Test 1: lecture 3 Flashcards
___ : molecular explanation for innate immune detection of pathogens – Pattern Recognition Receptors (PRRs) and Pathogen Associated Molecular Patterns (PAMPs)
Pattern Recognition Theory
___ distill microbial world into small number of specific signatures
TLRs
Cell Surface and Intracellular TLRs detect distinct classes of ___(cell surface structures vs. nucleic acids)
PAMPs Pathogen Associated Molecular Patterns
___ are crucial for initiation of innate inflammatory response programs
PRRs Pattern Recognition Receptors
___ recognition of microbial products leads to upregulation of antigen presentation and instructive cytokines in order to instruct pathogen-specific ___ response
innate
adaptive
Antiviral response module involves activation of distinct class of responses – type I IFN response and ___ responses to eliminate virally infected cells
Natural Killer (NK)
Unique evolutionary pressures shape the specificity and repertoire of the ___immune system
innate
host has to be able to identify pathogen. Pathogen is trying to avoid host
Pathogen Associated Molecular Patterns (PAMPs)
Receptors evolved to detect unique features of microbes that are distinct from the host cell physiology
how host tells a pathogen is there
___ are expressed on sentinel cells and signal the presence of infection
Pattern Recognition Receptors (PRRs)
PRRs allow ___ of response and self/non-self discrimination
specificity
___ immunity is encoded in the genome
innate
___ immunity is expressed by all cells in a particular type (macrophages)
innate
___ immunity triggers immediate response
innate
___ immunity recognizes broad classes of pathogen
innate
___ immunity requires gene re-arrangement
adaptive
___ immunity is by clonal distribution
adaptive
___ immunity is able to discriminate between even closely related molecular structures
adaptive
___ immunity is able to distinguish the type of pathogen
innate
gram + bacteria
gram negative bacteria
what two things are unique to gram + bacteria
what is unique about gram negative bacteria
___ bacteria contain two cell membranes
gram negative
LPS found on ___ bacteria is responsible for endotoxic shock
gram- negative
lipopolysaccharide
lipoteichoic acid, peptidoglycan, LPS and lipoproteins are unique to ___
____ are PRRs that detect repetitive carbohydrate structures
Soluble scavenger receptors
Soluble scavenger receptors are used to detect what kind of pathogen?
mannose binding lectin is a type of ___ and detect ___
soluble scavenger receptor which is a type of pattern recognition receptors
repetitive carb structures on bacteria and fungi
toll like receptors lead to the expression of
interleukin cytokines such as IL1beta, Il-8, IL-6 ect
___ part of TLR tiggers the expression of interleukin
NFK B
what TLR recognize fungi, gram + bacteria
6 and 2 recognize diacyl lipopeptides
1 and 2 recognize triacyl lipopeptides
what TLR recognizes Gram negative bacteria
TLR-4 recognizes LPS (lipopolysaccharide)
what TLR recognizes motile bacteria
TLR5 recognizes flagellin
TLR 6 and TLR 2 recognize ___ of ___
diacyl lipopeptides
fungi and gram + bacteria
TLR 1 and TLR 2 recognize ___ of ___
triacyl lipopeptides
fungi and gram + bacteria
TLR5 recognize ___
flagellin of motile bacteria
TLR4 and MD2 recognize ___
LPS of gram negative bacteria
what TLR detects dsRNA
3
what TLR detects ssRNA
7
what TLR detects CpGDNA
9
___ are intracellular TLR
surface TLR detect ___
bacteria and fungal PAMPs
easy to distinguish self/nonself
endosomal TLRs detect ___
nucleic acids
things can go wrong with detecting self/nonself
TLR___ activation by self-RNA and DNA is strongly implicated in lupus and psoriasis (autoimmune diseases)
7/9
NOD2
PRR that floats in the cytosol looking for nonself pathogen
recognize muramyl dipeptide of bacteria
Coincident detection of multiple PAMPs in distinct cellular locations may also allow the innate immune system to distinguish pathogens from ____:BOTH express PAMPs. ONLY pathogens invade
commensals: (good bacteria)
activation of TLR leads to ___
increased phagocytosis and phagosome- lysosome fusion
inflammatory cytokines: type 1 interferons, ani-microbial molecules and antigen presentation activity(MHC)
when TLR detects pathogen it will eat pathogen and trigger movement of MHC to the outside of the cell to hold little pieces of the pathogen and tell adaptive immunity “pathogen is here”
Express costimulatory molecules and cytokines for activation of lymphocytes
TLR signals induce dendritic cell “___” and expression of signals important for adaptive immunity
maturation
TLRs induce:
MHC/peptide complexes (increased antigen presentation- to be seen by Tcell)
CD80/CD86 costimulatory molecules
production of cytokines
what are the three signals to trigger T cell activation
TLR trigger:
MHC/peptide complexes (increased antigen presentation- to be seen by Tcell)
CD80/CD86 costimulatory molecules
production of cytokines
Full activation of T cells requires ___ antigen, ___ molecules, and cytokines
MHC-peptide
costimulatory
Misregulation or inappropriate activation of TLR___associated with autoimmunity
7/9 (lupus- these are nucleic acid receptor)
7 → ssRNA → RNA virus
9 → CpGDNA → DNA viruses
7 is found on X chromosome, if jumps to Y then there will be twice the expression → lupus
Systemic Lupus Erethymatosis (SLE) in dogs is rare, but is believed to be underdiagnosed. Caused by error in ___
TLR 7
for bacertia what is used to detect
LPS:
Lipopeptides:
Flagellin:
Peptidoglycans:
LPS: TLR4
Lipopeptides: TLR2
Flagellin: TLR5
Peptidoglycans: NOD1/2
what are two ways a cell detects double stranded viral RNA
TLR-3- detect nucleic acids outside of cell
RIG-I/MDA5- detect nucleic acids inside the cell meaning active virus replication is taking place
create interferons (antiviral)
____ detect double stranded nucleic acids outside the cell such as free virus particles, dead infected cells, and phagocytosed material
TLR-3
create interferons (antiviral)
___ detects nucleic acids inside the cell, meaning there is active viral replication
RIG-1/MDA5
create interferons (antiviral)
TLR-3 and RIG-1/MDA5 lead to activation of ___
type 1 interferons
IFN-alpha and IFN-beta
Type 1 interferons
made by TLR-3 and RIG-1/MDA5 in response to double stranded viral RNA
- induce resistance to viral replication
- increase MHC class 1 expression and antigen presentation
- activate dendritic cells and macrophages
- activate NK cells
___ activate NK cells to kill virus infected cell and increase MHC class 1 expression and antigen presentation in all cells
Type 1 interferons (IFN alpha and IFN- beta) made by TLR3 and MDA5/RIG-1 in response to double stranded viral RNA
NK cells produce ___ which is important for early control of intracellular pathogens
IFN gamma (interferon type 2)
IFN- ___ causes rapid killing of virally-infected cells
gamma (type 2 interferon)
stimulates neutrophils and macrophages to become more antimicrobial
produced by NK cells
which are stimulated by type 1 interferons to kill virus
___ is a protein in NK cells that creates pores
perforin
___ are in NK cells that are injected into cell to be killed
granzymes
NK cells recognize virus-infected cells due to virus attempt to evade adaptive immune response by downregulating ___
MHC I
how does NK cells know what to eat?
MHC class 1 will inhibit NK cells or lectinlike CD94:NKG2 will bind to killer inhibitory receptors → stop NK cells
if MHC class 1 are altered or absent → NK will kill
missing self recognition
NK cell responses are controlled by balance of activating and inhibitor signals
cytokines produced in response to bacteria are ___ and will effect ___ cells
TNF, IL-1, IL-12, IL-23, IL-17
macrophages and neutophils
cytokines produced in response to fungi are ___ and will effect ___ cells
IL-12, IL-23, IL-17
Macrophages,Neutrophils
cells in response to viruses produce what cytokines ___ which trigger what effector cells?
type 1 interferons (IFN-alpha, IFN-beta)
NK cells, CD8 T cells
RNA is detected by what PRR?
RNA: TLR3, TLR7, TLR9
intracellular RNA is detected by
MDA5/RIG-1
The___ immune system distills the microbial world into specific signals
innate
The ___ immune system distills the microbial world into specific signals. Identifies the type of pathogen. Recruits cells to neutralize the infectious agent (inflammation). Activates the appropriate type of ___ immunity
innate
adaptive