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Immunology > Assignment 11 - look at pictures too! > Flashcards

Assignment 11 - look at pictures too! Flashcards

1
Q

what are the 5 hallmarks of inflammation

A 
redness
heat
edema
pain
pus
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2
Q

how is redness and heat brought about

A

increased blood flow (vasodilation)

red cell extravasation (leaking out)

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3
Q

how is edema brought about?

A

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

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4
Q

how is pain brought about?

A

result of stimulation of nerve endings by bradykinin

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5
Q

how is pus brought about?

A

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

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6
Q

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

A 
o Complement system
o Mast cell degranulation
o Blood coagulation contact system = producing bradykinin 
o Macrophages, dendrites
o T-cells/b-cells
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7
Q

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

A

ALL increase vascular permeability & increase blood flow to infected site

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8
Q

what 4 proteins make up the coagulation pathway contact system?

A

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

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9
Q

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

A

Factor XII

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10
Q

what does activated Factor XII do?

A

converts prekallikrein –> kallikrein

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11
Q

what does enzymatically active kallikrein do?

A

cleaves kininogen –> bradykinin

cleaves C5 –> C5a by hydrolysis

activates neutrophils

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12
Q

what is bradykinin

A

potent vasodilator and increases vascular permeability

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13
Q

what is the role of C5a?

A

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

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14
Q

what is the stimulus for histamine release from mast cells

A

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

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15
Q

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

A

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

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16
Q

describe the role of P-selectin in acute inflammation

A

expressed on plasma membranes – not on circulating cells

induces rolling of the leukocytes on the endothelium

17
Q

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

A

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

18
Q

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

A

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?

19
Q

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

A

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)

20
Q

List the local effects of TNF and IL-1 on

monocyte/macrophages and vascular endothelium

A

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

21
Q

list the systemic effects of IL-1 and TNF

A

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
22
Q

explain how CRP increases in pts with Heart disease

A

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

23
Q

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

A

macrophages (leukocytes)

24
Q

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

A

neutrophils and monocytes (cells that mature to macrophages)

25
Q

what are metalloproteinases?

A

proteins that degrade the BM to allow cell migration

26
Q

what do macrophages secrete as a secondary even?

A

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

27
Q

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

A

Induced by histamine

Lead to leukocyte rolling on endothelium

28
Q

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

A

Induced by TNF and IL-1

Lead to leukocyte rolling on endothelium

29
Q

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

A

Produces vasodilation –>contributes to low blood pressure

Induce fever –>modifies hypothalamus

30
Q

list the integrins expressed on leukocytes

A

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

31
Q

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

A

VLA-4–>VCAM 1

IL-1 and TNF will promote expression of VCAM-1 on endothelial cell surface

32
Q

what are the members of the selectin family

A

P
E
L

33
Q

where are L selectins expressed?

A

on circulting lymphocytes in a NON inflammatory state!

34
Q

where are P and E selectin equally expressed?

A

activated endothelium

35
Q

what activates p-selectin

A

histamine from mast cells because of C5a

36
Q

what activates E selectin

A

TNF and IL-1

37
Q

what are the functions of P and E selectin in inflammation

A

rolling

38
Q

what is the important of cell rolling?

A

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

Immunology (12 decks)

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