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Flashcards in Intro to Innate Deck (31):
1

Innate Immunity

Protection against infections that relies on mechanisms that exist before infection, are capable of rapid responses to microbes, and react in essentially the same way to repeat infections

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Characteristics

Respond rapidly to the presence of microorganisms or foreign antigen

Not Ag specific, limited diversity

No immunologic memory

Stimulates the adaptive immune system

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Receptors of the Innate immune system

Toll-Like receptors
Mannose Receptors
NOD-like receptor

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Mechanical barriers of innate

Epithelial cells joined by tight junctions (skin, gut, lungs, eyes/nose/oral cavity)
Longitudinal flow of air or fluid, movement of mucus by cilia, tears, nasal cilia

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Chemical barriers of innate

Skin: FA, B defensins,lemellar bodies, cathelicidin
Gut: Low pH, enzymes (pepsidin) alpha defensins, regIII, Cathelicidin
Lungs: pulmonary surfactant, alpha defensins, cathelicidin
Eyes/Nose/Oral cavity: histatins, Beta defensins, enzymes in tears and saliva (lysozyme)

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Granulocytes

Eosinophils (1-3%)
Basophils (<1%)
Mast cells
=== release pharmacological mediators
responsible for combating multi-cellular parasites
play a major role in atopic disease

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Natural killer cells provide immunity against

intracellular infections, especially viral ones and cancer

Perforins and granzymes induce apoptosis in target cell
express variable combinations of activating and inhibiting receptors

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Neutrophils

migrate 7-10 hours in bode then home to tissue where they have 3d lifespan
neutrophils are released in response to infection from bone marrow in greater numbers == neutrophil leukocytosis

FIRST at site of inflammation

component of pus/abcess (pyogenic)

CD15+ CD16b+

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Neutrophils activated by

IL-1, TNF-alpha, IL-8
endothelial cells near infection site express selectin proteins that home neutrophils

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functions of macrophages

garbage collectors
Ag presenting cells
vicious killers

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Cell surface marker of monocytes/macrophages

`CD14 (TLR4) - recognizes and binds LPS

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Classical macrophages

induced by innate immunity and play a role in inflammation

TLR-Ligands, IFN-gamma

secrete ROS, NO, lysosomal enzymes to kill bacteria
secrete IL-1, IL-12, IL-23, chemokines to induce inflammation

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Alternative macrophages

induced by IL-4, IL-13 and play a role in tissue repair and control of inflammation
Secrete IL-10, TGF-Beta

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Activated macrophages have

increased phagocytic activity
increased ability to activate Th cells
higher levels of class II mHC/HLA on the cell surface

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Dendritic cells

professional APC
express high levels of Class II HLA/MHC and CD80
after capturing Ag in the tissues, migrate into blood or lymph and circulate to various lymphoid organs where they present Ag to T cells

Bridge innate and adaptive

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PAMPs

pattern associated molecular patterns - molecules/structures that are shared by various classes of microbes but are not present of self
recognize structures of microbes that are essential for survival and infectivity

LPS - Mannose residues, dsRNA

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DAMPs

damage associated molecular patterns
molecules released by stressed cells undergoing necrosis that act as endogenous danger signals to promote and exacerbate the inflammatory response

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Binding of PAMP ligands to ____ induces

PRRs induces intracellular signaling in the phagocytes leading to their activation

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toll-like receptors

several receptors specific for different microbial products
respond to exogenous and endogenous Ag

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TLR-1, -2 -6

Bacterial lipopeptides
(TLR-2 also specifically recognizes peptidoglycan)
EC

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TLR-4

LPS, EC

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TLR-5

Flagellin, EC

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TLR-3

dsRNA IC

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TLR-7. -8

ssRNA IC

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TLR-9

CpG DNA IC

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Binding of ligand to TLRs results in

phagocytosis and secretion of cytokines, increased ROS, increased cytoskeletal changes

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Chediak-Higashi syndrome

autosomal recessive - LYST gene defect
microtubule defect inhibits fusion
recurrent pyogenic infections - presence of giant granules in leukocytes

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Chronic granulomatous disease

inherited deficiency in NADPH oxidase
decreased production of ROS
chronic, recurrent infections with CATALASE-POSITIVE MICROORGANISMS
chronic inflammatory symptoms like gingivitis, enlarged lymph glands, tumor-like granuloma masses

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Type I IFN

directly inhibit viral replication
(alpha from leukocytes, beta from fibroblasts)
degrade mRNA = inhibition of protein synthesis
shuts down cellular protein synthesis

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Functions off IFN

Induce resistance to viral replication in all cells
Increase MHC class I expression and Ag presentation in all cells
Activate NK cells to kill virus infected cells

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NK functions

destroy bacteria, parasites, fungi, tumor cells, and virus infected cells

force cells to commit suicide
perforin proteins deliver granzyme B into target cell

fas ligand expressed on cell surface induces apoptosis in cells containing FAS receptor

provide cytokine support for macrophages