lecture 2- innate immunity Flashcards
what is a PAMP
molecules found on pathogens (bacteria, fungi etc.) necessary for the survival of the pathogen and cannot be mutated in an attempt to avoid the immune system
what is a DAMP
dead tissue like found in a myocardial infarction
how does the innate immune system ID microbes
PRRs (pattern recognition receptors) bind PAMPs and DAMPs
What are TLRs
TLRs are Toll like Receptors. These are a type of PRR and bind pathogen ligand
What does each specific TLR bind
TLR-2 - Gram positive bacteria (bacterial peptidoglycan)
TLR-4 -Gram negative bacteria (lipopolysaccharide), TLR-3, 7, 8 - RNA within the endosome
TLR-9- DNA containing unmethylated CpG in the endosome.
When a PRR (ex TLR) binds to a antigen what two general things can be induced
1.) Inflammation
2.) Antiviral state
via signal transduction using adaptor proteins, NFKB and IRF
Describe the inflammatory response
PAMP and DAMP binding causes inflammasome to be activated–> caspace activation–> IL1B activation and secretion which causes inflammation
(*note other proinflammatory cytokines apart from IL1B can be produced)
what are the innate immune functions of macrophages?
producing cytokines, and phagocytosing and killing bacteria through production of reactive oxygen and nitric oxide
Describe how a macrophage carries out its function of phagocytosing and killing bacteria
it has receptors (TLR, cytokine receptor, complement receptor) that activate cascades using iNOS, phagocyte oxidase, and cytokines
What do NK cells do?
- ) directly lyse cells
2. ) release IL(gamma) and enhance macrophage action
what mechanism stops NK cells from destroying normal cells
the NK cell has two receptors, an inhibitory receptor (which binds to MHCI) and and an activating receptor. A normal cell will have MHC1 and therefore upon binding NK the NK will be inhibited. an abnormal cell will lack the MHC1, and upon binding the NK will be activated
what are the source of different cytokines IL-1 IL-6 TNF, IL10 IL-12 Type I IFN (IFN-α or β) Interferon-γ (IFN-γ) IL8
IL1,6 are just macs TNF, IL10 are macs and Tcells IL 12 are macs and dendritic cells Type 1 IFN- macs and fibroblasts INF gamma- NK cells and T cells IL8- many cells
what do the cytokines do? TNF, IL1 IL6 IL8 IL12 IFN-y Type I IFN IL10
TNF,IL1= activate endothelial cells and neutrophils, also causes fever and weight loss
IL6- to do with liver and acute phase proteins
IL8(fx: chemokines)- leukocyte activation, chemotaxis, increases affinity for adhesion molecules
IL12- in NK cells it increases IFN-y and cytotoxicity
IFN-y= macrophage activation + antibody response
Type 1 IFN- increases antiviral state
IL10- suppresses immune system
How does a leukocyte (ex neutrophil) exit circulation and go to microbe
as blood flow increases the neutrophils are pushed to the sides of the arteries and endothelial cells express receptors. Selectins on the neutrophil bind selectins on the endothelial cells causing the neutrophil to slow down and roll, which causes more chemokines on the endothelium to bind the neutrophil causing activation of integrins to a high affinity state which causes the neutrophil to be in stable adhesion with endothelial cell allowing for migration out of circulation.
which selectins are on which cells
E, P, L
E and P selectins are on endothelial cells
L selectins are on recirculating B and T cells
So after the macrophage finally finds this microbe, how is the microbe actually killed?
the microbe binds to a receptor on macrophage (ex: leptin) then more receptors on the macrophage bind the microbe zipping the macrophage up around the microbe. Microbe is phagocytosed. The phagosome and lysosome fuse. Lysosomal enzymes NO, and ROS degrade microbe. NO comes from iNOS using arginine citrulline transport. ROS comes from O2 being converted by phagocyte oxidase.
How is the antiviral state achieved?
Type 1 IFN is released by an immune cell. This binds to microbe and causes 3 things to happen
(1) phosphorylation of translation initiation factor –> viral protein not made
(2) RNAse- viral RNA degraded
(3) inhibition of viral gene expression and protein assembly
But people still get sick, so somehow pathogens are beating the immune system, HOW!?!
PNEUMOCOCCI
decrease phagocytosis because they have a capsule of polysaccharide
But people still get sick, so somehow pathogens are beating the immune system, HOW!?!
STAPHYLOCOCCI
induce catalase which breaks down ROS
But people still get sick, so somehow pathogens are beating the immune system, HOW!?!
NISSERIA
STREPTOCOCCI
complement resistance
But people still get sick, so somehow pathogens are beating the immune system, HOW!?!
PSUEDOMONAS
resistant to antimicrobial peptides by making LPS resistant to peptide antibodies
