Inflammation (part 2)

Question 1

cells move out of vessels into the area of inflammation recruited by ________ agents

Answer 1

chemotactic

Question 2

name the 4 stages of the cellular events of inflammation

Answer 2

1. margination and rolling of WBC
2. Migration of leukocytes
3. chemotaxis
4. phaocytosis

Question 3

what are eicosanoids

Answer 3

lipid mediators in the innate immune repsonse

Question 4

name the 3 cell signaling molecules in the inflammatory process

Answer 4

1st, lipid mediators (eicosanoids) are released from activated cells - early recruitment of inflammatory cells from the bone marrow into vascular system

proinflammatory cytokines activate resident tissue cells

these resident tissue cells release chemokines to amplify inflammatory cell recruitment

Question 5

leukocyte tethering/rolling is mediated by….

Answer 5

selectins

Question 6

transmigration is also known as….

Answer 6

diapedesis

leukocyte crossing tight junction between endothelial cells

Question 7

what inflammatory mediators are involved in firm adhesion and diapedesis

Answer 7

chemokines – induce the expression of icams to allow for tight adhesion

Question 8

what is marginationn/tethering

Answer 8

leukocytes moving from axial flow to the margin of the vessels

Question 9

marginated leukocytes begin to roll on the endothelial surface by transient adhesion molecules.
WHAT ARE THESE MOLECULES

Answer 9

selectins

Question 10

adhesion of PMNs to endothelium occurs via…..

Answer 10

selectins and integrins

Question 11

what structure ON THE LEUKOCYTE mediates firm adhesion to endothelial cells

Answer 11

beta 2 integrins – binds to icam 1

Question 12

leukocyte diapedesis occurs mostly where?

Answer 12

in postcapillary venules

Question 13

name 3 different selectins.
what is their general function

Answer 13

P-selectin
L-selectin
E-selectin

aid in tethering/rolling

Question 14

ICAM-1 binds to….

Answer 14

beta 2 integrins on the leukocyte

aids in adhesion, arrest, and transmigration

Question 15

what is another term for CD31

Answer 15

PECAM-1

Question 16

what does CD31/PECAM-1 do

Answer 16

involved in arrest and transmigration

on the endothelial cell AND leukocyte

MAJOR MEDIATOR OF DIAPEDESIS

Question 17

of the selectins, which is the only one to NOT roll lymphocytes?

Answer 17

L-selectin

Question 18

what accomplishes firm adhesion

Answer 18

integrins

Question 19

define chemotaxis

Answer 19

process in which WBCs are attracted to the inflammation area according to the high concentration of certain products (ie: CXCL8/C5a/leukotriene b4)

Question 20

explain the mechanism of phagocytosis

Answer 20

bacterium containing opsonins such as C3b gets recognized by neutrophil C3b receptor and gets internalized through changes in the cytoskeleton. pseudopods form around teh microbe to enclose it within a phagosome. the phagosome releases ROS (O2 becomes O2- by NADPH oxidase and rapidly converted to H2O2.

primary granules containing “_ases” are released. phagosome fuses with lysosome to form a PHAGOLYSOSOME. death of pathogen and neutrophil itself

Question 21

name 6 phagocytic cells

Answer 21

microglia in the brain
macrophages
neutrophils
monocytes
dendritic cells
osteoclasts

Question 22

true or false

leukocytes can also kill microorganisms by nonoxidative mechanisms

Answer 22

true

-lysosomal hydrolases
-defensins
-lactoferrin
-lysozyme
etc

Question 23

disease: LAD (leukocyte adhesion deficiency)

what is the defect?

Answer 23

LAD-1 - defective B2 integrin expression or function

pathogenesis - leukocytes can’t reach the site of infection and no damage is done to the pathogen

Question 24

disease: hyper IGE recurrent infection syndrome

what is the defect?

Answer 24

poor chemotaxis

Question 25

disease: chediak-higashi syndrome what is the defect

Answer 25

defective lysosomal granules, poor chemotaxis

Question 26

disease: neutrophil-specific granule deficieny what is the defect

Answer 26

absent neutrophil granules (AND THUS DEFECTIVE PHAGOCYTOSIS)

Question 27

disease: chronic granulomatous disease what is the defect

Answer 27

deficient NADPH oxidase with absent H2O2 production. inability to destroy pathogen with ROS

Question 28

vasoactive mediators cause what? name some vasoactive mediators

Answer 28

cause vasodilation and increased vascular permeability, leading to EDEMA histamine serotonin bradykinin anaphylatoxins

Question 29

what do chemotactic factors do? name some chemotactic factors

Answer 29

recruit and stimulate inflammatory cells C5a chemokines

Question 30

name 3 things involved in acute inflammation and 3 things involved in chronic inflammation

Answer 30

acute: neutrophils platelets mast cells chronic: macrophages lymphocytes plasma cells

Question 31

mediators may be produced either ___ or ____

Answer 31

locally by cells at the site of inflammation OR circulate in the plasma (typically synthesized by the liver)

Question 32

name 3 plasma derived mediators as well as how they circulate and how they're activated

Answer 32

circulate as inactive precursors and are activated by proteolytic cleavage complement, kinin, and coagulation cascasdes

Question 33

name 5 cell derived mediators and how they're stored, and activated

Answer 33

histamine serotonin bradykinin prostaglandins leukotrienes stored in intracellular granulation and are secreted upon activation

Question 34

most mediators act by..

Answer 34

binding to specific receptors on target cells

Question 35

true or false mediators only have 1 target

Answer 35

FALSE may only have one, a few, or many targets

Question 36

mediators can stimulate their target cells to do what

Answer 36

release secondary effector molecules

Question 37

true or false mediator function is generally tightly regulated

Answer 37

TRUE mediators can be potentially harmful, so they quickly decay once activated and released from the cell. they are inactivated by enzymes and are either eliminated or inhibited

Question 38

all 3 plasma derived cascades -- coagulation, kinin and complement --- are mechanistically linked by initial activation of what?

Answer 38

HAGEMAN FACTOR -- factor XII of the coagulation cascade

Question 39

what is factor 12 (hageman factor) synthesized by? how is it activated?

Answer 39

synthesized by the liver and circulates in inactive form. is activated by collagen, basement membrane, or activated platelets

Question 40

what is responsible for pain during inflammation

Answer 40

bradykinin

Question 41

kinins act quickly and are rapidly inactivated by....

Answer 41

kinases

Question 42

name 4 effects of activation of Hageman factor (factor 12)

Answer 42

-conversion of plasminogen to plasmin (cleaves complement components to generate anaphylotoxins C3a and C5a) -conversion of prekallikrein to kallikrein (cleaves HMWK to kinins) -activation of alternative complement pathway -activation of the coagulation system

Question 43

_____ separate pathways can activate complement to form the membrane attack complex

Answer 43

THREE -- alternative, classical, mannose binding

Question 44

name 3 anaphylotoxins what do they do

Answer 44

C3a, C4a, C5a mediate smooth muscle contraction (bronchial and vascular constriction) and increase vascular permeability (EDEMA) -partly through stimulating mast cells which releases histamine causing vasoconstriction PROINFLAMMATORY

Question 45

name 2 opsonins what do they do

Answer 45

C3b iC3b bind to bacterium and enhance phagocytosis by allowing receptors on phagocytic cell membranes to recognize and bind

Question 46

name 2 proinflammatory molecules what do they do

Answer 46

C5a and MAC (membrane attack complex) induce mast cell and basophil degranulation

Question 47

what does factor p (properdin) do

Answer 47

stabilizes C3 convertase - C3bBb on pathogen surface

Question 48

what does factor H do?

Answer 48

works with factor I to turn C3b to iC3b (inactivated) factor I is the one that actually cleaves

Question 49

what does DAF and MCP do

Answer 49

disrupts C3 convertase - C3bBb on human cell surface and inactivates it to iC3b MCP uses factor I to cleave second class of complement control proteins

Question 50

another name for MCP

Answer 50

protectin

Question 51

explain anaphylactic shock

Answer 51

sudden blood pressure drop, airways narrow which blocks breathing rapid, weak pulse, skin rash, nausea, vomiting

Question 52

what can cause anaphylaxis

Answer 52

too many anaphylotoxins due to sepsis and other conditions