Innate Immunology

• Why do we need an immune response?

  • prevent infection
  • prevent cancer
  • remove dead or non-functioning components
• 5 major classes of pathogens

  • virus
  • bacterium
  • fungus
  • protozoal parasite
  • multicellular parasite
• Physical immune barriers

  • skin
  • cilia
  • hair
  • mucosal surfaces
  • flushing action - urine, tears
  • peristalsis
• Cilia are tiny hairs that can waft things away.
• Hair on the outside of our body can act as a surface for bacteria to adhere to and then shed off.
• Mucosa - any internal tissue exposed to an external environment
• Tears contain lysozymes that are antimicrobial.
• Desquamation - the shedding of the outer layer of the epidermis
• A large portion of immune cells in the skin are found in the dermis.
• Epidermis is the base layer of skin that is constantly dividing, cells get more mature as they head towards the surface
• Sebaceous glands produce oily secretions that can coat hairs and trap pathogens. The viscosity of the surface stops anything being able to penetrate the skin,
• The gut consists of an outer muscular layer that generates gut motility, the lamina propria mucosae, a highly vascularised zone composed of connective tissue and a plethora of immune cells and the mucosal epithelium with its mucus layer.
• The intestinal barrier consists of a thick layer of mucus, that constitutes a matrix embedding secretory immunoglobulin A, antimicrobial peptides, collectins and commensal gut bacteria.
• Goblet cells produce mucus, a thick secretion that will trap pathogens trying to breach the epithelial layer.
• Lymphocytes are one type of immune cell present in the lamina propria.
• Natural flora compete with pathogens for nutrients and space.
• Chemical immune defences

  • lysozymes
  • skin surface, fatty acids, normal flora
  • rapid pH change in gut
  • urinary tract flushing
  • normal gut flora
  • mucus lining trachea
  • removal of particles by cilia in nasopharynx
• Humans have approximately 10 times as many bacteria as cells. Viruses, fungi and protozoa are also regularly found in healthy individuals in much smaller quantities. The organisms occur in areas exposed to external environments e.g. skin, nose and mouth and intestinal and urogenital tracts. Internal organs and tissues are normally sterile.
• Cells of the innate immune system derive from myeloid precursors whereas cells associated with the adaptive immune system are derived from common lymphoid precursors.
• Innate immune system

  • first cellular line of defence
  • non-specific
  • can also damage surrounding tissue
  • initiates inflammation
• inflammation signs

  • injury
  • rubor, calor
  • tumor
  • dolor
  • loss of function
• Mast cells are present in tissue and when they encounter a pathogen they will degranulate and release pro-inflammatory mediators into the extracellular space.
• Granulocytes - a family of cells whose primary function is achieved by releasing granules into the extracellular space.
• pro-inflammatory mediators can go on to activate lots of different cells that play a role in the immune system.
• main constituent of mast cell granule is histamine
• Histamine is an incredibly pro-inflammatory molecule that increases vascular permeability among other effects.
• How does increasing vascular permeability promote inflammation?

  Allows fluid and immune cells to enter tissue.
• The main purpose of mast cells is to signal to other immune cells that they are needed at a site of infection.
• activation of endothelial cells by mast cells

  • upregulation of adhesion molecules
  • breakdown of tight junctions
  • exocytosis of welbel-palade bodies
  • inflammatory mediator production/secretion
• activation of smooth muscle cells by mast cells leads to vasodilatation
• Extravasation

  The process by which white blood cells leave the bloodstream and enter tissues through the walls of capillaries.
• Mediator release by mast cells leads to

  • cellular recruitment
  • vascular leakage
  • clot prevention
• Mast cell granules can get endothelial cells to increase the amount of adhesion molecules they present, so cells are more likely to stick and cause their function.
• Surface receptors on endothelial cells bind to leukocytes such as neutrophils and dendritic cells as well as any proteins that are circulating in the blood.
• Increased vascular permeability allows cytokines to spread out through the circulation.
• Mast Cell Degranulation

  Release of stored granules containing histamine, heparin, chemokines, enzymes, and eicosanoids, leading to increased blood flow, vasodilation, smooth muscle contraction, inflammation, and allergic reactions
• Dendritic Cell Functions

  Antigen presentation, immune surveillance, activation of T-cells, regulation of immune responses, and tolerance induction
• The main purpose of a dendritic cell is to take part of a pathogen and present it to other cells of the immune system.
• Dendritic cell pathway

  • antigen encounter
  • migration
  • antigen presentation
• Langerhans cells (LCs) are a specialized subset of dendritic cells (DCs) that populate the epidermal layer of the skin.