transcriptional responses to stress and infection

Question 1

What happens to naïve T cells after leaving the thymus?

Answer 1

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.

Question 2

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

Answer 2

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.

Question 3

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

Answer 3

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.

Question 4

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

Answer 4

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).

Question 5

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

Answer 5

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.

Question 6

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

Answer 6

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

Question 7

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

Answer 7

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.

Question 8

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

Answer 8

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.

Question 9

What is cross-presentation in T cells?

Answer 9

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.

Question 10

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

Answer 10

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.

Question 11

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

Answer 11

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.

Question 12

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

Answer 12

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

Question 13

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

Answer 13

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

Question 14

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

Answer 14

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.

Question 15

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

Answer 15

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

Question 16

What triggers the activation and survival of B cells?

Answer 16

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.

Question 17

What do naive B cells express on their surface?

Answer 17

Membrane-bound IgM and IgD (BCR).

Question 18

Where do B cells encounter antigens for activation?

Answer 18

In secondary lymphoid tissues.

Question 19

What is signal 1 in B cell activation?

Answer 19

Binding of antigen to the BCR.

Question 20

How is signal 1 enhanced in B cells?

Answer 20

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

Question 21

What are thymus-independent (TI) antigens?

Answer 21

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

Question 22

What are the two types of TI antigens?

Answer 22

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

Question 23

What are thymus-dependent (TD) antigens?

Answer 23

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

Question 24

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

Answer 24

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

Question 25

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

Answer 25

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

Question 26

Where do germinal centers form, and what occurs there?

Answer 26

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

Question 27

What is somatic hypermutation (SHM)?

Answer 27

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

Question 28

What enzyme is critical for SHM and class switching?

Answer 28

Activation-induced deaminase (AID).

Question 29

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

Answer 29

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

Question 30

What are follicular T helper (TFH) cells?

Answer 30

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

Question 31

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

Answer 31

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

Question 32

How do conjugate vaccines improve responses to TI antigens?

Answer 32

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

Question 33

What is a centroblast, and where is it found?

Answer 33

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

Question 34

What is a centrocyte, and where is it found?

Answer 34

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

Question 35

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

Answer 35

IgM and IgD (via differential mRNA splicing).

Question 36

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

Answer 36

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