Immunology Chapter 3 Innate Immune System

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synthesize and deploy peptides and proteins w/ antimicrobial activity
ex. psoriasin - small protein w /potent antibacterial activity against E. coli

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skin and epithelia

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first detection event in host
soluble or membrane-bound molecules capable of precisely discriminating b/t self and nonself
recognize particular overall molecular patterns

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pattern recognition receptors (PRRs)

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include combinations of sugars, certain proteins, particular lipid-bearing molecules, and some nucleic acid motifs
located on pathogens

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pathogen-associated molecular patterns (PAMPs)

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mannose-binding lectin (MBL)
C-reactive protein (CRP)

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initiators of the complement system

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lysis of invaders

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opsonization

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straddles the innate and adaptive immune system
activation cascade can be activated either by molecules that recognize PAMPs or by antibodies binding to specific foreign antigens

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complement system

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detect microbial products
very important
11 have been described for humans
allow dendritic cells and macrophages to detect a broad spectrum of pathogens

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TLRs
toll-like receptors

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hormone- or growth-factor-like proteins that communicate via cell receptors to induce specific cell activities

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cytokines

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agents that cause cells to move toward higher concentrations of the agent

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chemoattractants

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major subgroup of cytokines whose signature activity is their capacity to act as chemoattractants

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chemokines (not all chemoattractants are chemokines)

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when bound to membranes, increases affinity to intercellular adhesion molecules (ICAMs) on the endothelium

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integrin

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most important and versatile regulators of leukocyte traffic, selectively controlling the adhesion, chemotaxis, and activation of a variety of leukocyte subpopulations

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chemokines

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4 steps of neutrophil extravasion

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rolling
activation by chemoattractant stimulus
arrest and adhesion
transendothelial migration

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an important group of cytokines w/ antiviral action

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interferons

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more than 800 different types
range in size from 6 to 59 amino acid residues, most are positively (cationic) charged

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antimicrobial peptides

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kill microbes rapidly, typically w/in minutes
kill wide variety of bacteria
neutrophils are rich sources
paneth cells also secrete them

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defensins

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family of pentameric proteins of which C-reactive protein belongs to
bind ligands in calcium-dependent reaction

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pentraxins

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important part of the innate immune system that recognizes and signals a resonse to lipopolysaccharide

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lipopolysaccharide-binding protein (LBP)

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most recent group of receptors found to play roles in innate immunity
cytosolic, NOD1 and NOD2 recognize products derived from bacterial peptidoglycans

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NOD proteins (nucleotide-binding oligomerization domain)

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membrane-spanning proteins that share a common structural element in their extracellular region, repeating segments of 24 to 29 amino acids containing the sequence xLxxLxLxx (x amino acid, L leucine)
these structural motifs are called leucine-rich repeats (LRRs)

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Toll-like receptors
TLR

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main functions include:
phagocytosis
reactive oxygen and nitrogen species
antimicrobial peptides

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neutrophils

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key functions include:
phagocytosis
inflammatory mediators
antigen presentation
reactive oxygen and nitrogen species
cytokines
complement proteins

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macrophages

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key functions include:
antigen presentation
costimulatory signals
reactive oxygen species
interferon
cytokines

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dendritic cells

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key functions include:
lysis of viral-infected cells
interferon
macrophage activation

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natural killer cells

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essential for the innate defense against bacteria and fungi

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neutrophils

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reactive oxygen species are generated by this enzyme complex

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NADPH phagosome oxidase (phox) enzyme complex

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oxygen consumed by phagocytes to support ROS production by the pox enzyme is provided by a metabolic process known as..

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respiratory burst

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increased susceptibility to fungal and bacterial infection observed in patients afflicted w/ this disease
caused by a defect in the ability of phox to generate oxidizing species

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chronic granulomatous disease

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following activation by receptors such as TLRs or exposure to appropriate cytokines, phagocytes express high levels of this enzyme
oxidizes L-arginine to yield L-citrulline and nitric oxide (NO)

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inducible nitric oxide synthetase

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secreted by NK cells
powerful mediator of macrophage activation and an important regulator of Th cell development, establishing a direct link b/t NK cells and the adaptive system

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Interferon-gamma

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besides communicating with both innate and adaptive immunity, these cells:
generate reactive oxygen species and nitric oxide
produce antimicrobial peptides
some produce type I interferons

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dendritic cells

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transmission of signals to the cell interior

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signal transduction

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connects the detector to effector mechanisms in response to signals

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signal transduction pathway

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what receptor of innate immune system?

target (source): microbial cell wall components
effect: activation, opsonization, lysis

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complement (bloodstream, tissue fluids)

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what receptor of innate immune system?

target: mannose-containing microbial carbohydrates (cell walls)
effect: complement activation, opsonization

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mannose-binding lectin (MBL) (bloodstream, tissue fluids)

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what receptor of innate immune system?

target: phosphatidylcholine, pneumococcal polysaccharide (microbial membranes)
effect: complement activation, opsonization

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C-reactive protein (CRP) (bloodstream, tissue fluids)

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what receptor of innate immune system?

target: bacterial lipopolysaccharide (gram-negative bacterial cell walls)
effect: delivery to cell membrane

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Lipopolysaccharide (LPS) receptor
LPS-binding protein (LBP) (bloodstream, tissue fluids)

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what receptor of innate immune system?

target: microbial components not found in host
effect: induces innate responses

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toll-like receptors (cell surface or internal compartments)

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what receptor of innate immune system?

target: bacterial cell wall components
effect: induces innate responses

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NOD (Nucleotide-binding oligomerization domain) family receptors (intracellular)

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what receptor of innate immune system?

target: many targets; gram-positive and gram-negative bacteria, apoptotic host cells
effect: induces phagocytosis or endocytosis

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scavenger receptors (SRs) (cell membrane)