Innate Immunity

Descrição

Innate responses will be in shades of blue. Anything in red is associated with the adaptive responses.
GraceEChem
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GraceEChem
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Resumo de Recurso

Innate Immunity
  1. Antigens
    1. Invoke immune responses (B-cell)
      1. "Antibody generators"
      2. WBCs
        1. Innate: macrophages, respond to all
          1. Adaptive: B & T cells, specific response
          2. Skin barrier
            1. pH
              1. Shedding
                1. [NaCl]
                2. Mucous Membranes
                  1. lysozyme (attack cell wall)
                    1. lactoferrin (sequesters Fe)
                      1. Lactoperoxidase (superoxide radicals)
                      2. Antimicrobial Peptides (AMPs)
                        1. Cationic peptides (highly conserved, damage bacteria pm)
                          1. 1st class (a-helic, no cysteine, prod by macrophages)
                            1. Cathelicidin (LL-37)
                              1. Protect kidney in UT w/neutrophils
                                1. Humans protected by zwitterionic (0 charge) membranes
                              2. 2nd class: Defensins (disulfide linked, neutrophils, epithelial)
                                1. Kill phagocytosed bact. by binding to membrane and forming pores for lysis
                                2. 3rd class: larger, enriched for specific am. ac.
                                  1. Histatin
                                    1. In saliva, anti-fungal (c. albicans)
                                3. Bacteriocins
                                  1. Produced by normal flora
                                    1. Lethal to related species
                                      1. Colicins (E. coli) form pores & binds to specific recptors (porins)
                                4. Complement System
                                  1. Major activities
                                    1. Defense against bacterial infections
                                      1. Crosstalk b/w innate and adaptive immunity
                                        1. Disposing waste
                                        2. Opsonization
                                          1. Decorating microbes with "opsonins" for recognition by phagocytic cells
                                            1. Stimulates macrophages for phagocytosis
                                          2. Activation of C proteins
                                            1. Enzymatic cleavage
                                              1. C#b proteins bind to complex
                                                1. C#a proteins diffuse to be inflammatory mediators (binds to receptor)
                                              2. Functions
                                                1. Opsonization (C3b)
                                                  1. Inflammation (C#a)
                                                    1. Cell lysis via MAC
                                                    2. The Three Pathways
                                                      1. Alternative
                                                        1. Antibody-independent, initiated by foreign cell surfaces
                                                          1. C3 cleaves to C3 convertase
                                                            1. C3 convertase cleaves with C3 to C5 converstase
                                                              1. C5 goes to be the MAC
                                                          2. Lectin
                                                            1. Lectin or Mannose-Binding Lecting (MBL) binds to carbohydrates
                                                              1. 2 serine protesase (MASP-1, MASP-2)
                                                                1. Activates with C3 and Lectin
                                                                  1. Mannose Binding Proteins (MBP) on pathogen surfaces
                                                                    1. Enhance phagocytosis
                                                            2. Classical
                                                              1. Initiated by forming Ag-Ab (Antigen-Antibody) complex
                                                                1. Part of Acquired & not as fast
                                                                  1. Produces cleavage products that help in:
                                                                    1. Opsonization
                                                                      1. Chemotaxis
                                                                        1. MAC
                                                                        2. C1 is activated when bound to antibody
                                                                          1. Yields C2 & C4
                                                                            1. C4a diffuses
                                                                              1. C2a diffuses
                                                                                1. C4b and C2b become C3
                                                                        3. Complement Proteins
                                                                          1. C3b
                                                                            1. Opsonin
                                                                            2. C#a
                                                                              1. Show immune cells infection site
                                                                                1. Recruit macrophages & neutrophils
                                                                                2. C5b
                                                                                  1. Form MAC for lysis
                                                                              2. Pathogen Recognition
                                                                                1. Opsonin-Independent Mechanism
                                                                                  1. Pathogen recognition, specific and non
                                                                                    1. Mediated by:
                                                                                      1. Lectin-carbohyd
                                                                                        1. Protein-protein
                                                                                          1. Hydrophob
                                                                                            1. Pathogen-Associated Molecular Patterns (PAMPs)
                                                                                              1. Detected by Pattern Recognition Receptors (PRRs)
                                                                                                1. Can trigger phagocytes
                                                                                                  1. Toll Like Recptors (TLRs)
                                                                                                    1. Signaling recptors
                                                                                                      1. Recognize/bind unique PAMPS
                                                                                                        1. Triggers signal to initiate host response
                                                                                                    2. LPS in Gram -
                                                                                                      1. Peptidoglycan in Gram +
                                                                                                        1. Binding activates NFkB transcription factor (Key for Cytokine gene transcription)
                                                                                                          1. Cytokine
                                                                                                            1. Acts as signal molecule
                                                                                                              1. Recognized by receptors on immune cell
                                                                                                                1. Trigger their function
                                                                                                    3. Intracellular Digestion (Phagocytosis)
                                                                                                      1. Autophagy
                                                                                                        1. Tags internal microbes for destruction w/Ubiquitin
                                                                                                          1. Phagophore encircles
                                                                                                            1. Fuse with lysosome to degrade

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