Inflammation

Question 1

4 Cardinal signs of inflammation

Answer 1

redness
swelling
heat
pain

Question 2

Acute Inflammation

Answer 2

-measure in hours or days

Question 3

3 Major components of acute inflammation

Answer 3

Dilation of small vessels leading to increased blood flow (redness and heat)
Increased vascular permeability enabling plasma proteins and leukocytes to leave the blood stream (swelling)
Accumulation of leukocytes at site of infection/injury, leukocyte activation and elimination of pathogen

Question 4

Potential outcomes of acute inflammation

Answer 4

resolution of infection
abscess formation
scarring
chronic inflammation

Question 5

Chronic Inflammation

Answer 5

prolonged response (weeks or months) in which inflammation, tissue injury and attempts at repair coexist

Question 6

Mediators of vasodilation

Answer 6

prostaglandins, nitric oxide, histamine

Question 7

Mediators of increased bascular permeability

Answer 7

histamine, bradykinin, leukotrienes, PAF

Question 8

Mediators of chemotaxis, leukocyte recruitment and activation

Answer 8

TNF, IL-1, Chemokine (C3a and C5a), Leukotrine B4, bacterial products (PAMPs)

Question 9

Mediators of fever

Answer 9

IL-1, TNF, prostaglandins

Question 10

Mediators of pain

Answer 10

prostaglandins, bradykinin

Question 11

Mediators of tissue damage

Answer 11

lysosomal enzymes of leukocytes, reactive oxygen species, nitric oxide

Question 12

Histamine

Answer 12

vasoactive amine that is preformed and stored in mast cell granules, released immediately following mast cell activation
principle mediator of vascular permeability
stimulates release of NO which causes vasodilation

Question 13

Prostaglandin D2

Answer 13

lipid mediator of inflammation

Question 14

Bradykinin

Answer 14

released because of activation of hageman factor (Factor XII)
increased vascular permeability and causes contraction of smooth muscle, dilation of blood vessels, and pain when injected into skin

Question 15

Proinflammatory cytokines

Answer 15

major ones are: TNGalpha, IL-1, and IL6

upregulate adhesion molecules.

Question 16

Chemokines

Answer 16

generated because of introduction of pathogen

C5a and C3a promote leukocyte migration to site of infection

Question 17

Lysosomal enzymes, ROS, and NO

Answer 17

released from activated leukocytes
toxic to microbe
also damages host tissue

Question 18

Steps of leukocyte extravasation

Answer 18

1) rolling or tethering via selectins and selectin ligands
2) leukocyte activation via chemokines
3) tight adhesion vis integrins and integrin ligands
4) transendothelial migration
5) migration along a chemokine gradient

Question 19

Fever

Answer 19

produced in response to pyrogens
advantages: immune system functions more effectively at higher than normal body temp, host cells are some what protected from the deleterious effects of tumor necrosis factor-alpha at high temps, pathogens grown more poorly
inhibitors of cyclooxygenase such as aspirin, block prostaglandin E2 synthesis, therefore reducing fecer

Question 20

Neutrophil rolling

Answer 20

histamine generation upregulates endothelial cell p-selectin
p-selectin binds to neutrophil p-selectin glycolipid (PSGL-1) which is constitutively expressed
interaction between P-selectin and PSGL-1 slows the neutrophil in a low affinity interaction

Question 21

Neutrophil binding

Answer 21

ICAM-1 is upregulated on endothelial surface

LFA-1 binds to ICAM-1 and causes neutrophil to stop rolling in a high affinity interaction

Question 22

Tranedothelial migration

Answer 22

Neutrophils and endothelial cells constitutively express CD31 (PECAM-1)
PECAM-1 is concentrated at intracellular junctions
Neutrophils squuze between the endothelial cells, then penetrate the basement membrane using surface expressed matrix metalloproteinases
PMNs are induced to migrate toward the site of inflammation by chemotactic substances

Question 23

function of PMNs

Answer 23

phagocytose extracellular bacteria to prevent spread

release toxic substances that damage host tissue and inflammation

Question 24

Monocyte extravasation

Answer 24

PMN’s predominate in early inflammatory infiltration and are later replaced by macrophages
Peaks after about 2 days
Macrophages have anti-microbial activity and anti-inflammatory/pro-resolving activity

Question 25

M1

Answer 25

Classical activated pro-inflammatory macrophage

produce proinflammatory cytokines, ROS and NO

Question 26

M2

Answer 26

alternatively activated pro-resolving macrophage

produce anti-inflammatory cytokines such as IL-10 and TGF beta

Question 27

Wound Healing

Answer 27

initiated by TGF beta by inducing migration of fibroblasts to the site
Also stimulated secretion of collagen

Question 28

Neutrophilia

Answer 28

increased peripheral blood neutrophils
often accompanies acute inflammation
IL-1 and TNF cause an accelerated release of PMNs from bone marrow
sustained release by macrophage and t lymphocyte-derived release of granulocyte colony stimulating factor

Question 29

Acute phase response

Answer 29

may occur during systemic inflammation as a result of macrophage derived IL-6
increased plasma level of acute phase proteins causes accelerated erythrocyte sedimentation rate

Question 30

Shock

Answer 30

high level of TNG

Question 31

Delerterious effects of TNF in bloodstream

Answer 31

systemic vasodilaition with vascular permeability and consequent intravascular volume loss leads to hypotension and shock
systemic activation of coagulation system causes multisystem organ failure and serious bleeding