Antigens, Antibodies, and the Adaptive Immune Responce

• In response to pathogens, vertebrate immune systems use two interconnected systems

  • Innate immunity – Non-specific. Remove/control infection
  • Adaptive immunity
• There are physical barriers of the body which are the first line of defence from microorganisms. (These include the skin and mucous membranes.) Once the barriers have been breached then an immune response is initiated.
• The innate immune system is the first line of defence and is effective at eliminating or at least controlling the spread of the infection.
• The innate immune system response time is minutes to hours of the innate immune response in comparison to days for the adaptive immune response because the innate immune system is non-specific and recognises common chemical structures of many pathogens.
• Adaptive immunity takes longer to develop (typically 5-6 days) and that is because it requires the innate immune system to encounter the antigen first in order to develop a fully effective adaptive immune response.

  It is also because fewer cells have a receptor which recognises the specific antigen – B & T cell receptor.
• It is the adaptive immune response which is key in vaccination but still needs the innate immune response to activate it.
• All cellular elements of the blood come from HSC (pluripotent hematopoietic stem cells within the bone marrow). These cells divide to produce two types of stem cells in a process called haematopoiesis:

  • Common lymphoid progenitor (gives rise to the lymphoid cells e.g. B cell, T cell etc.)
  • Common myeloid progenitor (gives rise to the myeloid cells e.g. granulocytes and erythrocytes).
• Bone marrow is the major site for haematopoeisis in humans. While T and B cells have antigen receptors other leukocytes do not - Innate lymphoid cells (ILC) and NK cells are not antigen specific.
• The rearranging genes that encode the antigen receptors of lymphocytes produce vast repertoires of B cells (B) and T cells (T) in which each cell expresses a single receptor and very few cells express identical receptors.
• Because of the breadth of the repertoires, an adaptive immune response can be made to any pathogen. The drawback is that only a small number of cells will be able to respond to a given pathogen.
• Upon infection these few cells are triggered to divide, forming expanded clones of pathogen-specific B cells and T cells. These differentiate into large numbers of effector T cells and B cells that work together to eliminate the infection
• Substances that can be recognized by the immunoglobulin receptor of B-cells or by the T-cell receptor when complexed with MHC are called antigens
• A substance that induces a specific immune response is called an immunogen
• Although a substance that induces a specific immune response is normally called an antigen it is more appropriately called an immunogen
• Antigenicity is the ability to combine with antibodies or cell surface receptors.
• Clearly all molecules that are immunogenic are also antigenic but this is not true of the reverse as antigenicity does not necessarily mean immunogenicity e.g.
• Haptens are small molecules that are incapable of initiating an immune response on their own but can be linked to other molecules.
• To elicit an immune response the molecule must be recognized as foreign or non-self. For example, BSA (bovine serum antibody) when injected into a cow will not cause an immune response but it will in a rabbit.
• Collagen, which is well conserved through evolution is a poor immunogen.
• Molecular size also matters when determining immunogenicity. Generally, the larger the molecule the better the response. Small peptides generally need to be coupled to a carrier - generally, the more complex the molecule, the better the immunogenicity.
• A homopolmer is all the same aa is usually a poor immunogen regardless of size.
• Different individual animals of the same species will have a different response to the same antigen. This depends on several factors including B & T cell receptor genes and genes encoding other immune regulators. MHC genes products have been shown to play a key role in determining the extent of response to an immunogen.
• Low doses may fail to activate the immune response because it does not activate sufficient lymphocytes or because it can induce a state of tolerance. Interestingly, a single high dose can induce tolerance.
• A single dose gives a poor response whereas a repeated administration (boosters) work better. This increases the clonal proliferation of B and T cells specific for the immunogen.
• Immunogens can be ‘given’ IV, ID, SC, IM, IP and this will influence which organs and populations will be involved.
• To protect against infection, the immune system must recognize bacteria, viruses, parasites and so on as immunogens.

  As well as proteins, polysaccharides can also act as immunogens and to a much lesser extent lipids.
• immune cells don’t even recognise the entire molecule, only discrete sites called EPITOPES or ANTIGENIC DETERMINANTS.
• T- and B- cells seem to recognise different epitopes on the same molecule. The recognition of antigens by T- and B-cells is different.
• B lymphocytes have immunoglobulin on their surface that recognize epitopes directly on antigens. - Different B Lymphocytes are generated with different surface immunoglobulins, each specific for a unique epitope.
• In a series of analysed proteins, the major antigenic determinants were located in the most mobile/flexible regions. It was suggested that this mobility maximises complementarity with the antibody’s binding site

  (flexibility analogous to conformational change) Allowing binding that might only happen ineffectively if it were rigid.
• binding to a flexible epitope is generally of lower affinity than binding to a rigid epitope.
• The subset that is recognised by a particular species (or individual) varies

  i.e. some epitopes are immunogenic, others are not. Some are more immunogenic than the rest: these are known as immunodominant.
• Multivalent antigen has more than one epitope or more than one copy of the same epitope.
• There can be different epitopes represented only once on the protein surface and these can be bound with antibodies of different specificity.
• There can also be a multivalent antigen that has the same epitope repeated across the protein surface - The antibodies have identical antigenic specificity.
• Linear epitope is sequential and composed of a single segment of polypeptide chain.
• Discontinuous epitope is conformational and composed of amino acids from different parts of the polypeptide chain that have been brought together by protein folding.
• Different types of epitopes behave differently when a protein is denatured, reduced or fragmented
• Reduction of disulphide bonds in conformational HEL epitope will cause the

  non-sequential epitope to be lost and the Ab to native HEL will become unable to bind to reduced HEL
• Most Abs against globular proteins bind only when in their native conformation