Question 1

Cell-mediated immunity (CMI): In which of the following immunologic scenarios does CMI play a central and necessary role?

Accepted Answer

Introduction / Context: Cell-mediated immunity (CMI) is driven primarily by T lymphocytes and activated macrophages rather than by circulating antibodies. Recognizing clinical settings where CMI dominates helps clinicians anticipate pathology and select appropriate diagnostic tests or therapies. Given Data / Assumptions: Delayed-type hypersensitivity (DTH) is a T cell–mediated response. Allograft rejection requires T cell recognition of foreign MHC/peptides. Graft-versus-host reaction arises from donor T cells attacking host tissues. Concept / Approach: CMI involves CD4+ Th1 cells, CD8+ cytotoxic T cells, and activated macrophages. DTH (e.g., tuberculin skin test) is a hallmark Th1-mediated reaction. Transplant immunology centers on T cell recognition leading to cytotoxicity and cytokine-mediated damage. GVH is likewise T cell driven, but initiated by donor cells in an immunocompromised host. Step-by-Step Solution: Map each listed condition to T cell–mediated mechanisms. Confirm antibody is not the primary effector in these processes. Integrate the three scenarios under the umbrella of CMI. Choose the inclusive option “All of the above.” Verification / Alternative check: Histology of rejected grafts and GVH lesions shows T cell infiltration and cytokine signatures. DTH testing relies on T cell memory rather than serum antibody levels. Why Other Options Are Wrong: Any single choice alone is incomplete. Immediate hypersensitivity only: Type I hypersensitivity is IgE-mediated and not representative of CMI. Common Pitfalls: Confusing Type II/III antibody-mediated reactions with CMI; transplant and DTH reactions are classic T cell phenomena. Final Answer: All of the above.

Question 2

Cytokines in delayed-type hypersensitivity (DTH): Which lymphokines are secreted by DTH (Th1) cells to modulate macrophage function and cell migration?

Accepted Answer

Introduction / Context: Delayed-type hypersensitivity (Type IV) reactions are orchestrated by Th1 cells that secrete cytokines to recruit, retain, and activate macrophages at the site of antigen exposure. Understanding which mediators are produced clarifies the cellular mechanisms underlying granuloma formation and tuberculin skin tests. Given Data / Assumptions: DTH involves cytokines that influence macrophage behavior and leukocyte trafficking. Nomenclature may vary, but functions include activation, stimulation, and migration inhibition. Th1 profile (e.g., IFN-gamma, IL-2) underlies these effects. Concept / Approach: Th1 cells produce interferon-gamma, which activates macrophages (macrophage activating factor effect). Additional factors historically termed migration inhibiting factor limit macrophage egress, concentrating them at the lesion. Collectively, these cytokines enhance microbicidal activity, antigen presentation, and tissue inflammation characteristic of DTH. Step-by-Step Solution: Associate Th1 cytokines with macrophage activation and retention. Recognize historical terms (e.g., MIF) describing these functions. Acknowledge overlapping nomenclature but similar functional outcomes. Select the inclusive option indicating all are secreted. Verification / Alternative check: Experimental models show that blocking IFN-gamma reduces macrophage activation and abrogates DTH lesions, underscoring the Th1 cytokine axis. Why Other Options Are Wrong: Single mediators alone do not reflect the coordinated Th1 response. Interleukin-4 only: More typical of Th2 responses, not DTH. Common Pitfalls: Assuming one cytokine is solely responsible; DTH is polycytokine-driven with synergistic effects on macrophages. Final Answer: All of the above.

Question 3

T-helper cell dysregulation: Excessive activity of helper T (Th) cells is most likely to lead to which clinical-immunological outcome?

Accepted Answer

Introduction / Context: T-helper (Th) cells coordinate immune responses by delivering help to B cells and activating macrophages and cytotoxic T cells. While essential for defense, overactive or dysregulated Th responses can break self-tolerance and drive autoimmune disease. Given Data / Assumptions: Overactivity implies heightened cytokine production and co-stimulation. Loss of regulatory balance (e.g., Treg insufficiency) is a common backdrop. Outcome of interest is pathological, not healthy optimization. Concept / Approach: Excess Th1/Th17 responses can perpetuate chronic inflammation and autoreactive lymphocyte activation, resulting in tissue damage (e.g., in rheumatoid arthritis, multiple sclerosis, psoriasis). Th cell help also accelerates class switching and affinity maturation of autoreactive B cells, amplifying autoantibody production and immune complex disease. Step-by-Step Solution: Define “overactivity” as pathologically increased Th help and cytokines. Connect this to enhanced activation of autoreactive clones. Recognize clinical manifestation: autoimmune pathology. Choose autoimmunity as the likely consequence. Verification / Alternative check: Therapies that dampen Th signaling (e.g., anti–IL-17, anti–IL-6, CTLA-4–Ig) alleviate autoimmune diseases, validating the causal role of excessive Th activity. Why Other Options Are Wrong: Optimal responses without pathology: Describe healthy regulation, not overactivity. None of the above / Immunodeficiency: Overactivity leads to inflammation and autoimmunity, not deficiency. Common Pitfalls: Ignoring the role of regulatory T cells; autoimmunity often reflects imbalance between effector Th and Treg compartments. Final Answer: Autoimmunity.

Question 4

Therapeutic immunology: Which of the following are used clinically as immunosuppressive agents to dampen unwanted immune responses (e.g., after transplantation or in autoimmune disease)?

Accepted Answer

Introduction / Context: Immunosuppressive therapies are essential to prevent transplant rejection and to treat autoimmune and inflammatory disorders. Different agents act at distinct points in lymphocyte activation, proliferation, or survival. Given Data / Assumptions: We are considering standard clinical agents that reduce immune activity. Multiple drug classes with different mechanisms exist. Choice focuses on whether each listed item is used for immunosuppression. Concept / Approach: Cyclosporine inhibits calcineurin, blocking IL-2 transcription and T cell activation. Methotrexate, at immunomodulatory doses, inhibits folate-dependent pathways and exerts anti-proliferative and anti-inflammatory effects (elevates adenosine), widely used in rheumatology. Anti-lymphocytic (anti-thymocyte) serum contains polyclonal antibodies that deplete T cells, used in transplant induction or rejection episodes. Step-by-Step Solution: Evaluate each agent's known immunosuppressive mechanism. Confirm clinical use in transplantation or autoimmunity. Recognize that all three qualify as immunosuppressants. Select “All of these.” Verification / Alternative check: Guidelines for solid-organ transplantation and autoimmune disease management list these agents among recommended therapies, confirming their immunosuppressive status. Why Other Options Are Wrong: Any single option omits other valid agents. Erythropoietin only: Primarily hematopoietic; not an immunosuppressant. Common Pitfalls: Assuming methotrexate is purely chemotherapeutic; at low doses it is a mainstay disease-modifying antirheumatic drug with immunomodulatory effects. Final Answer: All of these.

Question 5

Immunological tolerance: Which mechanisms contribute to the induction and maintenance of immunological tolerance to self antigens?

Accepted Answer

Introduction / Context: Immunological tolerance prevents destructive responses against self tissues. Multiple, non-redundant mechanisms operate at different stages of lymphocyte development and activation to enforce self-tolerance and avert autoimmunity. Given Data / Assumptions: Tolerance occurs centrally (thymus/bone marrow) and peripherally (secondary lymphoid tissues). Mechanisms may delete, silence, or actively suppress self-reactive lymphocytes. Physiologic conditions are considered, not experimental ablations. Concept / Approach: Clonal deletion removes strongly self-reactive T and B cells during development (negative selection) or in the periphery via apoptosis. Clonal anergy renders lymphocytes unresponsive when antigen is encountered without adequate co-stimulation or in the presence of inhibitory signals. Suppression by regulatory T cells (Treg) actively maintains tolerance through cytokines (e.g., IL-10, TGF-beta), metabolic disruption, and inhibitory receptor engagement. Step-by-Step Solution: Enumerate the main tolerance mechanisms: deletion, anergy, suppression. Associate each with its operational context (central vs. peripheral). Recognize their complementary roles in preventing autoimmunity. Choose the inclusive option indicating all mechanisms contribute. Verification / Alternative check: Genetic defects in Treg pathways (e.g., FOXP3) or failures in deletion/anergy correlate with severe autoimmune syndromes, underscoring the necessity of all three strategies. Why Other Options Are Wrong: Any single mechanism alone is insufficient to explain physiological tolerance breadth. Somatic hypermutation only: Increases antibody affinity; does not induce tolerance. Common Pitfalls: Overemphasizing central deletion while neglecting peripheral regulation; self-tolerance is safeguarded at multiple checkpoints. Final Answer: All of these.

Question 6

Immunology – identifying the negative phase In immunology, the phenomenon known as the “negative phase,” which represents a transient fall in antibody levels immediately after antigen exposure, is most prominently observed in which type of humoral i…

Accepted Answer

Introduction / Context: The immune system exhibits different patterns of antibody response depending on whether the body is encountering an antigen for the first time (primary response) or during subsequent exposures (secondary response). A key phenomenon to understand is the “negative phase,” which refers to an initial dip in circulating antibody levels after antigen introduction. Given Data / Assumptions: Antibody titers can fluctuate after antigen administration. Primary responses differ from secondary in timing and magnitude. Negative phase describes the short period of antibody decline before synthesis of new antibodies begins. Concept / Approach: In the primary immune response, existing natural antibodies (low-affinity IgM) may bind the introduced antigen, forming immune complexes. This temporarily reduces measurable free antibody levels, producing the negative phase. Later, B-cell activation and clonal expansion lead to rising IgM and IgG levels. In secondary responses, memory B cells rapidly generate antibodies, typically masking or eliminating any negative phase. Step-by-Step Solution: Step 1: Define negative phase = transient decline in antibody titer post-antigen exposure.Step 2: Link to mechanism: antigen binding clears pre-existing antibodies.Step 3: Identify context: occurs during first exposure, i.e., primary humoral response.Step 4: Conclude that the correct answer is “Primary humoral response.” Verification / Alternative check: Experimental antibody titer curves show a brief dip in antibody concentration before the classic lag, log, plateau, and decline phases of the primary response. Why Other Options Are Wrong: Secondary response: rapid IgG rise, no clear negative phase. Both: not correct; it is characteristic of the primary response. None: incorrect, because the negative phase is well-documented in primary responses. CMI only: irrelevant; negative phase refers specifically to antibody titers. Common Pitfalls: Confusing the “lag phase” with the “negative phase.” The lag phase is the delay before antibody increase, while the negative phase specifically refers to the transient decline in circulating antibodies. Final Answer: Primary humoral response.

Question 7

Immunology – classification of eye lens antigens Lens antigens of the eye, which are normally hidden from immune recognition under physiological conditions, are best described as:

Accepted Answer

Introduction / Context: Certain body sites (eye, brain, testis) are immunologically privileged, meaning their antigens are isolated from the immune system under normal conditions. Eye lens proteins provide a classical example. Given Data / Assumptions: Lens proteins are not normally exposed to immune surveillance. Exposure may occur after trauma or surgery. Immune response against these antigens may lead to autoimmunity. Concept / Approach: Sequestrated antigens are hidden (sequestered) in anatomical locations without lymphatic drainage or exposure. When released, they can be recognized as “foreign” by the immune system despite being self-antigens, provoking autoimmunity. This is distinct from cross-reacting antigens (shared epitopes with microbes) and neoantigens (new epitopes created by mutation or chemical alteration). Step-by-Step Solution: Step 1: Define sequestrated antigens as self-antigens normally hidden from immune system.Step 2: Identify lens proteins as such an example.Step 3: Select “Sequestrated antigens” as correct. Verification / Alternative check: Clinical examples include sympathetic ophthalmia, an autoimmune condition triggered by lens antigen exposure following ocular injury. Why Other Options Are Wrong: Cross-reacting antigens: involve mimicry with microbial epitopes, not sequestration. Neoantigens: result from mutations or modifications, not anatomical sequestration. None: incorrect because sequestration is a well-established category. Self-antigens with molecular mimicry: different mechanism, not sequestration. Common Pitfalls: Confusing sequestrated with cross-reactive antigens; only sequestrated antigens are physically hidden from immune surveillance. Final Answer: Sequestrated antigens.

Question 8

Autoimmune diseases – recognizing classic examples Which of the following conditions are recognized examples of autoimmune disease in clinical immunology?

Accepted Answer

Introduction / Context: Autoimmune diseases arise when the immune system loses tolerance to self-antigens and mounts pathogenic responses against host tissues. Recognizing prototypical examples is essential for clinicians, microbiologists, and exam candidates. Given Data / Assumptions: Autoimmunity includes organ-specific and systemic disorders. Multiple immune mechanisms may be involved (autoantibodies, immune complexes, T-cell–mediated injury). The listed conditions are common textbook entities. Concept / Approach: Rheumatoid arthritis involves autoantibodies (e.g., rheumatoid factor, anti-CCP) and synovial inflammation. Systemic lupus erythematosus is a systemic immune complex disease with diverse autoantibodies (ANA, anti-dsDNA, anti-Sm). Polyarteritis nodosa is a necrotizing vasculitis of medium-sized arteries often associated with immune-mediated injury. Because each is a well-established autoimmune disorder, the inclusive option is correct. Step-by-Step Solution: Identify each listed disease and its autoimmune basis.Confirm that all three are standard autoimmune exemplars.Select “All of the above.” Verification / Alternative check: Standard rheumatology and immunology texts classify RA, SLE, and PAN as autoimmune, supporting the selection. Why Other Options Are Wrong: Individual options (RA, SLE, PAN) are correct but incomplete. “None” contradicts established nosology. Common Pitfalls: Confusing PAN with ANCA-associated vasculitides; PAN is classically ANCA-negative but still immune-mediated and placed within autoimmune/immune complex disorders. Final Answer: All of the above.

Question 9

Assessing cell-mediated immunity (CMI) Which of the following laboratory or clinical methods can be used to detect or evaluate T-cell–mediated (cell-mediated) immune responses in humans?

Accepted Answer

Introduction / Context: Cell-mediated immunity (CMI) encompasses T-cell effector functions such as delayed-type hypersensitivity, macrophage activation, and cytotoxic T-lymphocyte (CTL)–mediated lysis. Measuring CMI is important in diagnosing infections, immune deficiencies, and vaccine take. Given Data / Assumptions: CMI testing focuses on T-cell–dependent reactions. Both in vivo and in vitro methods exist. Humoral assays alone do not directly reflect CMI. Concept / Approach: Migration inhibition assays measure lymphokine-mediated suppression of leukocyte migration. CTL assays quantify target cell killing by antigen-specific T cells. Delayed-type hypersensitivity skin tests (e.g., PPD) reflect antigen-specific memory T-cell activity in vivo. Because all three evaluate T-cell–dependent responses, the most inclusive answer is correct. Step-by-Step Solution: Map each method to a T-cell function (cytokine release, cytotoxicity, DTH).Recognize that each provides evidence of CMI.Choose “All of the above.” Verification / Alternative check: Clinical immunology practice routinely uses DTH skin testing; research labs employ CTL assays and migration inhibition as functional readouts. Why Other Options Are Wrong: Each single method is valid but incomplete alone. Complement fixation assesses antibodies and complement activation, not CMI. Common Pitfalls: Equating antibody titers with CMI; humoral immunity is distinct from T-cell–mediated mechanisms. Final Answer: All of the above.

Immune Response Questions