Immunology

Question 1

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

Answer 1

antigen receptors 
diversity 
self-antigen-receptors 
tolerance 
self-reactive

Question 2

What are the two broad categories of tolerance?

Answer 2

Central and peripheral tolerance

Question 3

How do central and peripheral tolerance differ?

Answer 3

Central - occurs in thymus + bone marrow during development

Peripheral - occurs in secondary lymph organs (lymph nodes) and peripheral tissues after development

Question 4

Describe the 4 mechanisms of tolerance

Answer 4

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

Question 5

T/F T cells faults are more frequent than B cells

Answer 5

False, B cell faults are more common because tolerance is less efficient

However, the faults are more easily removed

Question 6

What happens when immature B cell binds to a low affinity, non-cross-linking self molecule?

Answer 6

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

Question 7

What happens when immature B cell binds to a soluble self molecule circulating in the serum?

Answer 7

Cells that activate and differentiate in the bone marrow will be inactivated in the periphery. They express IgD instead and thus become anergic

Question 8

What is clonal deletion?

Answer 8

When immature B cell binds to multivalent self molecule, the extensive cross linking will trigger apoptosis

Question 9

What signals are required for mature B cells to survive

Answer 9

cross linking of surface Ig to antigen

CD4 help via CD40L

Question 10

What happens if B cells don’t have T cell help? What is the significance of this in terms of tolerance?

Answer 10

the life span is shortened

B cell tolerance is dependent on T cell tolerance

Question 11

T/F T cell help is required even after hyper-mutation

Answer 11

Yes, T cell help is needed through B cell lifespan

Question 12

Why are T cells “technically” self-reactive?

Answer 12

T cells see the complex of antigen peptide and MHC molecule. MHC is a self-antigen, so T cells are self-reactive

Question 13

What does positive selection achieve for the T cell?

Answer 13

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

Question 14

What does negative selection involve?

Answer 14

T cells are exposed to MHCs associated with self-antigens. Those that react will undergo apoptosis

Question 15

What is needed in order for negative selection to occur

Answer 15

ectopic expression of tissue specific antigens (self-antigens)

Question 16

What is the role of autoimmune regulator of expression (AIRE)?

Answer 16

crucial for the expression of tissue specific antigens in thymic epithelial cells

Question 17

What happens if AIRE is mutated?

Answer 17

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

Question 18

What are the three signals to activate mature T cells?

Answer 18

TCR to MHC+antigen
CD28 to CD80/86
Cytokine

Question 19

T/F T cells die without co-stimulation

Answer 19

False, they become anergic

Question 20

What is the key identifier of T reg?

Answer 20

foxP3 protein

Question 21

What do Treg cells secret?

Answer 21

immunosuppressive cytokine like IL-10 and TGF-b
express CTLA4
molecules that create immunosuppressive environment

Question 22

How does CTLA4 work?

Answer 22

It binds to CD28 with higher affinity, therefore preventing T cells from activating

Question 23

How can auto-reactive cells that are normally silent be activated?

Answer 23

1) entry into immune-privileged sites (bypass ignorance)
2) infection, which generates antigen and co-stimulation
3) autoreactive B cells get T cell help

Question 24

T/F autoimmune responses always result in autoimmune disease

Answer 24

False, autoimmune response should stop after tissue repair

Question 25

T/F autoimmune diseases always involve autoimmune response

Answer 25

True

Question 26

Describe type II and type III hypersensitivity

Answer 26

i) Type II involves antibody mediated damage

ii) Type III involves deposition of immune complexes

Question 27

What are the two classes of autoimmune disease? What is an example of each?

Answer 27

organ specific, like diabetes, with CD8 cells killing beta cells
systemic, like SLE

Question 28

What is the role of CD4 cells in multiple sclerosis?

Answer 28

some T cells can react to myelin antigen and promote inflammatory response

Question 29

Which CD4 cells damage the myelin in MS?

Answer 29

Th1 and Th17

Question 30

Which HLA types are associated with MS?

Answer 30

DR15 and DQ6

Question 31

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

Answer 31

when antigens are similar to autoantigens

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