T cell Ontogenesis Flashcards
[7-minute video]: T-cell development I
[9-minute video]: T-cell development II
[8-minute video]: Positive and Negative Selection
[24-minute video]: T-cell development with Ninja Nerd
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Briefly outline the process of T cell ontogenesis.
(1) Haematopoietic stem cells in the bone marrow differentiate into lymphoid precursor cells. Lymphoid precursor cells have the potential to develop into three main types of lymphocytes: T lymphocytes, B lymphocytes and Natural Killer cells.
(2) Lymphoid precursor cells destined to become T cells migrate from the bone marrow to the thymus. These migrating cells are referred to as pro-thymocytes.
(3) In the thymus, pro-thymocytes undergo a series of maturation steps. The thymus provides a specialized environment that supports the development and differentiation of T cells.
🩺 Positive selection: T cells that can recognize self-MHC molecules with moderate affinity are selected for survival.
🩺 Negative selection: T cells that bind too strongly to self-antigens presented by MHC molecules are eliminated to prevent autoimmunity.
(4) The T cells differentiate into two subtypes: CD4+ T cells [which assist other immune cells by secreting cytokines that enhance the immune response] and CD8+ T cells [which directly kill infected or abnormal cells by recognizing antigens presented by MHC class I molecules.]
What are the three stages in the maturation of T cells in the thymus?
(1) Proliferation of immature cells
(2) Expression of antigen receptor genes
(3) Selection of lymphocytes that express useful antigen receptor (TCR)
Discuss the first stage of maturation of T cells: proliferation of immature cells.
A population of lymphoid precursor cells from the bone marrow enters the thymus via the bloodstream. These progenitors are the precursors to T cells. Once in the thymus, these progenitor cells undergo extensive cell division to generate a large population of immature thymocytes. This expansion is crucial for providing a diverse pool of cells for further development.
Discuss the second stage of maturation of T cells: expression of antigen receptor genes.
Immature thymocytes each make distinct T cell receptors by a process of gene rearrangement. This gene rearrangement process is inherently error-prone. Some thymocytes fail to produce functional TCRs, while others may produce TCRs that are autoreactive (i.e., they recognize self-antigens).
Discuss the third stage of maturation of T cells: selection.
Positive Selection: Thymocytes with TCRs that can moderately bind to self-MHC molecules are selected for survival. This occurs in the thymic cortex and ensures that the T cells can recognize antigens presented by the body’s own MHC molecules.
Negative Selection: Thymocytes with TCRs that bind too strongly to self-antigens are eliminated through apoptosis. This process occurs in both the cortex and medulla of the thymus and prevents the development of autoreactive T cells that could cause autoimmune diseases.
Explain how T cells acquire the cluster of differentiation surface markers.
🧬 Double Negative (DN) Stage: Thymocytes lack both CD4 and CD8 surface markers. This stage is further divided into four sub-stages (DN1, DN2, DN3, DN4) based on the expression of other surface markers like CD25 and CD44.
🧬 Double Positive (DP) Stage: Thymocytes express both CD4 and CD8 surface markers. This stage is crucial for positive and negative selection.
🧬 Single Positive (SP) Stage: Thymocytes mature into either CD4+ helper T cells or CD8+ cytotoxic T cells, depending on their interaction with MHC class II or class I molecules, respectively.
Explain the role of thymic epithelial cells in T cell development.
Thymic epithelial cells are located in the cortex of the thymus. These cells present self-peptides bound to MHC class I and II molecules to developing thymocytes. This interaction is essential for positive selection, where thymocytes that can moderately bind to self-MHC molecules receive survival signals.
[Diagram 1]
Briefly discuss the activation and functions of Cytotoxic T lymphocytes.
🩺 CTLs recognize and bind to antigens presented by class I MHC molecules on surface of infected or abnormal cells. This recognition is facilitated by the T-cell receptor on the CTL.
🩺 Upon recognizing an antigen CTLs become activated. This activation often requires additional signals from helper T cells.
🩺 Once activated, CTLs release cytotoxic granules containing perforin and granzymes. Perforin creates pores in the target cell membrane, allowing granzymes to enter the cell.
🩺 Granzymes induce apoptosis by degrading essential cellular components.
🩺 CTLs also release cytokines such as tumor necrosis factor and interferon-gamma (IFN-γ), which help enhacne the immune response and recruit other immune cells to the site of infection.
Briefly discuss the function of Helper T cells.
🩺 Th cells help activate and direct other immune cells, including B cells, cytotoxic T cells, and macrophages.
🩺 Th cells secrete various cytokines that regulate the immune response. These cytokines can enhance the activity of other immune cells, promote inflammation, and help in the differentiation of other T cells.
Briefly discuss the following subsets of Th cells:
(a) Th1 cells
(b) Th2 cells
(a) Th1 cells: produce cytokines like interferon-gamma (INF-γ) and interleukin-2 (IL-2), which activate macrophages and promote the destruction of intracellular pathogens.
(b) Th2 cells: secrete cytokines such as interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-10 (IL-10), which help B cells produce antibodies and are essential for combating extracellular pathogens.
Briefly discuss the following subsets of Th cells:
(a) Th17 cells
(b) Regulatory T cells
(a) Th17 cells: produce interleukin-17 (IL-17) and are involved in the defense against extracellular bacteria and fungi, as well as in the pathogenesis of autoimmune diseases.
(b) Regulatory T Cells (Tregs): express CD4, CD25, and FoxP3, and they help maintain immune tolerance by suppressing the activation and function of other T cells, preventing autoimmune responses.
