Overview of the Immune System

• functions of the immune system:

  1. immunological recognition (pathogen present)
  2. immune effector functions (activation and deployment of immune cells and associated factors)
  3. immune regulation (knowing when to limit or step-up a response; failure can be problematic, waste resources and energy)
  4. immunological memory (long-lasting protection - protect from repeated infections)
• body tolerance is developed a baby when growing and allows us to recognise when a pathogen (anything foreign to the body) is present
• the haematopoietic stem cell can diversify into the common lymphoid precursor (giving rise to B and T cells and NK cells) and the common myeloid precursor (giving rise to mast cells, granulocyte-macrophage progenitor and eventually neutrophils, basophile and eosinophils, and a macrophage dendritic cell precursor and eventually the dendritic cell and monocyte/macrophage)
• Monocytes and macrophages are the same cells but in different stages of maturation, the monocyte is within the blood and macrophage is within tissues
• NK cells work alongside both macrophages and effector T cells
• B and T cells are only used when required as they require a lot of resources and energy but they are highly specific
• lymph nodes are concentrated in the trunk of the body to be closer to the organs - there are very few below the groin as there are no essential organs below there. this is where the B and T cells are stored and produced from
• primary lymphoid tissues include the bone marrow and the thymus and are where lymphocytes are produced
• secondary lymphoid tissues include the spleen, appendix, adenoid, tonsils and lymph nodes
• lymphocyte recirculation occurs as follows:

  heart - artery - lymph node - efferent lymphatic - vein - heart
• the efferent lymphatic releases cells from the lymph node out to the heart into the circulatory system with the cells driven to the site by chemical signals and stress proteins. they stop in the artery before moving to the tissue
• extracellular pathway of infection:

  • free pathogens (virus, bacteria, etc) appear randomly in the interstitial spaces, blood and lymph and are noticed by macrophages that then trigger antibodies, complement cascade phagocytosis and neutralisation
  • free pathogens (streptococcus pneumoniae) often have substances which have lots of sugars which stick to epithelial surfaces as they have receptors which bind to the cell causing stress and causing antibodies especially IgA and antimicrobial peptides to become activated
• intracellular pathway of infection can be:

  • cytoplasmic (listeria monocytogenes) - cytotoxic T cells and NK cells are the defence
  • vesicular (Legionella pnuemophila) - t-cells and NK-cell dependant macrophage activation are the defence
• The intracellular pathway of infection is when pathogens jump into the cell and are encapsulated in vesicles and they replicate, they then go into the cell's membrane which then circulates the body whilst being recognised as self
• direct mechanism of tissue damage by pathogens include:

  • Exotoxin production - tonsillitis and tetanus
  • endotoxin production (in cell destruction) - gram-negative sepsis, typhoid fever, plague
  • direct cytopathic effect (bac have target and that's how cell is killed) - chicken pox, cold sore, flu
• indirect mechanism of tissue damage by pathogens include:

  • immune complexes - systematic conditions such as kidney disease and syphilis
  • anti-host antibody (can destroy self tissue) - rheumatic fever
  • cell-mediated immunity (rely on t helper cells help) - tuberculosis, tuberculoid leprosy
• antibodies involved in the indirect mechanism of tissue damage by pathogens clump things together and can become huge, cause blockages and tissue damage
• Peyer's patch in the small intestinal tissue is full of immune cells, the lumen is where food/saliva is with most things not liking the low pH environment although some have adapted to be acidophiles
• interleukins (IL-) is more common and have a variety of actions dependent on cell/cytokine interaction often switching things on or off
• TNF superfamily (tumor necrosis family) are regulators of immune responces and often alpha
• interferons (INF-) are antiviral proteins
• TGF-beta superfamily (tumor growth factor) regulation of immune cells often switching off or negative growth factor
• chemokines (CXC-, CCL, etc) coordinate cell migration, adhesion and activation - aiding stress factors
• innate immune system include neutrophil, basophil, eosinophil, monocyte, macrophage, mast cell, NK cells (myeloid cell lineage)
• the innate immune system is an immediate response to pathogens and is non-specific
• the adaptive immune system composed of t and b lymphocytes is activated from days 1-7
• the macrophage is an antigen-presenting cell and hoovers everything in its path - both pathogenic and cells which have changed and waste products
• the macrophage matures from blood monocytes and are found in tissues microglial (nerve) cells and kupffer (liver) cells and is involved in the respiratory burst where there is a release of reactive oxygen species such as superoxide hydrogen peroxide and hypochlorous acid
• macrophages reuse and repurpose the cellular material that they ingest, but when they become overwhelmed they go through cell death themselves
• macrophages phagocytose material and present on the surface and an immune response is mounted when non-self proteins are recognised.
• the macrophage expresses receptors for many bacterial constituents - mannose receptor, glucan receptor and LPS (lipopolysaccharide receptor CD14)
• bacteria binding to macrophage receptors initiate the release of cytokines chemokines and small lipid mediators of inflammation
• macrophages engulf and digest bacteria to which they bind:

  • phagosome - phagocytosis occurs
  • lysosome - degradation if inter and extracellular components
  • phagolysosome - oxidative burst occurs
• an activated macrophage secrete a range of cytokines:

  • Il-1beta
  • TNF-alpha
  • IL-6
  • CXCL8 (IL-8)
  • IL-12
• IL-1beta activates the vascular endothelium allowing self-cells to move from artery to tissue with its increased permeability, activates lymphocytes local tissue destruction and increases access of effector cells
• TNF-alpha activates the vascular endothelium and increases vascular permeability, which leads to increased entry of IgG complement, and cells to tissues and increased fluid drainage to lymph nodes
• IL-6 is involved in lymphocyte activation and increased antibody production and induces acute phase protein production
• CXCL8 (IL-8) is chemotactic factor which recruits neutrophils, basophils and t cells to the site of infection
• IL-12 activated NK cells and induces the differentiation of CD4 T-cells into Th1 cells
• the acute phase response occurs when bacteria induce macrophages to produce IL-6, which acts on hepatocytes to induce the synthesis of acute-phase proteins