Immune System

Subdivisions of the Immune System

Innate Immune System

  • Function: immune system present from birth
    • This is a more “primitive” component of the immune system: provides “first-line” defense
    • The cardinal signs of inflammaton (tumor = swelling, rubor = redness, calor = heat, dolor = pain) are manifestations of the innate immune system response
    • Recognition of organisms via pattern-recognition receptors (PRR’s): these recognize “non-self” antigens from the invading organisms
    • Innate immune system acts immediately to respond to an infection/exposure
    • Innate immune system activates and instructs the actions of the adaptive immune system
    • Innate immune system regulates inflammation, maintaining immunologic homeostasis
  • Components
    • Non-Cellular Components of the Innate Immune System
      • Physical Barriers to Invasion: tight junctions in the skin, epithelial and mucous membrane surfaces, mucus itself)
      • Cell Surface Receptors that Detect Microorganisms and Initiate a Defensive Response: Toll‐like receptors, etc
      • Epithelial and phagocytic cell enzymes (eg, lysozyme) which selectively disrupt microbial cell membranes
      • Inflammation‐related serum proteins (eg, complement which also disrupts microbial membranes, C‐reactive protein, lectins such as mannose‐binding lectin and ficolins, hemopexin and haptoglobin, which deny iron to invasive microbes)
      • Surface and phagocyte granule antimicrobial peptides (defensins, cathelicidin, and many more)
    • Cellular Components of the Innate Immune System
      • Phagocytes: myelocytic neutrophils, monocytes, and macrophages
      • Inflamamtory Cells Which Release Cytokines and Other Mediators: macrophages, mast cells, lymphoid natural‐killer (NK) cells

Adaptive Immune System

  • Function: immune system that evolves over lifetime of exposure to micro-organisms in the environment
    • This is a more “modern” component of the immune system: provides more sophisticated, but delayed defense
    • Antigen‐specific responses to a foreign antigen or pathogen: typically requires days-weeks to fully respond
    • Cells exposed to microbial antigens are selected for clonal expansion
    • Immunologic Priming: initial contact with an antigen -> subsequent antigen exposure leads to more rapid and vigorous immune responses (ie: immunologic memory)
  • Components: both are derived from a common progenitor cell
    • T-Lymphocytes: principal effectors of antigen-mediated cellular immunity
      • Cell-mediated immunity is responsible for defense against pathogens that replicate intracellularly (viruses, mycobacteria, and some bacteria), cells which exhibit aberrant differentiation (neoplasms), and allogenic cells (graft rejection)
      • T-cell responses are initiated by antigen-presenting cells: dendritic cells and monocytes/macrophages (note: monocytes may also differentiate into dendritic cells)
      • T-cell clonal expansion subsequently occurs
      • T cells are categorized on the basis of the pattern of cytokines that they secrete, which results in either humoral immune response (TH2) or cell‐mediated immune response (TH1)
    • B-Lymphocytes: principal effectors of humoral immunity
      • B-cells are activated after T-cells -> antibodies are produced when B cells encounter antigens and subsequently undergo activation, proliferation, and differentiation
      • Neonates rely predominantly on maternal IgG (passed through the placenta) and maternal IgA (transferred through colostrum and breast milk)
      • After infancy, the child’s immunoglobulins gradually increase as levels of maternal antibodies wane
  • Location
    • T cell precursors arise from hematopoietic stem cells and home to the thymus for maturation
    • Mature T-cells, B-cells, monocytes, and dendritic cells enter the circulation -> home to peripheral lymphoid organs (lymph nodes, spleen), mucosal surface‐associated lymphoid (MALT) tissue (gut, genitourinary, and respiratory tracts), skin, and mucous membranes