Immune tolerance and immune recognition Flashcards
As TCR is diverse, how do T cells not mistakenly kill ‘self’ cells
By developing immune tolerance which prevents autoimmunity but permits appropriate antipathogen responses. Negative selection of thymic education, TMEC express variety of tissue restricted antigens, its failure leads to autoimmune disease
How does thymic education work
Positive selection-thymocyte checks whether its receptor binds to MHC I or II at thymic cortex and loses expression of CD4 or 8 or both depending on which one it binds to
Negative selection-eliminates high affinity self reactive T cells at thymic medullary epithelial cells. If safe, enters peripheral circulation
After thymic education, how does peripheral mechanisms of immune tolerance ensure that T cell doesn’t respond to ‘self’?
Anergy-T cells remain in circulation but unresponsive to further stimulation (signal 2). APC doesn’t express cosstimulatory molecules. If the T cell sees antigens all the time without inflammation->tolerance
Regulatory T cells-controls and suppresses effector whose job is to eliminate pathogen. Inhibitory effect on Th1 (no proliferation and cytokine production) and APC (reduce costimulation, alter cytokinee production
Anergy is important for tolerance of what
antigens not expressed in thymic education, food antigens, commensal bacteria
What are the 2 types of regulatory T cells and what do they do
nTreg-naturally occuring, produced in thymus, respond to self antigens, protection from autoimmunity
aTreg-aadaptive, induced, develop in periphery, constant low level exposure to antigen, protection from autoimmunity, regulation of responses to food antigens
How to prevent Treg function
anti tumour responses, vaccination
What is DAMP expressed by
Damaged Associated Molecular Patterns are associated by endogenous, dead, dying, stressed cells
What are the key properties of PAMPs
Conserved products of microbial metabolism
unique to microbes, invariant between members of a given class, vital for microbial fitness
Where does activation of naive lymphocytes happen and what does it involve
migration of naive T cells into lymph nodes->secretion of cytokines and chemokines->upregulation of adhesion molecules on endothelial venules that lines arterioles going into lymph nodes. Signals allowing chemokines to migrate out of lymph nodes=blocked and increase size cellularity of lymph nodes
What is required in the activation of naive lymphocytes
Signal 1, 2, signal 3 (cytokines) instruct T cells to polarise to type of T cell good at clearing that particular bacteria. Differentiate, proliferate, gain effector function
Sketch a graph of how the no. of antigen specific T cells in efferent lymphatics change with time
ref. notes
sequesterefd at low level as differentiation+proliferation->burst out of lymph nodes+move to site of infection and increase in several orders of magnitude
What happens to the effector response when infection is removed
Innate system no longer activated->inflammation subsides
Antigen is cleared-the stimulus for T cell is removed
Most effector T and B are removed-death by neglect/cytokine/starvation
apoptotic cells are removed by macrophages
