Patho

• Innate immunity


  Epithelial barrier, phagocytic cells, dendritic cells, NK cells, complement system
• TLR signaling


  • Leads to inflammation, interferons, lymphocyte activation
• NLRs


  Cytosolic receptors (NOD, NOD2) that detect products of necrotic cells, ion disturbance, microbial products
• NLR signaling


  Leads to inflammasome formation, which activates pro-IL-1β, IL-1β
• NLRP3


  Inflammasome component, its dysfunction leads to autoinflammatory syndromes, treated with IL-1 antagonists
• CLRs


  Detect fungal glycans
• RIG-I


  Detects microbial DNA/RNA
• 1. protein coupled receptors


  On neutrophils, macrophages, leukocytes, recognize N-formylated peptides
• B cell antigen receptor


  Recognizes specific antigen
• T cell receptor


  Recognizes MHC-presented antigen
• T cells


  Localize to T cell zones in spleen and lymph nodes
• CD4


  Important T cell co-receptor, signals T cell activation
• CD28


  Recognizes B7 costimulatory molecules, provides activating signal to T cells
• CD80/86 (B7)


  Costimulatory molecules expressed by APCs, provide activating signal to T cells
• Coinhibitory receptors


  CTLA-4, PD-1, block T cell activation signals
• NK cells


  Recognize glycolipids, express CD16, CD56, can be activated or inhibited by MHC class I
• MHC class I


  Expressed on all nucleated cells, recognized by CD8+ T cells and NK cells
• MHC class II


  Expressed on dendritic cells, macrophages, B cells, recognized by CD4+ T cells
• HLA genes are located on chromosome 6
• Identical twins can accept grafts without fear of rejection, others may reject due to minor histocompatibility antigens
• IgM


  First antibody class expressed on B cell receptor
• CD21


  Binds complement breakdown products, involved in B cell activation
• Epstein-Barr virus


  Uses CD21 as a receptor to infect B cells
• NK cells


  Innate immune cells that express inhibitory and activating receptors, can induce target cell lysis via perforin and granzymes
• Dendritic cells


  Most important antigen presenting cells, present antigen to T cells in lymph nodes
• Plasma cells


  Terminally differentiated B cells that secrete antibodies
• Follicular dendritic cells


  Present antigen to B cells, promote antibody responses
• Lymph nodes


  Encapsulated collections of lymphoid cells and innate immune cells
• Spleen


  Filters blood-borne antigens via sinusoids
• Germinal center formation


  Occurs when a B cell in a follicle responds to an antigen
• Cytokines of innate immunity

  • IL-1, IL-12, TNF, Type I IFN
• Cytokines of adaptive immunity

  • IL-4, IL-5, IL-17, IFN-γ
• Granulocyte-colony stimulating factor


  Stimulates production of granulocytes during inflammation
• IL-2


  Growth factor that acts on T lymphocytes
• CD40L


  Member of the TNF superfamily, important for T cell help of B cells
• Cytotoxic T lymphocytes


  Depend on perforin and granzymes for target cell lysis
• B cell activation pathways

  1. T cell dependent (CD4+ T cell help)

  2. T cell independent (antigen crosslinking, antibody)
• Antibody class switching


  T cell stimulated, results in antibodies with higher affinity
• IgG


  Opsonizes pathogens for phagocytosis, activates complement via classical pathway
• IgA


  Found in mucosal tissues, neutralizes microbes