Assignment 11 - look at pictures too!

Question 1

what are the 5 hallmarks of inflammation

Answer 1

redness
heat
edema
pain
pus

Question 2

how is redness and heat brought about

Answer 2

increased blood flow (vasodilation)

red cell extravasation (leaking out)

Question 3

how is edema brought about?

Answer 3

caused by leakage of fluid from circulation into tissues (increased vascular permeability)

Question 4

how is pain brought about?

Answer 4

result of stimulation of nerve endings by bradykinin

Question 5

how is pus brought about?

Answer 5

accumulation of dead phagocytes and bacteria along with byproducts of tissue destruction

Question 6

What does tissue damage, microbial infections, toxic agents induce inflammation activate?

Answer 6

o Complement system
o Mast cell degranulation
o Blood coagulation contact system = producing bradykinin 
o Macrophages, dendrites
o T-cells/b-cells

Question 7

what does the activation of the complement system, mast cell degranulation, blood coagulation contact system, macrophage, dendrites, T and B cells generally cause?

Answer 7

ALL increase vascular permeability & increase blood flow to infected site

Question 8

what 4 proteins make up the coagulation pathway contact system?

Answer 8

Factor XII
Factor XI
prekallikrein
kininogen (high molec. weight)

Question 9

collagen exposed in damaged tissue + platelet membranes serves as a target for what?

Answer 9

Factor XII

Question 10

what does activated Factor XII do?

Answer 10

converts prekallikrein –> kallikrein

Question 11

what does enzymatically active kallikrein do?

Answer 11

cleaves kininogen –> bradykinin

cleaves C5 –> C5a by hydrolysis

activates neutrophils

Question 12

what is bradykinin

Answer 12

potent vasodilator and increases vascular permeability

Question 13

what is the role of C5a?

Answer 13

anaphylatoxin that binds to receptors on basophils and mast cells inducing degranulation and histamine release

Question 14

what is the stimulus for histamine release from mast cells

Answer 14

o Mast cells express FCeR
o FCeR binds to IgE antibodies with active Fc regions that have a bound antigen
o Antigens bind to FAB region of IgE via crosslinks to the FCeR
o triggering mast cells to release histamine

Question 15

explain the role of histamine on the expression of P-selectin on the endothelial cels?

Answer 15

P-selectin is moved from the cytoplasm to the plasma membrane in the presence of histamine

Question 16

describe the role of P-selectin in acute inflammation

Answer 16

expressed on plasma membranes – not on circulating cells

induces rolling of the leukocytes on the endothelium

Question 17

describe the other effects of histamine on the endothelium and the role that this plays in acute inflammation?

Answer 17

When histamine is released it causes vasodilation of the precapillary arterioles = increased blood flow to capillary beds

there is then induced contraction of endothelial cells in the capillary beds and post cap venues = increased vascular permeability + edema

Question 18

how is the alternative pathway activated and what are the consequences of activating the alternative pathway?

Answer 18

presence of infection - deposition of C3b
generates C5a/5b
these anaphylatoxins with their cognate receptors on mast cells cause mast cell degranulation and release histamine + others = enhance the effect mediated by kallikrein mediated hydrolysis of C5 and C5a fragment?

Question 19

List the chemokines that macrophages secrete and describe the role of each. List the cytokines they secrete.

Answer 19

o Secrete cytokines (IL-1, IL-6, IL-12, TNF)
o Secrete chemokines (MCP-1, IL-8)
o Secrete matrix metalloprotieinases (degradation)
o Secrete tissue inhibitors of matrix metalloproteinases (regulation)

Question 20

List the local effects of TNF and IL-1 on

monocyte/macrophages and vascular endothelium

Answer 20

Monocyte and macrophages
Enhance cytotoxicity of macrophages

Vascular endothelium
Expression of E-selectin on endothelium (cell rolling)
Expression of VCAM-1 and ICAM-1 on
endothelium (firm adhesion)
Induce secretion of IL-8 (CXCL8) and MCP1 (CCL2) by endothelial cells
Auto and paracrine activation of Mφ

Question 21

list the systemic effects of IL-1 and TNF

Answer 21

o TNF and IL-1 stimulate endothelial cells to express adhesive molecules

• E-selectin
• VCAM-1
• Chemokines IL-8
• MCP-1
• Produce vasodilation
• Induce fever

Question 22

explain how CRP increases in pts with Heart disease

Answer 22

o IL-6 induces secretion of acute phase proteins from the liver called CRP
o CRP serves as an opsonin for enhanced phagocytosis of bacteria
o People with heart failure will have higher levels of CRP

Question 23

how are the first responders in mediating the clearance of necrotic tissue and/or invading organisms present at inflammatory sites?

Answer 23

macrophages (leukocytes)

Question 24

the activation of macrophages leads to processes that recruit what to the site of inflammation?

Answer 24

neutrophils and monocytes (cells that mature to macrophages)

Question 25

what are metalloproteinases?

Answer 25

proteins that degrade the BM to allow cell migration

Question 26

what do macrophages secrete as a secondary even?

Answer 26

TIMPS (tissue inhibitors of matrix matalloproteinases) to downreg their activity

Question 27

what is the stimulus for expression of p-selectin on the endothelium?

Answer 27

Induced by histamine | Lead to leukocyte rolling on endothelium

Question 28

what is the stimulus for E-selectin expression on the endothelial cell surface?

Answer 28

Induced by TNF and IL-1 | Lead to leukocyte rolling on endothelium

Question 29

describe the effects of IL-1 and TNF on the vascular endothelium

Answer 29

Produces vasodilation -->contributes to low blood pressure | Induce fever -->modifies hypothalamus

Question 30

list the integrins expressed on leukocytes

Answer 30

PSGL-1 --> p-selectin Ligand:e-selectin --> eselectin MAC-1 --> ICAM-1 LFA-1--> ICAM 1 or ICAM 2

Question 31

name the counter molecules for VLA-4 and the effect of IL-1 and TNF on its expression

Answer 31

VLA-4-->VCAM 1 | IL-1 and TNF will promote expression of VCAM-1 on endothelial cell surface

Question 32

what are the members of the selectin family

Answer 32

P E L

Question 33

where are L selectins expressed?

Answer 33

on circulting lymphocytes in a NON inflammatory state!

Question 34

where are P and E selectin equally expressed?

Answer 34

activated endothelium

Question 35

what activates p-selectin

Answer 35

histamine from mast cells because of C5a

Question 36

what activates E selectin

Answer 36

TNF and IL-1

Question 37

what are the functions of P and E selectin in inflammation

Answer 37

rolling

Question 38

what is the important of cell rolling?

Answer 38

prolongs the duration of time to which leukocytes are exposed to chemoattractants and activators secreted into this inflammatory microenvironment