antigenic variation

Examples of antigenic variation in the following topics:

• Extracellular Immune Avoidance

  • This is referred to as antigenic variation.
  • The constant change of these antigens is why vaccines have not been created.
  • Another common strategy that is used is to mask antigens with host molecules in order to evade detection by the immune system.

• Antibody Structure

  • Variations in antibody structure allow great diversity of antigen recognition among different antibodies.
  • This is why there are numerous antibodies that can each recognize a different antigen.
  • The portion of an antigen that is recognized by the antibody is known as the epitope.
  • The pentamer arrangement means that these macromolecules can bind ten identical antigens.
  • This class supports antigen recognition and subsequent maturation of B cells to plasma cells.

• Emergence of Viral Pathogens

  • If one of these new forms of an antigen is sufficiently different from the old antigen, it will no longer bind to the receptors and viruses with these new antigens can evade immunity to the original strain of the virus.
  • Two processes drive the antigens to change: antigenic drift and antigenic shift (antigenic drift being the more common).
  • Antigenic drift is a mechanism for variation by viruses that involves the accumulation of mutations within the antibody-binding sites so that the resulting viruses cannot be inhibited as well by antibodies against previous strains, making it easier for them to spread throughout a partially immune population.
  • Antigenic drift occurs in both influenza A and influenza B viruses.
  • Alternatively, the change can occur by antigenic shift .

• Precipitation Reactions

  • Precipitation reactions are based on the interaction of antibodies and antigens.
  • These reactions depend on the formation of lattices (cross-links) when antigen and antibody exist in optimal proportions.
  • Precipitation reactions differ from agglutination reactions in the size and solubility of the antigen and sensitivity.
  • Antigens are soluble molecules and larger in size in precipitation reactions.
  • Precipitation methods include double immunodiffusion (qualitative gel technique that determines the relationship between antigen and antibody), radial immunodiffusion (semi-quantitation of proteins by gel diffusion using antibody incorporated in agar), and electroimmunodiffusion (variation of the double immunodiffusion method reaction that uses an electric current to enhance the mobility of the reactants toward each other).

• Enzyme-Linked Immunosorbent Assay (ELISA)

  • Enzyme-linked immunosorbent assay (ELISA) is a method of quantifying an antigen immobilized on a solid surface.
  • The amount of antibody that binds the antigen is proportional to the amount of antigen present, which is determined by spectrophotometrically measuring the conversion of a clear substance to a colored product by the coupled enzyme.
  • Several variations of ELISA, seen in , exist but the most commonly used method is the sandwich ELISA.
  • The antigen serves as bridge, so the more antigen in the test solution, the more enzyme-linked antibody will bind .
  • The concentration of antigens can be inferred from absorbance readings of standard solutions.

• Antigens and Antigen Receptors

  • At the molecular level, an antigen is characterized by its ability to be "bound" at the antigen-binding site of an antibody.
  • The distinct molecular surface features of an antigen capable of being bound by an antibody (a.k.a. antigenic determinant).
  • Some antigens start out as exogenous antigens, and later become endogenous.
  • A native antigen is an antigen that is not yet processed by an APC to smaller parts.
  • Antigen specificity is due primarily to the side-chain conformations of the antigen.

• Antigenic Determinants and Processing Pathways

  • An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, T cells which can use epitopes to distinguish between different antigens, and only bind to the antigen that they are specific to.
  • Epitopes determine how antigen binding and antigen presentation occurs.
  • This is why polysaccharides are generally T-independent antigens and proteins are generally T-dependent antigens.
  • The determinants need not be located on the exposed surface of the antigen in its original form, since recognition of the determinant by T cells requires that the antigen be first processed by antigen presenting cells.
  • In order for an antigen presenting cell (APC) to present an antigen to a naive T cell, it must first be processed into a form in which the antigenic determinant can be recognized by the T cell receptor.

• MHC Polymorphism and Antigen Binding

  • Diversity of antigen presentation, mediated by MHC classes I and II, is attained in multiple ways:
  • Human MHC class I and II are also called human leukocyte antigen (HLA).
  • The variations in the MHC molecules (responsible for the polymorphism) are the result of the inheritance of different MHC molecules, and they are not induced by recombination, as it is the case for the antigen receptors.
  • The human leukocyte antigen (HLA) system is the name of the major histocompatibility complex (MHC) in humans.
  • This group of genes resides on chromosome 6, encodes cell-surface antigen-presenting proteins and has many other functions.

• Monoclonal Antibodies

  • They are also very useful in immunohistochemistry, which detect antigen in fixed tissue sections, and the immunofluorescence test, which detects the substance in a frozen tissue section or in live cells.
  • Variations also exist within this treatment, such as radioimmunotherapy, where a radioactive dose localizes on a target cell line, delivering lethal chemical doses to the target.
  • Human immunoglobulin genes are transferred into the murine genome, after which the transgenic mouse is vaccinated against the desired antigen, leading to the production of monoclonal antibodies.
  • Schematic diagram of an antibody and antigens.

• Phagocytes

  • These are the general mechanisms used by phagocytosis to engulf and kill pathogens, however some variations can occur.
  • Monocytes ingest foreign or dangerous substances and present antigens to other cells of the immune system.
  • They express MHC class II molecules which make them the ideal antigen presenting cell.
  • Mast cells express MHC class II molecules and can participate in antigen presentation; however, the mast cell's role in antigen presentation is not very well understood.
  • Mast cells can consume and kill and process their antigens.