Tour with the Immune System’s T Cells
What is a T cell?
A T cell is a type of white blood cell that is a part of the immune system. T cells play a crucial role in defending the body against various threats like infections and cancer. There are several specialized types, each with a unique function in the immune system. T cells are crucial for immune defence: they have the ability to destroy harmful pathogens, send signals to control the immune system’s response against diseases such as cancer.
How Are T Cells Made?
T cells originate from Hematopoietic Stem Cells (HSCs) within the bone marrow. Stem cells can differentiate into various cell types: myeloid cells (neutrophils and macrophages) and lymphoid cells (B cells and T cells.) For the pathway of a T cell, the HSCs differentiate to become lymphoid progenitor cells which are uncommitted, precursor cells that then develop into lymphocytes (T cells, B cells, and NK cells).
The progenitor cells (a specialized cell that can divide to produce more progenitor cells or differentiate into a more specialized cell type) then migrate from the bone marrow to the thymus through the bloodstream. The thymus is an organ that is located in the upper chest and houses T cell maturation.
T cells have the ability to recognize specific antigens through their receptors (TCRs). These T cell receptors are composed of alpha and beta chains. The alpha and beta chain TCR is a protein complex found on the surface of the T cell that allows it to recognize and bind to specific antigens. The genes that are encoded in these chains are located separately within the T cell DNA. The DNA rearrangement process then occurs in the thymus: the TCR gene segments are randomly combined to create unique TCRs for each T cell. This makes the TCRs capable of recognizing a wide range of antigens.
After DNA rearrangement, the immature T cells (thymocytes) will then go through both positive and negative selection.
Positive Selection: Ensures that only T cells capable of recognizing self-MHC (major histocompatibility complex (MHC) molecules found on the surface of cells in an individual's own body that are responsible for binding and displaying antigen peptides to T-cells) survive
Negative Selection: Thymocytes that react strongly with self-antigens are eliminated in the thymus to prevent the development of autoimmune diseases.
What is the T Cell Lineage and Types of T Cells?
After T cells mature in the Thymus, they are then classified based on their surface markers.
Naive T Cells: These are mature but not yet activated T cells that circulate through lymphoid tissues and wait to encounter a specific antigen. When a naive T cell encounters an antigen presented by an antigen-presenting cell (APCs), it undergoes activation. Activated T cells produce cytokines: signaling molecules that can modulate immune response. After activation, the T cell goes through clonal expansion and differentiation into the types of T Cells.
CD4+ T Cells (Helper T Cells): These cells coordinate the immune response by signaling other immune cells (macrophages, B cells, and cytotoxic T cells). There are 4 subtypes:
Th1 cells: Help activate macrophages. Macrophages are a type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells.
Th2 cells: Help activate B cells to produce antibodies. B cells are a type of white blood cell that produces antibodies.
Th17 cells: Help activate neutrophils. Neutrophils are the most abundant type of white blood cell produced in the bone marrow and are the first line of defense against infections.
Tfh cells: Help B cells in places such as the lymph nodes and the spleen.
CD8+ T Cells (Cytotoxic T Cells): Directly responsible for killing infected or cancerous cells. They are the main effectors in tumor cell destruction and release perforins (pore-forming protein that creates channels in target cell membranes) and granzymes (enzymes that catalyze the cleavage of peptide bonds) to induce apoptosis (cell death).
Regulatory T Cells (Tregs): Suppress excessive immune responses (by producing inhibitory cytokines like IL-10, TGF- β, and IL-35) and help maintain immune homeostasis, prevent autoimmune diseases, and prevent the immune system from overreacting to foreign invaders. T regs are also involved in various other immune functions -tolerance to self-antigens and suppression of allergy and asthma.
Characterized by the expression of the surface marker CD4, CD25, and the transcription factor FOXP3
Can modulate the function of dendritic cells, which are important for initiating immune responses.
Suppress immune cells by disrupting their metabolism, leading to their death or reduced activity.
T Cells and Tumors
T cells play a crucial role in anti-tumor immunity by recognizing tumor antigens through their TCRs. The TCR binds to the tumor peptides on the surface of tumor cells or antigen-presenting cells. Tumors greatly affect the immune system. They create an immunosuppressive environment and disrupt the activity of T cells, macrophages, and dendritic cells. They also have the ability to activate pathways that suppress the immune system. Tumors can also damage the bone marrow, which is the site of immune cell production; this weakens the body’s defenses. Tumors also disrupt the process of antigen presentation to Naive T cells; preventing the immune system from activating T cells that can effectively recognize and target tumor cells.
Cytotoxic CD8+ T cells are the primary effector cells, recognizing and directly killing tumor cells displaying cognate antigens. CD4+ T cells, particularly T helper 1 (Th1) cells, play a vital supportive role by secreting cytokines that enhance the activation, proliferation, and effector functions of CD8+ T cells and other immune cells.
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Written By: Keira Crasta
