Block C - Regulation of Immune Response Flashcards
Describe how T cells are activated? (4 marks)
-T cells bind to their respective MHC complex on the APC via a TCR, CD4+ bind to MHC II while CD8+ bind to MHC I.
-in addition to this, T cells require a second signal for full activation, which is known as co-stimulation
-this comes from interactions in the immunological synapse which is of CD28 on the T cell to ligands on the APC like B7-1 and B7-2
-T cells also rely on cytokines produced by the APC or other immune cells to promote their proliferation and differentiation, for examples IL-2
Describe the role of the subset Th1? (3 marks)
-Promote cell-mediated immunity.
-Produces interferon-gamma (IFN-γ), which activates macrophages and enhances their ability to kill intracellular pathogens.
-Important in defense against viral and certain bacterial infections
Describe the role of the subset Th2? (3 marks)
-Support humoral immunity and help in the response to extracellular parasites.
-Produce interleukin-4 (IL-4), IL-5, and IL-13, which promote B cell activation and antibody production, especially IgE.
-Key in allergic responses and protection against helminths (worms)
Describe the role of the subset Th17? (3 marks)
-Involved in inflammatory responses and defense against extracellular bacteria and fungi.
-Produce IL-17 and IL-22, which recruit neutrophils and promote inflammation.
-Important in development of autoimmune diseases with Th1 cells and chronic inflammation.
Describe the role of the subset Treg? (3 marks)
-Suppress immune responses to maintain tolerance and prevent autoimmunity.
-Produce anti-inflammatory cytokines like IL-10 and transforming growth factor-beta (TGF-β).
-Help regulate and limit the immune response, preventing excessive inflammation.
Describe the role of the subset Th9? (3 marks)
-Involved in the response to parasites and contribute to allergic inflammation.
-Produce IL-9, which supports mast cell proliferation and activity.
-Less well-defined, but implicated in asthma and allergy
PQ. Describe the concept of plasticity in T helper (Th) subsets. Discuss how environmental factors influence this plasticity and how the plasticity can influence disease. (10 marks)
-plasticity refers to the ability to change from one subset to another in response to varying environmental stimuli, signals and cytokines
-this ability to shift their roles and adapt allows the immune system to respond effectively to a wide variety of pathogens, whether they are intracellular or extracellular
-the presence of IL-12 encourages the development of Th1 cells, while IL-4 mediates Th2 cells. however when the cytokine environment changes, such as in the presence of IL-12, Th2 can acquire properties of Th1
-Th17 cells can convert to Treg cells under high levels of TGF-β
-however while T cell plasticity ensures that we have a flexible immune system, its also evolved in the pathogenesis of cancer, autoimmunity diseases and chronic conditions
-T cell plasticity can lead to an imbalance in Th subset activity, often resulting in an overactive Th1 or Th17 response, which promotes inflammation and tissue damage.
-In conditions like rheumatoid arthritis and multiple sclerosis, increased Th17 activity is observed.
-The ability of Th cells to shift towards more inflammatory profiles can exacerbate these diseases.
-Tumor microenvironments may promote the differentiation of Th cells into Tregs, which suppress anti-tumor responses.
-this can inhibit the activity of effector T cells, highlighting the need for therapies that can reprogram T cells to be more cytotoxic.
Give 2 examples of plasticity in T helper cells?
-the presence of IL-12 encourages the development of Th1 cells, while IL-4 mediates Th2 cells. however when the cytokine environment changes, such as in the presence of IL-12, Th2 can acquire properties of Th1
-Th17 cells can convert to Treg cells under high levels of TGF-β
Explain how T helper plasticity can contribute to pathogenesis of diseases? (5 marks)
-T cell plasticity can lead to an imbalance in Th subset activity, often resulting in an overactive Th1 or Th17 response, which promotes inflammation and tissue damage.
-In conditions like rheumatoid arthritis and multiple sclerosis, increased Th17 activity is observed.
-The ability of Th cells to shift towards more inflammatory profiles can exacerbate these diseases.
-Tumor microenvironments may promote the differentiation of Th cells into Tregs, which suppress anti-tumor responses.
-this can inhibit the activity of effector T cells, highlighting the need for therapies that can reprogram T cells to be more cytotoxic
Where are ILC’s usually found?
predominantly found in tissues, especially in mucosal sites like the gut, lungs, and skin
ILC1 is similar to which T helper subset?
Th1
ILC2 is similar to which T helper subset?
Th2
ILC3 is similar to which T helper subset?
Th17
Compare the development of ILCs to T cells?
ILCs develop from common lymphoid progenitors in the bone marrow like T cells but do not undergo gene rearrangement like T and B cells. They mature in peripheral tissues, particularly in mucosal sites.
Compare the 2 types of Tregs
Natural Tregs (nTregs) develop in the thymus and play a key role in maintaining peripheral tolerance while Induced Tregs (iTregs) arise from naive T cells in the periphery in response to specific signals, such as TGF-β and retinoic acid. They are important in maintaining tolerance in tissues.
Explain how Treg cells downregulate the immune response
Tregs produce immunosuppressive cytokines such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β). These cytokines can inhibit the activity of effector T cells (like Th1 and Th2 cells). Treg can consume IL-2, limiting its availability to other immune cells, particularly effector cells. This helps regulate the activation and proliferation of effector cells.
