Block C - Regulation of Immune Response Flashcards
(40 cards)
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.
Which APC do Tregs modulate?
dentritic cells
Why do we need Tregs? (4 marks)
-helps prevent of autoimmunity by inhibiting self-reactive T cells
-promotes tolerance to harmless antigens, such as food proteins and commensal microbes in the gut. This is vital for preventing allergic reactions and excessive inflammatory responses to non-harmful stimuli.
-Tregs help control inflammation and plays a role in limiting tissue damage during immune responses, reducing the risk of chronic inflammatory diseases
-Tregs modulate the activity of other immune cells, including effector T cells and dendritic cells.
Describe Tregs role in cancer
In the context of cancer, Tregs can have a dual role. While they can suppress anti-tumor immunity which leads to immune evasion by tumors, they also help in preventing uncontrolled inflammation that can damage healthy tissue and cause cancer
How are naiive T cells reprogrammed to become Tregs
In the thymus, the presence of the cytokine, TGF-β, encourages the expression of the transcription factor FoxP3, which is essential for Treg function.
Tregs need constant stimulation from what cytokine to survive?
IL-2
What is FoxP3 and its importance with Tregs? (2 marks)
-FoxP3 (Forkhead box protein P3) is a critical transcription factor, which is critical for differentiation of CD4+ T cells into Tregs during thymic development.
-FoxP3 also regulates the expression of cytokines IL-10 and TGF-β which are involved in immune suppression and help modulate the activity of effector T cells.
Outline the clinical relevence of mutations in the FoxP3 in diseases (2 marks)
-mutations in FoxP3 can lead to severe autoimmune diseases.
-for example, mutations in the FoxP3 gene are associated with immune dysregulation, polyendocrinopathy, enteropathy, and X-linked syndrome (IPEX syndrome)
nTregs make up ____% of peripheral CD4+ cells?
A. 10-15%
B. 3%
C. 18%
D. 5-10%
D
