transcriptional responses to stress and infection Flashcards

5-6

1
Q

What happens to naïve T cells after leaving the thymus?

A

Naïve T cells (CD4+ or CD8+) recirculate via blood/lymphatics through secondary lymphoid tissues (lymph nodes, spleen) and require contact with specific antigen and antigen-presenting cells (APCs) for activation.

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2
Q

What are the primary roles of CD4+ and CD8+ effector T cells?

A

CD4+ T cells (helper): Secrete cytokines to help other immune cells.
CD8+ T cells (cytotoxic): Kill infected cells presenting specific peptide/MHC class I complexes.

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3
Q

What is the function of cell adhesion molecules (CAMs) in T cell activation?

A

CAMs mediate interactions between T cells and other cells, facilitating movement and antigen recognition. Examples:

  1. Naïve T cell with high endothelial venules (HEV).
  2. T cell with APC.
  3. Effector T cell with target cell.
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4
Q

How many signals are required for T cell activation, and what are they?

A

Three signals:
1. TCR interaction with MHC/peptide on APC (Signal 1).
2. Co-stimulatory molecule interaction (e.g., B7 on APC binds CD28 on T cell, Signal 2).
3. Cytokines released by APC bind cytokine receptors on T cell (Signal 3).

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5
Q

What is CTLA-4, and why is it important?

A

CTLA-4 is a molecule expressed by activated T cells. It binds B7 on APC with higher affinity than CD28, delivering a negative signal to dampen the T cell response. Mutations are linked to autoimmune diseases and are a target for cancer therapy.

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6
Q

What happens to naïve T cells that do not encounter their specific antigen?

A

They leave the lymph node via cortical sinuses into the lymphatics, re-enter circulation, and continue recirculating.

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7
Q

What is interleukin-2 (IL-2), and what is its role in T cell activation?

A

IL-2 is a cytokine critical for T cell proliferation and survival. Activated T cells express a high-affinity IL-2 receptor and secrete IL-2, leading to rapid clonal expansion of antigen-specific T cells.

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8
Q

What are dendritic cells (DCs), and how do they activate T cells?

A

Conventional DCs (DC2, DC3): Potent APCs that activate naïve T cells.
Plasmacytoid DCs (pDC, DC6): Important in viral infections, secrete type I interferons.
Mature DCs express high levels of MHC, co-stimulatory molecules, and adhesion molecules, ensuring efficient activation of T cells.

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9
Q

What is cross-presentation in T cells?

A

Specialized dendritic cells can present exogenous antigens via MHC class I molecules, allowing activation of naïve CD8+ T cells to target infected cells lacking co-stimulatory signals.

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10
Q

What differentiates B cells as APCs from dendritic cells and macrophages?

A

B cells use BCR to internalize and present antigens specifically.
BCR engagement upregulates B7, enabling B cells to provide Signal 2 to T cells.
Unlike DCs, B cells are antigen-specific APCs.

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11
Q

How are APCs activated, and what is the “danger signal”?

A

APCs are activated by pathogen-associated molecules binding to pattern recognition receptors (PRRs), like TLRs. This “danger signal” upregulates MHC and co-stimulatory molecule expression, ensuring T cells receive Signal 2.

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12
Q

What controls the differentiation of CD4+ T cells into subtypes?

A

Cytokines (Signal 3) released by APCs and the surrounding environment/pathogen influence the differentiation of CD4+ T cells into specific effector subsets.

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13
Q

What is the role of high endothelial venules (HEVs) in T cell trafficking?

A

HEVs allow naïve T cells to enter lymph nodes from the blood and migrate to T cell areas rich in dendritic cells and macrophages.

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14
Q

Why are co-stimulatory signals necessary for T cell activation?

A

Co-stimulatory signals ensure that T cell activation occurs only in the presence of pathogens, preventing inappropriate activation. Example: B7 on APC binding to CD28 on T cell.

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15
Q

What happens to self-reactive B cells in the bone marrow?

A

They undergo clonal deletion, receptor editing, or downregulation of BCR expression (anergy).

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16
Q

What triggers the activation and survival of B cells?

A

Binding of non-self antigens activates B cells, leading to their survival and differentiation into plasma cells that produce the same antibody as the BCR.

17
Q

What do naive B cells express on their surface?

A

Membrane-bound IgM and IgD (BCR).

18
Q

Where do B cells encounter antigens for activation?

A

In secondary lymphoid tissues.

19
Q

What is signal 1 in B cell activation?

A

Binding of antigen to the BCR.

20
Q

How is signal 1 enhanced in B cells?

A

By the binding of antigens coated with complement (e.g., C3d) to CR2 on the B cell, forming the BCR co-receptor complex.

21
Q

What are thymus-independent (TI) antigens?

A

Antigens that provide signal 2 directly through the antigen itself or through extensive BCR crosslinking.

22
Q

What are the two types of TI antigens?

A

TI-1: Provide signal 2 via additional receptors (e.g., TLR4).
TI-2: Contain repeated epitopes, such as polysaccharides, that crosslink BCRs.

23
Q

What are thymus-dependent (TD) antigens?

A

Antigens requiring CD4+ T cell help for B cell activation, including interaction via CD40/CD40L and cytokines.

24
Q

How do B cells present antigen to CD4+ T cells?

A

B cells internalize the antigen, process it, and present it on MHC class II molecules.

25
Q

What role does CD40/CD40L play in B cell activation?

A

CD40L on T cells binds CD40 on B cells, providing signal 2 and triggering class switching and proliferation.

26
Q

Where do germinal centers form, and what occurs there?

A

Germinal centers form in B cell follicles of secondary lymphoid tissues; B cells undergo somatic hypermutation, isotype switching, and differentiation.

27
Q

What is somatic hypermutation (SHM)?

A

A process introducing point mutations in Ig V regions, increasing antibody affinity.

28
Q

What enzyme is critical for SHM and class switching?

A

Activation-induced deaminase (AID).

29
Q

What is the role of follicular dendritic cells (FDC) in germinal centers?

A

FDCs capture antigens and present them to centrocytes, aiding in affinity maturation.

30
Q

What are follicular T helper (TFH) cells?

A

Specialized CD4+ T cells in B cell follicles that provide help to B cells via cytokines and CD40 signaling.

31
Q

What happens to B cells with low-affinity BCRs in germinal centers?

A

They either die by apoptosis or recycle to the dark zone for further mutation.

32
Q

How do conjugate vaccines improve responses to TI antigens?

A

By linking a TI antigen (e.g., polysaccharide) to a protein carrier, converting it into a TD antigen.

33
Q

What is a centroblast, and where is it found?

A

A rapidly dividing B cell in the germinal center undergoing SHM and class switching.

34
Q

What is a centrocyte, and where is it found?

A

A non-dividing B cell in the germinal center, selected based on BCR affinity for antigen.

35
Q

What BCR isotypes can be co-expressed by a single B cell?

A

IgM and IgD (via differential mRNA splicing).

36
Q

How do signals for B cell activation differ from T cell activation?

A

B cells require signals from antigen binding (BCR), T cells (CD40/CD40L), and cytokines, while T cells require MHC/peptide binding and co-stimulation.