transcriptional responses to stress and infection Flashcards
5-6
What happens to naïve T cells after leaving the thymus?
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.
What are the primary roles of CD4+ and CD8+ effector T cells?
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.
What is the function of cell adhesion molecules (CAMs) in T cell activation?
CAMs mediate interactions between T cells and other cells, facilitating movement and antigen recognition. Examples:
- Naïve T cell with high endothelial venules (HEV).
- T cell with APC.
- Effector T cell with target cell.
How many signals are required for T cell activation, and what are they?
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).
What is CTLA-4, and why is it important?
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.
What happens to naïve T cells that do not encounter their specific antigen?
They leave the lymph node via cortical sinuses into the lymphatics, re-enter circulation, and continue recirculating.
What is interleukin-2 (IL-2), and what is its role in T cell activation?
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.
What are dendritic cells (DCs), and how do they activate T cells?
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.
What is cross-presentation in T cells?
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.
What differentiates B cells as APCs from dendritic cells and macrophages?
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.
How are APCs activated, and what is the “danger signal”?
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.
What controls the differentiation of CD4+ T cells into subtypes?
Cytokines (Signal 3) released by APCs and the surrounding environment/pathogen influence the differentiation of CD4+ T cells into specific effector subsets.
What is the role of high endothelial venules (HEVs) in T cell trafficking?
HEVs allow naïve T cells to enter lymph nodes from the blood and migrate to T cell areas rich in dendritic cells and macrophages.
Why are co-stimulatory signals necessary for T cell activation?
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.
What happens to self-reactive B cells in the bone marrow?
They undergo clonal deletion, receptor editing, or downregulation of BCR expression (anergy).