13 Inflammation and Cytokines Flashcards by Ryan Bird

In the beginning of the inflammatory cycle - Injury causes?

Exposed collagen, platelet-activating factor release and tissue factor release from endothelium

How well did you know this?

Not at all

Perfectly

Platelets bind to? And then?

Collagen release growth factors (platelet-derived growth factor) - leads to PMN and macrophage recruitment

How well did you know this?

Not at all

Perfectly

What cells have the dominant role in wound healing? What do they release?

Macrophages
Growth factors (PDGF) and cytokines (IL-1, TNF-a)

How well did you know this?

Not at all

Perfectly

PDGF

Chemotactic and activates PMNs/macrophages
Chemotactic and activates fibroblasts (collagen and ECM proteins)
Angiogenesis
Epithelialization
Chemotactic for smooth muscle cells
Accelerates wound healing

How well did you know this?

Not at all

Perfectly

EGF (epidermal growth factor)

Chemotactic and activates fibroblasts
Angiogenesis
Epithelialization

How well did you know this?

Not at all

Perfectly

PAF (platelet-activating factor)

Generated by phospholipase in endothelium - phospholipid

Chemotatic for inflammatory cells - increased adhesion molecules

How well did you know this?

Not at all

Perfectly

Factors chemotatic for inflammatory cells?

PDGF
IL-8
LTB-4
C5a and C3a
PAF

How well did you know this?

Not at all

Perfectly

Factors chemotatic for fibroblasts?

PDGF
EGF
FGF

How well did you know this?

Not at all

Perfectly

Angiogenesis factors

PDGF
EGF
FGF
IL-8
Hypoxia

How well did you know this?

Not at all

Perfectly

Epithelialization factors

PDGF
EGF
FGF

How well did you know this?

Not at all

Perfectly

How long to PMNs survive?

1-2 days in tissue

7 days in blood

How well did you know this?

Not at all

Perfectly

How long do platelet survive?

7-10 days

How well did you know this?

Not at all

Perfectly

Lymphocyte functions?

Chronic inflammation (T-cells)
Antibody production (B-cells)

How well did you know this?

Not at all

Perfectly

Eosinophils

IgE receptors that bind to allergen
Release major basic protein - stimulates basophils and mast cells to release histamine
Eosinophils are increased in parasitic infections

How well did you know this?

Not at all

Perfectly

Basophils

Main source of histamine in blood

NOT found in tissues

How well did you know this?

Not at all

Perfectly

Mast cells

Primary cell in type I hypersensitivity reactions

Main source of histamine in tissues

How well did you know this?

Not at all

Perfectly

Histamine effects

Vasodilation, tissue edema, post-capillary leakage

Primary effector in type 1 HSR (allergic reactions)

How well did you know this?

Not at all

Perfectly

Bradykinin effects

Peripheral vasodilation, increased permeability, pain, pulmonary vasoconstriction

How well did you know this?

Not at all

Perfectly

Nitric oxide (NO)

Arginine precursor (nitric oxide synthase)
Activates guanylate cyclase and increases cGMP, resulting in vascular smooth muscle dilation
AKA endothelium-derived relaxing factor

How well did you know this?

Not at all

Perfectly

Endothelin

Causes vascular smooth muscle constriction

Opposite effect of nitric oxide

How well did you know this?

Not at all

Perfectly

Main initial cytokine response to injury and infection?

Release of TNF-a and IL-1

How well did you know this?

Not at all

Perfectly

What produces TNF-a

Macrophages

How well did you know this?

Not at all

Perfectly

Effect of TNF-a

Increases adhesion molecules
Procoagulant
Activates neutrophils and macrophages (more cytokine production and cell recruitment)

How well did you know this?

Not at all

Perfectly

What causes cachexia in patients with cancer?

TNF-a

How well did you know this?

Not at all

Perfectly

What can high levels of TNF-a cause?

Circulatory collapse and multisystem organ failure

What produces IL-1?

Macrophages

Effects of IL-1?

Fever (PGE2 mediated in hypothalamus) | Raises thermal set point

How do NSAIDs decrease fever?

Reduce PGE2 synthesis - decreasing its concentration in the hypothalamus

Why do you get fever with atelectasis?

Alveolar macrophages release IL-1

IL-6

Increases hepatic acute phase proteins (C-reactive protein, amyloid A)

Interferons

Released by lymphocytes Target viral infection Activate macrophages, natural killer cells and cytotoxic t-cells Inhibit viral replication

What is the most potent stimulus for hepatic acute phase proteins?

IL-6

What increases in response to inflammation?

``` C-reactive protein (osponin, activates complement) Amyloid A and P Fibringoen Haptoglobin Ceruloplasmin Alpha-1 antitrypsin C3 (complement) ```

What decreases in response to inflammation?

Albumin Pre-albumin Transferrin

Selectins

``` L-selectins (on leukocytes) Bind E (endothelial) and P (platelet) selectins Causes rolling adhesion ```

Beta-2 integrins

CD11/18 - on leukocytes Bind ICAMs Anchoring adhesion

ICAM, VCAM, PECAM, ELAM

On endothelial cells - bind beta-2 integrin molecules on leukocytes and platelets

What causes rolling adhesion?

Selectins L- leukocytes E - endothelial P - platelet

What causes anchoring adhesion?

``` Beta-2 integrins (on leukocytes) Binding ICAM (on endothelial cells) ```

What is involved in transendothelial migration?

ICAM, VCAM, PECAM, ELAM | Beta-1 and 2 integrins

What activates classic complement pathway?

Antigen-antibody complex - IgG or IgM

C1, C2, C4?

Classic pathway

What activates the alternative complement pathway?

Endotoxin, bacteria, exogenous stimuli

B, D P (properidin)

Alternative pathway

What complement factor is common to and the convergence point for both pathways?

What cofactor is required for both complement pathways?

Magnesium

Which complement factors are anaphylatoxins?

C3a, C4a, C5a Increase vascular permability Bronchoconstriction Activate mast cells and basophils

What makes up the membrane attack complex?

C5b-9b Causes cell lysis by creating hole in cell membrane Attacks bacteria

Opsonization

Targets antigen for immune response | C3b, C4b

Complement which is chemotaxis for inflammatory cells

C3a, C5a

Prostaglandins are produced from

Arachidonic precursors

Effects of PGI2/PGE2?

Vasodilation Bronchodilation Increased permeability Inhibits platelets

Effect of NSAIDs

Inhibits cycloxygenase | Reversible

Effect of Aspirin

Inhibits cyclooxygenase Irreversible Inhibits platelet adhesion by decreasing TXA2

Effect of steroids on inflammation

Inhibit phospholipase, which converts phospholipids to arachidonic acid Therefore, inhibits inflammation

Source of leukotrienes

Arachidonic precursors

What are the slow-reacting substance of anaphylaxis? | What do theycause?

``` LTC4, LTD4, LTE4 Bronchoconstriction Vasoconstriction Followed by increased permeability (Wheal and flare) ```

Effect of LTB4

Chemotatic for inflammatory cells

When do catecholamines peak after injury?

24-48hrs

Where is epinephrine released from?

Adrenal medulla | Postganglionic neurons

Where is norepinephrine released from?

Adrenal medulla

What is the neuroendocrine response to injury?

Efferent nerves from site of injury stimlate CRF, ACTH, ADH, growth hormone, epinephrine and noreepinephrine release

What is thyroid hormone's role in injury or inflammation?

NOTHING

What are the CXC chemokines? What do they do?

IL-8, Platelet factor 4 Chemotaxis, angiogenesis, wound healing C = Cysteine, X = another amino acid

What oxidants are generated in inflammation?

``` Superoxide anion radical (NADPH oxidase) Hydrogen peroxide (xanthine oxidase) ```

What are the cellular defenses against oxidative species?

Superoxide anion radical (superoxide dismutase) Converts to hydrogen peroxide Hydrogen peroxide (Glutathione peroxidase, vatalase)

What is the primary mediator of reperfusion injury?

PMNs

Chronic granulomatous disease

NADPH-oxidase system enzyme defect in PMNs | Results in decreased superoxide radical formation