inflammation and innate immunity

immidiate, general, complement and phagocytes

innate immunity attributes

gradual, specific, b and T cells

adaptive immunity attributes

complement, phagocytes, b cells, and t cells

4 immune compartments

alternative,classcial, lectin

three complement systems

formation of membrane attack complex

what is the result of complement system

alternative complement system

activated spontaneously by hydrolysis C3 and further triggered by structures on microorganisms and other foreign surfaces

classical complement system

antibody-antigen complex binds C1 complex, most active in bacterial infections

lectin complement system

Pattern recognition receptors, such as mannose-binding lectin (MBL) bind to carbohydrates on pathogens.

opsonization, cytolysis, promote antibody production, chemotaxis, removal of immune complexes and apoptotic cells

roles of complement

innate immune recognition

distinguishes between self and non self, pathogen associated molecular patterns (PAMPs), and damage associated molecular patterns (DAMPs)

toll-like receptors (TLRs)

cell associated patteern recognition receptor with multiple targets

NOD-like receptors (NLRs)

cell-associated pattern recognition receptors that are cytoplasmic

RIG-like receptors (RLRs)

cell associated pattern recognition receptor that is cytoplasmic and sense viruses

C-type lectin receptors

cell associated pattern recognition receptor that targets microbial carbohydrates in bacterial,viral,and fungal cell membranes

TLR2

receptor that recognizes bacterial peptidoglycan on cell surface

TLR3

toll like receptor that recognizes viral endosomal dsRNA

TLR4

receptor that targets gram negative bacteria LPS on cell surface

TLR7 and TLR8

viral endsomal ssRNA

NF-kB

transcription factor that leads to increased expression of proteins involved in acute inflammation (cytokines, adhesion molecules, and costimulatory molecules) and stimulation of adaptive immunity

cytokines

TNF,IL-1, IL-6

chemokines

CCL2 and CXCL8

endothelial adhesion molecules

E-selectin

costimulatory molecules

CD80 and CD86

interferon regulatory factor

triggered by viral infections to produce type I interferon (IFN-alpha and beta), induces an antiviral state in neighboring cells

TNF-a, IL-1, IL-6

major inflammatory cytokines

activate endothelial cells, activate resident immune cells, stimulate phagocytosis and production of prostaglandins

local effects of major inflammatory cytokines

act on the hypothalamus as endogenous pyrogens (fever inducer)

systemic effects of major inflammatory cytokines

inhibits myocardial contractility (hypotension), intravascular thrombosis, wasting of muscle and fat cells (cachexia)

systemic effects of TNFa (inflammatory cytokine)

cytokine storm

massive release os inflammatory cytokines caused by bacterial sepsis, toxic shock, and large-scale

systemic inflammatory reesponse syndrome (SIRS)

part of thee cytokine storm that causes vascular collapse, disseminated intravascular coagulation severe metabolic disturbances

IL-8 (CXCL8)

chemokine, recruiter of neutrophils

prostaglandins

product of cyclooxygenase pathway that causes vasodilation/vascular permeability; inflaammatory paain, hyperalgesia and fever

leukotrienes

product of lipoxygenase pathway that are mediators of allergic reactions and inflammation

chemokines

lead immune cells and WBCs to sites of infection, activated by PRR activation and inflammatory cytokines

monocyte chemoattractant protein

chemokine that is a recruiter of monocytes

biogenic amines (histamine)

released from mast cell cause vasodialtion and vascular leak

cytokines (TNF)

released from mast cell leads to inflammation

enzymes (tryptase)

released from mast cell causes tissue damage

macrophage

phagocytosis, release ROS and NO to kill phagocytosed bacteria, repair damaged tissues by stimulating angiogenesis and fibrosis

Dendritic cell

antigen presenting cell that activates B and T cells

neutrophils, monocytye/macrophage, natural killer cells, eosinophils, basophils

recruited inflammatory cells

neutrophil

first recruited to site of inefection, phagocytosis and ROS killing, production of antimicrobial peptides (Human Neutrophil Peptides (HPNs))

monocytes/ macrophage

most active against bacteria and viruses, promote further inflammation (chemokine and cytokine production) and mediate tissue repair (protease and growth factor production)

natural killer cells

kill infected cells and activate macrophages, perforin expression (holes in target membrane), and FcR expression (stimulate antibody-dependent cellular cytotoxicity (ADCC))

eosinophils

specialized to fight parasitic infections, active in allergic responses

basophils

infiltrate sites of allergic inflammation and release mediators and cytokines