Innate Immunity PDF

Innate Immunity Self-Nonself Discrimination Missing Self the IS reacts to the basis of self-nonself di...

Innate Immunity Self-Nonself Discrimination Missing Self the IS reacts to the basis of self-nonself discrimination includes Major Histocompatability Complex (MHC) proteins I " invading organisms (bacteria, viruses, fungi, parasites) both innate and adaptive immune mechanisms i cell-surface mlcs that defines a cell as self transplanted blood cells or organs (unless "matched") , 2 examples of innate immune pathways of self- allows IS to distinguish between self and nonself the IS has the ability to react to non self nonself discrimination: the IS doesnt react against "self" antigens MHC Class 1 prots are on surface of every nucleated cell in body aka : immunological tolerance 1) Natural Killer Cell recognition of "missing self" MHC1 prots inhibit killing activity of NK cells (type of ILC) exception : autoimmune disease 2) the alternative pathway of complement activation Natural Killer Cells have different receptors NK Cell Function - virus infection NK Cell Function - stress inhibitory type of innate lymphoid cell inhibits MHC1 on cell surface stressed cell : · activating inhibitory receptors recognize MH mlcs allows them to escape damaged self signal turns NK Cells off susceptible to NK cells cancerous MHC1 engage w inhib receptors on NK infected cell - downregulates the MHC1 > attacks kills activating ligands upregulated inhibitory receptors are not engaged healthy cell - NK cell inhibition NK cell activates kills cells NK cell can recogn kills cancerous cells Mechanism of Killing by NK Cells The Complement System component(s) of plasma that complement complement fxns include : antibody action to kill target cells 1) Directly kill cells (Alternative pathway) complex network of 50 prots w roles in 2) Interact with antibodies to kill cells (Classical pathway) : innate immunity, adaptive immunity, and 3) Interact with lectins to kill cells (Lectin pathway) opsonize : irreversibly marking inflammation 4) Opsonize pathogens to flag them for phagocytosis smt for destruction 5) Function as a chemoattractant to recruit leukocytes and induce inflammation The Alternative Pathway of Complement Activation is an innate immune pathway of self-nonself discrimination 1000s of C5s can be cleaved at nice many mlcs of C9 come tg, forming pore : promotes killing of nonself cells unless they have inhib mlcs amplifies killing by alt complement mbn-attack complex s relies on spontaneous cleavage of C3 to C3b prot in blood once bacteria + C5b interact : rapidly kills cell formation of fluid-phase C3 convertase · formation of C5 convertase cascade of events: forms mbn attack complex cytoplasm contents leak out cleaves C3 into 2 , activates IS Self-nonself Discrim by Alt Complement Pathway Inflammation the alt path is happening in our bodies at all times redness and swelling w heat and pain its good and bad decay-accelerating factor (DAF,CD55) complement loss of fxn can be a consequence cause w o inflammation : infections and death receptor 1 (CR1, CD35) interact w and promote inflammation coordinates immune responses, dissociation of C3 convertases on surface of ur body cells mice that were genetically deficient in DAF : didnt make it to fetal stage wound healing and metabolism most pathogens lack these proteins and are killed by alt path bc alt path is destroying these paths unresolved inflammation can cause disease Purpose of Inflammation The Inflammatory Circuit 1) coordinates the delivery of blood components (plasma and 3) containment of infection or injury by neutrophils, leukocytes) to a site of infection or injury macrophages, and endothelial cells sensors include : - redness and swelling is caused by cells and fluids exiting blood 4) Tissue repair, wound healing, and return to homeostasis neutrophils macrophages vessels and entering infected or injured areas monocytes 2) controls our metabolism, thermogenesis (body temperature) and aspects of behaviour. fever slows the replication of bacteria and viruses makes you sleepy pain and loss of fxn alert the host to problem, preventing further damage Inflammatory Stimuli - Exogenous Inducers Inflammatory Stimuli - Endogenous Inducers Inflammatory Signals from outside of cell from inside of cell 3 cytokines play the most important role as mediators of inflammation PAMPs (lipopolysaccharide, dsRNA, ssRNA, flagellin) DAMPs (burn, frostbite, impact, puncture) induce Interleukin-1 beta (IL-1 beta) chemicals such as alum or asbestos interacting w cellular inflammation Tumour Necrosis Factor alpha (TNF alpha) receptors (TLRs, NLRs) signals include ATP, uric acid, mitochondrial DNA, Interleukin-6 (IL-6) toxins and venom components (phytochemicals, bee sting) histones, Heat Shock Proteins, S100, HMGB1 complement proteins: C3a, C5a acting through C3aR, C5aR