CH 7 innate immunity

first line defense

physical and mech barrier

skin, low temp/pH

lining of GI, genitourinary, respt. tract

first line defense: biochem barriers

synthesize, secrete to trap or destroy

antimicrobial peptides (cathelicidins, defensis, collectin)

normal microbe (release chem)

type of immunity

innate resistance

adaptive (acquired)

second line defense

inflammatory response

cellular, chem component

nonspecific

no memory cell

cardinal sign inflammation

redness

heat swell

pain

loss function

inflammation vascular response

blood vessel dilate

increase vascular permeability

WBC adhere

plasma protein system

provide biochem barrier againts invading pathogen

inactive enzyme

• complement

• clotting

• kinin

complement system

destroy pathogen directly

cell lysis, inflammation, opsonization

pathways: classical, lectin, alternative

complement system: classical

antibodies and antigens

complement system: lectin

mannose contain bacterial carbohydrate

complement system: alternative

gram negative bacteria and fungal cell wall polysaccharide

clotting (coagulation) system

fibrinous mesh at injured/inflamed site

stop bleeding

scaffolding for healing

clotting (coagulation) system: extrinsic

activated by tissue factor outside vascular space

clotting (coagulation) system: intrinsic

activated in vascular space when vessel wall damage

kinin system

activate and assist inflammatory cell

pain, vasodilation

bradykinin

dilate blood, smooth muscle contraction, leukocyte chemotaxis

carboxypeptidase

inhibit C3a and C5a

histaminase

degrade histamine and kallikrein

down-regulate inflammatory response

arylsulfatase

inhibit histamine

control inflammation and inhibit three plasma proteins

kinase

inhibit kinins

C1-esterase inhibitor

inhibit complement

cellular mediators

mast cell

granulocyte

monocyte/macrophages

NK cell/ lymphocyte

cellular fragment

biochem mediators

destroyed or damage cells

tissue regeneration or repair

pattern recognition receptors (PRR)

toll-like receptor

complement receptors

scavenger receptors

toll-like receptors (TLRs)

recog pathogen associated molecular pattern

complement receptor

recog complement fragment

scavenger receptor

promote phagocytosis

inflammatory response

tissue injury occur or when PAMP are recog by PRRs on cell of innate immune system

chemokines or cytokines

reg innate or adaptive resistance by affecting other neighboring cell

proinflammatory or antiinflammatory

synergistic or antagonistic

interleukin, interferons, tumor necrosis factor

interleukins

cytokines

produced by macrophages and lymphocyte

help reg inflammation

interferons

cytokines

protect against viral infection

viral double stranded ribonucleic acid

prevent from infecting healthy cells

IFN a, b, y

IFN a/b

induce production of antiviral protein

IFN y

increase microbicidal activity of macrophages

chemokins

WBC chemotaxis

produced by macrophages, fibroblast, endothelial cell

CC- B

CXC- a

mast cell

cellular bag of granules in loose connective tissue close to blood vessel

degranulation or synthesis of lipid-derived chem mediators

mast cell degranulation: release histamine

cause temp and rapid constriction of large blood vessel dilation of postcapillary venules

H1 receptor

H2 receptor

H1 receptor

proinflammatory

smooth muscle cell of bronchi

bronchoconstriction

H2 receptor

anti inflammatory

parietal cell of stomach mucosa

secretion of gastric acid

mast cell degranulation: chemotactic factor

neutrophil chemotactic factor: neutrophils

eosinophil chemotactic anaphylaxis: eosinophils

leukotrienes

product of arachidonic acid from mast cell membrane

important in larger staged of inflammation

prostaglandins

induce pain

like leukotrienes

platelet-activating factor

activate platelets

like leukotrienes

endothelium

maintain normal blood flow

produce nitric oxide and prostacyclin

platelets

cellular fragment formed from megakaryocyte

thrombocytes

stop bleeding adn degranulation

neutrophils

polymorphonuclear neutrophils

remove debris in sterile lesions

phagocytosis of bacteria in non-sterile lesions

eosinophils

provide defense against parasites and reg vascular mediators

control vascular effect of inflammation

basophils

cytokine IL-4

allergies and asthma

dendritic cell

provide link between innate and acquired immune

peripheral organ and skin

guide dev of T cell (helper)

monocyte, macrophages

monocyte produced in bone marrow, dev into macrophages

help wound healing

phagocytosis

cell ingests and dispose of foreign material

phagocytosis steps

Opsonization → Recognition → Engulfment → Phagosome formation → Phagolysosome → Destruction. Neutrophils dominate early inflammation; macrophages dominate later and aid healing

natural killer (NK) cell

recog and eliminate cell that are infected with viruses and cancer cell in blood

lymphocyte

main component of adaptive immune response

heat manifestation of inflammation

vasodilation and increase blood flow

manifestation of inflammation redness

vasodilation and increase blood flow

swelling manifestation of inflammation

exudate accumulation and fluid from capillary permeability

pain manifestation of inflammation

pressure exerted by exudate accumulation, prostaglandins, bradykinins

local manifestation inflammation

dilute toxins

carry plasma protein and leukocyte to injury site

carry bacterial toxin and debris away from site

exudate

fluid and cell

serous exudate

watery exudate

indicate early inflammation

fibrinous exudate

thick, clotted exudate

more advanced inflammation

purulent (suppurative) exudate

pus

bacterial infection

hemorrhagic exudate

exudate containing blood

bleeding

fever

caused by exogenous and endogenous pyrogens

act on hypothalamus

leukocytosis

increase number circulating leukocyte

increase immature cell

increase plasma protein synthesis

actue phase reactants

chronic inflammation

2 weeks or longer

unsuccessful acute inflammatory response

wound healing: regeneration

favorable outcome

wound healing: resolution

return injured tissue to original structure and function

wound healing: repair

Replacement of destroyed tissue with scar tissue

collagen restore

wound healing process

filing in wound

sealing in wound (epithelialization)

shrinking wound (contraction)

primary intention

wound heals under conditions of minimal tissue loss

original tissue function restored

secondary intention

wound req more tissue replacement

scar formation

phase I: inflammation (wound healing)

1. Platelets, neutrophils, macrophages 

2. Clot form scaffold 

3. Debridement

phase II: reconstruction (wound healing)

healing begin 3-4 days after injury and continue for 2 weeks

1. Fibroblasts produce collagen 

2. Epithelialization 

3. Wound contraction

phase III: remodeling, maturation (wound healing)

several week after injury and last 2 years

1. Scar maturation 

2. Collagen reorganization

dysfunction during reconstructive phase

impaired collagen matrix

impaired epithelialization

impaired contraction

wound disruption

dehiscence

occur 5-12 day after suture

surgery req

wound pull apart at suture line

inflammatory cell

• Neutrophils: First responders

• Monocytes/Macrophages: Cleanup + cytokines

• Lymphocytes: Adaptive immunity

• NK cells: Kill infected cells

• Platelets: Clotting + inflammation