HRR: innate immunity Flashcards
Name three characteristics that distinguish the innate and adaptive immune
responses
The innate immune system is fast and has no memory, while the adaptive immune system is slower but has memory and gets stronger with subsequent responses
What does the innate immune system recognize for activation?
PAMPS and DAMPS via pattern recognition receptors; many receptors can detect the same pathogen, and the same receptor can detect many different pathogens
What are the two broad categories of innate immune response?
Inflammation and anti-viral defense
Peptidoglycans, terminal mannose, flagellin, double stranded RNA, and unmethylated CG rich oligonucleotides are examples of…
PAMPs
HMGB1 and extracellular ATP released from damaged mitochondria are examples of…
DAMPs
What are the 3 things associated with acute inflammation
Complement, phagocytic cells, and cytokines
In general, where are PRR’s found?
PRR’s can be found on the cell surface, in endosomal membranes, and in cytosol
What are the 5 types of pattern recognition receptors?
1.toll-like receptors
2.NOD-like receptors
3.Inflammasomes
4.Cytosolic RNA and DNA sensors
5.Circulating receptors in the blood
Toll-like receptors 3,7,8, and 9: where they are and what they do
They’re found on endosomal membranes and activate an antiviral defense
PAMP binding in membrane TLR initiates the production of ___, and PAMP binding in endosomal TLR initiates the production of___
transcription factors NF-kb; IRF-3
What does NF-kb do?
NF-kb will start the inflammatory process and stimulate adaptive immunity
What does IRF-3 do
IRF-3 produces interferons and activates the antiviral state
Describe NOD-like receptors
Cytosolic receptors that recognize PAMPs and DAMPs. They can be found in phagocytes and mucosal epithelial cells. They’re associated with the inflammatory pathway
Explain what an inflammasome is, and what it is composed of
Inflammasomes has an ultimate goal of secreting IL1-beta. It is composed of NLRP3, adaptors, and caspase-1
Describe how inflammasomes lead to secretion of IL-1beta
o NF-kb is formed and translocase to the nucleus to turn on the pro-IL1-beta gene
o Pro-IL1-beta exits the nucleus
o An inflammasome composed of NLRP3, adaptors, and caspases cleaves the pro-IL1-beta into IL-1beta.
o IL1-beta can exit the cell and lead to acute inflammation
What are RIG-like receptors? what do they induce?
A cytosolic RNA sensor. They recognize viral RNA by their length or lack of methyl cap; they induce type 1 interferon production
Describe cytosolic DNA sensors: what they do and what they induce
Recognize microbial dsDNA in the cytosol and induce type 1 interferon production as well as autophagy
Describe the pathway used by cytosolic DNA sensors
o cGAS floating in the cytoplasm binds to DNA in the cytoplasm
o cGAS forms cyclic dinucleotides that bind to STING
o STING’s kinase (TBK1) phosphorylates IRF3, releasing it from the complex
o IRF3 translocates to the nucleus and induces the antiviral response
What are the two PRR’s circulating in the blood
complement and acute phase proteins
Name mechanisms by which the epithelium of the skin prevents the entry of
microbes.
Providing a physical barrier, killing microbes via defensins and cathelicidins, and killing microbes via intraepithelial lymphocytes
List differences between monocytes and neutrophils, the primary phagocytes of innate immunity
Neutrophils: short lived and fast. They’re released from bone marrow during acute phase response
Monocytes: longer lived. They migrate to tissues in response to inflammation
Which chemicals are produced by neutrophils and monocytes respectively?
ROS; NO
Which phagocyte makes cytokines?
monocytes
Describe the functions of dendritic cells
They produce pro-inflammatory cytokines and migrate to lymph nodes to present antigens
Describe the functions of mast cells
The release vasoactive amines, proteolytic enzymes, and cytokines (TNF). They increase mucous production and leaky vessels
What two things are associated with antiviral defense?
NK cells and type I interferons
Describe natural killer cells: what they do, what they secrete/activate
They eliminate intracellular pathogens. They recognize infected or stressed cells and secrete IFN-gamma to activate macrophages and release granules to induce apoptosis
Describe activating and inhibitory NK cell receptors
NK cell activating receptors: recognize patterns associated with stressed, infected, or malignant cells. This alone with no presence of the inhibitory receptor will activate the NK cell.
Inhibitory NK receptors recognize class I MHC, which are ‘self’ molecules on human cells. This combined with the activating receptor keeps the NK cell from turning on.
Describe interferon I and the antiviral defense
They are found on most cells and are either made by dendritic cells (IFN-a) or fibroblasts (IFN-b). a virus present in a cell induces interferons. they activate OAS and PKR, which shuts down protein synthesis in the particular cell and leads to no viral production
Briefly describe complement
They’re synthesized largely in the liver and are distributed throughout the blood and lymph. They directly destroy microbes and generate signals that indicate an attack has happened.
What are the 3 mechanisms for initiating complement activation?
Alternate: microbe-based
Classical: antibody-based
Lectin: mannose binding lectin
Explain the three complement activation cascades to C5, and the common cascade from C5-C9
All 3 mechanisms cleave C3 into C3a and C3b via a unique C3 convertase. C3a will act as a signaling molecule. C3b binds to microbes, initiating cleavage of C5 into C5a and C5b. C5b will bind to the microbe and initiate the assembly of complement and C6-9
Name functions of C3a, C3b, and C5a
C3a: degranulate mast cells
C3b: increase phagocytosis
C5a: degranulate mast cells and recruit neutrophils
Name the acute phase proteins circulating in the blood
Complement, collectins, c-reactive protein
How do cytokines act?
Autocrine or paracrine methods
What are chemokines?
Subset of cytokines that stimulate and direct leukocyte migration
What does IL-10 do?
Is an antagonist for IL-1 receptor and has anti-inflammatory activity.
Explain the purpose and general mechanism of the innate immune system stimulation of adaptive immune responses
Various elements in the innate immune system act as costimulatory molecules, acting as the second required signal for the active immune system.
