unit 3 - Induced Innate Response

How phagocytes chase and bind to proteins

PRRs and TLRs recognize PAMP on pathogen

phagocyte response

leukocyte recognizes PAMP-TLR/PRR complex

pathogen engulfed and contained in phagosome

digestive enzyme and chemicals produced in lysosome

lysosome fuses with phagosome = phagolysosome

digested products expelled from cell

mechanisms to kill pathogens in phagosome

Oxygen dependent and oxygen independent mechansims

oxygen dependent mechanisms

transient increase in O2 consumption in phagocyte = respiratory/oxidative burst generating ROS

oxygen independent mechanisms

chemical and enzymes stored in lysosome destroy pathogen

issues with phagocytosis

pathogens can infect phagocyte

can be too big

cytokine

broad class of molecule chemical messenger; released in response to stimuli; coordinates immune response

chemotactic cytokines

released by tissue cells and immune cells; direct immune cells to site of infection

chemotactic gradient

how immune cells are directed to site of infection; immune cells migrate from low to high conc. via leading edge + chemokine receptors

chemotactic cytokine example

IL8

IL8 (CXCL8)

promotes migration of neutrophils to site of bacterial infection and tissue dmg

vasoactive cytokine

alter structure of blood vessels; responsible for vasodilation = WBC and extravasate

tumor necrosis factor (TNF-a)

vasoactive cytokine;

induce endothelial activation, promote vasodilation, increase vascular permeability

when TNF-a produces systematically

lead to septic shock

IL-6

indirect contribution to vascular change during systemic inflammation → fever and acute phase response

purpose of inflammation

eliminate cause of tissue dmg, remove cellular debris, initiate repair

inflammatory response

resident immune cells release pro inflammatory mediators

vasoconstriction

vasodilation → increased Blood to affected area = redness and warmth + increased permeability

immune components concentrate at site

threat controlled = create tissue environment supporting tissue repair

cardinal signs of inflammation

cytokine signal pain and numbness, edema, vasodilation

leukocyte recruitment

vasoactive signal → expression of ICAM

selectins make leukocyte (LK) roll along endothelium

LK integrin bind to ICAM at endothelial pore

endothelial cells make opening → LK extravasates

chemotaxis = LK migrate to site

systemic inflammation

inflammatory response extends beyond localized area; can lead to shock and multiple organ failure

hypercytokinemeia

excessive cytokine release

effects of hypercytokinemia

shock, fever, cytokine storm

cytokine storm

excessive cytokines → widespread inflammation, tissue dmg, organ dysfunction

cytokines can be

pro or anti inflammatory

fevers are induced by

pyrogenic cytokines

exogenous pyrogens

components of pathogens that can trigger immune cells to initiate fever

endogenous pyrogens

chemicals produced by immune cells that trigger fever

consequence of fever response

inhibit growth of temp sensitive microbes

reduce availability of iron

increases metabolic rate → phagocytosis, antigen present, leukocyte proliferation

liver produces more of what during inflammation

acute phase proteins

acute phase proteins include

complement proteins, clotting factors, c-reactive protein

complement proteins

lysis of pathogen

clotting factors

involved in blood coagulation to limit bleeding and pathogen spread

c-reactive protein

recognizes PAMPs and promotes phagocytosis of microbes with PAMPs

erythrocyte sedimentation rate (ESR)

indirect assessment of inflammation → inflammation present = faster sedimentation rate

ESR theory

fibrinogen and APPs cause enhanced RBC aggluination

inflammatory response in cells

inflammatory stimuli → cells activate PLA2 → release arachidonic acid from PM

AA build up = stress response → induces COX and LOX pathways

COX pathway leads to

prostaglandin release → fever, pain, vasodilation

LOX pathway leads to

leukotriene release → smooth muscle contraction, vasodilation, mucus secretion, neutrophil recruitment

how to treat inflammation

NSAIDS and corticosteroids