Adaptive Immunity

Describe the factors involved in the process of inflammation and the immune response, including innate and acquired immunity

The adaptive immune system responds to an exposure, demonstrating specificity and memory, with improved efficacy on repeat exposure.

Adaptive immunity may be:

• Active
  Primary immune response generated by exposure to antigen.
  • Infection
  • Vaccination
    An inactive (but still foreign and therefore antigenic) protein component of a pathogen is given to the patient, resulting in an immune response. Subsequent exposure to the whole pathogen triggers a secondary immune response.
• Passive
  Preformed antibody is given to the patient. This will provide treatment/coverage for the life of the antibody, but immunity will be lost when the antibody breaks down or supplies are exhausted.
  • Transplacental
  • Colostrum
  • Administration of serum

Components of the active immune system include:

• Cellular
  Predominantly T lymphocytes
• Humoral
  Including complement and antibody.

Adaptive Cellular Immunity

Lymphocytes are divided into two types:

• B lymphocytes
  Are produced in the bone marrow, and migrate to lymphoid (nodes, spleen, MALT) where they are renamed plasma cells and produce antibody. Functions include:
  • Production of antibody against specific antigens
  • Presentation of antigen to T-cells to active them
  • Proliferation to form memory cells

• T lymphocytes
  Are produced in the bone marrow and migrate to the thymus where they mature. T cells which express antibody to host protein apoptose, resulting in only 2% of immature T cells surviving. Mature T cells then spread to lymphoid tissue. There are five types of T cells, of which two are most important:
  • Helper T-cells
    2/3^rds of T-cells are helper cells, are are identified by their CD4 membrane protein. Functions include:
    • Cytokine production
    • B lymphocyte stimulation
    • Macrophage activation
  • Cytotoxic T-cells
    Are identified by their CD8 membrane protein. Functions include:
    • Destruction of virally infected and tumour cells
      All cells express proteins that they are producing on membrane MHC I molecules, for inspection by immune cells. Infected or tumour cells will express foreign proteins, and cause activation of cytotoxic T cells:
      • Induce apoptosis in the target cell
      • Rapid division of cytotoxic T cell, which then inspects other cells for infection
    • Transformation to memory cells

Adaptive Humoral Immunity

Antibodies Y-shaped immunoglobulins which:

• Are produced in response to a pathogen
• Are specific to that pathogen

Antibody functions include:

• Opsonisation
• Agglutination
  Each antibody can bind multiple pathogens, increasing target size for leukocytes.
• Inactivation of pathogen
  Antibody binding may disable the pathogen.
• Activation of complement
  Antibody-antigen complexes cause complement activation.

Primary Immune Response

The process of invasion of a new pathogen to antibody production takes ~5 days, and occurs in a number of steps:

• APC phagocytose a pathogen
  APCs include macrophages and dendritic cells.
• APC express antigen (bits of pathogen) on cell surface
• APC travel to lymphoid tissue and present it to B and T cells
• When an APC finds a B and T cell with a reciprocal antibody:
  • T helper cell becomes activated by APC
  • T helper cell rapidly proliferates ('clonal expansion')
    • Proportion become memory cells
  • B cells are activated by both the APC and a T-helper cell (requires both)
  • B cells rapidly proliferate
    • Proportion become memory cells
    • Proportion become plasma cells
      • Plasma cells produce antibody at a rate of 2000 molecules per second, which overrides normal cellular homeostasis, causing death within a week.
      • Antibody produced in a primary immune response is IgM, with some IgG produced later on.

Secondary Immune Response

Repeat invasion by the same pathogen is met with a much more rapid and aggressive immune response:

• APCs phagocytose a pathogen
• APCs express and present antigen
• Memory T and Memory B cells formed during the primary response are activated, and begin rapidly dividing and producing antibody

References

1. Kam P, Power I. Principles of Physiology for the Anaesthetist. 3rd Ed. Hodder Education. 2012.
2. Chambers D, Huang C, Matthews G. Basic Physiology for Anaesthetists. Cambridge University Press. 2015.