, CHAPTER LIST
Chapter 1: The Need for Self Recognition
Chapter 2: Antigens and Receptors
Chapter 3: Barriers to Infection
Chapter 4: Cells of the Innate Immune System
Chapter 5: Innate Immune Function
Chapter 6: Molecules of Adaptive Immunity
Chapter 7: Cells and Organs
Chapter 8: Generation of Immune Diversity: Lymphocyte Antigen Receptors
Chapter 9: Lymphocyte Development: B Cells and T Cells
Chapter 10: Lymphocyte Activation
Chapter 11: Lymphocyte Function
Chapter 12: Regulation of Adaptive Responses
Chapter 13: The Well Patient: How Innate and Adaptive Immune Responses
Maintain Health
Chapter 14: Hypersensitivity States
Chapter 15: Immunodeficiency
Chapter 16: Autoimmunity
Chapter 17: Transplantation
Chapter 18: Immune Pharmacotherapy
Chapter 19: Tumor Immunity
Chapter 20: Measurement of Immune Function
,Lippincott® Illustrated Reviews: Immunology, 3e —
Test Bank
Chapter 1: The Need for Self Recognition (Self vs Non-self, Tolerance,
Immune Surveillance)
1) Central tolerance failure (T cells)
A 19-year-old develops autoimmune endocrinopathy and chronic mucocutaneous
candidiasis. Genetic testing reveals a defect in a transcription factor required for thymic
expression of tissue-restricted antigens. Which mechanism of self-recognition most
directly failed?
A. Peripheral T-cell anergy due to absent co-stimulation
B. Negative selection of autoreactive thymocytes via presentation of tissue antigens
C. Complement-mediated lysis of autoreactive B cells in follicles
D. Neutrophil oxidative burst against self antigens
Answer: B
Rationale: Thymic self-recognition depends on central tolerance, where developing T
cells that bind self-peptide–MHC with high affinity undergo apoptosis (negative
selection). Expression of tissue-restricted antigens in the thymus (driven by specialized
transcriptional programs) enables deletion of organ-reactive T cells before they enter
circulation. Peripheral anergy (A) is a backup, not the primary defect described.
Complement (C) is not the main mechanism of central B-cell deletion, and neutrophils
(D) are irrelevant to thymic selection.
Key words: central tolerance, thymus, negative selection, tissue-restricted antigens,
autoimmunity
2) Central tolerance failure (B cells)
A 7-year-old has autoimmune hemolytic anemia. Bone marrow studies show immature B
cells that strongly bind a ubiquitous self-antigen are not being eliminated and instead
enter the periphery. Which normal self-recognition mechanism is most directly
impaired?
,A. Receptor editing of the B-cell receptor light chain
B. Somatic hypermutation in germinal centers
C. Isotype switching from IgM to IgG
D. MHC class I downregulation on developing B cells
Answer: A
Rationale: In the bone marrow, strongly self-reactive immature B cells are primarily
rescued from deletion by receptor editing (rearranging light-chain genes to reduce
self-reactivity). If editing fails, autoreactive clones can escape to the periphery and drive
autoimmunity. Somatic hypermutation and class switching (B, C) occur later after
antigen exposure, and MHC I downregulation (D) is not a normal tolerance step.
Key words: B-cell tolerance, bone marrow, receptor editing, autoimmunity, IgM
3) Peripheral tolerance and co-stimulation
A self-reactive T cell recognizes self peptide on an antigen-presenting cell (APC) in a
non-inflamed tissue environment. The APC presents antigen but expresses minimal B7
molecules. What is the most likely outcome for the T cell?
A. Clonal expansion into effector Th1 cells
B. Anergy due to signal 1 without adequate signal 2
C. Conversion into plasma cells
D. Activation of complement via classical pathway
Answer: B
Rationale: T-cell activation needs signal 1 (TCR–peptide–MHC) plus signal 2 (co-
stimulation, e.g., B7–CD28). Self-antigen presentation without co-stimulation promotes
anergy or deletion—an essential peripheral tolerance mechanism. (A) requires
inflammatory co-stimulation. (C) is B-cell biology, and (D) is antibody/complement-
driven, not primary here.
Key words: peripheral tolerance, co-stimulation, B7-CD28, anergy, self antigen
4) Tregs and self-recognition
A patient develops multi-organ autoimmunity early in life with severe eczema and
elevated IgE. The defect is in a transcription factor required for regulatory T-cell
development. Which function is most directly lost?
,A. Antigen processing by proteasomes
B. Suppression of autoreactive T cells via inhibitory cytokines and checkpoint signaling
C. Generation of neutrophil extracellular traps (NETs)
D. Activation of NK cells by missing-self recognition
Answer: B
Rationale: Regulatory T cells (Tregs) are pivotal for peripheral tolerance, suppressing
autoreactive T cells through inhibitory cytokines (e.g., IL-10, TGF-β) and contact-
dependent mechanisms (e.g., CTLA-4–mediated reduction of co-stimulation).
Proteasomes (A), NETs (C), and NK missing-self (D) are distinct innate/cellular pathways
not the core tolerance defect described.
Key words: Tregs, peripheral tolerance, suppression, CTLA-4, autoimmunity
5) Innate vs adaptive: “danger” context
A 30-year-old sustains a sterile crush injury. Local macrophages release inflammatory
cytokines even though no microbes are present. Which trigger best explains this innate
activation?
A. Recognition of pathogen-associated molecular patterns (PAMPs) only
B. Recognition of damage-associated molecular patterns (DAMPs) from injured cells
C. High-affinity binding of TCR to self-peptide–MHC
D. Antibody affinity maturation in lymph nodes
Answer: B
Rationale: Sterile tissue injury releases DAMPs (e.g., intracellular proteins, extracellular
matrix fragments) that activate innate pattern-recognition pathways and inflammation.
PAMP-only activation (A) would require microbes. TCR binding (C) is adaptive and
usually tolerized, and affinity maturation (D) is unrelated to immediate sterile
inflammation.
Key words: innate immunity, DAMPs, sterile inflammation, macrophages, pattern
recognition
6) Autoimmunity after infection: molecular mimicry
,Two weeks after a bacterial throat infection, a patient develops autoimmune
myocarditis. The implicated microbial epitope shares structural similarity with a cardiac
self-protein. What best explains the loss of self-tolerance?
A. Epitope spreading due to immune complex deposition only
B. Molecular mimicry activating cross-reactive lymphocytes
C. NK-cell missing-self recognition of cardiomyocytes
D. Failure of C3b opsonization
Answer: B
Rationale: Molecular mimicry occurs when pathogen epitopes resemble self epitopes
enough to activate lymphocytes that then cross-react with host tissues, breaking
tolerance. Epitope spreading (A) can occur later but does not require initial shared
similarity. NK missing-self (C) targets low MHC I, not classic post-infectious adaptive
autoimmunity. Complement opsonization (D) is not the central mechanism.
Key words: molecular mimicry, cross-reactivity, autoimmunity, post-infectious, tolerance
breakdown
7) Transplant rejection vs tolerance
A kidney transplant recipient stops immunosuppressive therapy and develops rising
creatinine with lymphocytic infiltration and endothelial injury. Which principle of self
recognition explains why rejection occurs?
A. The immune system ignores any antigen presented in lymph nodes
B. All nucleated cells lack MHC molecules
C. Donor MHC molecules are recognized as non-self by recipient T cells
D. Complement cannot be activated against cells with membranes
Answer: C
Rationale: Transplant rejection reflects the immune system’s ability to distinguish self
vs non-self MHC. Recipient T cells can recognize donor MHC directly or donor peptides
presented by recipient APCs, triggering effector responses. (A) is false—lymph nodes are
where priming occurs. (B) is false—nucleated cells express MHC I. (D) is false—
complement can damage membranes.
Key words: transplantation, allorecognition, MHC, rejection, self/non-self
, 8) Cancer immune surveillance: missing-self (innate)
A tumor downregulates MHC class I to evade cytotoxic T cells. Which immune cell is
most likely to increase killing of these tumor cells?
A. Neutrophils via oxidative burst
B. NK cells via missing-self recognition
C. Basophils via IgE crosslinking
D. Naïve B cells via receptor editing
Answer: B
Rationale: NK cells detect missing-self—reduced MHC I removes inhibitory signaling,
permitting NK cytotoxicity. Neutrophils (A) are not specialized for missing-self. Basophils
(C) are allergic/parasite pathways. Receptor editing (D) is central B tolerance, not tumor
killing.
Key words: immune surveillance, NK cells, missing-self, MHC I downregulation, tumor
evasion
9) Checkpoints and self-tolerance in tumors
A patient with metastatic melanoma receives checkpoint inhibitor therapy and develops
autoimmune colitis. Which concept best links the adverse effect to self recognition?
A. Blocking inhibitory signals lowers the threshold for T-cell activation against self
antigens
B. Enhancing complement prevents T cells from entering tissues
C. Decreasing PRR signaling eliminates adaptive immunity
D. Increasing MHC mismatch improves transplant tolerance
Answer: A
Rationale: Checkpoints are part of peripheral tolerance. Blocking inhibitory pathways
(e.g., CTLA-4, PD-1) can unleash anti-tumor immunity but also permits autoreactive T
cells to attack self tissues, causing immune-related adverse events (like colitis). The other
options contradict core immunologic logic.
Key words: checkpoint inhibition, peripheral tolerance, autoimmunity, immune-related
adverse events, self-recognition
Chapter 1: The Need for Self Recognition
Chapter 2: Antigens and Receptors
Chapter 3: Barriers to Infection
Chapter 4: Cells of the Innate Immune System
Chapter 5: Innate Immune Function
Chapter 6: Molecules of Adaptive Immunity
Chapter 7: Cells and Organs
Chapter 8: Generation of Immune Diversity: Lymphocyte Antigen Receptors
Chapter 9: Lymphocyte Development: B Cells and T Cells
Chapter 10: Lymphocyte Activation
Chapter 11: Lymphocyte Function
Chapter 12: Regulation of Adaptive Responses
Chapter 13: The Well Patient: How Innate and Adaptive Immune Responses
Maintain Health
Chapter 14: Hypersensitivity States
Chapter 15: Immunodeficiency
Chapter 16: Autoimmunity
Chapter 17: Transplantation
Chapter 18: Immune Pharmacotherapy
Chapter 19: Tumor Immunity
Chapter 20: Measurement of Immune Function
,Lippincott® Illustrated Reviews: Immunology, 3e —
Test Bank
Chapter 1: The Need for Self Recognition (Self vs Non-self, Tolerance,
Immune Surveillance)
1) Central tolerance failure (T cells)
A 19-year-old develops autoimmune endocrinopathy and chronic mucocutaneous
candidiasis. Genetic testing reveals a defect in a transcription factor required for thymic
expression of tissue-restricted antigens. Which mechanism of self-recognition most
directly failed?
A. Peripheral T-cell anergy due to absent co-stimulation
B. Negative selection of autoreactive thymocytes via presentation of tissue antigens
C. Complement-mediated lysis of autoreactive B cells in follicles
D. Neutrophil oxidative burst against self antigens
Answer: B
Rationale: Thymic self-recognition depends on central tolerance, where developing T
cells that bind self-peptide–MHC with high affinity undergo apoptosis (negative
selection). Expression of tissue-restricted antigens in the thymus (driven by specialized
transcriptional programs) enables deletion of organ-reactive T cells before they enter
circulation. Peripheral anergy (A) is a backup, not the primary defect described.
Complement (C) is not the main mechanism of central B-cell deletion, and neutrophils
(D) are irrelevant to thymic selection.
Key words: central tolerance, thymus, negative selection, tissue-restricted antigens,
autoimmunity
2) Central tolerance failure (B cells)
A 7-year-old has autoimmune hemolytic anemia. Bone marrow studies show immature B
cells that strongly bind a ubiquitous self-antigen are not being eliminated and instead
enter the periphery. Which normal self-recognition mechanism is most directly
impaired?
,A. Receptor editing of the B-cell receptor light chain
B. Somatic hypermutation in germinal centers
C. Isotype switching from IgM to IgG
D. MHC class I downregulation on developing B cells
Answer: A
Rationale: In the bone marrow, strongly self-reactive immature B cells are primarily
rescued from deletion by receptor editing (rearranging light-chain genes to reduce
self-reactivity). If editing fails, autoreactive clones can escape to the periphery and drive
autoimmunity. Somatic hypermutation and class switching (B, C) occur later after
antigen exposure, and MHC I downregulation (D) is not a normal tolerance step.
Key words: B-cell tolerance, bone marrow, receptor editing, autoimmunity, IgM
3) Peripheral tolerance and co-stimulation
A self-reactive T cell recognizes self peptide on an antigen-presenting cell (APC) in a
non-inflamed tissue environment. The APC presents antigen but expresses minimal B7
molecules. What is the most likely outcome for the T cell?
A. Clonal expansion into effector Th1 cells
B. Anergy due to signal 1 without adequate signal 2
C. Conversion into plasma cells
D. Activation of complement via classical pathway
Answer: B
Rationale: T-cell activation needs signal 1 (TCR–peptide–MHC) plus signal 2 (co-
stimulation, e.g., B7–CD28). Self-antigen presentation without co-stimulation promotes
anergy or deletion—an essential peripheral tolerance mechanism. (A) requires
inflammatory co-stimulation. (C) is B-cell biology, and (D) is antibody/complement-
driven, not primary here.
Key words: peripheral tolerance, co-stimulation, B7-CD28, anergy, self antigen
4) Tregs and self-recognition
A patient develops multi-organ autoimmunity early in life with severe eczema and
elevated IgE. The defect is in a transcription factor required for regulatory T-cell
development. Which function is most directly lost?
,A. Antigen processing by proteasomes
B. Suppression of autoreactive T cells via inhibitory cytokines and checkpoint signaling
C. Generation of neutrophil extracellular traps (NETs)
D. Activation of NK cells by missing-self recognition
Answer: B
Rationale: Regulatory T cells (Tregs) are pivotal for peripheral tolerance, suppressing
autoreactive T cells through inhibitory cytokines (e.g., IL-10, TGF-β) and contact-
dependent mechanisms (e.g., CTLA-4–mediated reduction of co-stimulation).
Proteasomes (A), NETs (C), and NK missing-self (D) are distinct innate/cellular pathways
not the core tolerance defect described.
Key words: Tregs, peripheral tolerance, suppression, CTLA-4, autoimmunity
5) Innate vs adaptive: “danger” context
A 30-year-old sustains a sterile crush injury. Local macrophages release inflammatory
cytokines even though no microbes are present. Which trigger best explains this innate
activation?
A. Recognition of pathogen-associated molecular patterns (PAMPs) only
B. Recognition of damage-associated molecular patterns (DAMPs) from injured cells
C. High-affinity binding of TCR to self-peptide–MHC
D. Antibody affinity maturation in lymph nodes
Answer: B
Rationale: Sterile tissue injury releases DAMPs (e.g., intracellular proteins, extracellular
matrix fragments) that activate innate pattern-recognition pathways and inflammation.
PAMP-only activation (A) would require microbes. TCR binding (C) is adaptive and
usually tolerized, and affinity maturation (D) is unrelated to immediate sterile
inflammation.
Key words: innate immunity, DAMPs, sterile inflammation, macrophages, pattern
recognition
6) Autoimmunity after infection: molecular mimicry
,Two weeks after a bacterial throat infection, a patient develops autoimmune
myocarditis. The implicated microbial epitope shares structural similarity with a cardiac
self-protein. What best explains the loss of self-tolerance?
A. Epitope spreading due to immune complex deposition only
B. Molecular mimicry activating cross-reactive lymphocytes
C. NK-cell missing-self recognition of cardiomyocytes
D. Failure of C3b opsonization
Answer: B
Rationale: Molecular mimicry occurs when pathogen epitopes resemble self epitopes
enough to activate lymphocytes that then cross-react with host tissues, breaking
tolerance. Epitope spreading (A) can occur later but does not require initial shared
similarity. NK missing-self (C) targets low MHC I, not classic post-infectious adaptive
autoimmunity. Complement opsonization (D) is not the central mechanism.
Key words: molecular mimicry, cross-reactivity, autoimmunity, post-infectious, tolerance
breakdown
7) Transplant rejection vs tolerance
A kidney transplant recipient stops immunosuppressive therapy and develops rising
creatinine with lymphocytic infiltration and endothelial injury. Which principle of self
recognition explains why rejection occurs?
A. The immune system ignores any antigen presented in lymph nodes
B. All nucleated cells lack MHC molecules
C. Donor MHC molecules are recognized as non-self by recipient T cells
D. Complement cannot be activated against cells with membranes
Answer: C
Rationale: Transplant rejection reflects the immune system’s ability to distinguish self
vs non-self MHC. Recipient T cells can recognize donor MHC directly or donor peptides
presented by recipient APCs, triggering effector responses. (A) is false—lymph nodes are
where priming occurs. (B) is false—nucleated cells express MHC I. (D) is false—
complement can damage membranes.
Key words: transplantation, allorecognition, MHC, rejection, self/non-self
, 8) Cancer immune surveillance: missing-self (innate)
A tumor downregulates MHC class I to evade cytotoxic T cells. Which immune cell is
most likely to increase killing of these tumor cells?
A. Neutrophils via oxidative burst
B. NK cells via missing-self recognition
C. Basophils via IgE crosslinking
D. Naïve B cells via receptor editing
Answer: B
Rationale: NK cells detect missing-self—reduced MHC I removes inhibitory signaling,
permitting NK cytotoxicity. Neutrophils (A) are not specialized for missing-self. Basophils
(C) are allergic/parasite pathways. Receptor editing (D) is central B tolerance, not tumor
killing.
Key words: immune surveillance, NK cells, missing-self, MHC I downregulation, tumor
evasion
9) Checkpoints and self-tolerance in tumors
A patient with metastatic melanoma receives checkpoint inhibitor therapy and develops
autoimmune colitis. Which concept best links the adverse effect to self recognition?
A. Blocking inhibitory signals lowers the threshold for T-cell activation against self
antigens
B. Enhancing complement prevents T cells from entering tissues
C. Decreasing PRR signaling eliminates adaptive immunity
D. Increasing MHC mismatch improves transplant tolerance
Answer: A
Rationale: Checkpoints are part of peripheral tolerance. Blocking inhibitory pathways
(e.g., CTLA-4, PD-1) can unleash anti-tumor immunity but also permits autoreactive T
cells to attack self tissues, causing immune-related adverse events (like colitis). The other
options contradict core immunologic logic.
Key words: checkpoint inhibition, peripheral tolerance, autoimmunity, immune-related
adverse events, self-recognition
