Immuno 9 Flashcards

An antigen-presenting cell displays a peptide derived from a normal host protein to a T lymphocyte. Which statement best describes this event?

A. APCs only present foreign antigens
B. Self antigens may be presented
C. Self proteins bypass antigen presentation
D. T cells immediately attack self peptides

A patient develops an immune response directed against proteins normally present in their own tissues. Failure of which process most directly explains this finding?

A. Microbial symbiosis
B. Antigen presentation
C. Immunologic tolerance
D. Lymphocyte generation

The intestinal immune system normally encounters large numbers of harmless commensal microorganisms without producing destructive inflammation. This relationship is best described as:

A. Autoimmunity
B. Hypersensitivity
C. Immune deficiency
D. Symbiosis

A lymphocyte is exposed repeatedly to an antigen but fails to mount an immune response. Which concept best describes this state?

A. Clonal expansion
B. Immunologic tolerance
C. Immune surveillance
D. Antigen sequestration

A lymphocyte recognizes an antigen, proliferates, and differentiates into effector and memory cells. The antigen is best described as:

A. Tolerogenic
B. Self-reactive
C. Immunogenic
D. Ignored

A self-reactive lymphocyte encounters antigen and is subsequently functionally inactivated or eliminated. The antigen has acted as:

A. Tolerogenic
B. Immunogenic
C. Mitogenic
D. Inflammatory

An antigen-specific lymphocyte encounters an antigen but produces no detectable reaction. This outcome is termed:

A. Clonal deletion
B. Peripheral tolerance
C. Central tolerance
D. Immunologic ignorance

Two lymphocytes recognize similar antigens, but one activates while the other becomes tolerant. What is it that you need that most directly determines these different outcomes?

A. Antigen size alone
B. Antigen plus additional signals
C. Lymphocyte lifespan alone
D. Antibody concentration alone

A therapy deliberately renders lymphocytes unresponsive to a particular antigen. What is the major potential benefit?

A. Prevent unwanted immune reactions
B. Increase memory-cell formation
C. Enhance antigen immunogenicity
D. Promote lymphocyte proliferation

A developing lymphocyte encounters a self-antigen within a generative lymphoid organ and becomes tolerant. This represents:

A. Immunologic ignorance
B. Peripheral tolerance
C. Effector differentiation
D. Central tolerance

A mature lymphocyte encounters a self-antigen in a secondary lymphoid organ and is rendered unresponsive. This represents:

A. Central tolerance
B. Peripheral tolerance
C. Immunologic ignorance
D. Productive immunity

A self-antigen is absent from both thymus and bone marrow during lymphocyte development. Which mechanism must primarily maintain tolerance to this antigen later?

A. Peripheral tolerance
B. Central tolerance
C. Clonal expansion
D. Effector differentiation

An antigen-presenting cell displays a peptide derived from a normal host protein to a T cell. Which principle best explains this event?

A. APCs recognize only microbial proteins
B. Self proteins avoid antigen presentation
C. APCs can present self proteins
D. T cells present their antigens

Why are self-antigens normally encountered by lymphocytes despite the absence of tissue injury?

A. Self proteins mimic microbial antigens
B. APC presentation includes self antigens
C. Complement exposes intracellular proteins
D. Antibodies release hidden self antigens

An immature T cell strongly recognizes self-antigen during thymic development. Which two mechanisms principally establish central T-cell tolerance?

A. Anergy and antibody neutralization
B. Apoptosis and regulatory T-cell generation
C. Complement activation and phagocytosis
D. Memory formation and clonal expansion

T lymphocytes developing in the thymus possess receptors capable of recognizing which antigen repertoire?

A. Only thymic self antigens
B. Only peripheral self antigens
C. Only foreign microbial antigens
D. Many self and foreign antigens

An immature thymocyte binds strongly to a self peptide presented by a self MHC molecule. What is the expected immediate consequence?

A. Apoptosis is triggered
B. Memory cells develop
C. Antibodies are secreted
D. Effector cells proliferate

Apoptotic elimination of an immature T cell that strongly recognizes self-antigen is called:

A. Positive selection
B. Peripheral tolerance
C. Negative selection
D. Immunologic ignorance

Why does negative selection protect against autoimmunity?

A. It increases antibody specificity
B. Self-reactive cells die before maturation
C. It removes foreign-reactive lymphocytes
D. Mature T cells lose MHC

Some immature CD4+ T cells bind self-antigen with high affinity but survive. What may they become?

A. Plasma cells
B. Memory B cells
C. Cytotoxic T cells
D. Regulatory T cells

Negative selection is especially likely when which combination is present in the thymus?

A. High antigen, high receptor affinity
B. Low antigen, low receptor affinity
C. High antigen, low receptor affinity
D. Low antigen, absent MHC

Which self-antigens may commonly induce thymic negative selection?

A. Viral and bacterial proteins
B. Only endocrine hormones
C. Plasma and common cellular proteins
D. Only tissue-restricted proteins

A self protein normally expressed only in certain peripheral tissues is called a:

A. Foreign antigen
B. Tissue-restricted antigen
C. Common cellular antigen
D. Plasma antigen

What is the principal role of AIRE in central T-cell tolerance?

A. Activates mature peripheral T cells
B. Suppresses all thymic MHC expression
C. Produces regulatory-cell cytokines
D. Expresses peripheral antigens in thymus

Why can AIRE deficiency produce autoreactive mature T cells?

A. Foreign antigens remain thymic
B. MHC molecules disappear completely
C. Tissue antigens escape thymic display
D. All immature T cells undergo apoptosis

An autoreactive T cell escapes the thymus after failing central tolerance. What may happen when it later encounters its antigen?

A. It undergoes mandatory apoptosis
B. It attacks peripheral tissues
C. It becomes a plasma cell
D. It loses antigen specificity

Which organs are most frequently targeted in the autoimmune disease associated with defective AIRE?

A. Endocrine organs
B. Skeletal muscles
C. Articular cartilage
D. Peripheral nerves

A mature T cell recognizes a self-antigen in peripheral tissue and becomes functionally unresponsive. Which mechanism has occurred?

A. Peripheral tolerance
B. Central tolerance
C. Positive selection
D. Clonal expansion

Which outcomes can peripheral tolerance produce after mature T cells recognize self-antigens?

A. Memory formation and proliferation
B. Anergy, death, or suppression
C. Affinity maturation and switching
D. Activation and effector differentiation

Why is peripheral tolerance particularly important for certain self-antigens?

A. They cannot bind self MHC
B. They activate complement directly
C. They are absent from thymus
D. They exist only during infection

Peripheral tolerance may protect against autoimmunity even for self-antigens expressed in the thymus because:

A. Thymic MHC lacks self peptides
B. Peripheral APCs delete all T cells
C. Self-antigens prevent TCR expression
D. Central tolerance may be incomplete

A naïve T lymphocyte recognizes its specific peptide-MHC complex. Which additional requirement normally promotes proliferation and differentiation?

A. Costimulatory signaling
B. Antibody secretion
C. Complement fixation
D. Histamine release

In the two-signal model of naïve T-cell activation, signal 1 consists of:

A. Cytokine secretion
B. Antigen recognition
C. Costimulator expression
D. Inhibitory receptor signaling

In the two-signal model, signal 2 is principally provided by:

A. Self MHC molecules
B. T-cell receptors
C. APC costimulators
D. Plasma proteins

A self-reactive T cell receives signal 1 without adequate signal 2. Which outcome is most likely?

A. Rapid memory formation
B. Strong clonal expansion
C. Enhanced effector differentiation
D. Anergy or death

Antigen recognition without sufficient costimulation may also make a T cell more susceptible to:

A. Regulatory T-cell suppression
B. Complement-mediated lysis
C. Antibody-dependent cytotoxicity
D. Neutrophil phagocytosis

Dendritic cells within normal uninfected tissues are typically characterized by:

A. Strong constitutive costimulation
B. An immature functional state
C. High antibody production
D. Continuous T-cell activation

What is characteristic of immature dendritic cells in normal peripheral tissues?

A. Abundant inhibitory antibodies
B. High IL-2 secretion
C. Little costimulator expression
D. Strong innate activation

A self-reactive T cell survives after recognizing self-antigen but can no longer respond effectively to it. This cell is:

A. Deleted
B. Activated
C. Anergic
D. Memory-derived

Which setting normally favors induction of T-cell anergy?

A. Foreign antigen with inflammation
B. Strong costimulation during infection
C. Antigen plus innate activation
D. Self-antigen with low costimulation

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A T cell repeatedly recognizes antigen without costimulation. What may happen to the TCR signaling apparatus?

A. It becomes constitutively activated
B. It loses signaling capability
C. It increases antibody production
D. It activates complement proteins

Following antigen recognition without costimulation, ubiquitin ligases contribute to anergy by:

A. Increasing TCR gene transcription
B. Producing additional costimulators
C. Targeting signaling proteins for destruction
D. Preventing antigen-MHC binding

Proteins modified by ubiquitin ligases during anergy are ultimately targeted for:

A. Extracellular antibody binding
B. Nuclear DNA integration
C. Membrane receptor secretion
D. Intracellular proteolytic destruction

Which inhibitory receptors are emphasized in peripheral T-cell tolerance?

A. CTLA-4 and PD-1
B. CD4 and CD8
C. B7-1 and B7-2
D. MHC-I and MHC-II

CTLA-4 is also designated:

A. CD279
B. CD152
C. CD28
D. CD40

PD-1 is also designated:

A. CD152
B. CD80
C. CD279
D. CD86

CTLA-4 and PD-1 belong to which receptor family discussed in these slides?

A. TNF receptor family
B. Toll-like receptor family
C. Integrin receptor family
D. CD28 receptor family

What is the functional consequence of increased CTLA-4 or PD-1 expression on an anergic T cell?

A. Increased clonal expansion
B. Inhibition of later responses
C. Increased antibody secretion
D. Enhanced complement activation

A T cell integrates signals from its antigen receptor, CD28, and inhibitory receptors. Which pair represents the best-defined T-cell coinhibitors?

A. CTLA-4 and PD-1
B. CD28 and B7
C. TCR and CD28
D. PD-L1 and PD-L2

Which receptors provide the principal activating signals discussed for T lymphocytes?

A. CTLA-4 and PD-1
B. TCR complex and CD28
C. PD-L1 and B7
D. CD152 and CD279

A regulatory T cell suppresses activation of nearby responding T cells. Which receptor is constitutively expressed on this Treg?

A. CD28
B. PD-L1
C. TCR
D. CTLA-4

CTLA-4 directly reduces T-cell costimulation primarily by:

A. Blocking and removing APC B7
B. Degrading the TCR complex
C. Binding PD-L1 and PD-L2
D. Activating CD28 phosphatases

CTLA-4 and CD28 can produce opposing T-cell effects because both interact with:

A. PD-L1
B. B7 molecules
C. TCR complexes
D. PD-L2

An APC expresses relatively limited amounts of B7. Which receptor is most likely to preferentially bind the available B7?

A. PD-1
B. TCR
C. CTLA-4
D. CD28

Why does CTLA-4 preferentially occupy B7 when ligand concentrations are limited?

A. CTLA-4 has higher B7 affinity
B. CD28 cannot recognize B7
C. B7 selectively inhibits CD28
D. CTLA-4 increases B7 synthesis

During an acute infection, an APC markedly increases surface B7 expression. Why can T-cell costimulation still occur despite CTLA-4 expression?

A. CTLA-4 loses B7 affinity
B. PD-1 converts into CD28
C. B7 stops binding CTLA-4
D. Excess B7 remains for CD28

Which two factors principally determine whether B7 engages CTLA-4 or CD28?

A. TCR number and antigen size
B. Receptor affinity and B7 level
C. MHC class and cytokine type
D. T-cell age and location

Following antigen stimulation, which cells can express PD-1?

A. Only regulatory T cells
B. Only activated CD4 cells
C. CD4 and CD8 T cells
D. Only activated CD8 cells

Which molecules serve as ligands for PD-1?

A. PD-L1 and PD-L2
B. B7-1 and B7-2
C. CD28 and CTLA-4
D. TCR and MHC-II

PD-1 binds its ligand on an adjacent cell. What occurs next in PD-1 signaling?

A. CD28 becomes ubiquitinated
B. B7 is removed from APC
C. TCR undergoes proteolysis
D. Cytoplasmic tyrosines are phosphorylated

Phosphorylated tyrosines within the PD-1 cytoplasmic tail recruit which signaling molecule?

A. Tyrosine kinase
B. Tyrosine phosphatase
C. Ubiquitin ligase
D. Serine protease

The enzyme recruited by activated PD-1 suppresses T-cell responses primarily by inhibiting:

A. MHC peptide presentation
B. B7 surface expression
C. Kinase-dependent TCR/CD28 signals
D. CTLA-4 transcription

A patient has prolonged antigen exposure producing chronic T-cell activation. Which change is most expected?

A. Increased PD-1 expression
B. Decreased PD-1 expression
C. Loss of PD-L1 expression
D. Increased CD28 affinity

During prolonged inflammation, cytokines promote which change that enhances PD-1-mediated inhibition?

A. Reduced TCR expression
B. Reduced B7 synthesis
C. Loss of CTLA-4
D. Increased PD-1 ligand expression

A drug prevents CTLA-4 from binding B7. Which immediate effect would be most expected?

A. Reduced PD-1 phosphorylation
B. Increased B7 removal
C. Increased CD28 costimulation
D. Decreased TCR expression

A mutation prevents PD-1 from recruiting its intracellular phosphatase. Which signaling pathways would escape normal PD-1 inhibition?

A. TCR and CD28 pathways
B. CTLA-4 and B7 pathways
C. PD-L1 and PD-L2 pathways
D. MHC-I and MHC-II pathways

The PD-1 inhibitory pathway is most active in which setting?

A. Initial thymocyte development
B. Chronic repeated antigen stimulation
C. Brief antigen-free periods
D. Acute complement activation

Where do the majority of self-reactive regulatory T cells develop?

A. Spleen
B. Bone marrow
C. Peripheral tissues
D. Thymus

Which phenotype is most characteristic of regulatory T cells?

A. CD4+ with high CD25
B. CD8+ with low CD25
C. CD4+ with low CD28
D. CD8+ with high CD28

CD25 expressed at high levels on Tregs represents which receptor component?

A. CTLA-4 cytoplasmic domain
B. TGF-β receptor subunit
C. IL-2 receptor α-chain
D. CD28 receptor β-chain

Which transcription factor is required for regulatory T-cell development and function?

A. FoxP3
B. AIRE
C. NF-κB
D. STAT1

Loss-of-function mutations in FoxP3 most directly impair:

A. B-cell antibody production
B. Thymic MHC expression
C. Regulatory T-cell function
D. Neutrophil oxidative burst

A child has severe systemic multiorgan autoimmunity caused by a FoxP3 mutation. Which disorder is most likely?

A. DiGeorge syndrome
B. APECED syndrome
C. Hyper-IgM syndrome
D. IPEX syndrome

What does the “E” in IPEX represent?

A. Endocrinopathy
B. Enteropathy
C. Encephalopathy
D. Erythroderma

Which term is included in the full expansion of IPEX?

A. Polyendocrinopathy
B. Pancytopenia
C. Polyneuropathy
D. Polymyositis

Survival and normal function of regulatory T cells depend strongly on:

A. IL-1
B. IL-4
C. IL-2
D. IL-17

Which statement best illustrates IL-2's opposing immunologic roles?

A. Suppresses B cells and macrophages
B. Promotes T-cell proliferation, maintains Tregs
C. Activates neutrophils, inhibits lymphocytes
D. Blocks TCR and CD28 signaling

IL-2 promotes conventional immune responses primarily by:

A. Removing B7 from APCs
B. Inducing FoxP3 expression
C. Blocking CD28 signaling
D. Stimulating T-cell proliferation

How does IL-2 contribute to immune suppression?

A. Directly destroys effector lymphocytes
B. Prevents antigen presentation
C. Eliminates APC costimulators
D. Maintains functional regulatory T cells

TGF-β promotes regulatory T-cell generation primarily by increasing:

A. CD28 expression
B. FoxP3 expression
C. B7 expression
D. TCR affinity

Which cytokines released by Tregs directly suppress immune-cell activation?

A. IL-2 and IL-4
B. IFN-γ and TNF
C. IL-10 and TGF-β
D. IL-1 and IL-6

IL-10 and TGF-β released by Tregs suppress activation of which cells?

A. Lymphocytes, dendritic cells, macrophages
B. Erythrocytes, platelets, neutrophils
C. Osteoblasts, hepatocytes, fibroblasts
D. Mast cells, eosinophils, basophils

A regulatory T cell suppresses an APC by removing surface B7 molecules. Which Treg receptor mediates this effect?

A. CD28
B. CTLA-4
C. PD-L1
D. TCR

Removal of B7 from an APC primarily prevents responding T cells from receiving:

A. TCR antigen recognition
B. MHC peptide presentation
C. IL-2 receptor signaling
D. CD28-mediated costimulation

Why are regulatory T cells especially effective at consuming available IL-2?

A. They express high CD25 levels
B. They secrete abundant IL-2
C. They lack inhibitory receptors
D. They express excess B7

A Treg consumes IL-2 in the local environment. What is the principal consequence for nearby responding T cells?

A. Increased antigen recognition
B. Increased memory differentiation
C. Reduced growth-factor availability
D. Enhanced CD28 costimulation

A T cell recognizes antigen presented by a normal activated APC. Which combination most directly promotes its survival and expansion?

A. IL-2 and antiapoptotic proteins
B. Fas and Fas ligand
C. Cytochrome c and caspases
D. PD-1 and CTLA-4

What is the major function of antiapoptotic proteins induced during normal T-cell activation?

A. Increase FasL expression
B. Prevent mitochondrial mediator release
C. Activate cytosolic caspases
D. Degrade TCR signaling proteins

A mature T cell recognizes self-antigen without adequate costimulation. Which intracellular change favors apoptosis?

A. Increased IL-2 production
B. Increased antiapoptotic proteins
C. Relative antiapoptotic protein deficiency
D. Increased CD28 signaling

During the intrinsic pathway of self-reactive T-cell deletion, proapoptotic proteins directly promote:

A. FasL binding
B. TCR degradation
C. IL-2 secretion
D. Cytochrome c release

Cytochrome c released from mitochondria ultimately promotes apoptosis through activation of:

A. Caspases
B. Phosphatases
C. Ubiquitin ligases
D. Costimulators

During a normal immune response, what counteracts T-cell proapoptotic proteins?

A. Fas and FasL
B. Cytochrome c
C. Antiapoptotic proteins
D. Caspase-8 and -10

Which stimuli normally induce antiapoptotic proteins in activated T cells?

A. Self-antigen alone
B. Fas engagement alone
C. Repeated TCR signaling
D. Costimulation and growth factors

Which pathway mediates apoptosis following mitochondrial cytochrome c release?

A. Death-receptor pathway
B. Intrinsic apoptotic pathway
C. Complement pathway
D. Perforin pathway

Why can self-antigen recognition favor the intrinsic apoptotic pathway?

A. Poor antiapoptotic protein induction
B. Excessive CD28 costimulation
C. Increased microbial cytokines
D. Strong innate immune activation

Recognition of self-antigen can alternatively induce coexpression of:

A. CD28 and B7
B. Fas and Fas ligand
C. TCR and MHC
D. PD-L1 and PD-L2

Fas is also designated:

A. CD25
B. CD28
C. CD95
D. CD152

Fas ligand is expressed mainly on:

A. Resting dendritic cells
B. Naïve B lymphocytes
C. Thymic epithelial cells
D. Activated T lymphocytes

Engagement of Fas by FasL causes apoptosis through which pathway?

A. Extrinsic death-receptor pathway
B. Intrinsic mitochondrial pathway
C. Complement-mediated pathway
D. Perforin-mediated pathway

What is the major downstream event shared by both intrinsic and extrinsic apoptosis?

A. IL-2 production
B. Caspase activation
C. B7 expression
D. CD28 engagement

Deletion of self-reactive lymphocytes refers to:

A. Functional anergy only
B. Treg differentiation only
C. Apoptotic elimination
D. Receptor editing

A child has lymphocyte accumulation and autoimmune disease. Which mutation is most directly implicated?

A. AIRE
B. FOXP3
C. FAS
D. CD28

Mutations in which caspases can produce a disorder resembling FAS deficiency?

A. Caspase-1 and -2
B. Caspase-3 and -6
C. Caspase-5 and -7
D. Caspase-8 and -10

Defective Fas-mediated lymphocyte apoptosis is associated with:

A. Autoimmune lymphoproliferative syndrome
B. IPEX syndrome
C. DiGeorge syndrome
D. Hyper-IgM syndrome

Most microbial antigens differ from self-antigens during T-cell development because microbial antigens are generally:

A. Continuously expressed in thymus
B. Presented without inflammation
C. Bound by resting APCs
D. Absent from the thymus

Self-antigens in peripheral tissues are commonly displayed by:

A. Resting costimulator-deficient APCs
B. Highly activated macrophages
C. Strongly stimulated dendritic cells
D. Cytokine-producing neutrophils

Presentation of self-antigen by resting APCs most strongly favors:

A. Effector-cell expansion
B. Anergy, death, or Treg suppression
C. Strong memory-cell formation
D. Cytotoxic differentiation

Why do resting APCs presenting self-antigen generally provide little costimulation?

A. Self-antigens destroy B7
B. T cells remove all MHC
C. Innate immunity is absent
D. Caspases degrade CD28

Microbial antigens tend to activate T cells because microbes also stimulate:

A. Peripheral T-cell deletion
B. Regulatory-cell development
C. Mitochondrial apoptosis
D. Innate immune responses

Innate immune responses to microbes promote T-cell activation primarily by increasing:

A. Costimulators and cytokines
B. Fas and FasL only
C. Cytochrome c release
D. Anti-CD28 antibodies

Autoantibody production in systemic lupus erythematosus is suspected to reflect defective tolerance in:

A. B cells alone
B. Helper T cells alone
C. Cytotoxic T cells only
D. B cells and helper T cells

Central tolerance of developing B lymphocytes occurs primarily in the:

A. Bone marrow
B. Thymus
C. Spleen
D. Lymph node

An immature B cell strongly recognizes self antigen in the bone marrow. Which outcomes are most likely?

A. Anergy or memory formation
B. Receptor editing or deletion
C. Isotype switching or proliferation
D. Plasma-cell differentiation or activation

Before receptor editing begins, an immature B cell has already:

A. Expressed IgG and IgA
B. Deleted its heavy-chain gene
C. Rearranged immunoglobulin genes
D. Entered peripheral lymphoid tissue

Which immunoglobulin is expressed by the immature B cell undergoing central tolerance?

A. IgA
B. IgG
C. IgE
D. IgM

At the stage immediately before receptor editing, RAG genes are normally:

A. Shut off
B. Maximally activated
C. Permanently deleted
D. Expressed only by T cells

Recognition of self antigen during receptor editing causes the immature B cell to:

A. Destroy its heavy chain
B. Reexpress RAG genes
C. Express class-switched antibodies
D. Become a plasma cell

Reexpression of RAG during receptor editing primarily resumes recombination of the:

A. Heavy-chain constant region
B. TCR β-chain gene
C. Light-chain gene
D. MHC class II gene

Why can the original heavy-chain gene not simply undergo another complete recombination?

A. RAG cannot bind heavy chains
B. Heavy chains lack variable regions
C. IgM prevents further recombination
D. Some gene segments were lost

During successful receptor editing, the newly generated light chain associates with:

A. The previously expressed heavy chain
B. A newly synthesized heavy chain
C. An existing T-cell receptor
D. A class-switched constant region

The primary goal of receptor editing is to produce:

A. Higher-affinity self recognition
B. A new antigen specificity
C. Increased IgM secretion
D. Permanent B-cell activation

An immature B cell remains strongly self-reactive after receptor editing. What is the expected outcome?

A. Apoptotic deletion
B. Clonal expansion
C. Memory differentiation
D. Isotype switching

Deletion of strongly self-reactive immature B cells is initiated by:

A. Excessive IL-2 secretion
B. Death signals
C. CD28 costimulation
D. T-cell help

Negative selection of B cells preferentially removes cells with:

A. Low-affinity microbial receptors
B. Low-avidity self recognition
C. High-affinity self receptors
D. Absent surface IgM

Negative selection can eliminate B cells recognizing which forms of self antigen?

A. Membrane or soluble self antigens
B. Only soluble microbial antigens
C. Only intracellular viral antigens
D. Only thymic peptide antigens

An immature B cell recognizes self antigen with relatively low avidity. Which outcome is favored?

A. Receptor editing
B. Anergy
C. Immediate deletion
D. Plasma-cell differentiation

What happens to an anergic self-reactive B cell?

A. It immediately undergoes apoptosis
B. It increases receptor expression
C. It survives but becomes unresponsive
D. It undergoes class switching

Which additional change accompanies B-cell anergy?

A. Increased IgM secretion
B. Increased RAG expression
C. Increased heavy-chain recombination
D. Reduced antigen-receptor expression

A mature B lymphocyte recognizes a self protein in a peripheral lymphoid tissue but receives no helper T-cell signal. What is the most likely outcome?

A. Plasma-cell differentiation
B. B-cell anergy
C. Receptor editing
D. Class switching

What directly causes anergy in a mature self-reactive B cell that lacks T-cell help?

A. Blocked BCR signaling
B. Increased RAG expression
C. Excess IL-2 production
D. Strong CD28 signaling

What may happen to an anergic B cell after it leaves a lymphoid follicle?

A. It undergoes receptor editing
B. It becomes a plasma cell
C. It enters the thymus
D. It is excluded from follicles

Why may follicle-excluded anergic B cells eventually die?

A. They express excess FasL
B. They lose all surface IgM
C. They lack survival stimuli
D. They undergo heavy-chain editing

Which organisms are included in the normal human microbiome described here?

A. Bacteria and viruses
B. Only bacteria
C. Viruses and fungi
D. Only extracellular organisms

Where do normal commensal microbes commonly reside?

A. Bone marrow and thymus
B. Intestine, respiratory tract, skin
C. Bloodstream and lymph nodes
D. Spleen, liver, and kidney

Mature lymphocytes in mucosal tissues can recognize commensal microbes but normally:

A. Delete all microbial antigens
B. Convert into plasma cells
C. Produce autoantibodies
D. Do not react destructively

Which immune population contributes prominently to intestinal tolerance of commensal microbes?

A. IL-10-producing regulatory T cells
B. IFN-γ-producing Th1 cells
C. IL-17-producing Th17 cells
D. Activated cytotoxic T cells

Which regulatory population contributes to maternal tolerance of paternal fetal antigens?

A. Central CD8+ Tregs
B. Activated Th1 cells
C. Memory B cells
D. Peripheral FoxP3+ Tregs

Which mechanism also contributes to fetal tolerance in the healthy pregnant uterus?

A. Exclusion of inflammatory cells
B. Strong Th1 generation
C. Increased placental presentation
D. Enhanced neutrophil recruitment

Which mechanism enables the placenta to maintain maternal-fetal immune tolerance?

A. It secretes autoantibodies.

B. It strongly activates CD28 to stimulate T cells.

C. It presents paternal antigens poorly due to a lack of classical MHC class I and II molecules.

D. It induces receptor editing in maternal lymphocytes.

Which immune response is relatively difficult to generate in the healthy pregnant uterus?

A. Regulatory T-cell activity
B. Harmful Th1 responses
C. FoxP3 expression
D. Peripheral tolerance

Autoimmunity is best defined as:

A. Immune response against self antigens
B. Loss of all immune responses
C. Infection-induced antibody production
D. Tolerance to microbial antigens

Which two factors are considered principal contributors to development of autoimmunity?

A. Susceptibility genes and environmental triggers
B. Aging and antibody class switching
C. Complement and neutrophil activation
D. BCR editing and somatic mutation

What is a major consequence of genetically defective self-tolerance?

A. Loss of all lymphocytes
B. Persistence of autoreactive T and B cells
C. Elimination of regulatory T cells only
D. Failure of antigen presentation

How can environmental stimuli precipitate autoimmune disease in a genetically susceptible individual?

A. By preventing inflammation
B. By deleting all autoreactive cells
C. By causing injury and inflammation
D. By suppressing costimulation

Which products are primarily responsible for tissue injury once autoimmune lymphocytes are activated?

A. Histamine and complement only
B. Cytokines and microbial toxins
C. Neutrophils and platelets
D. Effector T cells and autoantibodies

Human autoimmune diseases are usually best described as:

A. Monogenic and uniform
B. Heterogeneous and multifactorial
C. Acute and self-limited
D. Exclusively antibody-mediated

Why may an autoimmune disease appear clinically long after the initiating event?

A. Autoimmune reactions can precede symptoms
B. T cells require years to mature
C. Antibodies cannot injure tissues early
D. Self antigens develop only later

Inherited susceptibility to most autoimmune diseases is best described as:

A. Usually caused by one gene
B. Primarily determined by infections
C. Controlled by multiple gene loci
D. Independent of inherited variation

Which genes contribute the greatest inherited risk for most autoimmune diseases?

A. MHC genes
B. FAS genes
C. NOD2 genes
D. FOXP3 genes

Genome-wide association studies of autoimmune disease commonly identify polymorphisms that are:

A. Always absent in healthy people
B. Either predisposing or protective
C. Necessarily disease-causing mutations
D. Restricted to coding sequences

The association between a particular HLA allele and an autoimmune disease is commonly expressed as:

A. Allelic penetrance
B. Mutation frequency
C. Antibody titer ratio
D. Odds ratio or relative risk

Why are multiple risk alleles usually required for development of common autoimmune diseases?

A. MHC genes are never inherited
B. Individual alleles have small effects
C. All alleles must encode cytokines
D. Each allele prevents lymphocyte activation

Why may class II MHC polymorphisms strongly influence autoimmune disease susceptibility?

A. They regulate neutrophil function
B. They activate complement proteins
C. They control CD4+ T-cell responses
D. They determine antibody isotypes

How may a particular MHC allele promote activation of autoreactive T cells?

A. Efficiently presents pathogenic self peptides
B. Blocks all peptide presentation
C. Prevents CD4 differentiation
D. Eliminates self-reactive B cells

How might an MHC allele impair central T-cell tolerance?

A. Enhances thymic self presentation
B. Inefficiently displays thymic self antigens
C. Eliminates all regulatory T cells
D. Increases Fas-mediated apoptosis

A polymorphism in PTPN22 may promote autoimmunity by causing:

A. Impaired antibody class switching
B. Reduced antigen presentation
C. Uncontrolled B- and T-cell activation
D. Loss of intestinal microbes

PTPN22 polymorphisms are associated with all of the following EXCEPT:

A. Rheumatoid arthritis
B. Systemic lupus erythematosus
C. Type 1 diabetes mellitus
D. Crohn disease

Variants in NOD2 are associated with Crohn disease primarily because they may cause:

A. Reduced resistance to intestinal microbes
B. Excess CTLA-4 signaling
C. Increased thymic negative selection
D. Loss of IL-23 signaling

Polymorphisms involving CD25 may promote autoimmunity by altering the balance between:

A. B cells and macrophages
B. Effector and regulatory T cells
C. Neutrophils and monocytes
D. Th1 and plasma cells only

CD25 encodes which immune receptor component?

A. IL-23 receptor
B. CTLA-4 receptor
C. IL-2 receptor α chain
D. TCR β chain

Polymorphisms involving the IL-23 receptor may influence autoimmunity because IL-23 promotes development of:

A. Regulatory B cells
B. Cytotoxic NK cells
C. Anti-inflammatory Th2 cells
D. Proinflammatory Th17 cells

Which inhibitory receptor gene is also implicated by autoimmune-associated polymorphisms?

A. CTLA4
B. CD28
C. CD40
D. PD-L2

Many autoimmune-associated polymorphisms are located primarily in:

A. Immunoglobulin constant regions
B. Promoters and enhancers
C. Mitochondrial coding sequences
D. TCR variable regions only

How do Mendelian autoimmune disorders differ from most common autoimmune diseases?

A. They require many weak alleles
B. They lack genetic contributions
C. Single mutations have high penetrance
D. They occur only after infection

Which group contains genes whose single-gene mutations can cause Mendelian autoimmunity?

A. NOD2, CD25, IL23R, PTPN22
B. HLA-B, HLA-C, CD28, PD1
C. TCR, B7, CD40, IL2
D. AIRE, FOXP3, FAS, CTLA4

An infection in peripheral tissue activates local innate immunity. Which change most directly increases the risk of activating self-reactive T cells?

A. Reduced cytokine production
B. Increased APC costimulators
C. Decreased antigen presentation
D. Loss of MHC expression

Why can activated tissue APCs promote autoimmunity during infection?

A. They destroy self antigens
B. They suppress all T cells
C. They stimulate self-reactive T cells
D. They eliminate costimulatory molecules

Which cytokine produced during innate antiviral responses is specifically associated with lupus when produced excessively?

A. Type I interferon
B. IL-4
C. IL-5
D. IL-13

Microbial peptides resemble self antigens and activate lymphocytes that then attack host tissue. This mechanism is called:

A. Epitope spreading
B. Receptor editing
C. Molecular mimicry
D. Clonal deletion

Molecular mimicry refers to:

A. Self antigens hiding from immunity
B. Microbial and self antigen cross-reaction
C. B cells changing receptors
D. T cells losing costimulation

In rheumatic fever, antibodies generated against streptococci can cross-react with:

A. Renal basement membrane
B. Pancreatic islet antigens
C. Thyroid receptors
D. Myocardial antigens

Which autoimmune complication is classically linked to streptococcal molecular mimicry?

A. Rheumatic heart disease
B. Type 1 diabetes
C. Multiple sclerosis
D. Graves disease

Periodontal bacterial infection has been associated with which autoimmune disease?

A. SLE
B. Rheumatoid arthritis
C. Crohn disease
D. Myasthenia gravis

How may periodontal bacteria promote rheumatoid arthritis?

A. By blocking MHC expression
B. By inhibiting B-cell receptors
C. By citrullinating self proteins
D. By destroying regulatory T cells

Citrullinated self proteins may promote autoimmunity because they are:

A. Recognized as nonself
B. Unable to bind antibodies
C. Rapidly degraded
D. Hidden from APCs

A self antigen normally hidden from the immune system is released after tissue injury. What may follow?

A. Improved central tolerance
B. Loss of antibody production
C. Autoimmune reaction
D. Reduced inflammation

Why are some sequestered self antigens normally ignored?

A. They are not usually encountered
B. They cannot bind MHC
C. They are always intracellular enzymes
D. They lack peptide sequences

Exposure to sunlight is a recognized environmental trigger for which autoimmune disease?

A. Rheumatic fever
B. Systemic lupus erythematosus
C. Type 1 diabetes
D. Crohn disease

In SLE, autoantibodies commonly target:

A. Self nucleic acids and nucleoproteins
B. Only collagen fibers
C. Only cell-surface receptors
D. Only mitochondrial proteins

Why might ultraviolet radiation promote lupus?

A. It prevents apoptosis
B. It eliminates nuclear antigens
C. It increases thymic tolerance
D. It may release nuclear antigens

Ultraviolet radiation is thought to expose nuclear self antigens partly by causing:

A. Cellular apoptosis
B. B-cell receptor editing
C. T-cell anergy
D. Reduced cytokine release