Innate Immune System

Innate Immune System

1. Innate/nonspecific immunity

   • Nonspecific defense that is always active against infection, but lacks ability to target specific invaders
     • Skin (integument)
       • Defensins
         • Antibacterial enzyme
       • Basic physical barrier against the outside world
     • Respiratory system
       • Lysozyme
         • Nonspecific bacterial enzyme secreted in saliva and tears
       • Cilia
         • Mucous membranes that trap particulates and push them to the oropharynx to be swallowed or expelled
   • Gastrointestinal tract
     • Acid eliminates most pathogens.
     • Gut bacteria
       • Many invaders cannot compete with present gut flora, and therefore die off.
   • Complement system
     • Classical pathway
       • Requires binding of antibody to pathogen
     • Alternative pathway
       • Doesnt require antibodies
     • Nonspecific defense proteins in blood. Punch holes in bacteria cell walls (osmotic instability). Cannot be modified to target specific organisms
   • Interferons
     • Proteins that prevent viral replication and dispersion
     • Decrease permeability of nearby cells making it harder for virus to infect.
     • Upregulate MHC class I and II
     • Responsible for flu-like symptoms
   • Cells of the innate immune system
     • Monocytes
       • Macrophages
         • Antigen presenting cell. When a bacterial invader enters a macrophage-resident tissue, macrophages: 1. Phagocytose invader through endocytosis. 2. Digests invader using enzymes. 3. Present peptides (antigen) of invader (using MHC) to adaptive immune system
         • Major Histocompatibility Complex
           • MHC Class I pathway
             • Endogenous pathway (displays proteins from within the cell). Present in all nucleated cells. Displays to cytotoxic (CD8) cells
           • MHC Class II pathway
             • Present on macrophages, dendritic cells, and some B-cells (adaptive). Displays exogenous antigens (originate outside the cell) to T-helper cells (CD4)
           • Displays antigens to adaptive immune system.
         • Pattern recognition receptors (PRR)
           • Toll-like receptors
             • Most common PRR. Single, membrane-spanning, non-catalytic receptors
           • Able to recognize category of invader (bacteria vs. virus vs. fungi, etc). Aids in production of appropriate CYTOKINES
           • Cytokines
             • Chemicals that stimulate inflammation and recruit additional immune cells
       • Blood-borne
     • Antigen Presenting cells
       • Dendritic Cells
         • Antigen presenting cells in the skin
       • B cells (adaptive immunity)
     • Natural killer cells
       • Nonspecific lymphocyte. Can detect down regulation of MHC (brought on by certain pathogen defenses) and induce apoptosis in virally infected cells. Can offer protection against growth of cancer as well
     • Granulocytes
       • Neutrophils
         • Leukocyte. Short lived (5 days). Phagocytic (particularly opsonized bacteria)
         • Chemotaxis
           • Method by which neutrophils can follow bacteria
         • Pus
           • Dead neutrophils form pus
       • Eosinophils
         • Primarily involved in allergic reactions and parasitic infections .
         • Histamine
           • Inflammatory mediator. Vasodilation & increased blood vessel leakiness allows other immune cells to disseminate
       • Basophils
         • Mast Cells
           • Smaller granules than basophils. Exist in tissue, mucosa, epithelium. Degranulation (exocytosis of granule contents) occurs when antigen binds to mast cell, causing histamine release, leading to inflam/allergic rxn
           • Basophils and mast cells also release HISTAMINE in response to allergens
         • Large purple granules. Least populous under normal conditions