Immune System Introduction & Innate Immunity

MICB 202 Topic 1: Introduction to the Immune System & Topic 2: Innate Immunity

The body has three level of defense:

• anatomical and physiological barriers e.g. skin
• innate response – quick, first line of internal defense, non-adaptive because same every time, does not improve with re-exposure to same pathogen
• adaptive – slower to respond but specific to pathogen. antibody-mediated (humoral) or cell-mediated

Cells of the immune system:

• erythocytes – RBCs
• platelets – blood clotting
• leukocytes = WBCs
  • myeloid cells
    • monocytes -> macrophages
    • mast cells
    • granulocytes: neutrophils, basophils, eosinophils  –
  • lymphoid cells
    • T lymphocytes
      • cytotoxic
      • helper
      • regulatory
    • B lymphocytes – produces antibodies
    • natural killer cells – similar function to CTL, kills cells infected with certain viruses but do not require MHCI for activation
• All blood cells from hematopoietic stem cell. Self-renewing stem cells (one mature, one become stem cell again). in bone marrow, umbilical cord blood
• MSC -> myeloid precursor (MLP) or lympoid precursor (CLP)
• Dendritic cells are either mlp or clp

Location of the immune system

• Primary lymphoid organs
  • where lymphocytes mature
  • bone marrow
  • thymus
• secondary
  • spleen
  • lymph nodes
• lymphatic system = blood – RBC. Everything but RBC. Clear

Innate Immunity

• opsonization = coating of pathogen to help phagocytosis
• immediate innate:
  • lysozyme (tears, salivia) degrades peptidoglycan
  • defension  – bind to bacteria and disrupt cell walls
  • complement proteins
• Induced
  • alarm cytokines

Recognizing a pathgeon

• Il-1 receptor is a TLR
• toll-like receptor TLR
• phagocytosis receptor
• soluble PRRs
• PAMPS e.g. LPS (gram – ) or peptidoglycan (+)
• pattern recognition receptors
• gram negative reco by resident macrophages in tissue
  1. LPS + LBP
  2. CD14
  3. TLR MD2
  4. NF -kB  transcription factor
  5. alarm cytokines: TNF a, Il-1, il6
• inflammatory response
  1. mast cell – histamine
  2. tnf a, il 1, il 6 act on blood vessles
  3. increase vascular permeability, red, heat, swell
  4. tnf a, il1, il 6  expression of adhesion molecules on endothelial cell -> stick cells to the cell wall, and squeez through
  5. extravasation
  6. macrophages release il 8   – recruit more monocytes neutrophils
  7. acidic phagosome + lysosome
  8. clotting (coagulation proteins), skin repair. keep the bacteria in one location
  9. pus from dead cells
• Complement system
  • cleavage of a protein makes two smaller proteins
  • activated by series of reactions in a set order
  • Classical complement pathway
    1. antibodies IgM or IgG
  • Alternative pathway
    1. spontaneous formation of C3 convertase
    2. spontaneous splitting of C3 into C3a and C3b
  • C3 convertase is very important. it splits c3 into c3a and c3b
  • Purpose of C3a   -> make macrophages release TNF a
  • Purpose of C5a -> make mast cells release histamine, attract neutrophils and macrophages
  • purpose of c3b – > opsonization, recruits proteins to make C5 convertase
  • c5 convertase -> splits c5 into c5a and c5b
  • c5b helps form membrane attack complex
• Opsonization
  • antibodies bind pathogen with variable/bivalent side
  • antibodies bind macrophage with constant region through Fc receptors (FcR)
• Dendritic  cells = go between innate and adaptive
  • Immature= Langerhan cells
  • express same PRRs as macrophages
  • migrate to lymph node
  • express both MHCI and MHCII
  • During maturation which is after PRR engaged, express more MHC I and MHC II, co-stimulatory proteins