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30 Cards in this Set
- Front
- Back
TLR Recognition leads to:
|
_Ag Presentation
_ Cytokines (IL 12 IL 18) _ Costimulatory Molecules |
|
Recognition Systems in the Innate
(7) |
TLR
Chemokine Cytokine Mannose NLR RLR Scavenger/C Type Lectin |
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Chemokine Receptors are for:
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Migration into Tissue
|
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Cytokine Receptors are for:
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Killing of Microbes
Inflammation Enhance Adaptive |
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Mannose Receptors are for:
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Tissue Repair
Killing Microbes |
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NLR =
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NOD-Like Receptors
Complementary to TLR's - Intracellular |
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RLR=
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RIG-I-
Like- RNA helicases |
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Characteristics of Innate Receptors
(5) |
Specifically Inherited
Expressed by all cells of a particular type Triggers Immediate Response Recognise Broad Class of Pathogen Interact w/ Range of Structures w/in a given type |
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Characteristics of Adaptive Receptors
(4) |
Encoded in multiple gene segments
Need gene rearrangement Have clonal distribution Able to SPECIFY even with closely related structures |
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Pattern Recognition Receptors note a mix of:
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Pattern Signals
Danger Signals |
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Scavenger Receptors/C Type Lectin Are For:
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Receptor Mediated Endocytosis
Phagocytosis of Apoptotic Bodies Cell Adhesion |
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RLR's are
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RNA Helicases
Important for anti VIRAL Recognise non-self RNA molecules generated in cytoplasm |
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RLR's signal through
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Signalling pathway -> Activating Transcription Factors (IRF-3 + NF kB)
-> Activating antiviral response (including _Type 1 IFN's) |
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Innate's strategy?
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Get too specific? = You miss things
|
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Innate Focuses on
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Highly Conserved Structures: PAMPs
|
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PAMP Recognition leads to:
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Activation of:
- Phagocytosis - Antimicrobial Peptide Synthesis - Induction of NO Induction of: - Inflammatory Cytokines and Chemokines - Co stimulatory molecules on APC |
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Signalling Pathways in TLR's?:
(2) |
MyD88 Dependent
TRIF Dependent |
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Adaptor Molecules for TLRs
(5) |
MyD88 - Universal Adaptor - Used by all bar TLR 3
Mal - Used to recruit MyD88 for TLR 2 + 4 TRIF - activates NFkB + IRF 3 for TLR 3 TRAM - Recruits TRIF for TLR 4 SARM - Switches off TLR engagement for TLR 3 + 4 |
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MyD88 stands for
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Myeloid Differentiation
|
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MAL stands for
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MyD88 adaptor like
|
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TRAM stands for
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TRIF Related Adaptor Molecule
|
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SARM's purpose is for:
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Balance and Control
|
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Examples of inappropriate TLR Activation
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SLE - Lupus - TLR 7 + 9 Activated by Self DNA --> AUTOREACTIVE T CELL DEVELOPMENT
Psoriasis - TLR 9 - LL37 binds to self DNA + Activates pDC via TLR 9 --> _Type 1 IFN + Psoriatic Lesions |
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TLR Polymorphisms leading to _susceptibility to:
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Asthma
Meningitis Leprosy |
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TLR as a Target in Drugs
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TLR 3 Agonist - Used in HIV + HBV
TLR 7 Agonist (Loxiribine) used in cancer |
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Examples of NLR's
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CIITA
NOD 1 NOD 2 NLRP2 NLRP3 NLRC4 |
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Purpose of NLRS
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ACTIVATING INFLAMMASOME
MHC-2 Expression Inflammatory Pathways |
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What is Inflammasome?
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Molecular Platform to Activate Caspase-1'
Multiprotein Complex (w/ Caspase 1 and cytosolic Proteins who regulate Caspase 1) |
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Activated caspase-1 leads to?
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Activation of pro-inflammatory cytokines
IL1B IL18 IL33 --> HOST CELL DEATH |
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How is Inflammasome Activated?
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NLR's! (3) - NLRP1 NLRP3 NLRC4
also by DNA |