Immunology

Question 1

is there immunological memory in the innate response?

Answer 1

no

only in acquired response

Question 2

which types of immune response can distinguish self from non cell?

Answer 2

acquired

Question 3

when does innate and acquired response occur?

Answer 3

innate = 0-96 hrs
acquired = >96hrs

Question 4

which response is germline encoded?

Answer 4

innate

can therefore act quicker

Question 5

what do regulatory T cells do?

Answer 5

secrete cytokines that dampen down response

Question 6

which type of response is autoimmune disease most associated with?

Answer 6

acquired

Question 7

slide 4

Answer 7

….

Question 8

what do Th1 cells do?

Answer 8

activate macrophages via IFN gamma

Question 9

TFH cell function?

Answer 9

helps activate B cells

occurs in germinal centre

Question 10

B cells vs T cells?

Answer 10

B cells see and bind to any type of antigen

T cells have to see peptide only antigens - presented by MHC I or II

Question 11

what does CD8 do once activated by helper T cells?

Answer 11

differentiate into cytotoxic cells

migrate from lymph nodes into infected site and directly kill infected cells (ones that express antigenic peptides)

Question 12

what are plasma cells?

Answer 12

effector B cells that secrete antibodies which bind to opsonised pathogens to induce phagocytosis
also activate complement

Question 13

which antibody important in type 2 and 3 hypersensitivity?

Answer 13

IgG

Question 14

what is autoimmunity?

Answer 14

presence of adaptive immune responses against self tissue

Question 15

what gives different polypeptides that group to form different antigen receptors?

Answer 15

random rearrangement of antigen receptor genes

means everyone has some self reactive immune cells/antigen receptors

Question 16

how are self reactive immune cells filtered?

Answer 16

tested in lymph nodes

killing mechanism for self reactive T and B cells but some can escape so secondary mechanism needed

Question 17

what si the second mechanism?

Answer 17

regulatory T cells

destroy most of the remaining self reactive cells and those that are left aren’t really effective

Question 18

what causes development of autoimmune disease?

Answer 18

defective filtering of self reactive immune cells - breakdown of tolerance system?

Question 19

what is the tolerance system?

Answer 19

general term means failure to amount an immune response

central tolerance = process of eliminating developing B or T cells that are reactive to self

Question 20

describe the pathogenesis of autoimmunity?

Answer 20

genetic susceptibility > initiating event > breakdown of self tolerance and loss of immune regulation > activation of auto-reactive T and B cells > hypersensitivity reactions > autoimmune phenomena or disease

Question 21

what gene mutation can cause problems/deficiency with regulatory T cells?

Answer 21

FOXP3
leads to deficiency of reg T cells
HLA (MHC) genes on chromosome 6
causes problems with binding of MHC and antigenic peptide

Question 22

which MHC is presented by all cells?

Answer 22

MHC I
additional MHC II on antigen presenting cells
sex hormone genes (females higher rates of autoimmunity)

Question 23

how many MHC types presented on antigen presenting cells?

Answer 23

12?

6 from each parent?

Question 24

how can polymorphism of HLA genes affect immunity?

Answer 24

lots of variants
so some variants like to present certain peptides (like self peptides) more than other variants so can be more likely to develop autoimmune disease

Question 25

what environmental factors can initiate autoimmunity?

Answer 25

molecular mimicry incurrent infections tissue damage (release of previously hidden self antigens which aren't shown at time of cell production/filtering) superantigens

Question 26

slide 11 table

Answer 26

….

Question 27

what drives most autoimmunity diseases?

Answer 27

hypersensitivity reactions

Question 28

classic picture of myasthenia gravis?

Answer 28

droopy eyelid muscle weakness fatigue reversible symptoms

Question 29

what is myasthenia gravis?

Answer 29

autoimmune neuromuscular disorder | auto-reactive antibodies (IgG) bind with acetylcholine receptors on muscle cells

Question 30

function of ACH recptor?

Answer 30

expressed at neuromuscular junction postsynaptic involved in contraction

Question 31

who gets myasthenia gravis and what causes it?

Answer 31

any age | most unknown cause but thymic tumour and HLA associations sometimes

Question 32

how does myasthenia gravis present clinically?

Answer 32

insidious onset first symptoms usually eye fatigue and muscle weakness can first appear in/after pregnancy or with anaesthtic administration

Question 33

what cells are involved in myasthenia gravis?

Answer 33

CD4 Th cells | AChR protein antigens activate auto reactive B cells

Question 34

what is early onset MG associated with?

Answer 34

increased adaptive immune response in thymus

Question 35

key MHC class II presenting cells?

Answer 35

dendritic | macrophages

Question 36

how does MG develop?

Answer 36

1. CD4 T cells activated by unfolded AChR subunits expressed by thymic epithelial cells 2. effector Th cells stimulate auto-reactive B cells to produce anti-AChR antibodies 3. Thymic Myoid cells are attacked by these antibodies and release AChR-immune complexes 4. these complexes activate other antigen presenting cells, perpetuating the response

Question 37

what can AChR antibodies do?

Answer 37

prevent binding of ACH at neuromuscular junction by binding to the ACh receptor causes defect in nerve impulse at NMJ leading to impaired contraction eventually the receptors are destroyed altogether Bind complement leading to destruction of muscle end plate (type HS)

Question 38

how can AChR activate complement and what is the result of this?

Answer 38

antibody binding to the AChR activates the complement cascade, resulting in formation of the membrane attack complex (MAC) and localised destruction of the post synaptic membrane this leads to a simplified post synaptic membrane which lacks the normal deep folds and has a flat surface

Question 39

how is MG treated via increasing neurotransmission?

Answer 39

anti-cholinesterase agens - stops breakdown of ACh

Question 40

how is MG treated through reducing autoimmunity?

Answer 40

immunosuppressive drugs plasmapheresis IV immunoglobulin Eculizumab

Question 41

what is Eculizumab?

Answer 41

monoclonal antibody binds to C5b so it cant be cleaved and membrane attack complex cant be formed inhibits complement

Question 42

how can surgery be used for MG?

Answer 42

thymectomy | - if MG associated with thymus cancer

Question 43

what type of gene encodes for HLA proteins and what is the significance of this?

Answer 43

highly polymorphic gene | allows for different HLA variants, some of which bind to different peptide antigens