Flashcards in Immunology Deck (31):
Lymphocytes generate ________ in a random fashion in order to increase ________ and ensure protection, but sometimes ______ can be generated, which, if released, can damage self. Therefore, _______ serves to protect us from _________ lymphocytes
What are the two broad categories of tolerance?
Central and peripheral tolerance
How do central and peripheral tolerance differ?
Central - occurs in thymus + bone marrow during development
Peripheral - occurs in secondary lymph organs (lymph nodes) and peripheral tissues after development
Describe the 4 mechanisms of tolerance
1) delete: kill off cell with self-receptor
2) anergise - switches off the self-reactive cell
3) ignore - never see the antigen, in immune-privileged sites
4) regulate - through Treg cells
T/F T cells faults are more frequent than B cells
False, B cell faults are more common because tolerance is less efficient
However, the faults are more easily removed
What happens when immature B cell binds to a low affinity, non-cross-linking self molecule?
antigen binds to surface immunoglobulin, but not enough to cross link, then the B cell is clonally ignored. It can mature, but the low affinity prevents it
What happens when immature B cell binds to a soluble self molecule circulating in the serum?
Cells that activate and differentiate in the bone marrow will be inactivated in the periphery. They express IgD instead and thus become anergic
What is clonal deletion?
When immature B cell binds to multivalent self molecule, the extensive cross linking will trigger apoptosis
What signals are required for mature B cells to survive
cross linking of surface Ig to antigen
CD4 help via CD40L
What happens if B cells don't have T cell help? What is the significance of this in terms of tolerance?
the life span is shortened
B cell tolerance is dependent on T cell tolerance
T/F T cell help is required even after hyper-mutation
Yes, T cell help is needed through B cell lifespan
Why are T cells "technically" self-reactive?
T cells see the complex of antigen peptide and MHC molecule. MHC is a self-antigen, so T cells are self-reactive
What does positive selection achieve for the T cell?
1) determine whether the cell is CD4 or CD8 (thymocyte expresses both)
2) get rid of cells that can't recognise MHC (by neglect)
3) ensure that T cells only recognise antigen-associated MHC
What does negative selection involve?
T cells are exposed to MHCs associated with self-antigens. Those that react will undergo apoptosis
What is needed in order for negative selection to occur
ectopic expression of tissue specific antigens (self-antigens)
What is the role of autoimmune regulator of expression (AIRE)?
crucial for the expression of tissue specific antigens in thymic epithelial cells
What happens if AIRE is mutated?
AIRE defect will mean that circulating antigens cannot be presented to immature T cells, so T cells are more likely to be self-reactive, and ultimately leads to multiple systemic autoimmune disease
What are the three signals to activate mature T cells?
TCR to MHC+antigen
CD28 to CD80/86
T/F T cells die without co-stimulation
False, they become anergic
What is the key identifier of T reg?
What do Treg cells secret?
immunosuppressive cytokine like IL-10 and TGF-b
molecules that create immunosuppressive environment
How does CTLA4 work?
It binds to CD28 with higher affinity, therefore preventing T cells from activating
How can auto-reactive cells that are normally silent be activated?
1) entry into immune-privileged sites (bypass ignorance)
2) infection, which generates antigen and co-stimulation
3) autoreactive B cells get T cell help
T/F autoimmune responses always result in autoimmune disease
False, autoimmune response should stop after tissue repair
T/F autoimmune diseases always involve autoimmune response
Describe type II and type III hypersensitivity
i) Type II involves antibody mediated damage
ii) Type III involves deposition of immune complexes
What are the two classes of autoimmune disease? What is an example of each?
organ specific, like diabetes, with CD8 cells killing beta cells
systemic, like SLE
What is the role of CD4 cells in multiple sclerosis?
some T cells can react to myelin antigen and promote inflammatory response
Which CD4 cells damage the myelin in MS?
Th1 and Th17
Which HLA types are associated with MS?
DR15 and DQ6