Path V

Question 1

What are the 5 functions of inflammation?

Answer 1

1. dilute (toxins and mediators of inflammation)
2. destroy- invading organisms
3. dispose- remove dead tissue, leukocytes, bacteria
4. develop/prepare tissue for healing
5. deter: activate, modify, and participate in the establishment of acquired immunity (I guess deter refers to detering future pathogens?)

Question 2

5 general categories of things that participate in the inflammatory response

Answer 2

1. vascular endothelial cells
2. vascular basement membrane
3. ECM
4. leukocytes
5. tissue cells

Question 3

What are the four functions of the chemical mediators of the inflammation?

Answer 3

1. initiate the inflammatory response
2. amplify it
3. modify it.
4. terminate it

Question 4

What is the first step of inflammation?

Answer 4

vascular dilation leading to increased local bloodflow

Question 5

What 7 factors promote vascular dilation?

Answer 5

histamine, NO, bradykinin, PAF, neuropeptides, prostaglandins, lipoxins

Question 6

What is vascular endothelial activation/damage (3 forms)

Answer 6

direct damage, endothelial contraction or cytoskeletal reorganization, or leukocyte directed injury mediated by the release of toxic oxygen species and lysozpmes

Question 7

What factors medaite endothelial contraction or cytoskeletal reorganization in the vascular endothelial activation?

Answer 7

histamine, serotonin, leukotrienes, fibrin split products, PAF

Question 8

What are the three types of activation in the the vascular endothelial response?

Answer 8

redistribution of adhesion molecules on the cell surface, conformational changes leading to increaded binding affinity, and induction of increased numbers of adhesin molecules

Question 9

What factors promote the vascular endothelial activation?

Answer 9

TNF=alpha, IL1, PAF, IL8, IL16, free radicals, leukotrienes, thrombin, factor X

Question 10

What is P-selectin? What does it do, where is it found?

Answer 10

a protein constitutively expressed on endolthelial cells in low amts
stored within weibel-palade bodies within endothelial cells but can be redistributed on to the cell surface.
participates in the rolling phase by binding to leukocyte surface glycoproteins showing sialyl-Lewis X

Question 11

What factors induce the redistribution of P-selectin to endothelial cell surfaces? (5)

Answer 11

thrombin, PAF, INF-gamma, TNF-alphal and IL-1

Question 12

What is E-selectin? Who does it bind and what does it do?

Answer 12

binds leukocyte sialyl-Lewis X even better than P selectin. participates in the rolling and adhesion phase

Question 13

What factors promote the expression of E-selectin?

Answer 13

TNF-alpha, IFN-gamma, IL-1, PAF (JUST LIKE P-selectin)

Question 14

What is L selectin?

Answer 14

present on the sufrace of leukocytes, L-selectin participates in the rolling phase by binding to the groteoglycan GlyCam-1 on endothelial cells

Question 15

What facorts induce the expression of L-selectin?

Answer 15

TNF-alpha, IL-1, PAF, INF-gamma

Question 16

What is ICAM-1?

Answer 16

It is a mediator of firm adhesion. It attaches to integrins MAC-1 on neutrophils and LFA-1 on macrophages and lymphocytes. They are converted to an active for by TNF-alpha, IL-1, and IL8

Question 17

What factors induce ICAM-1 expression?

Answer 17

TNF-alpha, IL-8, and IL1

Question 18

What is PECAM-1

Answer 18

an adhesion molecule expressed at endothelial cell junctions under influence of TNF-alpha and IL1. It acts as an anchoring system to promote leukocyte transmigration through the endothelial junctions. Binds VLA-4.

Question 19

What are the effects of fluid and protein leakage into the tissues?

Answer 19

1. dilutes the conc. of toxins and CMOIs
2. allows proteins important to the inflammatory response to get to the site
3. expands the ECM to allow easier migration of the cellular components of the immune system
4. larger proteins remain in the vascular space.
5. relatively greater loss of water leads to incr. intravascular protein/RBC concentrations so even with incr. blood vol reaching the area the blood flow becomes more sluggish (more sluggish blood flow)

Question 20

What is margination of leukocytes?

Answer 20

leukocytes travel along the vessel walls instead of in the central flow

Question 21

What 5 favors lead to leukocyte margination?

Answer 21

increased total blood flow

2. intravascular fluid loss
3. slower flow
4. incr. in cell and plasma protein conc.
5. pronounced axial flow of RBCs.

Question 22

What is leukocyte rolling? What interaction mediates this event?

Answer 22

activated endothelial cells interact with marginated leukocytes
this slows down the leukocytes
medated through P-selectin on endothelial cells and sialyl-Lewis X on leukocytes

Question 23

When does leukocyte activation occur? How?

Answer 23

occurs during or before rolling phase
prepares for firm adhesion to the endothelium by increasing sialyl-Lewis X on glycoproteins and L selectins and integrins conformational change

Question 24

What is the purpose of leukocyte activation?

Answer 24

primes the locomotion nad bacteriocidal mechanisms of the cells and increases the energy production and O2 consumption by the leukocytes

Question 25

What is leukocyte adhesion? Between molecules do we see this?

Answer 25

firm attachement of the clel to the endothelium to allow for initiation of the transmigration process Between endothilail ICAM 1 and MAC for neutrophils between ICAM1 and LFA 1 for macros and lymps between E-selectin and sialyl Lewis X interactions

Question 26

Where does transmigration take place?

Answer 26

in the post-capillary venules

Question 27

What helps with lekuocyte transmigration? (4)

Answer 27

gaps widened between the endothelial cells, locomotion of activated leukocytes, expression of adhesion molecs at the endothelial cell junctions like PECAM-1 and proteolytic enzymes made by leukocytes to separate cells and breakdown the basement membrane

Question 28

What is the definition of leukocyte migration?

Answer 28

locomotion of leukocytes through the extravascular matrix following a chemotactic gradient

Question 29

What interactions are important for leukocyte migration?

Answer 29

cell integrins with ECM components like fibronectin, integrins, and hyaluronan

Question 30

What initiates leukocyte movement and chemotaxis?

Answer 30

activation of phospholipase C via a G-proptein dependant receptor. leads to an influx of extracellular Ca and the release of internal Ca stores. this Ca allows for the assembly and activation of actin-myosin contractile elements that help leukocytes move via pseudopodia formation.

Question 31

What is the first step of leukocyte phagocytosis and killing?

Answer 31

activation, recognition, and attachment.

Question 32

How might a leukocyte recognize bacterial or other pathogenic bad guys?

Answer 32

Toll like receptors, G-protein coupled receptors, MAC-1 integrins (non-specific). Or, opsonins. Opsonins bind microorganisms and help them bind to specific receptors on the leukocytes.

Question 33

What are three major opsonins?

Answer 33

1. collectins 2. antibodies 3. complement fragments C3b and C3bi.

Question 34

What are collectins?

Answer 34

proteins which bind to exclusive bacterial carbohydrates like mannos, then bind complement, and bind C1 receptors.

Question 35

What two factors trigger phagocytic engulfment?

Answer 35

binding, as with Fc receptors | binding opsonins with additional stim by binding other factors (Extracellular fibronectin, lamellin, or cytokines).

Question 36

What mediates engulfment?

Answer 36

increased cytosolic Ca associated with G-protein/phopholipase C activation

Question 37

How do phagocytes KILL things>

Answer 37

increased glycolysis and O2 consumption --> "oxidative burst" this generates H2O2, via NADPH oxidase

Question 38

Through what three mechanisms is H2O2 killing of bacteria enhanced?

Answer 38

Fe++ oxidation to make OH radical from H2O2 Haber-Weiss rxn (also makes OH radical) myeloperoxidase from azurophilic granules makes HOCl, aka clorox bleach