The progress of infection can be summarized as a pathogen going through a series of steps:
Progress of Infection
The first three steps, ‘Portal of Entry’, through ‘Surviving Host Defences’ encapsulates all of the immune response. Some key events in the immunity are inflammation and the innate response, antigen processing and presentation, adaptive immunity and memory.
Several of these topics I’ve described here before including an outline of the development of lymphocytes (B and T Cells – sorry NK Cells) in an article here. The activation of B cells here, immunological memory in several places including here. Some of these topics I have yet to address (e.g. a good discussion of inflammation), and others (e.g. antigen processing and presentation) have been buried in other posts (see my lymphocyte development, B cell Activation or this post on Transmissible tumors).
This time, I thought I’d prevent a sketch of the humoral immune response and how this illustrates, like Mendel’s traits in a dihybrid cross, that each immune reaction is ‘independent’. A typical immune response is outlined below showing the development of antibodies following a primary response and then a more rapid and robust secondary response. If we want to compare this response to Mendel’s monohybrid cross, we can see the same response for antigen after antigen just as Mendel saw the same pattern of inheritance for any single trait he observed.
Response to a single antigen
Before we had the ability to ‘see’ this response on a molecular level, we could see its effects on people. Those who previously contracted a disease did not contract that same disease a second time. This immunological memory is the basis for vaccination, where we separate the disease-causing agent from the immunological memory-inducing agent for any given pathogen and then use only the later to vaccinate.
However, Mendel continued to examine traits and how they were inherited individually (i.e. the inheritance of one trait had no bearing on the inheritance of another). He called this independent assortment. Is there a similar experiment that can be done to show ‘independent immunity’?
Response to two antigens independently
Borrowing a figure from Abul Abbas’ text on Cellular and Molecular Immunology, we see that the response to one antigen has no bearing on the body’s response to a second, unique antigen. Like Mendel’s dihybrid crosses, the response to two antigens is, indeed, independent. (Note, the serum titer in this graph falls much lower than that in the first illustration – this second curve is more representative for real responses. Regardless, the antibody titer for a secondary response remains higher than that of the primary response.)
The primary response to antigen B is identical to the primary response to antigen A. The secondary response to antigen A results in a more rapid, robust response and eventually levels out to a higher steady-state of serum antibody.
To extend the analogy just a bit further, one might ask if there is such a thing in immunology that parallels the ‘linked genes’ of inheritance?
In fact, there is. The world’s first vaccine, developed by Edward Jenner in 1796, involved the use of cowpox pus to induce protective immunity to both cowpox and the related virus, smallpox. This seems to violate our rule of independent immunity, just as the Morgan lab found that genes for body color and wing formation were found to be inherited together in fruit flies, thus violating the Law of Independent Assortment (of alleles).
In the case of cowpox and smallpox, this comes from the similarity in antigens made by each of these viruses. That is, the cowpox antigens the body generates an immune response against are NOT (ENTIRELY) UNIQUE from antigens found in smallpox. When the vaccinated individual is challenged with smallpox, antibodies created to defend against a secondary challenge with cowpox react to the smallpox antigens as if this was a secondary response directed against smallpox.
Primary reaction to Cowpox antigen (A) is used for vaccination. Secondary reaction to Smallpox antigen (A’) upon challenge.