Inflammation

Question 1

5 cardinal signs of inflammation

Answer 1

redness, swelling, heat, pain, loss of function

Question 2

what are the 3 purposes of infmammation

Answer 2

1 recruit leukocytes to damage and activate their effector functions

2 liquiefy surrounding tissue to prevent microbial spread

3 healing

Question 3

when is inflammation harmful?

Answer 3

1 tissue damage d/t inflammation and not the pathogen

2 aggregates of chronically activated leukocytes form granulomas, which interfere w/ organ fxn

3 distorted repair mechanisms that lead to scarring (ie cirrhosis)

4 persistent inflammation = cancer

Question 4

DC function

Answer 4

patrol tissue, process antigen, migrate to lymph nodes/spleen and present to T cell

Question 5

DC maturation

Answer 5

encounter danger signals (LPS) that cause them to upregulate CD80 and 86, which will costimulate T-cells

Question 6

where do inflammatory mediators come from

Answer 6

already present in circulatoin as zymogens

cell derived: slow- transcription/translation d/t external signal

cell derived: fast- presynthesized are released

Question 7

how do inflammatory mediators work?

Answer 7

1 bind to target cells (chemokines, cytokines)

2 enzymatic activity (lysosomal proteases)

3 oxidative damage (H2O2)

4 they are heavily regulated

Question 8

leukocyte migration

Answer 8

rolling, adhesion, diapedesis

selectins attact leukocytes for slowing down and rolling along endothelium

integrins are important for adhesion and diapedesis

Question 9

integrins

Answer 9

important proteins for adhesion/diapedesis

inactive bent conformation changes to a straight conformation upon straightening out

Question 10

histamine

Answer 10

found from mast cells/ basophils

released d/t IgE, c3a, c3b, il1, il-8

leads to dilatoin and increased permeability

effects via H1 receptors

Question 11

serotonin

Answer 11

found in platelets

released upon aggregation (d/t collagen, thrombin, ADP, Ag/Ab complex)

dilation/increased permeablity

Question 12

complement cascade

Answer 12

central component is C3. cleaved into C3a and C3b. c3b cleaves c5, where c5b joins MAC attack complex

Question 13

c3a and c5a

Answer 13

anaphylatoxins

bind to mast cells and release histamine

c5a is also a chemoattractant and increases leukocyte adhesoin to endothelium

Question 14

eicosanoids

Answer 14

derivatives of arachidonic acid

local, short lived

prostaglandins, lipoxins, thromboxane

Question 15

chemokines

Answer 15

activates and attract leukocytes. become attached to surface proteoglycans that creates a gradient cells respond to. some specificty w/ which cells are attached to which chemokines, but promiscuity is common

4 classes, CXC or CC being most common

Question 16

chemokine receptors

Answer 16

7 transdomain receptors

Question 17

nitric oxide

Answer 17

released from endothelial cells in response to Ca, short lived, vasodilator

binds Hg- Hg sink

Question 18

No synthesis

Answer 18

nitric oxide synthase produced from l-arginine

eNOS and nNOS are constituitively made but inactive until Ca flux

iNOS is made de novo following macrophage activation

Question 19

platelet activating factor

Answer 19

increases permeability

promotes aggregation/adhesion

attracts neutrophils

Question 20

cytokines

Answer 20

produced by WBCs

important for inflammation, especially IL-1 and TNF-a:

signal through NF-kB

Question 21

old drug therapies

Answer 21

glucocorticoids and aspirin

target NF-kB signaling

aspirin inhibits Cox 2, and slows degradation I-kB

glucocorticoids induce synthesis of I-kB

Question 22

new drug therapies

Answer 22

target the inflammatory cytokine TNF-a