Fiber Chaper 13. INFLAMMATION AND CYTOKINES Flashcards Preview

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Flashcards in Fiber Chaper 13. INFLAMMATION AND CYTOKINES Deck (58)
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1

Three phases of inflammation

1. Injury: causes exposed collagen, PAF and TF release

2. Platelets bind collagen: release growth factors (platelet derived growth factor PDGF) and leads to PMN and macrophage recruitment

3. Macrophages: dominant role in wound healing; release important growth factors (PDGF) and cytokines (IL-1 and TNF-a)

2

PDGF

-chemotactic and activated inflammatory cells (PMHs and macrophages) and fibroblasts, which leads to collagen and ECM proteins

-angiogenesis

-epithelialization

-chemotactic for smooth muscle cells

-has been shown to accelerate wound healing

3

EGF

epidermal growth factor

-chemotactic and activates fibroblasts

-angiogenesis

-epithelialization

4

FGF

fibroblastic growth factor

-chemotactic and activates fibroblasts, which leads to collagen and ECM proteins

-angiogenesis

-epithelialization

5

PAF

platelet activating factor

-is not stored, generated by phospholipase in endothelium, is a phospholipid

-chemotactic for inflammatory cells; increases adhesion molecules

6

Chemotactic factors

For inflammatory cells: PDGF, IL-8, LTB-4, C5a, C3a, PAF

For fibroblasts: PDGF, EGF, FGF

7

Angiogenesis factors

PDGF, EGF, FGF, IL-8, hypoxia

8

Epithelialization factors

PDGF, EGF, FGF

9

PMNs last how long?

1-2 days in tissues, 7 days in blood

10

Platelets last how long?

7-10 days

11

Lymphocytes do what?

Chronic inflammation (T cells) and antibody productions (B cells)

12

Type 1 Hypersensitivity (allergic reactions)

-Eosinophils: IgE receptors that bind to allergen, release major basic protein, which stimulates basophils and mast cells to release histamine; increased in parasitic infections

-Basophils: main source of histamine in blood; not found in tissue

-Mast cells: primary cell in type 1 hypersensitivity reactions; main source of histamine in tissues

-Histamine: vasodilation, tissue edema, postcapillary leakage; primary effector in type 1 hypersensitivity reactions

-Bradykinin: peripheral vasodilation, increased permeability, pain, pulmonary vasoconstriction (inactivated by ACE)

13

What is the main source of histamine in blood? Tissues?

Blood: basophils

Tissue: mast cells

14

What does histamine do?

-Released by basophils (in blood) and mast cells (in tissue) in response to major basic protein released by eosinophils (which have IgE receptos which bind allergen)

-Vasodilation, tissue edema, postcapillary leakage

15

What causes peripheral vasodilation, increased permeability, pain, and pulmonary vasoconstriction in a type 1 hypersensitivity reaction?

Bradykinin

16

What inactivates bradykinin?

ACE; located in lung

17

Nitric oxide

also called endothelium derived relaxing factor

arginine -> (via NOS) -> nitric oxide

NO activates guanylate cyclase and increases cGMP resulting in vascular smooth muscle dilation

18

What is the precursor to nitric oxide?

arginine

19

What does NO do?

activated guanylate cyclase and increases cGMP to cause vascular smooth muscle dilation

20

What does the opposite of NO?

Endothelin (causes vascular smooth muscle constriction)

21

Main initial cytokine response to injury and infection

TNF-alpha and IL-1 release

22

TNF-alpha

-Macrophages are largest producers of TNF-a

-Increases adhesion molecules

-Procoagulant

-Cachexia in cancer patients

-Activates neutrophils and macrophages -> more cytokine production and cell recruitment

-High concentrations can cause circulatory collapse and multisystem organ failure

23

IL-1

-Macrophages are main source

-Effects similar to TNF-a and synergized TNF-a

-Responsible for fever (PGE2 mediated in hypothalamus): raises thermal set point, NSAIDs can decrease fever by reducing PGE2 synthethis

-Alveolar macrophages: cause fever with atelectasis by releasing IL-1

24

What cytokine causes fever?

IL-1

25

What cytokine causes cachexia?

TNF-a

26

IL-6

Increases hepatic acute phase proteins (CRP and amyloid A)

27

What are interferons?

Released by lymphocytes in response to viral infection or other stimulants

-Activate macrophages, natural killer cells, and cytotoxic T cells

-Inhibit viral replication

28

Hepatic acute phase response proteins

-IL-6: most potent stimulus

-CRP: opsonin, activates complement

-Amyloid A and P

-Fibrinogen

-Haptoglobin

-Ceruloplasmin

-Alpha-1 antitrypsin

-C3

-(albumin, pre-albumin, and transferrin are DECREASED)

29

Cell adhesion molecules

-Selectins, bet-2 integrins, ICAM, VCAM, PECAM, ELAM

30

Selectins

L-selectins on leukocytes, bind to E- (endothelial) and P- (platelet) selectins all causing ROLLING ADHESIONS