Lecture 10 t cells 2

Introduction to T Cells

In this lecture, the focus is on different types of T cells, specifically T helper cells, and their roles in the immune system. T cells are a critical component of the adaptive immune system, and understanding their functions is essential for comprehending immune responses.

Overview of T Cell Development

T cell precursors originate in the bone marrow and migrate to the thymus where they undergo a maturation process. Initially, they are double negative thymocytes (CD4- CD8-), which later become double positive (CD4+ CD8+) and eventually develop into single positive thymocytes (either CD4+ or CD8+). The differentiation into CD4+ T helper cells is dependent on interaction with MHC class II molecules.

CD4 T Cells: Functions and Subsets

CD4+ T cells are essential for coordinating immune responses. They can be classified into several subsets, including:

• T helper 1 (Th1)

• T helper 2 (Th2)

• T helper 17 (Th17)

• Regulatory T cells (Tregs)

• T follicular helper cells (Tfh)

Each subset has distinct roles, depending on the type of pathogen and the immune response required.

Th1 Cells

Th1 cells are crucial in combating intracellular pathogens, such as viruses and some bacteria. They are activated by IL-12 cytokine and predominantly produce interferon-gamma (IFN-γ), which activates CD8+ T cells and macrophages, enhancing their ability to kill infected cells. This positive feedback loop reinforces Th1 mediated immune responses while inhibiting Th2 responses. transcription factors are STAT 1 STAT 4 and T bet. T bet is the master regulator of Th 1 cell.

Th2 Cells

Th2 cells respond to large extracellular pathogens like helminths. Their activation is primarily driven by interleukin-4 (IL-4), which also stimulates B cells to produce antibodies, particularly IgE. The key transcription factors (guide t cells to th2) involved in Th2 differentiation are STAT6 and GATA3 and cmaf. Th2 cells help in recruiting eosinophils and mast cells, which play roles in allergies and asthma.

Th17 Cells

Th17 cells are important for inflammatory responses and are associated with autoimmune diseases, have critical functoins in anti microbial immunity against gastrointestinal pathogens at epithelia/mucosal barriers. They are driven by cytokines such as IL-6, TGF-β, and IL-23, and need a master transcription factor - RORγt, primarily producing IL-17. . This cytokine helps recruit neutrophils and enhance local inflammation, thus playing a double-edged role in immunity and autoimmunity.

T Follicular Helper Cells (Tfh)

Tfh cells facilitate B cell activation and affinity maturation in germinal centres. They express CxCr5 on cell surface allowing them to get closer to B cells, secrete IL-21 and express CD40L, which interacts with CD40 on B cells to promote antibody responses. Transcriptoin factor is Bcl - 6 same as B cells.Their proper function is critical for effective vaccination, as they help generate memory B cells capable of high-affinity responses.

Regulatory T Cells (Tregs)

Tregs through dominance tolerance mechanism are essential for maintaining immune tolerance and preventing autoimmune responses. They can develop in the thymus or be induced in the periphery in response to self-antigens, and their master regulator is FOXP3. Tregs exert their effects through cytokine production (e.g., IL-10, TGF-β) and by direct cell contact, inhibiting the activation of effector T cells.

Immune Tolerance and Autoimmunity

(e.g In pregnancy, cancer cells) The balance between effector T cells and regulatory T cells is crucial for preventing autoimmune diseases. An excess of effector T cells or a deficiency in regulatory T cells can lead to unchecked inflammation and autoimmunity. For instance, conditions like multiple sclerosis and rheumatoid arthritis are associated with the overactivation of T helper cells, particularly Th1 and Th17 subsets.

Conclusion

Understanding T cell differentiation and function is pivotal in medical biotechnology and immunology. Each T cell subset has tailored responses to different pathogens and can influence the outcome of immune responses, including pathology in autoimmune diseases. This lecture lays the groundwork for further exploration into vaccination and immune therapeutic strategies.