Ch3 Acute Inflammation EC

Question 1

What are the cardinal signs of acute inflammation? What are their mediators?

Answer 1

Rubor/Calor - Histamine mediated vasodilation of arterioles
Tumor - Histamine mediated increase in venular permeability (contract endothelial cells)
Dolor - PGE2/Bradykinin
Functio laesa (loss of function)

Question 2

Is edema fluid an exudate or a transudate?

Answer 2

Transudate (low protein and cell levels)

moves across intact BM

Question 3

What is margination and what its mechanism?

Answer 3

PMNs pushed to periphery
~liver releases fibrinogen
~RBCs form rouleaux
~forces PMNs into periphery

Question 4

Describe the rolling of PMNs

Answer 4

Occurs in venules
L-selectin on PMNs binds E&P selectins on endothelial cells
IL-1 and TNF stimulate expression of selectins

Question 5

L-selectin

Answer 5

selectin ligand on Leukocytes (rolling)

Question 6

E-selectin and P-selectin

Answer 6

selectins on endothelial cells (rolling)

Question 7

Weibel-Palade bodies

Answer 7

“glue factory” in endothelial cells
~P-selectin
~vWF
~platelet adhesion molecules

Question 8

Describe firm adhesion in PMN extravasation

Answer 8

Beta2 integrin activated by C5a and LTB4

Activation of ICAM by IL-1 and TNF

Question 9

What substances inhibit activation of Beta-2 integrins?

Answer 9

Corticosteroids and Catecholamines

Reason PMN levels increase w/ corticosteroids and during MI - all in blood because they can’t stick

Question 10

What substances increase activation of Beta-2 integrins?

Answer 10

Endotoxins

causes circulating PMN level to decrease

Question 11

Delayed separation of umbilical cord

Answer 11

Leukocyte adhesion defect due to selectin deficiency

also see severe gingivitis, poor wound healing, peripheral blood leukocytosis

Question 12

Transmigration

Answer 12

Movement of PMNs from venules into interstitial space (via type IV collagenase and binding of PECAM-1)

Formation of pus (dilutes toxins and provides opsonins)

Question 13

Chemotactic mediators

Answer 13

C5a
IL-8
LTB4
Kallikrein

Question 14

Opsonins

Answer 14

IgG and C3b

Enhance PMN ability to ingest bacteria

Question 15

Bruton agammaglobinemia

Answer 15

Opsonization defect (lack of IgG) 
Cannot mature B cells

Question 16

Describe neutrophil ingestion

Answer 16

Engulf bacteria in phagosomes

Lysosomes combine and empty hydrolytic enzymes (forming phagolysosome)

Question 17

Chediak-Higashi syndrome

Answer 17

Cannot form phagolysosomes due to a defect in microtubule function

Question 18

What cells contain the MPO system?

Answer 18

PMNs and monocytes (NOT macrophages)

Question 19

NADPH oxidase complex

Answer 19

Converts O2 to superoxide

Question 20

SOD

Answer 20

Converts superoxide to H2O2

Question 21

MPO system

Answer 21

Combines H2O2 with Cl to make COCl

Question 22

Chronic Granulomatous Disease

Answer 22

XR mutation in CYBB 
Defective NADPH oxidase
Absent respiratory burst
MPO present
Susceptible to Cat+ infections (others can be killed because they supply the H2O2 for MPO to generate HOCl)

Pneumonia, Skin, Visceral organs, and Bones

NBT dye test (turns blue if superoxide present)
Oxidation of dihydrorhodamine to fluorescent rhodamine used more commonly now

Question 23

Myeloperoxidase deficiency

Answer 23

Superoxide and H2O2 are produced (normal respiratory burst)

Can’t make HOCl

Question 24

G6PD deficiency

Answer 24

Lack of NADPH interferes with normal function of O2 dependent MPO system

Question 25

Lactoferrin

Answer 25

(Oxygen independent killing) Binds Fe that is necessary for normal bacterial growth and production lactoFERRIN

Question 26

Major Basic Protein

Answer 26

(oxygen independent killing) | Eosinophil product that is cytotoxic to helminths

Question 27

Prostaglandins source and function

Answer 27

Source: Macrophages, endothelial cells, platelets, (PGH2 major precursor of PGs and thromboxanes) PGE2: Vasodilation, pain, fever PGI2: Vasodilation, inhibition of platelet aggregation

Question 28

Thromboxane A2 source and function

Answer 28

Platelets (converted from PGH2 by thromboxane synthase) Vasoconstriction, platelet aggregation

Question 29

Leukotrienes source and function

Answer 29

Leukocytes LTB4 chemotaxis and activation of adhesion molecules LTC4/LTD4/LTE4 vasoconstriction, increased venule permeability, bronchoconstriction Zileuton inhibits 5-lipoxygenase Montelukast is a LTE receptor antagonist

Question 30

Bradykinin source and function

Answer 30

Product of kinin system activated by factor XII Vasodilation, increased venular permeability, pain

Question 31

Chemokines source and function

Answer 31

Leukocytosis, endothelial cells Activate PMNs and stimulate migration

Question 32

C3a/C5a

Answer 32

Stimulate mast cell release of histamine C5a also activation of adhesion molecules/chemotaxis

Question 33

C3b

Answer 33

Opsonization

Question 34

C5-C9

Answer 34

MAC and cell lysis

Question 35

IL-1, TNF source and function

Answer 35

Macrophages Initiates PGE2 synthesis in anterior hypothalamus leading to fever Activates adhesion molecules/chemotaxis TNF promotes apoptosis

Question 36

IL-6 function

Answer 36

Increases liver synthesis of acute phase reactants

Question 37

IL-8 function

Answer 37

Chemotaxis

Question 38

Histamine source and function

Answer 38

Mast cells Vasodilation, increased venular permeability

Question 39

NO source and function

Answer 39

Endothelial cells, macrophages Vasodilation, bactericidal

Question 40

Why is fever beneficial in acute infection?

Answer 40

Right shifts OBC enhances delivery of O2 for killing | Decreases viral replication also

Question 41

Lipoxins

Answer 41

Resolution of acute inflammation | inhibit chemotaxis and promote apoptosis

Question 42

Resolvins

Answer 42

Resolution of acute inflammation | Inhibit recruitment of inflammatory cells