Topic 6: T Cell Immunity and Effector Mechanisms Flashcards
What are the 3 basic facts about T-lymphocytes?
- Specificity in lymphocytes is generated by clonal selection
- The TCR recognises peptide antigen presented by MHC
- There are 2 major types of T lymphocytes- helper T cells (CD4+) and cytotoxic T cells (CD8+)
How do T cells kill obligate intracellular pathogens?
- CD4 cells activate macrophages to upregulate killing
- CD8 cells kill infected macrophages
How do T cells kill viruses?
- CD8 cells kill virally infected cells
- antibodies also play a role in neutralising extracellular viruses
How do T cells kill tumours?
- CD8 cells recognise mutated cancer peptides on the MHC Class I of tumour cells
How is T cell mediated immunity activated in the lymph node/spleen?
- Afferent lymphatic vessel brings dendritic cells into lymph nodes/spleen
- Dendritic cells present antigen peptides on their MHC Class II
- The naïve T cells that are circulating in the lymph nodes/spleen if they are complementary for the presented antigen will bind to the antigen and they will bind, be activated and differentiate into effector CD4 and CD8 cells
- The differentiated T cells leave the lymphocyte and enter circulation and migrate to the site of infection
- Effector T cells then use their effector mechanisms to kill intracellular microbes (CD4= secretion of cytokines, CD8= cytotoxic cell killing)
What are the 5 key stages from T cell activation to T cell effector function?
- Antigen recognition
- Activation of T cell
- Clonal expansion
- Differentiation
- Effector functions
What molecules engage the T Cell activation signal transduction pathway?
APC surface: MHC peptide complex, B7 and ICAM-1
T cell surface: TCR complex (TCR alpha and beta chains, CD3 chain and sigma chain), CD4/8, CD28
What is the role of co-receptors CD4 and CD8?
- Signal transduction:
- The ectodomains bind to the invariant region of MHC Class II/MHC Class I
- They have large cytoplasmic domains so once activated create a binding domain for the tyrosine kinase Ick which phosphorylates the ITAMs on TCR associated CD3 and ζ chains
- Phosphorylation of ITAMs creates binding sites for the tyrosine kinase ZAP which phosphorylates a range of adaptor proteins that activate second messenger pathways
What is the role the adhesion molecules in T cell activation?
- Adhesion
- T cell adhesion molecule= LFA-1
- Adhesion molecule ligand = ICAM-1
- When the TCR/MHC + peptide interaction takes place the adhesion molecule of the T cell LFA-1 is changed in confirmation to a high affinity state so it will bind ICAM-1 on the signalling cell more strongly and stabilise the connection between the T cell and the signalling cell
What are the 2 signals required to activate a T Cell?
- Signals transduced through the TCR complex binding with MHC + peptide
- Costimulatory signal (e.g. CD28 interacting with B7 on activated APC)
What genes are transcribed by T cell activation?
- C-Fos and C-Myc: transcription factors that control cell cycle- driving the T cell into cell division
- CD40 ligand and Fas ligand: membrane effector molecules that enable activated T cells to interact with other immune cells
- Il-2, IFN-ỿ, IL-4: cytokines
- High affinity IL-2 receptor (IL-2 signalling triggers cell proliferation and differentiation)
What 3 types of T helper cells can the undifferentiated T0 cell differentiate into?
- What determined this pathway?
- Th1 cell
- Th2 cell
- Th17 cell
- The type of differentiation is driven by the cytokines surrounding the Th0 cell
What are Th1 cells?
What cytokine drives their differentiation?
What is the key cytokine they produce?
What kind of pathogens are they important in targeting?
What negative effects can they have?
- T helper 1 cells
- IL-12 and also IFN-y drive the differentiation
- Th1 cells secrete IFN-y which means they activate macrophages and promote the secretion of antibodies
- Th1 cells are important in targeting intracellular pathogens
- Negative: highly pro-inflammatory and not effective against large pathogens
What are Th2 cells?
What cytokine drives their differentiation?
What is the key cytokine they produce?
What kind of pathogens are they important in targeting?
What negative effects can they have?
- T helper 2 cells
- IL-4 drives their differentiation
- The key cytokines they produce are IL-4 (B cell activation and production of neutralising antibodies and IgE) and IL-5 (promotes eosinophils) as well as IL-13
- Important in targeting helminths
- Can cause atopic disease (due to production of IgE and activation of mast cells)
What are Th17 cells?
What cytokine drives their differentiation?
What is the key cytokine they produce?
What kind of pathogens are they important in targeting?
What negative effects can they have?
- T helper 17 cells
- Differentiation driver by IL-1, IL-6, IL-21 and TGF-B
- The key cytokines produced are IL-17 (induction of proinflammatory cytokines and IL-22 (promotes integrity of epithelial barriers)
- Target extracellular pathogens such as extracellular bacteria and fungi
- Negative effects: autoimmunity- inflammation
