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20 Cards in this Set
- Front
- Back
How does the innate immune system recognize a threat? |
PAMPS = pathogen-associated molecular pattern
Evolutionarily conserved arrangement of molecules that the innate immune system can recognize
Distinct from molecules present in a normal, healthy host |
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What is a bacterial example of a PAMP? |
Peptidoglycan cell wall structure |
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What is the difference between a PAMP and a MAMP? |
They mean the same thing
MAMP = microbe-associated molecular patterns - introduced because molecular patterns are present in nonpathogenic microbes as well (such as commensal bacteria), so the name PAMP is somewhat misleading - MAMP has never been widely adopted |
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What does the immune system use to recognize PAMPS? |
Pattern Recognition Receptors (PRRs) |
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What are two types of PRRs based on function? |
Signaling PRRs: stimulate proinflammatory signaling and cytokine release - mostly found on macrophages and dendritic cells - Toll-like receptors most important (also NOD-like and RIG-like)
Phagocytic PRRs: stimulate uptake of microbes by endocytosis or phagocytosis - found on neutrophils, macrophages and dendritic cells - Mannose receptor most important
Others: CRP (important), mannose-binding lectin |
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What are 3 groups of PRRs based on location? |
1. Extracellular receptors - mannan-binding lectin - C-reactive protein (CRP)
2. Cell surface receptors - Toll-like receptors (1,2,4,5,6,10,11) - Mannose receptor - Scavenger receptor
3. Intracellular receptors - NOD-like receptors - RIG-like receptors - Toll-like receptors (3,7,8,9) |
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Toll-like receptors |
- detect PAMPS from bacteria, viruses, fungi and protozoa
- Usually expressed on plasma membrane of monocytes, macrophages, B lymphocytes and T lymphocytes (i.e. immune cells)
- also found on epithelium exposed to external environment such as intestinal/respiratory tracts |
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What happens when a Toll-like receptor finds a PAMP? |
- PAMP binds to the TLR, MyD88 and TRIF (signaling adapter molecules inside the cell) are recruited
- Signalling cascade is activated to propagate and amplify the signal
- transcription factor NFκB is released, goes into nucleus to activate gene transcription
- proinflammatory cytokines and chemokines are released from cell to attack bacteria/viruses/parasites |
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How are TLRs different from NOD-like and RIG-like receptors? |
TLRs are transmembrane receptors with sensing domain facing outward, so they cannot detect invaders of the cytosol
TLRs = first line of defense
NLRs detect cytosolic bacterial PAMPS RLRs detect viral RNA in cytosol = second line of defense for bacteria/viruses that end up in cytosol |
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Which PAMPS do NOD1 and NOD2 receptors detect? What happens when they find them? |
Peptidoglycans of intracellular bacteria (such as Listeria monocytogenes)
NOD1 or NOD2 then initiate signaling cascades that activate NFκB, and proinflammatory cytokines and chemokines are expressed (similar to TLR activation) |
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Which PAMPS do RIG-like receptors recognize? What happens when they find them? |
Recognize viral RNAs in cytosol
RIG1 will initiate signaling pathways that activate NFκB and also lead to expression of type 1 interferons (cytokines that specifically elicit antiviral responses) |
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How does the mannose receptor work? |
It is a phagocytic PRR - transmembrane surface PRR, expressed on macrophages and DCs
Recognizes terminal mannose, fucose and N-acetylglucosamine residues (common in microbes but not in mammalian cells)
Triggers phagocytosis of bound microbes, they are destroyed and their antigens presented to T cells |
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What are DAMPS? How are they different from PAMPS? |
Damage-associated molecular patterns They are endogenous (made by host animal), not foreign invaders
Associated with cellular and tissue injury, when intracellular contents (DNA, ATP, Uric acid etc) are released after necrosis and recognized by PRRs |
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What is an inflammasome? |
Signaling cascade that is activated when both PAMPS and DAMPS are recognized (indicates tissue damage AND microbial invasion so this is really bad)
- PAMPS and DAMPS together cause molecular complexes in macrophages to be formed
- NFκB activates expression of inactive IL-1β and IL-18
- Other complexes activate protease caspases which activate IL-1β and IL-18
- These pro-inflammatory cytokines are released from macrophage to activate leukocytes and inflammation |
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What are 2 consequences of danger signal recognition by sentinel cells? |
1. Activation of macrophages which 2. secrete proinflammatory cytokines
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What are 3 examples of non-protein proinflammatory mediators? |
Histamine Nitric oxide Prostaglandins (lipid mediators) |
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What are cytokines and what do they do? Give some examples |
Cytokines are small proteins or glycoproteins involved in cell-cell communication within the immune system
Interleukins: produced by leukocytes and act on other leukocytes (can be pro or anti-inflammatory)
Interferons: important in coordinating immune response to viral infections (usually pro-inflammatory
Also important is TNF-α (tumonecrosis factor) - does the same thing as interleukins |
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What are chemokines and what do they do? |
A group of cytokines that direct movement of immune cells |
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What is LPS? |
Lipoolysaccharides
"prototypical endotoxin"
conserved molecular pattern seen on outer wall of gram-negative bacteria
Recognized by Toll-like receptors |
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Systemic effects of PRR binding of PAMPS |
Intracellular signal cascades activate leukocytes:
- Can help to trigger and regulate adaptive immune response - Release of immune mediators such as cytokines not only attack invader but can also lead to systemic effects such as inflammation or fever
Initiates/enhances binding and internalization of microbes to phagocytes (mannose receptor, scavenger receptors)
Chemotaxis of immune cells (more cells recruited)
Complement activation (mannose binding lectin, CRP) |