I2: Overview Of Innate And Adaptive Immunity

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core functions of the immune system

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protects the host against microbial invaders
rejects newly emerging malignant cells
responds to damaged tissues

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the adaptive immune system is

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a deliberate system for recognizing discrete foreign determinants (antigens)

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adaptive immune system develops only

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in response to challenge

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adaptive immune system is mediated by

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lymphocytes

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the receptors of adaptive immunity are

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highly diverse

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innate immunity is a

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rapid system for recognizing conserved microbial patterns and lysing, phagocytizing or signaling danger

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innate immunity is

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present at birth

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the patterns in innate immunity are

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widely distributed, highly conserved, and include simple families of cell surface receptors

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cells of innate immunity

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macrophages, NK cells, neutrophils

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cells of adaptive immunity

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B-lymphocytes
T helper lymphocytes
Cytotixic T lymphocytes

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function of B-lymphocytes

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produces antibodies

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T helper lymphocyte function

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promotes antibody function, can produce cytokines that activate macrophages for phagocytosis and killing

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cytotoxic T lymphocyte

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lyses tumor cells or foreign transplants

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B cell antigen receptor

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membrane form of antibody
binds antigens
transmembrane signaling initiates B cell activation

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T cell antigen receptor

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similar to BCR but not membrane bound
doesnt recognize the antigen but recognizes peptides presented by MHC

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Exogenous antigens

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Extracellular bacteria
antigens are presented on Th cells

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Endogenous antigens

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intracellular virus
antigens are presented on Tc cells

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6 categories of immune-mediated human disease

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alleriges
autoimmune disease
Transplantation rejection
cancer
immunodeficiency
infection-related

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physical first lines of defense against microbial pathogens

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skin/mucous membranes
mucocilliary movement and peristalsis
low pH and fatty acid content
Mucins
Competition by normal flora
lung surfactants
Fe2+-binding proteins
enzymes

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lung surfactants act to

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lower surface tension; promote physical clearance
promote microbial uptake/ingestion
binds microbe and pathogenic cell

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examples of Fe2+ binding proteins

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lactoferrin and transferrin
- compete for iron at sites of infection

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lysozymes function to

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degrade bacterial cell wall peptidoglycans

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three major innate immune mechanisms of host defense

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direct lysis of microbe
phagocysosis and intracellular killing of microbe
danger signaling to other immune cells

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PAMPS

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pathogen-associated molecular pattern
widely distributed structures found on many diverse organisims

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PAMPS are essential

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to microbial survival and host recognition structures are highly conserved.

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antimicrobial peptide example

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LL37

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antimicrobial peptides recognize

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negatively charged phospholipids of exterior microbial surfaces of many bacterial and fungal species

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antimicrobial peptides also

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intercalate and cause membrane damage- cell wall disruption

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recognition of LPS in gram-negative leads to

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danger signaling/ systemic inflammatory response

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LPS binds

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LBP

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LBP-LPS complex binds

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cell surface CD14

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CD14 function

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passes LPS-LBP complex to toll-like receptor 4

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mannose binding protein/lectin

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binds to properly spaced microbial mannose residues and promotes uptake
it is an opsonin

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TLRs are linked to

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transcription factors via adaptors/ protein kinases

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TLR adapter protein
TLR kinase
Transcription factors linked to TLR

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MyD88
IRAK
NF-kB, IRF-3

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TLR also triggers

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phagocytosis and intracellular killing of microbes

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broad pattern ligands

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bacterial parasites
gram-positive bacteria and fungi
gram-negative bacteria
flagellated bacteria
viral dsRNA
viral ssRNA
viral ssRNA
bacterial DNA elements

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NLR are

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NOD-like receptors are cytosolic proteins that recognize intracellular pathogens by recognizing conserved patterns

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NLR triggers

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inflammatory gene expression and or cell death in infected cells

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NLR are

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cytosolic equivalents of membrane TLR

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chemotaxis

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directed cell migration through a chemical gradient containing a chemoattractant

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phagocytosis

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engulfing solid particles by cell membrane to form an internal phagosome

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steps of phagocytosis

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chemoattraction
recognition and attachment
ingestion into phagosome
fusion of phagosome with lysosome
kililng and digestion
release

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microbe-derived chemoattractant

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lipoteichoic acid
bacterial formyl-methyionyl peptides

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hose-derived chemoattractant

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antimicrobial-derived peptide
complement peptides
inflammatory mediators
chemokines (IL-8)

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opsonophagocytosis

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prepare for uptake
binding of opsonin-coated particle

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opsonin

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recognizes a microbial structure
molecule that acts as a binding enhancer for phagocytosis

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opsonin binds

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receptor on a phagocytic cell

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three mechanisms of intracellular killing by phagocytic cells

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respiratory burst
nitrogen-dependent killing
oxygen and nitrogen independent killing

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respiratory burst =

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single electron reduction of molecular oxygen to produce toxic radicals and oxidants

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enzymes in respiratory burst

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NADPH oxidase makes superoxide
superoxide dismutase makes hydrogen peroxide
myeloperoxidase grabs a halide and forms OCl- (bleach)

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NOS-2 sustains

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high level NO production my macrophages, neutrophils, hepatocytes, other cells

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NO is effective against

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certain intracellular bacteria and parasites

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cellular components of oxygen and nitrogen independent killing

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defensins and cathelicidins
bactericidal permeability-increases protein
lysoszyme, lactoferrin
lysosomal enzymes: cathepsin G, lipases, nucleases

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Eptihelial cells function in innate immunity

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barrier
mucus secretion
defensin production
respond to microbial flora
produce chemotactic factors

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intra-epithelial function in innate immunity

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intestinal and lung epithelium
primary T cells
Expressed antigen receptors with limited diversity
recognize conserved microbial structures
produce cytokines that activate inflammatory cells

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natural killer function in innate immunity

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rapidly produce cytokines
can recognize microbe-infected host cells
lyse infected host cells
recognize damaged or stressed host cells

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cytokines

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polypeptide "hormones" of the immune system
bind cell surface receptors
mediate cell to cell signaling

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SIRS

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systemic inflammatory response syndrome

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SIRS is the

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leading cause of death in the ER

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SIRS is initiated by _____, _____, and _____

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infection, acute trauma, massive tissue damage

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sepsis

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if infection is present or suspected

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process of SIRS

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cytokine production
thrombosis
hypotension--hypoxia
lower tissue oxygenation
ischemic injury
respiratory distress syndrome, cardiac suppression, renal damage
end organ damage, death