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INNATE IMMUNITY (PAMPS (DAMPs (Recognized by (PRRs (CLRs (Dectins (Dectin…

- - - - PRRs
        
        TLRs
        
        Intracell
        
        3,7,8,9
        
        3, dsDNA; 9, CgP motifs, ss/dsDNA; 7+8, ssDNA
        
        UNC93B required
        
        1 more item...
        
        before phagosome formation
        
        Enhanced by HSPs + HMBG1
        
        Membrane
        
        1,2,4,5,6
        
        Ligand binding at LEU-rich regions induce dimerization – recruitment of TIR-domain adaptor proteins – recruitment of PKs – activation of transcription factors
        
        NF-kB
        
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        AP-1
        
        1 more item...
        
        IRF3
        
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        IRF7
        
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        2+4 recognize LPS
        
        Cytoplasmic domain similar to cytoplasmic domain for IL-1 receptor.
        
        CYTOSOLIC
        
        NLRs
        
        1) LEU-rich domain. 2) NACHT [NAIP, CIITA, HEP-E, TP1] domain for oligomerization. 3) Effector domain for recruitment = signaling complexes.
        
        effector domaine
        
        CARD
        
        NOD1
        
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        NOD2
        
        2 more items...
        
        NLRP (pyrin)
        
        14 variants
        
        1 more item...
        
        Muramyl dipeptide, LPS, pore-forming toxins, RNA.
        
        1 more item...
        
        Cristalline substances
        
        2 more items...
        
        BIR
        
        RLRs
        
        RIG-1
        
        dsDNA, RNA-DNA heteroduplexes
        
        discriminative, will not recognize capped strands form host
        
        MDA5
        
        1) 2 N-terminal caspase recruitment domains. 2) RNA helicase domain. 3) C-terminal domain. [2+3 for recognition]
        
        Binding leads to phosphorylation and activation of transcription factors
        
        3 more items...
        
        CDSs
        
        STING
        
        DAI
        
        RNA polymerase 3
        
        AIM-2
        
        CLRs
        
        Dectins
        
        Dectin-1
        
        B-glugan
        
        Cytokine production and adaptive immunity enhancers
        
        1 more item...
        
        Dectin-2
        
        high mannose oligosaccharides
        
        Mannose
        
        CD206
        
        D-mannose, L-fucose, N-acetyl-D-glucosamine
        
        Bind as a first step of phagocytosis
        
        Bind carbs in Ca++ dependent manner.
        
        Soluble in plasma/EC fluids
        
        Intergal Membrane proteins
        
        Conserve CH recognition domain
        
        DC-SIGN
        
        gp120 (HIV)
        
        BDCA2, CD207, ICAM-3, Carcinoembryonic antigen, Langerin/CD207
        
        Scavenger
        
        SR-A
        
        LPS, lipoteichoic acid, nucleic acid, B-glucan, proteins
        
        CD36
        
        FPR-1
        
        GPCR
        
        Peptides containing N-formylmethionyl residues
        
        chemoattraction for leukocytes, induce cytoskeletal changes for enhanced motility
        
        Mainly phagocytes and DC
- - - - Epithelial Barriers
        
        Skin
        
        keratin for penetration blockage
        
        Intraepithelial T
        
        yd TCR
        
        aB TCR
        
        cytokine secretion, phagocyte activation, infected cell killing.
        
        cathelicidin
        
        stimulated by cytokines and MB products
        
        C-terminal LL-37 can bind and neuter LPS
        
        Mucosas
        
        Respiratory
        
        cilia
        
        Defensins
        
        a and B
        
        also produced by granulocytes, NK, cytotoxic T
        
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        cytotoxicity and inflammatory cell activation
        
        GIT
        
        peristalsis
        
        Genitourinary
        
        pH
        
        mucins
        
        tight junctions won't allow passage
      - Phagocytes
        
        Macrophages
        
        Neutrophils
      - Dendritic Cells
        
        Most varied presentation of TLRs and PRRs
        
        Major source of I IFN
        
        Take up antigens – transport to lymph nodes – interact with T – direct naive T into IFN-y-producing Th1 or IL-17-producing Th17
      - Natural Killer Cells
        
        germline DNA-encoded receptors
        
        Killing of infected cells once they develop with no further need to differentiate
        
        IFN-y enhances macrophage activity, holds on and allows time for adaptive T to develop
        
        discriminates
        
        Healthy cells
        
        inhibitory receptors
        
        2 more items...
        
        Damaged cells
        
        activating receptors
        
        4 more items...
        
        CD56+, CD3-, CD16+
        
        Activation – granule exocytosis – perforin facilitates granzyme entrance to infected cell – granzyme initiates apoptosis
        
        IL-12/15
      - Mast Cells
- - - - nTreg
      - iTreg