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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

antigen receptors


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?

foxP3 protein


What do Treg cells secret?

immunosuppressive cytokine like IL-10 and TGF-b
express CTLA4
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


What is molecular mimicry? What is an example of this?

when antigens are similar to autoantigens

Rheumatic fever, where the antigens on Strep is similar to antigens of the heart muscle