1Which antibody class primarily mediates type I hypersensitivity reactions?
type I hypersensitivity
Easy
A.IgG
B.IgE
C.IgM
D.IgA
Correct Answer: IgE
Explanation:
Type I (immediate) hypersensitivity is mediated by IgE antibodies bound to mast cells and basophils, triggering their degranulation on allergen exposure.
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2Which cell releases histamine during a type I hypersensitivity reaction?
type I hypersensitivity
Easy
A.Mast cell
B.Cytotoxic T cell
C.Neutrophil
D.Plasma cell
Correct Answer: Mast cell
Explanation:
Mast cells (and basophils) degranulate and release histamine and other mediators when allergen cross-links IgE bound to their surface.
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3Which of the following is a classic example of a type I hypersensitivity reaction?
type I hypersensitivity
Easy
A.Serum sickness
B.Anaphylaxis
C.Hemolytic disease of the newborn
D.Contact dermatitis
Correct Answer: Anaphylaxis
Explanation:
Anaphylaxis is an acute, systemic type I hypersensitivity reaction. The other options represent type IV, type III, and type II reactions respectively.
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4Type II hypersensitivity reactions are primarily mediated by antibodies directed against:
type II hypersensitivity
Easy
A.IgE-bound allergens
B.Soluble circulating antigens
C.Sensitized T lymphocytes
D.Cell surface or tissue antigens
Correct Answer: Cell surface or tissue antigens
Explanation:
Type II (cytotoxic) hypersensitivity involves IgG or IgM antibodies binding antigens on cell surfaces or tissues, leading to cell destruction via complement or phagocytosis.
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5Which condition is a typical example of type II hypersensitivity?
type II hypersensitivity
Easy
A.ABO blood transfusion reaction
B.Arthus reaction
C.Poison ivy dermatitis
D.Hay fever
Correct Answer: ABO blood transfusion reaction
Explanation:
A mismatched ABO transfusion reaction is type II, with antibodies attacking antigens on donor red blood cells causing their destruction.
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6Which antibody classes are mainly involved in type II hypersensitivity?
type II hypersensitivity
Easy
A.IgD and IgM
B.IgG and IgM
C.IgA and IgE
D.IgE and IgD
Correct Answer: IgG and IgM
Explanation:
Type II reactions are mediated by IgG and IgM antibodies that bind to cell-surface antigens and activate complement or effector cells.
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7Type III hypersensitivity reactions are caused by the deposition of:
type III hypersensitivity
Easy
A.Antigen-antibody immune complexes
B.Autoreactive B cells
C.Sensitized T cells
D.Free IgE molecules
Correct Answer: Antigen-antibody immune complexes
Explanation:
Type III (immune complex) hypersensitivity results from deposition of antigen-antibody complexes in tissues, activating complement and causing inflammation.
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8Which of the following is a classic example of type III hypersensitivity?
type III hypersensitivity
Easy
A.Graves' disease
B.Tuberculin skin test
C.Serum sickness
D.Anaphylactic shock
Correct Answer: Serum sickness
Explanation:
Serum sickness is a prototypical type III reaction caused by circulating immune complexes depositing in tissues such as joints and kidneys.
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9The localized inflammatory response caused by immune complex deposition at a site of antigen injection is called the:
type III hypersensitivity
Easy
A.Prausnitz-Küstner reaction
B.Arthus reaction
C.Shwartzman reaction
D.Wheal-and-flare reaction
Correct Answer: Arthus reaction
Explanation:
The Arthus reaction is a localized type III hypersensitivity where immune complexes deposit at the injection site, causing local vasculitis and inflammation.
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10Type IV hypersensitivity is also known as:
type IV hypersensitivity
Easy
A.Immune complex hypersensitivity
B.Cytotoxic hypersensitivity
C.Immediate hypersensitivity
D.Delayed-type hypersensitivity
Correct Answer: Delayed-type hypersensitivity
Explanation:
Type IV is called delayed-type hypersensitivity because the response develops over 24-72 hours and is mediated by T cells rather than antibodies.
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11Which cells mediate type IV hypersensitivity reactions?
type IV hypersensitivity
Easy
A.T lymphocytes
B.Platelets
C.Mast cells
D.B lymphocytes
Correct Answer: T lymphocytes
Explanation:
Type IV hypersensitivity is cell-mediated by sensitized T lymphocytes (and macrophages), not by antibodies.
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12The tuberculin (Mantoux) skin test is an example of which type of hypersensitivity?
type IV hypersensitivity
Easy
A.Type II
B.Type IV
C.Type III
D.Type I
Correct Answer: Type IV
Explanation:
The tuberculin test is a classic type IV delayed reaction, showing induration 48-72 hours after intradermal injection due to T-cell activity.
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13The main antigens responsible for graft rejection between individuals are the:
immunologic basis of graft rejection
Easy
A.ABO blood group antigens only
B.Rh factor antigens
C.Major histocompatibility complex (MHC) antigens
D.Heat shock proteins
Correct Answer: Major histocompatibility complex (MHC) antigens
Explanation:
Graft rejection is primarily driven by differences in MHC (HLA) antigens between donor and recipient, which the immune system recognizes as foreign.
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14A graft transferred between genetically identical individuals is called a(n):
immunologic basis of graft rejection
Easy
A.Isograft
B.Autograft
C.Xenograft
D.Allograft
Correct Answer: Isograft
Explanation:
An isograft is a graft between genetically identical individuals (e.g., identical twins) and is not rejected due to matching antigens.
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15A graft between two different species is termed a:
immunologic basis of graft rejection
Easy
A.Xenograft
B.Isograft
C.Autograft
D.Allograft
Correct Answer: Xenograft
Explanation:
A xenograft is transplanted between different species and is strongly rejected due to major antigenic differences.
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16Tissue typing before transplantation is primarily performed to match:
tissue typing
Easy
A.Enzyme concentrations
B.Blood glucose levels
C.Body temperature
D.HLA antigens
Correct Answer: HLA antigens
Explanation:
Tissue typing matches donor and recipient HLA (MHC) antigens to reduce the likelihood of graft rejection.
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17In which structure of the human genome are HLA genes located?
tissue typing
Easy
A.Chromosome 21
B.Chromosome 6
C.Chromosome 1
D.Chromosome 14
Correct Answer: Chromosome 6
Explanation:
The HLA (MHC) genes are located on the short arm of chromosome 6 in humans.
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18Which type of T cell is the main effector in cell-mediated graft rejection?
cell mediated graft rejection
Easy
A.Cytotoxic T cells
B.Regulatory T cells
C.Natural killer T cells only
D.Plasma cells
Correct Answer: Cytotoxic T cells
Explanation:
Cytotoxic (CD8+) T cells directly recognize and destroy graft cells bearing foreign MHC antigens, driving cell-mediated rejection.
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19Which type of graft rejection typically occurs days to weeks after transplantation and is mainly cell-mediated?
cell mediated graft rejection
Easy
A.Latent rejection
B.Chronic rejection
C.Acute rejection
D.Hyperacute rejection
Correct Answer: Acute rejection
Explanation:
Acute rejection develops within days to weeks and is primarily driven by T-cell-mediated immune responses against graft antigens.
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20Hyperacute graft rejection typically occurs:
clinical manifestations of graft rejection
Easy
A.Several weeks after transplantation
B.Months to years after transplantation
C.Only after immunosuppression stops
D.Within minutes to hours of transplantation
Correct Answer: Within minutes to hours of transplantation
Explanation:
Hyperacute rejection occurs within minutes to hours due to preformed antibodies against donor antigens, causing rapid thrombosis and graft loss.
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21A patient develops wheezing, urticaria, and hypotension within minutes of a bee sting. Which mediator released from mast cells is primarily responsible for the immediate vascular changes seen in this reaction?
type I hypersensitivity
Medium
A.Histamine
B.Complement C3b
C.Interferon-gamma
D.Lysozyme
Correct Answer: Histamine
Explanation:
Type I hypersensitivity involves IgE-mediated mast cell degranulation. Preformed histamine causes immediate vasodilation, increased vascular permeability, and smooth muscle contraction, producing the acute anaphylactic signs.
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22The late-phase reaction of type I hypersensitivity, occurring several hours after allergen exposure, is characterized by tissue infiltration primarily of which cell type?
type I hypersensitivity
Medium
A.Plasma cells
B.Erythrocytes
C.Cytotoxic T cells
D.Eosinophils
Correct Answer: Eosinophils
Explanation:
The late-phase response is driven by newly synthesized mediators and cytokines (e.g., IL-5) that recruit eosinophils, which contribute to sustained inflammation and tissue damage hours after the initial IgE-mediated reaction.
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23A newborn develops hemolytic disease due to maternal anti-Rh antibodies. This condition is best classified as which type of hypersensitivity?
type II hypersensitivity
Medium
A.Type I (IgE-mediated)
B.Type III (immune complex)
C.Type IV (cell-mediated)
D.Type II (antibody-mediated cytotoxicity)
Correct Answer: Type II (antibody-mediated cytotoxicity)
Explanation:
Hemolytic disease of the newborn results from IgG antibodies binding to antigens on fetal red cells, triggering complement-mediated lysis and phagocytosis. This antibody-directed destruction of cells defines type II hypersensitivity.
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24In Graves' disease, autoantibodies bind the TSH receptor and stimulate thyroid hormone production. This is considered an atypical type II reaction because the antibodies:
type II hypersensitivity
Medium
A.Alter receptor function rather than destroy cells
B.Form circulating immune complexes
C.Activate cytotoxic T lymphocytes
D.Trigger IgE-mediated degranulation
Correct Answer: Alter receptor function rather than destroy cells
Explanation:
Graves' disease is a type II reaction where stimulating autoantibodies mimic TSH and continuously activate the receptor, altering cell function instead of causing lysis. This subtype is sometimes classified as type V hypersensitivity.
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25A patient develops fever, arthralgia, and proteinuria about 10 days after receiving antivenom serum. The renal damage is most likely caused by:
type III hypersensitivity
Medium
A.Direct T-cell attack on tubular epithelium
B.Autoantibodies against the TSH receptor
C.Deposition of antigen-antibody complexes in glomeruli
D.IgE binding to mast cells in the kidney
Correct Answer: Deposition of antigen-antibody complexes in glomeruli
Explanation:
Serum sickness is a type III reaction. Circulating immune complexes deposit in vessel walls and glomeruli, activating complement and recruiting neutrophils, which cause the systemic and renal inflammation seen here.
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26Which feature distinguishes the Arthus reaction from anaphylaxis?
type III hypersensitivity
Medium
A.It occurs within seconds of exposure
B.It is mediated by IgE antibodies
C.It is a localized immune-complex reaction at the injection site
D.It is caused by cytotoxic T cells
Correct Answer: It is a localized immune-complex reaction at the injection site
Explanation:
The Arthus reaction is a localized type III response occurring when antigen injected into a sensitized individual forms immune complexes locally, activating complement and causing vasculitis at the site over several hours.
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27A positive tuberculin (Mantoux) skin test produces induration peaking at 48–72 hours. This delayed response is mediated primarily by:
type IV hypersensitivity
Medium
A.IgE-coated mast cells
B.Complement-fixing IgM antibodies
C.Sensitized CD4+ T cells and macrophages
D.Circulating immune complexes
Correct Answer: Sensitized CD4+ T cells and macrophages
Explanation:
The tuberculin reaction is a classic type IV (delayed-type) hypersensitivity. Sensitized CD4+ Th1 cells release cytokines that recruit and activate macrophages, producing induration that peaks 48–72 hours after antigen exposure.
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28Contact dermatitis from nickel jewelry is a type IV reaction. The nickel ions act as haptens by:
type IV hypersensitivity
Medium
A.Binding self proteins to become immunogenic
B.Directly cross-linking IgE on mast cells
C.Forming soluble immune complexes in serum
D.Activating complement via the classical pathway
Correct Answer: Binding self proteins to become immunogenic
Explanation:
Small molecules like nickel are haptens that are not immunogenic alone. They conjugate with skin proteins to form complete antigens, which sensitize T cells and drive the delayed cell-mediated contact dermatitis.
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29A graft transplanted between genetically identical twins is generally accepted without rejection. This type of graft is called a:
immunologic basis of graft rejection
Medium
A.Autograft
B.Xenograft
C.Isograft (syngeneic graft)
D.Allograft
Correct Answer: Isograft (syngeneic graft)
Explanation:
An isograft is transplanted between genetically identical individuals such as monozygotic twins. Because MHC molecules are identical, the recipient's immune system does not recognize the graft as foreign, so rejection does not occur.
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30Which molecules are the principal targets recognized by the recipient's T cells during allograft rejection?
immunologic basis of graft rejection
Medium
A.Immunoglobulin isotypes
B.Complement regulatory proteins
C.MHC (HLA) molecules
D.ABO blood group enzymes
Correct Answer: MHC (HLA) molecules
Explanation:
Allograft rejection is driven mainly by recognition of foreign MHC (HLA) molecules on donor cells. Differences in HLA between donor and recipient are the strongest determinant of graft rejection intensity.
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31In direct allorecognition, recipient T cells recognize:
immunologic basis of graft rejection
Medium
A.Complement fragments deposited on the graft
B.Donor peptides presented by recipient MHC
C.Free circulating donor antibodies
D.Intact donor MHC molecules on donor antigen-presenting cells
Correct Answer: Intact donor MHC molecules on donor antigen-presenting cells
Explanation:
In direct allorecognition, recipient T cells directly bind intact allogeneic MHC molecules displayed on donor antigen-presenting cells. This pathway is responsible for the strong, early acute rejection response.
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32Before a kidney transplant, a crossmatch test is performed by mixing recipient serum with donor lymphocytes. A positive crossmatch indicates:
tissue typing
Medium
A.Complete HLA identity between donor and recipient
B.Preformed recipient antibodies against donor antigens
C.Successful induction of graft tolerance
D.Absence of any immune response to the graft
Correct Answer: Preformed recipient antibodies against donor antigens
Explanation:
A positive crossmatch means the recipient has preformed antibodies that bind donor lymphocytes, predicting hyperacute rejection. Transplantation is contraindicated when the crossmatch is positive.
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33Which HLA loci are considered most important to match for improving solid organ graft survival?
tissue typing
Medium
A.HLA-A, HLA-B, and HLA-DR
B.Only HLA-C
C.ABO antigens alone
D.HLA-E, HLA-F, and HLA-G
Correct Answer: HLA-A, HLA-B, and HLA-DR
Explanation:
Matching at HLA-A, HLA-B (class I) and HLA-DR (class II) loci most strongly influences graft survival. Better matching at these loci reduces the risk and severity of rejection.
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34Acute cellular rejection of a transplanted organ is primarily mediated by which effector cells?
cell mediated graft rejection
Medium
A.CD8+ cytotoxic T lymphocytes
B.Neutrophils via immune complexes
C.Eosinophils
D.Plasma cells secreting IgE
Correct Answer: CD8+ cytotoxic T lymphocytes
Explanation:
Acute cellular rejection is dominated by CD8+ cytotoxic T lymphocytes that recognize donor MHC and directly kill graft cells, along with CD4+ T cells that amplify the response through cytokine release.
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35Cyclosporine and tacrolimus prevent cell-mediated graft rejection mainly by:
cell mediated graft rejection
Medium
A.Blocking IgE binding to mast cells
B.Neutralizing complement in serum
C.Depleting all circulating B cells
D.Inhibiting calcineurin and blocking IL-2 production
Correct Answer: Inhibiting calcineurin and blocking IL-2 production
Explanation:
Calcineurin inhibitors like cyclosporine and tacrolimus block the calcineurin–NFAT pathway, suppressing IL-2 transcription. Reduced IL-2 limits T-cell proliferation, dampening cell-mediated rejection.
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36A transplanted kidney turns cyanotic and mottled within minutes of vascular anastomosis. This hyperacute rejection is caused by:
clinical manifestations of graft rejection
Medium
A.Chronic fibrosis of graft vasculature
B.Delayed macrophage infiltration
C.Preformed antibodies activating complement in graft vessels
D.Slowly developing cytotoxic T-cell responses
Correct Answer: Preformed antibodies activating complement in graft vessels
Explanation:
Hyperacute rejection occurs within minutes because preformed recipient antibodies bind donor endothelium, activate complement and coagulation, and cause thrombosis and ischemic destruction of the graft.
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37Chronic graft rejection typically presents months to years after transplantation and is characterized histologically by:
clinical manifestations of graft rejection
Medium
A.Dense neutrophil infiltration within hours
B.Rapid vascular thrombosis within minutes
C.Vascular fibrosis and progressive luminal narrowing
D.Immediate complement-mediated hemolysis
Correct Answer: Vascular fibrosis and progressive luminal narrowing
Explanation:
Chronic rejection develops slowly and is marked by intimal proliferation, vascular smooth muscle thickening, and fibrosis leading to luminal narrowing (graft arteriosclerosis) and gradual loss of graft function.
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38Which mechanism best explains how molecular mimicry contributes to autoimmune disease?
Molecular mimicry occurs when a microbial epitope structurally resembles a self antigen. Immune responses generated against the pathogen cross-react with host tissue, triggering autoimmunity, as in rheumatic fever.
A.IgE-mediated mast cell degranulation in the thyroid
B.Immune complex deposition in the thyroid vasculature
C.T-cell and antibody-mediated destruction of thyroid follicular cells
D.Stimulating antibodies overactivating the TSH receptor
Correct Answer: T-cell and antibody-mediated destruction of thyroid follicular cells
Explanation:
Hashimoto's thyroiditis is an organ-specific autoimmune disease in which autoreactive T cells and antibodies (e.g., anti-thyroid peroxidase) destroy thyroid follicular cells, leading to progressive hypothyroidism.
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40Systemic lupus erythematosus (SLE) is characterized by antibodies against nuclear components and tissue injury mediated largely by:
systemic autoimmune disease
Medium
A.Hyperacute complement activation within minutes
B.Direct cytotoxic destruction of neurons only
C.Immune complex deposition (type III mechanism)
D.IgE-mediated anaphylaxis
Correct Answer: Immune complex deposition (type III mechanism)
Explanation:
SLE features autoantibodies such as anti-dsDNA and anti-nuclear antibodies that form immune complexes. These deposit in skin, joints, and glomeruli, activating complement and causing the widespread systemic tissue damage typical of a type III process.
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41A patient develops anaphylaxis within minutes of a bee sting. During the late-phase reaction (6–12 hours later), tissue biopsy shows a predominant cellular infiltrate. Which cell type and mediator combination is MOST characteristic of this late phase rather than the immediate phase?
type I hypersensitivity
Hard
A.Neutrophils driven by C5a alone
B.Basophils releasing preformed tryptase
C.Mast cells releasing preformed histamine
D.Eosinophils recruited by IL-5 and eotaxin
Correct Answer: Eosinophils recruited by IL-5 and eotaxin
Explanation:
The immediate phase is dominated by preformed mast cell mediators (histamine, tryptase). The late phase (hours later) is characterized by recruitment of eosinophils, basophils, and Th2 cells via cytokines such as IL-5 and chemokines like eotaxin, causing sustained inflammation.
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42A researcher measures a patient's total serum IgE and finds it normal, yet the patient has a strongly positive skin prick test and clinical allergy to peanut. What is the BEST explanation for allergy despite normal total IgE?
type I hypersensitivity
Hard
A.Skin prick tests measure IgG rather than IgE
B.Allergen-specific IgE can be elevated even when total IgE is within normal range
Correct Answer: Allergen-specific IgE can be elevated even when total IgE is within normal range
Explanation:
Clinical allergy depends on allergen-specific IgE bound to mast cells, not total IgE. A patient may have high specific IgE to peanut while total IgE remains normal, so specific IgE and skin testing are more clinically relevant.
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43In Goodpasture syndrome, autoantibodies target the non-collagenous (NC1) domain of the chain of type IV collagen. Why are the kidney and lung selectively affected in this disease?
type II hypersensitivity
Hard
A.Both organs express the chain of type IV collagen in their basement membranes
B.Both organs have fenestrated endothelium allowing IgE entry
C.Both organs harbor resident autoreactive B cells only
Correct Answer: Both organs express the chain of type IV collagen in their basement membranes
Explanation:
The NC1 epitope is expressed predominantly in glomerular and alveolar basement membranes. Anti-GBM antibodies bind these shared targets, producing the combined pulmonary hemorrhage and glomerulonephritis characteristic of Goodpasture syndrome.
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44A newborn of a group O mother develops mild hemolytic disease, while a different group A infant of an Rh-negative mother sensitized in a prior pregnancy develops severe disease. Which statement BEST explains the difference in severity between ABO and Rh hemolytic disease of the newborn?
type II hypersensitivity
Hard
A.ABO incompatibility requires prior sensitization like Rh does
B.Anti-A/B antibodies are exclusively IgG and cross the placenta more efficiently
C.Anti-Rh (D) is mainly IgG which crosses the placenta, whereas natural anti-A/B is largely IgM
D.Rh antigens are poorly expressed on fetal red cells
Correct Answer: Anti-Rh (D) is mainly IgG which crosses the placenta, whereas natural anti-A/B is largely IgM
Explanation:
Anti-D produced after sensitization is IgG, which crosses the placenta and causes severe hemolysis. Naturally occurring anti-A/B are predominantly IgM and cross poorly, so ABO HDN is usually milder and can occur in a first pregnancy.
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45In an Arthus reaction, a patient injected intradermally with antigen develops localized edema, hemorrhage, and necrosis over several hours. What is the KEY pathogenic event distinguishing this from a type I reaction at the same site?
type III hypersensitivity
Hard
A.Antigen-specific CD8 T cell cytotoxicity of keratinocytes
B.Direct antibody binding to cell surface antigens causing lysis
C.Local immune complex deposition activating complement and neutrophil influx
D.Mast cell degranulation triggered by cross-linked IgE
Correct Answer: Local immune complex deposition activating complement and neutrophil influx
Explanation:
The Arthus reaction is a localized type III response: antigen combines with pre-existing IgG to form immune complexes in vessel walls, activating complement (C5a) and recruiting neutrophils, causing vasculitis and necrosis over hours—unlike the minutes-scale IgE-mediated type I reaction.
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46The size and solubility of immune complexes influence their pathogenicity. Which type of immune complex is MOST likely to deposit in tissues and cause type III disease?
type III hypersensitivity
Hard
A.Very large insoluble complexes formed in extreme antibody excess
B.Small-to-intermediate soluble complexes formed near antigen excess
C.Complexes composed exclusively of IgE and antigen
D.Monomeric antibody bound to a single soluble antigen
Correct Answer: Small-to-intermediate soluble complexes formed near antigen excess
Explanation:
Large complexes formed in antibody excess are efficiently cleared by phagocytes. Small-to-intermediate soluble complexes, favored in slight antigen excess, evade clearance and deposit in vessels, glomeruli, and joints, driving type III pathology.
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47A tuberculin skin test is read at 48–72 hours as an area of induration. Which mechanism explains why the peak response is delayed rather than immediate?
type IV hypersensitivity
Hard
A.Mast cells must synthesize new leukotrienes de novo
B.Time is required for antigen presentation and clonal recruitment of sensitized Th1 cells and macrophages
C.Complement components require 48 hours to assemble on membranes
D.Circulating IgG must first form immune complexes at the site
Correct Answer: Time is required for antigen presentation and clonal recruitment of sensitized Th1 cells and macrophages
Explanation:
Type IV (delayed) hypersensitivity depends on antigen processing by APCs, recruitment and activation of memory Th1 cells, and cytokine-driven macrophage accumulation. These cellular events take 24–72 hours, producing the delayed induration.
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48In contact dermatitis to nickel, the metal itself is too small to be immunogenic. What immunological concept explains how nickel triggers a type IV response?
type IV hypersensitivity
Hard
A.Nickel directly cross-links IgE on Langerhans cells
B.Nickel is a superantigen activating all T cells nonspecifically
C.Nickel forms soluble immune complexes deposited in the dermis
D.Nickel acts as a hapten binding self-proteins to form a complete antigen
Correct Answer: Nickel acts as a hapten binding self-proteins to form a complete antigen
Explanation:
Small chemicals like nickel are haptens: they covalently modify self-proteins, creating neoantigens that are processed and presented by Langerhans cells to sensitize Th1/CD8 cells, producing delayed contact hypersensitivity.
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49Hyperacute rejection of a transplanted kidney occurs within minutes of vascular anastomosis. Which pre-existing immunological factor is MOST responsible?
immunologic basis of graft rejection
Hard
A.Preformed recipient antibodies against donor HLA or ABO antigens
B.Recipient macrophages responding to ischemia-reperfusion injury
C.Naive recipient T cells recognizing donor MHC via direct presentation
D.De novo alloantibody produced after grafting
Correct Answer: Preformed recipient antibodies against donor HLA or ABO antigens
Explanation:
Hyperacute rejection is antibody-mediated: preformed anti-donor antibodies (from prior transfusion, pregnancy, or transplants, or ABO mismatch) bind endothelium immediately, activating complement and clotting, causing rapid thrombosis. Cross-matching prevents it.
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50A recipient's T cells can recognize donor alloantigen via two pathways. Which statement correctly contrasts direct versus indirect allorecognition?
immunologic basis of graft rejection
Hard
A.Direct: recipient T cells recognize intact donor MHC on donor APCs; indirect: recipient T cells recognize donor peptides on recipient MHC
B.Direct recognition is the dominant driver of chronic late rejection
C.Direct: recipient T cells recognize donor peptides on recipient APCs; indirect: recognition of intact donor MHC
D.Both pathways require processing of donor MHC by recipient APCs
Correct Answer: Direct: recipient T cells recognize intact donor MHC on donor APCs; indirect: recipient T cells recognize donor peptides on recipient MHC
Explanation:
In direct allorecognition, recipient T cells respond to intact donor MHC molecules displayed on donor (passenger) APCs, driving acute rejection. In the indirect pathway, donor MHC is processed and presented as peptides by recipient APCs, contributing to chronic rejection.
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51A patient awaiting a kidney transplant has a high panel reactive antibody (PRA) of 85%. What does this value indicate for transplant planning?
tissue typing
Hard
A.The recipient will require no crossmatch before transplant
B.The recipient has strong T cell immunity to most donors
C.The recipient is broadly sensitized and will be incompatible with most potential donors
D.The recipient's own HLA is unusually rare in the population
Correct Answer: The recipient is broadly sensitized and will be incompatible with most potential donors
Explanation:
PRA reflects the percentage of a donor panel against which the recipient has preformed anti-HLA antibodies. A PRA of 85% means the recipient is highly sensitized and would have a positive crossmatch with most donors, greatly limiting compatible organs.
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52A complement-dependent cytotoxicity (CDC) crossmatch is positive between donor lymphocytes and recipient serum. What is the correct interpretation and consequence?
tissue typing
Hard
A.Donor and recipient are HLA-identical and ideal for transplant
B.Recipient lacks anti-donor antibodies; transplant can proceed safely
C.Recipient has antibodies against donor HLA; transplant is contraindicated due to hyperacute rejection risk
D.Result indicates only T cell mismatch requiring more immunosuppression
Correct Answer: Recipient has antibodies against donor HLA; transplant is contraindicated due to hyperacute rejection risk
Explanation:
In a positive CDC crossmatch, recipient serum antibodies bind donor lymphocytes and fix complement, killing them. This signals preformed anti-donor HLA antibodies and predicts hyperacute rejection, so a positive crossmatch contraindicates transplantation.
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53In acute cellular rejection of a solid organ graft, which effector mechanism causes direct parenchymal cell destruction?
B.CD8 cytotoxic T lymphocytes recognizing donor MHC class I and inducing apoptosis
C.Neutrophils releasing preformed histamine into the interstitium
D.IgE-mediated mast cell degranulation on graft endothelium
Correct Answer: CD8 cytotoxic T lymphocytes recognizing donor MHC class I and inducing apoptosis
Explanation:
Acute cellular rejection is driven by alloreactive CD8 CTLs that recognize donor MHC class I and kill graft cells via perforin/granzyme and Fas pathways, aided by CD4 Th1 cells producing cytokines that recruit macrophages.
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54Calcineurin inhibitors such as cyclosporine and tacrolimus are used to prevent cellular rejection. What is their primary molecular mechanism?
cell mediated graft rejection
Hard
A.Inhibiting complement C3 convertase formation
B.Depleting circulating B cells via CD20 targeting
C.Directly lysing activated cytotoxic T lymphocytes
D.Blocking calcineurin-dependent NFAT activation and thereby IL-2 transcription in T cells
Correct Answer: Blocking calcineurin-dependent NFAT activation and thereby IL-2 transcription in T cells
Explanation:
Cyclosporine (via cyclophilin) and tacrolimus (via FKBP) inhibit calcineurin phosphatase, preventing dephosphorylation and nuclear translocation of NFAT. This blocks IL-2 gene transcription, suppressing T cell activation and proliferation central to cellular rejection.
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55A kidney transplant recipient presents 8 months post-transplant with gradually rising creatinine, proteinuria, and biopsy showing interstitial fibrosis, tubular atrophy, and vascular intimal thickening. Which type of rejection is MOST consistent with these findings?
clinical manifestations of graft rejection
Hard
A.Chronic rejection
B.Hyperacute rejection
C.Acute cellular rejection
D.Accelerated rejection
Correct Answer: Chronic rejection
Explanation:
Chronic rejection develops over months to years with progressive graft dysfunction, fibrosis, tubular atrophy, and characteristic vascular changes (graft arteriosclerosis with intimal thickening). It responds poorly to immunosuppression, unlike acute rejection.
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56In graft-versus-host disease (GVHD) following allogeneic bone marrow transplant, which triad of organs is classically involved and why does this reaction occur?
clinical manifestations of graft rejection
Hard
A.Skin, liver, and gut, because donor T cells attack recipient tissues
B.Bone, joints, and muscle, because of complement deposition
C.Brain, spleen, and pancreas, due to recipient CTL activity
D.Kidney, lung, and heart, because recipient antibodies attack the graft
Correct Answer: Skin, liver, and gut, because donor T cells attack recipient tissues
Explanation:
GVHD arises when immunocompetent donor T cells in the graft recognize the immunocompromised recipient's alloantigens as foreign. The skin (rash), liver (cholestasis), and gastrointestinal tract (diarrhea) are the classic target organs.
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57Central and peripheral tolerance mechanisms normally prevent autoimmunity. A mutation in the AIRE gene causes APECED/APS-1. What is the underlying defect?
introduction to autoimmune disorders
Hard
A.Overactivation of regulatory T cells suppressing all immunity
B.Failure of B cell receptor editing in the bone marrow
D.Impaired expression of tissue-specific self-antigens in the thymus, allowing autoreactive T cells to escape negative selection
Correct Answer: Impaired expression of tissue-specific self-antigens in the thymus, allowing autoreactive T cells to escape negative selection
Explanation:
AIRE (autoimmune regulator) drives ectopic expression of peripheral tissue antigens by thymic medullary epithelial cells, enabling negative selection of autoreactive thymocytes. Loss of AIRE lets self-reactive T cells escape, causing multi-organ autoimmunity (APS-1).
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58Molecular mimicry is proposed as a mechanism triggering autoimmunity after infection. Which example BEST illustrates this concept?
introduction to autoimmune disorders
Hard
A.Serum sickness, where immune complexes deposit in joints
B.Contact dermatitis, where nickel haptens modify self-proteins
C.Anaphylaxis, where IgE binds a food allergen
D.Rheumatic fever, where antibodies to streptococcal M protein cross-react with cardiac myosin
Correct Answer: Rheumatic fever, where antibodies to streptococcal M protein cross-react with cardiac myosin
Explanation:
Molecular mimicry occurs when microbial antigens structurally resemble self-antigens. In rheumatic fever, anti-streptococcal M protein antibodies cross-react with cardiac myosin and valve tissue, producing autoimmune carditis.
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59In Graves disease, hyperthyroidism results despite low circulating TSH. What is the immunologic mechanism producing this paradox?
organ specific autoimmune disease
Hard
A.Stimulatory autoantibodies bind and activate the TSH receptor, driving thyroid hormone output independent of pituitary TSH
B.Cytotoxic T cells destroy thyroid follicular cells, releasing stored hormone
C.Autoantibodies to thyroglobulin directly stimulate hormone synthesis
Correct Answer: Stimulatory autoantibodies bind and activate the TSH receptor, driving thyroid hormone output independent of pituitary TSH
Explanation:
Graves disease is a type II (stimulatory) hypersensitivity: thyroid-stimulating immunoglobulins (TSI) bind the TSH receptor and mimic TSH, causing continuous hormone production. High thyroid hormone feeds back to suppress pituitary TSH, hence low TSH with hyperthyroidism.
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60A young woman with SLE develops glomerulonephritis. Serology shows high anti-dsDNA titers and low serum C3 and C4. What best explains the low complement levels?
systemic autoimmune disease
Hard
A.Genetic deficiency of complement synthesis unrelated to disease activity
B.Overproduction of complement inhibitors by hepatocytes
C.Consumption of complement by immune complex deposition and activation in tissues
D.Increased complement inactivation by regulatory T cells
Correct Answer: Consumption of complement by immune complex deposition and activation in tissues
Explanation:
Lupus nephritis is a type III process: anti-dsDNA immune complexes deposit in glomeruli and activate the classical complement pathway, consuming C3 and C4. Falling complement with rising anti-dsDNA correlates with active nephritis and is used to monitor disease.
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