency, not autoimmune. Measles/Mumps/Influenza: acute viral infections. Common Pitfalls: Equating chronicity with autoimmunity; many chronic infections are not autoimmune. Final Answer: Lupus (systemic lupus erythematosus)

Question 15

Cancer Genetics—Chromosomal Translocations Specific, recurrent chromosomal translocations are classically associated with which category of malignancy?

Accepted Answer

Introduction / Context: Balanced chromosomal translocations can create fusion genes or dysregulate oncogene expression. These events are particularly characteristic of hematologic malignancies, where they serve as diagnostic markers, prognostic indicators, and therapeutic targets. The question asks which tumor category most classically shows specific translocations. Given Data / Assumptions: Examples: t(9;22)(BCR-ABL) in chronic myeloid leukemia; t(15;17)(PML-RARA) in acute promyelocytic leukemia; t(8;14)(MYC-IgH) in Burkitt lymphoma. Solid tumors often harbor copy-number changes and point mutations; some also have translocations, but specificity is most iconic in leukemias/lymphomas. Concept / Approach: Match the hallmark genetic mechanism with tumor categories. Recurrent, lineage-defining translocations are typical of leukemias and lymphomas; thus “some leukemias” is the best answer among the options provided. Step-by-Step Solution: Step 1: Recall canonical translocations in hematologic cancers.Step 2: Compare with common genetics of colon, breast, and pancreatic cancers (more often point mutations, CNVs, and structural variants without pathognomonic balanced translocations).Step 3: Choose leukemias. Verification / Alternative check: Diagnostic practice uses FISH/RT-PCR for fusion transcripts in leukemias to guide targeted therapy (e.g., ATRA/arsenic for PML-RARA). Why Other Options Are Wrong: Colon/breast/pancreatic cancers: while structural variants exist, classic, highly recurrent translocations are less emblematic. Benign tumors rarely show hallmark balanced translocations used diagnostically. Common Pitfalls: Over-generalizing from rare solid-tumor translocations to all solid tumors. Final Answer: Some leukemias

Question 16

Innate Immunity—Chronic Granulomatous Disease (CGD) CGD results from failure of the phagocyte oxidative burst (NADPH oxidase). Which host defense mechanism is most directly impaired?

Accepted Answer

Introduction / Context: Chronic Granulomatous Disease (CGD) is caused by defects in the NADPH oxidase complex that generates reactive oxygen species (ROS) within phagolysosomes. Without an oxidative burst, phagocytes can ingest microbes but have difficulty killing catalase-positive organisms, leading to recurrent infections and granuloma formation. This item targets the specific immune function that fails in CGD. Given Data / Assumptions: NADPH oxidase → superoxide → downstream ROS crucial for microbial killing. Phagocytosis is intact; intracellular killing is impaired. Greatest susceptibility to catalase-positive pathogens (e.g., Staphylococcus aureus, Serratia marcescens). Concept / Approach: Distinguish between uptake (phagocytosis) and killing (oxidative burst). CGD primarily disrupts the killing phase inside neutrophils/macrophages. T-cell cytotoxicity, antigen processing for MHC I, and NK recognition are separate pathways and are not the direct deficit in CGD. Step-by-Step Solution: Step 1: Identify the defective machinery: NADPH oxidase in phagocytes.Step 2: Map the functional consequence: absent ROS → poor intraphagosomal killing.Step 3: Choose the option that explicitly states “intracellular killing of bacteria after phagocytosis.” Verification / Alternative check: DHR (dihydrorhodamine) flow cytometry shows reduced oxidative burst in CGD; nitroblue tetrazolium (NBT) test historically used shows failure to reduce dye. Why Other Options Are Wrong: CTL killing, DC maturation, MHC I processing, NK recognition: not primarily dependent on phagocyte oxidative burst. Common Pitfalls: Confusing failure of phagocytosis with failure of killing; overlooking the catalase-positive pathogen pattern. Final Answer: Macrophage/neutrophil intracellular killing of bacteria after phagocytosis

Question 17

Pediatric Immunity—Maternal IgG and the Physiologic Nadir Infants are especially susceptible to bacterial infections when circulating IgG levels are lowest. During which age window is this susceptibility greatest?

Accepted Answer

Introduction / Context: Passive maternal IgG is actively transported across the placenta and protects the newborn for several months. Endogenous IgG production in the infant increases gradually. A “physiologic nadir” in total IgG occurs when maternal IgG has decayed but the infant’s own IgG has not fully risen, increasing susceptibility to pyogenic bacterial infections. This question identifies that window. Given Data / Assumptions: Maternal IgG half-life ≈ 21–30 days; substantial decline by 3–6 months. Infant IgG synthesis rises through the first year of life. Risk of encapsulated bacterial infections increases as maternal antibodies wane. Concept / Approach: Locate the overlap between waning maternal IgG and still-developing endogenous production. Most sources place the nadir around 3–6 months, with generally increased susceptibility spanning roughly 3–12 months; hence option C best captures the clinically relevant window among the choices provided. Step-by-Step Solution: Step 1: Maternal IgG protects through early months (highest at birth).Step 2: By ~3 months, maternal IgG has fallen considerably; infant IgG is rising but still low.Step 3: Choose 3–12 months as the period of greatest susceptibility among the given bands. Verification / Alternative check: Pediatric immunology references describe the physiologic hypogammaglobulinemia of infancy peaking around 3–6 months, with vulnerability extending into later infancy. Why Other Options Are Wrong: In utero: maternal IgG is high; fetus is protected. 0–3 months: antibody levels still relatively protective. 12–24 months and beyond: endogenous Ig production is stronger. Common Pitfalls: Assuming protection monotonically increases from birth; forgetting the transient nadir. Final Answer: 3–12 months of age

Question 18

Tumor Suppressors—Retinoblastoma Genetics Retinoblastoma in children most commonly results from mutation in which class of gene?

Accepted Answer

Introduction / Context: Retinoblastoma is a pediatric eye tumor that provided the classic model for tumor suppressor gene function and the “two-hit hypothesis.” The RB1 gene encodes the retinoblastoma protein (pRB), a negative regulator of the G1→S transition in the cell cycle. This item asks you to identify the gene class most directly implicated in retinoblastoma pathogenesis. Given Data / Assumptions: RB1 loss leads to uncontrolled E2F activity and cell-cycle progression. Hereditary cases inherit one mutant RB1 allele and acquire a second somatic hit. Concept / Approach: Decide whether the driver is activation of an oncogene or loss of a tumor suppressor. Retinoblastoma arises from biallelic inactivation of RB1, making it the prototypical tumor suppressor gene–driven cancer. Step-by-Step Solution: Step 1: Recall pRB function: inhibits E2F, restraining G1→S transition.Step 2: Loss of RB1 removes this brake, enabling proliferation.Step 3: Select “tumor suppressor (loss of RB1)” as the correct class. Verification / Alternative check: Knudson’s two-hit model was formulated from bilateral vs unilateral retinoblastoma data, consistent with tumor suppressor loss rather than oncogene activation alone. Why Other Options Are Wrong: Kinase/cyclin activation are oncogene mechanisms but are not the hallmark initiating lesion in retinoblastoma. Oncogenic viruses are not the primary cause here. GPCR activation is not the canonical driver. Common Pitfalls: Confusing oncogene gain-of-function with tumor suppressor loss-of-function; forgetting the two-hit requirement. Final Answer: Tumor suppressor (loss of RB1 function)

Question 19

Immunology – DiGeorge's syndrome is characterized by congenital absence or severe hypoplasia of the thymus (T-cell deficiency). Which mouse model most closely mimics this human condition for experimental study?

Accepted Answer

Introduction: DiGeorge's syndrome (22q11.2 deletion syndrome) classically involves thymic aplasia or hypoplasia, leading to profound T-cell immunodeficiency. To study T-cell–dependent immunity, researchers often turn to mouse models that reproduce an absent or nonfunctional thymus. This question asks which mouse strain most faithfully mirrors the thymic defect of DiGeorge's syndrome. Given Data / Assumptions: DiGeorge's syndrome presents with absent/underdeveloped thymus and reduced mature T cells. Mouse strains differ in the specific immune components that are defective. We want the closest phenotypic match for thymic absence and T-cell deficiency. Concept / Approach: The nude mouse carries a Foxn1 mutation causing athymia (no thymic epithelium), resulting in a severe quantitative and functional deficit of T cells, while leaving B cells largely present but lacking T-cell help. This mirrors the thymic abnormality in DiGeorge's. By contrast, RAG-1/2 knockout mice cannot perform V(D)J recombination and therefore lack both T and B cells, which is broader than the typical DiGeorge profile. CD3 alterations affect TCR signaling rather than thymus development per se. Step-by-Step Solution: Identify hallmark of DiGeorge's: thymic aplasia → T-cell deficiency.Map to mouse models: Nude mouse = athymic due to Foxn1 mutation.Exclude broader defects: RAG-1/2 KO = no T or B cells, not a pure thymus-development model.Conclude: Nude (athymic) mouse best models DiGeorge's T-cell defect. Verification / Alternative check: Phenotyping of nude mice shows near absence of mature peripheral T cells with intact B-cell development but impaired T-dependent responses, paralleling thymic aplasia syndromes. Adoptive thymic transplantation rescues T-cell development, confirming the thymus-centric defect. Why Other Options Are Wrong: Knockout mouse lacking RAG-1 and RAG-2: abolishes both T and B lymphocytes; not specific to thymus. “Mouse without a thymus”: vague, not a standard defined model; lacks mechanistic similarity. Recombinant mouse altering CD3: affects signaling; does not inherently remove the thymus. Severe macrophage-deficient mouse: defects are innate, not thymus/T-cell development. Common Pitfalls: Equating global lymphopenia (RAG KO) with thymic aplasia, or assuming any T-cell signaling defect models thymus absence. Final Answer: Nude (athymic) mouse with Foxn1 mutation

Disease Associated with Immune System Questions