Test 2: Innate Immunity Flashcards
T/F: Innate immunity is independent
False!
Adaptive and innate immunity help each other
What is the first step in innate immune response?
Recognition of pathogen by host cells
What is involved in the extracellular defense mechanism?
in the interstitial spaces, blood, and lymph: complement, macrophages and neutrophils
on the epithelial surfaces: antimicorbiral peptides
What do extraceullar defense mechanisms allow?
accessible to soluble molecules and phagocyte
What is involved in the intracellular defense mechanism?
in the cytoplasm: NK cells
in the vesicles: activated macrophages
What do intracellular defense mechanisms require?
require killing or activation of infected cells
What are important characteristics unique to innate immunity?
- recognize structures shared by various classes of microbes but not present on normal host cells
- limited diversity
What are Pathogen Associated Molecular Patterns (PAMPs)?
molecules expressed and/or produced solely by microbes
Where are Pattern Recognition Receptors (PRRs)?
PRR expression and ligands are redundant and are localized at plasma and endosomal membrane, and in the cytosol
- they also recognize similar types of ligand
What are Toll-like receptors (TLRs)?
expressed on cells that are components of the innate immune system
What does TLR-4 recognize?
LPS
What does TLR-3 recognize?
double stranded RNA
How does toll like receptors signal transduction work?
recruit adaptor proteins, MyD88 and TRIF which leads to activation of transcription factors and cytokine production
What does TLR3 recruit and trigger?
TLR3 recruits TRIF and triggers IFNa/B production
What does the NLRP3 inflammasome lead to?
inflammasome assembly leads to caspase-1 activation and results in cleavage of pro-IL1B and secretion of IL-1B
- then, accumulation of neutrophils and monocytes at site
What are the functions of the epithelia?
- physical barrier: saliva (oral cavity)
- chemical barrier: kill microbes by disrupting outer membranes of bacteria and some viruses
- cellular barrier
What is the most abundant cell?
neutrophils
- 1x10^11 per day
- short lived: 6 hrs in blood if don’t encounter anything
- no lysosome
What mediates the earliest phase of inflammatory responses?
neutrophils
(recognize and then kill microbe)
What cell is 10x less abundant in blood and long lived?
mononuclear phagocytes
- monocytes differentiate into macrophages in tissues
What mediates the later stages of innate immune response (1 or 2 days after infection)?
macrophage
- also divide and persist at inflammation site
- (2nd responder)
What are the functions of classical/M1 macrophages?
- trigger inflammation for enhanced adaptive immunity
- kill microbes
What do dendritic cells do?
posses dendrites and have phagocytic capabilities
What are the classical dendritic cells?
- link innate and adaptive immune responses
- capture/display microbial antigens to naive T lymphocytes
- tune T cell response by secreting cytokines
(activate T cells)
What are the plasmacytoid dendritic cells?
- produce type 1 interferon that possess antiviral activities
- bind dsRNA via TLR3
What are the Natural Killer cells?
- do not express somatically rearranged clonal disturbed antigen receptors so kill the infected cells and are NOT phagocytes
(don’t need to be activated to kill)
T/F: NK cells will kill our own cells
False!
They should not because signals from inhibitors receptors block signals from activating receptors.
If there is a lack of inhibitory receptor engagement, it will trigger activated and kill cell
How do NK cells kill virus-infected cells?
perforin/granzyme
Where are mast cells, basophils, and eosinophils found?
mast cells: tissues (skin, lungs, near b.v. in tissues)
basophils and eosinophils: blood
What happens upon activation of mast cells, basophils, and eosinophils found?
release proteolytic enzymes and substance that contribute to inflammation (histamine, PG, heparin, leukotrienes, TNFa)
- and protect against helminth
What are the 2 signals involved in lymphocyte activation?
signal 1= antigen bind to antigen receptor
signal 2= molecules provided by innate cells
- this will allow for proliferation and differentiation
What is the third signal involved in lymphocyte activation?
differentiation signal
Which is essential for effective host defense at early stages of infection and which is essential for microbe clearance?
adaptive vs innate
innate immunity= essential for effective host defense at early stages of infection
adaptive immunity= essential for microbe clearance
Which type of immunity has receptors encoded in germline?
innate immunity (have limited diversity)
What is the first step by which cells of innate immunity identify that microbes have invaded?
they express receptors with limited diversity allowing them to recognize molecules expressed by microbes
What is special about TLR4?
can recruit MyD88 and TRIF
After TLR4 recruits MyD88, what happens?
increased expression of cytokines, adhesion molecules, costimulators which leads to acute inflammation and stimulation of adaptive immunity
After TLR4 recruits TRIF, what happens?
production of type 1 interferon (IFNa,B) which leads to antiviral state
What are the components of the innate immune system?
epithelial barriers, phagocytes, NK, and granulocytes
T/F: macrophages and NK cells work together by killing microbes
True!
NK cells produce IFNy which activates macrophages and leads to killing of phagocytoses microbes
