Summer Immuno Lecture 9 Flashcards

A developing T cell first learns self-tolerance in which organ?

The thymic process that teaches developing T cells tolerance to self is called what?
A. Peripheral tolerance
B. Central tolerance induction
C. Clonal selection
D. Affinity maturation

T-cell precursors enter the thymus after exiting which site?

____ ____

A newly arrived thymocyte lacks CD4, CD8, and TCR. What best describes it?
A. Single-positive
B. Double-positive
C. Receptor-negative immature
D. Fully mature naive

After entering the thymus, immature T cells migrate outward to proliferate in which region?

In the thymic cortex, immature T cells begin gene rearrangement to form which receptor?

____ ____ ____

After successful TCR rearrangement, immature thymocytes begin expressing TCR plus which co-receptors?

____ and ____

A thymocyte expressing both CD4 and CD8 is called what?

____-____

A receptor-negative immature thymocyte is protected from apoptosis by high expression of what?

_____

Very immature thymocytes express little to no which apoptosis-related molecule?
A. CD4
B. TCR
C. Bcl-2
D. Fas antigen

The thymic test for MHC restriction is called what?
A. Positive selection
B. Negative selection
C. Peripheral deletion
D. Somatic hypermutation

Positive selection is performed mainly by which thymic cells?

_______

Positive selection asks whether a thymocyte’s TCR can recognize what?

______-______

A thymocyte cannot recognize self-MHC during positive selection. What is its fate?

______

cTECs generate some self-peptides for presentation by digesting their own cytoplasm through what process?

______

cTECs can load autophagy-derived peptides onto which molecule?

______ ______ ______

cTECs may also present protein fragments taken from which source?

______ ______

During or shortly after positive selection, thymocytes usually become what?
A. Double-negative
B. Single-positive
C. Antibody-secreting
D. Receptor-negative

After a thymocyte recognizes self-MHC, it begins expressing which chemokine receptor?

______

CCR7 expression directs selected thymocytes toward which thymic region?

_____

The medulla attracts CCR7-positive thymocytes because it contains abundant what?
A. AIRE protein
B. CCR7 ligands
C. BCR complexes
D. CD40 ligands

Negative selection occurs mainly in which thymic region?

______

Negative selection asks whether the thymocyte recognizes what?
A. Self-peptides
B. Foreign antibodies
C. Complement fragments
D. Chemokine gradients

A thymocyte strongly recognizes self-peptide on MHC. What happens?
A. It becomes CD8
B. It enters blood
C. It is destroyed
D. It becomes Tfh

Failure of negative selection can predispose to what?
A. IgA deficiency
B. Autoimmune disease
C. Neutrophil death
D. Complement depletion

Which medullary cell helps test thymocytes for self-tolerance?

______

mTECs help delete autoreactive T cells through which process?
A. Positive selection
B. Class switching
C. Negative selection
D. Antigen plucking

mTECs generate self-peptides partly through what cellular process?
A. Autophagy
B. Degranulation
C. Exocytosis
D. Opsonization

mTECs express which transcription factor to display tissue-specific antigens?

______

AIRE is best classified as what?
A. Chemokine receptor
B. Transcription factor
C. Death receptor
D. Co-stimulatory ligand

AIRE allows mTECs to express antigens normally found where?

_____ tissues

mTECs use AIRE to express more than how many tissue-specific proteins?
A. One thousand
B. Ten
C. One hundred
D. One million

A child has defective AIRE. Which process is most directly impaired?
A. TCR gene rearrangement
B. Negative selection
C. CD8 lineage choice
D. Cortex proliferation

What is the purpose of central tolerance induction?
A. Increase antibody affinity
B. Activate naive B cells
C. Prevent self-reactive T cells
D. Recruit neutrophils

Why is AIRE important for central tolerance?
A. It binds CD8 directly
B. It creates CCR7 ligands
C. It prevents TCR rearrangement
D. It displays peripheral antigens

The thymocyte migration sequence is best summarized as which pathway?
A. Medulla to cortex
B. Cortex to medulla
C. Spleen to thymus
D. Follicle to PALS

A second thymic cell type helps test developing T cells for self-tolerance in the medulla. What is this cell called?

_____ _____ cell

Thymic dendritic cells are abbreviated as what?
A. FDC
B. cTEC
C. TDC
D. Tfh

Thymic dendritic cells contribute to tolerance testing by presenting what?

_____-_____

TDCs present self-antigens on which molecules?

_____ molecules

In addition to making self-antigens, TDCs also receive self-antigens from which cells?

______

Medullary thymic dendritic cells are resident cells of which region?
A. Thymic cortex
B. Splenic PALS
C. Thymic medulla
D. Lymph-node cortex

Medullary TDCs develop from which precursor source?

______-______-______ precursors

The final thymic output should recognize which structure?
A. Free self-antigen
B. Complement-opsonized antigen
C. Self MHC-peptide complex
D. Antibody constant region

Mature thymic graduates should not recognize self-antigens presented by which cells?
A. B cells and FDCs
B. TDCs and mTECs
C. NK cells and CTLs
D. cTECs and neutrophils

A young thymus tests approximately how many double-positive cells daily?
A. 2 million
B. 6 million
C. 60 million
D. 600 million

Of the daily double-positive thymocytes tested, approximately how many single-positive cells exit?
A. 20 million
B. 2 million
C. 60 million
D. 600,000

Most double-positive thymocytes tested daily undergo what fate?
A. Clonal expansion
B. Class switching
C. Somatic hypermutation
D. Apoptosis

Roughly what percentage of tested thymocytes mature and exit daily?
A. 30%
B. 10%
C. 3%
D. 90%

The Goldilocks hypothesis addresses how one TCR can signal which outcomes?
A. Switching, mutation, apoptosis
B. Selection, deletion, activation
C. Opsonization, lysis, chemotaxis
D. Trafficking, adhesion, rolling

According to the Goldilocks hypothesis, why do so few thymocytes mature?
A. Most cannot signal correctly
B. Most lack bone-marrow origin
C. Most become plasma cells
D. Most migrate into spleen

A T cell survives thymic testing because its TCR interaction strength is “just right.” What does this imply?
A. Strong self-antigen binding
B. No MHC recognition
C. Balanced self-MHC recognition
D. Direct antibody binding

During positive selection, surviving T cells should have what type of interaction with self MHC-peptide?
A. Relatively weak
B. Extremely strong
C. Completely absent
D. Antibody-mediated

Why must self MHC-peptide interaction be relatively weak?
A. Allows focus on antigen
B. Prevents MHC expression
C. Blocks APC activation
D. Eliminates CD4 cells

In the Goldilocks model, interaction with self-peptide presented by medullary TDCs should be what?
A. Very strong
B. Very weak
C. Completely absent
D. Antibody dependent

A thymocyte binds self-peptide on medullary TDCs too strongly. What happens?
A. It becomes nTreg always
B. It is killed
C. It exits rapidly
D. It becomes CD8 only

A thymocyte’s interaction with self-peptide is weak enough to avoid deletion but sufficient for later APC interaction. What does this represent?
A. Goldilocks signaling
B. BCR crosslinking
C. Fc receptor binding
D. Complement activation

Even after thymic exit, many T cells die because they fail to find what?
A. B7 proteins
B. Cognate antigen
C. Fc regions
D. Complement fragments

If a naive T cell never finds cognate antigen, it dies after approximately how long?
A. 2 days
B. 1 week
C. 6 weeks
D. 6 months

Some T cells pass negative selection despite being self-reactive because their antigen is what?

very _____

Escaped self-reactive T cells often fail to cause disease because their cognate antigen is unlikely to be found where?
A. Bone marrow
B. Secondary lymphoid organs
C. Thymic cortex
D. Blood plasma

A T cell escapes deletion because its rare tissue-specific antigen was not encountered. What is this cell?
A. Self-reactive T cell
B. Marginal-zone B cell
C. Follicular helper cell
D. Thymic dendritic cell

Rare tissue-specific cognate antigens may allow some T cells to pass which process?
A. Positive selection
B. Negative selection
C. Class switching
D. Somatic hypermutation

In the thymic medulla, a subset of CD4 T cells becomes which regulatory population?

____

Natural regulatory T cells are selected mainly in which location?

Thymic ______

nTregs arise from which broad T-cell type?

_____ T cells

T cells with weak affinity for self-antigens are generally selected to become what?

_____ cells

T cells with too strong affinity for self-antigens are usually what?
A. Expanded
B. Destroyed
C. Class-switched
D. Exported

T cells with intermediate affinity for self-antigens are selected to become what?

______

nTreg-selected cells are induced to express which gene?
A. AIRE
B. Bcl-2
C. GlyCAM-1
D. Foxp3

Foxp3 expression is associated with which regulatory lineage?
A. Regulatory T cells
B. Marginal-zone B cells
C. Thymic dendritic cells
D. Cortical epithelial cells

nTregs become activated when they encounter which antigen type?
A. Self-antigen
B. Bacterial LPS
C. Viral dsRNA
D. Antibody Fc

Once activated, nTregs suppress which cells?
A. Plasma B cells
B. Potentially self-reactive T cells
C. Resident macrophages only
D. Follicular dendritic cells

The main protective role of nTregs is preventing damage from which cells?
A. Self-reactive T cells
B. Overactive neutrophils
C. IgE-producing B cells
D. Antigen-presenting macrophages

Both nTregs and iTregs express which protein?
A. CTLA-4
B. AIRE
C. Foxp3
D. CD40L

Which regulatory T-cell type protects mainly against self-reactive T cells?

Which regulatory T-cell type restrains overreaction to foreign invaders?

nTregs and iTregs both express Foxp3 but differ mainly in what?
A. Target of suppression
B. MHC class restriction
C. TCR gene number
D. Bone marrow origin

Which regulatory cell is naturally selected within the thymus?

______

Which regulatory cell is inducible from naive Th cells in peripheral settings?

______

A potentially self-reactive virgin T cell leaves normal circulation and enters kidney tissue. Which safety mechanism protects against autoimmunity here?
A. Central tolerance induction
B. Peripheral tolerance induction
C. Somatic hypermutation
D. Missing-self recognition

A virgin T cell recognizes antigen on a normal kidney cell but does not activate. What signal is missing?
A. Complement fixation
B. TCR rearrangement
C. Co-stimulation
D. Fc binding

Why does a normal kidney cell usually fail to activate a virgin T cell?

It lacks _____

A virgin T cell becomes anergized after recognizing antigen without co-stimulation. What is its eventual fate?

_____

A rare self-reactive virgin T cell receives such strong antigen crosslinking that co-stimulation is bypassed. Which backup mechanism limits it?

_____-_____ cell death

Most B cells are tolerized in which location?

_____ _____

A developing B cell recognizes self-antigen in the bone marrow. What process gives it another chance?

_____ _____

Receptor editing most directly involves rearrangement of which B-cell component?

_____ chain

A self-reactive B cell arises after somatic hypermutation. Why is T-cell help unlikely?
A. Matching Th cells are absent
B. B cells cannot present antigen
C. CD40 is always absent
D. Th cells lack MHC II

A virus-infected cell downregulates Class I MHC to evade CTLs. Which immune cell can kill it?

____ cell

In missing-self recognition, NK cells kill because they fail to receive what signal?

____ signal

The inhibitory signal for NK cells depends on recognition of which host molecule?
A. Class I MHC
B. Class II MHC

An NK cell cannot recognize the body’s Class I MHC. Without licensing, what risk would this create?

_____ _____ killing

NK cells must be licensed through which screening process?

_____ selection

During NK-cell licensing, functional NK cells must bind what?

____-____

NK cells that cannot bind self-MHC during licensing become what?

______

A self-reactive B cell after somatic hypermutation usually fails because it cannot efficiently get which two supports?
A. FDC antigen and Th help
B. CTL killing and FasL
C. NK licensing and IL-2
D. AIRE and TDC antigen

Which tolerance mechanism is specific to B cells in this material?
A. Peripheral anergy
B. Receptor editing
C. Missing-self recognition
D. Activation-induced death

Which of the following scenarios best illustrates the induction of peripheral tolerance?

A. A developing T cell undergoes apoptosis in the thymus.

B. An immature B cell undergoes receptor editing in the bone marrow.

C. A mature T cell recognizes an antigen but receives no costimulatory signal.

D. A licensed NK cell kills a tumor cell that has downregulated MHC Class I.

Instead of attempting to test every single T cell for self-reactivity, the immune system relies on five distinct tolerance-inducing mechanisms to prevent autoimmunity:

1. Central Tolerance (Thymic Deletion): Immature T cells that recognize abundant _____-_____ while still in the thymus are eliminated via _____ selection.

Instead of attempting to test every single T cell for self-reactivity, the immune system relies on five distinct tolerance-inducing mechanisms to prevent autoimmunity:

2. Restricted Trafficking (Ignorance): ____ ("virgin") T cells are physically separated from many tissue-specific self-antigens because their ____ ____ are strictly limited to the blood and secondary lymphoid organs.

Instead of attempting to test every single T cell for self-reactivity, the immune system relies on five distinct tolerance-inducing mechanisms to prevent autoimmunity:

3. Regulatory Suppression (nTregs): Self-reactive T cells that reach _____ lymphoid organs (like lymph nodes) are actively suppressed by naturally occurring regulatory T cells

Instead of attempting to test every single T cell for self-reactivity, the immune system relies on five distinct tolerance-inducing mechanisms to prevent autoimmunity:

4. Missing Activation Signals (Anergy/Death): If a naive T cell encounters a self-antigen in peripheral tissues, it fails to receive necessary T-cell receptor (TCR) _____ or _____. Deprived of these signals, the cell either enters a state of permanent unresponsiveness or dies.

Instead of attempting to test every single T cell for self-reactivity, the immune system relies on five distinct tolerance-inducing mechanisms to prevent autoimmunity:

5. Activation-Induced Cell Death (AICD): T cells that experience chronic, repetitive stimulation by persistent self-antigens are driven to undergo ______.

A double negative T cell is resistant to death because of _______

A double positive T cell can die due to its expression of _______

Summary of Somatic Hypermutation Process

1) B-Cells internalize the _____ and use MHC Class _____ to present the antigen to Tfh Cells.

2) B-Cells also provide _____ co-stimulation required for Tfh Cells to remain activated.

3) Tfh Cell provides the B-Cell w/ _____ co-stimulation to keep the B-Cell remained activated.

For this to work, B-Cell and Tfh Cell must recognize the _____ _____.

B cells become tolerant of self in the bone marrow through _____ editing.

What happens to B-cells w/ receptors that don’t bind to self-antigens (abundant in bone marrow)?

They are released to _____ w/ the blood & lymph