Antigens and Immunogenicity

Onto another post!

Describe the properties of an immunogen vs. an antigen

Let's start this off with some definitions!

• Immnogen: A substance that can induce an immune response. All immunogens are antigens.
• Antigen: A molecule that can react with a specific antibody and/or can be degraded into peptides recognisable by T-cells. Not always immunogenic.
• Epitope: The portion(s) of an antigen that can be bound by an antibody or a T-cell receptor. You may also think of these as the immunologically-reactive regions of an antigen.
• Valency: The number of things that an antigen or an antibody can bind at the same time. Antibody valency is the number of antigens that an antibody can bind (so your typical Y-shaped antibody will have a valency of 2), while antigen valency is the number of molecules that an antigen can bind to.

A quick note about stuff that's recognised by T-cells: while antibodies will recognise antigens in their native form (i.e. what they usually look like), T-cells are really fussy and will only recognise antigens once they've been processed and presented to them on MHC (major histocompatibility complex) molecules. Kinda like toddlers who will only eat vegetables if it's been disguised to look like junk food and is zooming into their mouth like an aeroplane.

Describe the factors contributing to immunogenicity

Immunogenicity is the ability of an immunogen to stimulate an immune response. Immunodominant epitopes are more immunogenic (i.e. induce a stronger immune response).

There are several different factors contributing to differences in immunogenicity:

• Foreignness: The more "foreign" a molecule is, the more immunogenic it is. Isogenic/autologous/self molecules are obviously the least immunogenic, followed by syngeneic (twins), allogeneic (different individual of the same species) and finally xenogeneic (someone of a different species).
• Molecular size: Generally, larger immunogens are better immunogens.
• Haptens: As mentioned in an earlier post, these are small molecules that are antigenic, but not immunogenic unless it's stuck to something else.
• Adjuvants: Adjuvants are substances that can enhance the immunogenicity of antigens despite not being immunogenic themselves. These are sometimes used in vaccines, such as Gardasil (the vaccine against HPV).
• Host biological system: In order to produce an immune response, the host must actually be capable of producing an immune response, i.e. not immunocompromised in any way.

Another point to make is that different cell populations might be involved depending on the route of exposure to an antigen. If exposure occurs subcutaneously or intramuscularly, the main response will be in the lymph nodes. If exposure is intravenous, there will be a general (i.e. systemic response), especially in the spleen. Finally, if exposure occurs intranasally or orally, the MALT of the mucosal membranes of these organs are likely to be involved.

Describe B-cell and T-cell receptors

B-cell receptors are essentially just membrane-bound antibodies. (Of course, antibodies can also exist in secreted form). B-cell receptors/antibodies, as I mentioned earlier, will recognise epitopes on antigens in their native form. An epitope can be made up of sequential amino acids, or discontinuous amino acids that are in the same area after protein folding.

It's important to note that antigen-antibody binding is non-covalent. That is, all of the bonds between antibody and antigen are hydrogen bonds, Van der Waals forces, and so on (see this early post for more info). For this to work, it is important that the antibody binding site has a complementary shape to the epitope that it's going to bind- the so-called "lock-and-key fit." Because of this, antibodies will show greater specificity for some antigens than others.

There isn't too much that we need to know about T-cell receptors at this stage, other than that they can only bind antigens that have been processed and presented to them.