Intro to Innate Flashcards
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
Characteristics
Respond rapidly to the presence of microorganisms or foreign antigen
Not Ag specific, limited diversity
No immunologic memory
Stimulates the adaptive immune system
Receptors of the Innate immune system
Toll-Like receptors
Mannose Receptors
NOD-like receptor
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
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)
Granulocytes
Eosinophils (1-3%) Basophils (<1%) Mast cells === release pharmacological mediators responsible for combating multi-cellular parasites play a major role in atopic disease
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
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+
Neutrophils activated by
IL-1, TNF-alpha, IL-8
endothelial cells near infection site express selectin proteins that home neutrophils
functions of macrophages
garbage collectors
Ag presenting cells
vicious killers
Cell surface marker of monocytes/macrophages
`CD14 (TLR4) - recognizes and binds LPS
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
Alternative macrophages
induced by IL-4, IL-13 and play a role in tissue repair and control of inflammation
Secrete IL-10, TGF-Beta
Activated macrophages have
increased phagocytic activity
increased ability to activate Th cells
higher levels of class II mHC/HLA on the cell surface
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
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
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
Binding of PAMP ligands to ____ induces
PRRs induces intracellular signaling in the phagocytes leading to their activation
toll-like receptors
several receptors specific for different microbial products
respond to exogenous and endogenous Ag
TLR-1, -2 -6
Bacterial lipopeptides
(TLR-2 also specifically recognizes peptidoglycan)
EC
TLR-4
LPS, EC
TLR-5
Flagellin, EC
TLR-3
dsRNA IC
TLR-7. -8
ssRNA IC
TLR-9
CpG DNA IC
Binding of ligand to TLRs results in
phagocytosis and secretion of cytokines, increased ROS, increased cytoskeletal changes
Chediak-Higashi syndrome
autosomal recessive - LYST gene defect
microtubule defect inhibits fusion
recurrent pyogenic infections - presence of giant granules in leukocytes
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
Type I IFN
directly inhibit viral replication
(alpha from leukocytes, beta from fibroblasts)
degrade mRNA = inhibition of protein synthesis
shuts down cellular protein synthesis
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
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
