cytokines, acute phase reactions, defensins

Question 1

what stimulates inflammation

Answer 1

activation of innate immune cells by pathogens

Question 2

responses go inflammation

Answer 2

swelling, redness, heat, pain, loss of function

Question 3

what happens when inflammation fails to give a resolution

Answer 3

leads to fibrosis, septic shock and chronic inflam

Question 4

t and b cell pathogen detection

Answer 4

individual t and b cells are highly selective for a specific pathogen species
immune memory for a faster secondary response

Question 5

innate immune cell pathogen detection

Answer 5

less selective than t and b, recognise broad classes of pathogens and not specific species, no immune memory, 1st line of defence
detect pathogens via pathogen associates molecular patten

Question 6

PAMP

Answer 6

pathogen associates molecular pattern

molecules or structures that are specific more microbes and viruses not visible to host cells

Question 7

PRR

Answer 7

pattern recognition receptor

invariant germline encoded receptors

Question 8

where are PRRs expressed

Answer 8

on innate immune cells and in some t, b and endothelial cells

Question 9

classes of PRRs

Answer 9

toll like, nod like, c type lectin, dna and rna

Question 10

what are cytokines

Answer 10

small proteins that mediate cell-cell communication during immune reactions
can have multiple targets

Question 11

where are cytokines produced

Answer 11

cells in the immune system

Question 12

main action of cytokines

Answer 12

on the immune system, some circumstances they target non immune cells

Question 13

how do cytokines stimulate cells

Answer 13

via cytokine receptors

Question 14

difff classes of cytokines

Answer 14

chemokines, interleukins and TNF

Question 15

what to cytokines recruit

Answer 15

immune cellss

Question 16

what do classical cytokines modulate

Answer 16

immune cell function

Question 17

what effect do chemokines have

Answer 17

homeostatic or immune effects on leukocyte migration

Question 18

chemokine types

Answer 18

4 groups divided based on the position of cysteine residues that mediate the formation of disulphide bridges in their 3d conformation

Question 19

what do macrophages secrete

Answer 19

inflammatory cytokines, IL-1beta, TNFalpha, IL-6, CXCL8, IL-12 - all leads to inflammation at site of infection

Question 20

IL-1beta and TNFalpha from macrophages

Answer 20

induce blood vessels to become more permeable, enabling effector cells and fluid containing soluble effector molecules to enter infected tissues

Question 21

IL-6 from macrophages

Answer 21

induces fat and muscle cells to metabolise , make heat and raise temp in infected tissue

Question 22

IL-12 from macrophages

Answer 22

recruits and activates NK cells that secrete cytokines that strengthen macrophages response to infections

Question 23

host defence peptides (HDP)

Answer 23

peptides that can initiate prokaryotic cells or viruses, produced by both proks and euks

Question 24

host defence peptides 3 main mechanisms of action

Answer 24

distribution of membrane integrity, bind precursors of cell wall formation to inhibit formation of bacterial cell wall and thus blocks bacterial replication, targets intracellular proteins to disrupt cell function

Question 25

mammalian host defence peptides

Answer 25

cathelicidin and defensins

Question 26

alpha defensins

Answer 26

restricted to certain mammalian species, mainly expressed in myeloid and paneth cells

Question 27

beta defensin

Answer 27

found in vertebrates and invertebrates immune and epithelial cells

Question 28

why are cytokines released

Answer 28

by macrophages in response to stimulation of pattern recognition receptors

Question 29

what doers release of cytokines require

Answer 29

de-novo transcription and translation of cytokine genes and is regulated at transcription, mRNA stability and mRNA translation

Question 30

what in cytokines allows their transport to the ER and subsequent secretion

Answer 30

their pro-sequence (IL-1 and TNF are exceptions, IL-1b requires processing by inflammosome, TNF is transported to the cell surface where it is expressed as a plasma membrane protein and then cleaved by the protease TACE which releases mature TNF from the membrane)

Question 31

TNF release..

Answer 31

attracts neutrophils and stimulates phagocytosis

Question 32

IL-1b release...

Answer 32

causes t cell polarisation

Question 33

IL-6 release..

Answer 33

promotes neutrophil and b cell survival and proliferation, t cell polarisation

Question 34

IFNbeta release...

Answer 34

promotes IL-10 production by macrophages for antiviral responses

Question 35

IL_10 release...

Answer 35

inhibits TNF, IL-6 and IL-12 production by macrophages

Question 36

IL-12 release...

Answer 36

results in Th1 driven T cell responses and NK cell actviation

Question 37

Acute phase reaction (APR)

Answer 37

involves changes in plasma conc of specific proteins in response to inflammation driven by cyotkines produced during localised inflam responses systemic not localised reponses changes due to altered protein synthesis in the liver some acute proteins are increased whilst others are decreased

Question 38

acute phase proteins in preventing spread of infection

Answer 38

c reactive protein, SAP, complement proteins

Question 39

acute phase proteins in wound healing

Answer 39

fibrinogen, von willebrant factor, coagulation

Question 40

acute phase proteins in preventing systemic inflammation

Answer 40

c reactive protein, SAP, proteinase inhibitors, haptoglobin, manganese superoxide dismutase and serum amyloid A

Question 41

c reactive protein

Answer 41

mayor acute phase protein in humans pentraxin (5 identical subunits) used as a marker of inflammation respond to IL-6 and IL-1beta hepatic expression by increasing in no dramatically

Question 42

T cell helper polarisation (2 steps)

Answer 42

1. antigen presentation 0 antigens presented as MHC class 2 molecules on an antigen presenting cell recognised by t cell receptors of a naive CD4 t cell - this stimulates the t cell to proliferate 2. polarisation - in response to cytokines secreted by the APC or other nearby immune cells, Th cell will polarise to take specific characteristics

Question 43

naive CD4 t cell proliferation in response to IL-12

Answer 43

Th1, promotes killing by macrophages, response to intracellular pathogens

Question 44

naive CD4 t cell proliferation in response to TGFbeta, IL-6, IL-1beta, IL-23

Answer 44

Th17, anti-fungal and anti-tumour immunity

Question 45

naive CD4 t cell proliferation in response to IL-4

Answer 45

Th2, promotes antibody production by B cells, anti-worm immune responses

Question 46

naive CD4 t cell proliferation in response to TGFbeta

Answer 46

Treg, immune suppressor

Question 47

what is autoimmune disease caused by

Answer 47

excessive production of pro-inflammitory cytokines

Question 48

autoinflammitory disorders

Answer 48

familial Mediterranean fever, noenatal onset multisystem inflam disease, TNF receptor-associated periodic syndrome, deficiency in IL/receptor antagonist, behcets disease most result from genetic mutations that increase IL-1 production of signalling

Question 49

cytokine directed therapy

Answer 49

anti-TNF therapy, binds to TNF and stops its ability to produce cells - approved for RA, psoriasis, prosatic arthritis, chrons disease, ulcerative colitis and ankylosing spondylitis

Question 50

IL-1ra anti-inflammitory cytokine

Answer 50

binds to the IL-1 receptor but does not activate intracellular signalling - it is a competitive inhibitor of Il-1