innate immunity and inflammation

Question 1

what cells are involved in the initiation of the immune response

Answer 1

macrophages
mast cells
immature dendritic cells

Question 2

what is the function of macrophages

Answer 2

phagocytosis
orchestrate immune response and present antigen

Question 3

where are macrophages found

Answer 3

liver - kupffer cells
brain/CNS - microglia
epidermis - langerhan cells
bone - osteoclasts

Question 4

how are macrophages made in adults

Answer 4

differentiation of circulating monocytes

Question 5

how are macrophages made in embryos

Answer 5

variable kinetics

Question 6

what is phagocytosis mediated by

Answer 6

PRRs (pattern recognition receptors) on surface and endosomes

Question 7

what chemokine is most associated with monocytes

Answer 7

MCP-1

Question 8

describe the steps in monocyte recruitment

Answer 8

• release alarm mediators eg. IL-1
• ingest and kill microbes trapped in NETs
• removal of exhausted/dead neutrophils
• start wound healing

Question 9

what is the difference between monocytes and neutrophils in an immune response

Answer 9

monocyte levels peak 6-8 hours later than neutrophils

Question 10

what does M1 do

Answer 10

pro inflammatory

Question 11

what does M2 do

Answer 11

anti-inflammatory

Question 12

what does upregulate expression of genes do in phagocytosis

Answer 12

• improve engulfment of microbes
• potentiate killing of microbes
• secrete chemokine and cytokines to recruit assistance - process and present antigen to T cells

Question 13

what does TNF do

Answer 13

• activation of local endothelium
• initiation of cytokine production
• upregulation of adhesion molecules

Question 14

what does IL-6 do

Answer 14

• triggers production of acute phase proteins from liver
• enhances antibody production from B cells inducing T cell production

Question 15

what does IL-8 do

Answer 15

• triggers neutrophil chemotaxis
• chemotactic of basophils and T cells
• activation of neutrophils and promotes angiogenesis

Question 16

what does IL-12 do

Answer 16

• activation of NK cells
• polarisation of T cells to T helper cells

Question 17

what does MIP-1 do

Answer 17

• chemokine
• recruitment of monocytes, NK, T cells, basophils and DCs

Question 18

what does MIP-1 beta do

Answer 18

• chemokine
• recruitment of monocytes, macrophages and neutrophils

Question 19

what is the acute phase response

Answer 19

change in profile of proteins secreted into the blood in response to activation by effector cytokines

Question 20

what is an acute phase protein

Answer 20

any protein that either increases or decreases in concentration in the blood in response to activation of hepatocytes by effector cytokines

Question 21

where are mast cells found

Answer 21

submucosal linings of airways
gut
skin
vascularised connective tissue

Question 22

what is the functions of mast cells

Answer 22

• contains histamine and other vasoactive and inflammatory substances

Question 23

when are cytoplasmic granules in mast cells released

Answer 23

• PAMP or DAMP engagement with PRRs
• complement factors C3a and C5a
• direct injury
• binding of antigen IgE to FcεR1

Question 24

what is the function of histamine

Answer 24

• Dilates post-capillary venules.
• Activates local blood vessel endothelium.
• Increases vascular permeability.
• Irritates local nerves (itch).

Question 25

what is the symptoms of an acute inflammatory response

Answer 25

rubor - redness via dilation of blood vessels dolor - pain via nerve irritation calor - heat by dilation of blood vessels tumor - tissue swelling by inflow of plasma and lymph

Question 26

what is the physiological function of inflammation

Answer 26

- allow elimination of initial causes of cell injury - induces local clotting to prevent infection spreading - remove necrotic cells - initiate repair process

Question 27

what does unregulated inflammation cause

Answer 27

- harmful causing host cell/tissue damage - severe inflammatory disorders eg. sepsis and SIRS

Question 28

what is acute inflammation

Answer 28

initial response of the body to harmful stimuli - increased movement of plasma and leukocytes from blood to tissue

Question 29

what is chronic inflammation

Answer 29

- pathological condition - tissue destruction and attempts to repair

Question 30

what is the causes of chronic inflammation

Answer 30

- persistent injury/ infection - prolonged exposure to toxins - autoimmune disease

Question 31

what does the inflow of phagocytes from blood vessels bring in the humoral response

Answer 31

- neutrophils - within an hour - monocytes - 6-8 hours

Question 32

what does the inflow of plasma bring in the humoral response

Answer 32

- complement - acute phase proteins - Ab

Question 33

what is extravasation

Answer 33

migration of leukocytes out of blood vessel into tissue

Question 34

what do cytokines do

Answer 34

act on blood vessels in endothelial cells causing dilation

Question 35

what happens when neutrophil surface carbohydrates bind weakly to selectins

Answer 35

- binding triggers conformational change in neutrophil integrins - high concentration of chemotactic factors guide neutrophils

Question 36

what upregulates neutrophil integrin adhesiveness

Answer 36

PECAM binding to neutrophils

Question 37

describe neutrophil microbe phagocytosis

Answer 37

- move up chemokine gradient - C3a and C5a activate killing mechanisms - meet complement opsonised molecules - C3b on opsonised microbe surface bind to neutrophil receptors - neutrophil engulfs microbe forming phagosome - destroy microbe by phagolysosome

Question 38

how do phagolysosomes kill microbes

Answer 38

oxygen dependent mechanism

Question 39

what does lysozyme do

Answer 39

splits mucopeptides

Question 40

what does lactoferrin do

Answer 40

removes free iron

Question 41

what does gelatinase do

Answer 41

degrades gelatin

Question 42

what is chronic granulomatous disease

Answer 42

- mutation in genes that encode subunits of NAPDH oxidases - leads to inadequate generation of H2O2 and O- - poor killing in phagolysosomes causing recurrent infections in skin, lungs, lymph nodes and liver

Question 43

how are neutrophil extraceullar traps formed

Answer 43

produced by dying neutrophils undergoing NETosis

Question 44

what is the function of NETS

Answer 44

capture microbes which can then be more efficiently phagocytose by neutrophils and macrophages

Question 45

how is innate response measured

Answer 45

- raised neutrophil count - increased erythrocyte sedimentation rate - serum markers - increased CRP/APPs and pro inflammatory cytokines

Question 46

how is inflammation treated

Answer 46

- steroids - glycodcoritouds - proteins - made by DNA recombination - non steroidal anti inflammatories - block activity of COX and reduce fever and pain

Question 47

how does NSAIDS reduce fever and pain

Answer 47

inhibit clotting by interfering with platelet thromboxane A2 production

Question 48

what does COX 1 inhibitors do

Answer 48

pain, clotting and stomach lining protection

Question 49

what does COX 2 inhibitors do

Answer 49

inflammatory related pain