Tag Archives: vaccination

Polio Does Not Go Gentle into that Good Night

While, as recently as 1988, there were as many as 350,000 cases of Polio per year, there were only 417 cases of polio recognized in 2013. At that time Polio was endemic in just three countries.

Old age … burn[s] and rave[s] at close of day.

So far this year there has been nearly 3 times the global number of cases of Polio as there was last year at this time.


Though wise men at their end know dark is right

It’s not often that scientists will rally around the idea of intentionally pushing an organism to extinction, but this is exactly what disease eradication is – and it is the ultimate goal of all vaccination programs. The eradication of Smallpox has been hailed as one of the great successes in modern medicine. In fact, the philosophical arguments against making eradication the goal are not meant to subvert eradication, but actually to prevent complacence in monitoring programs and to avoid wasting money on tracking down ‘one last case’ of disease.

This said, a goal of the World Health Organization does have an endgame strategy for polio and plans on having it eradicated by 2018.

Rage, rage against the dying of the light.

Despite our best efforts, The Polio Eradication Initiative, in its May 2014 Special Alert, reports, “WHO Director-General Margaret Chan declared the recent international spread of wild poliovirus a ‘public health emergency of international concern,’ and issued Temporary Recommendations under the International Health Regulations (2005) to prevent further spread of the disease as the high season approaches.” This declaration has the weight of international law for the 194 signee countries.

Curse, bless, me now with your fierce tears, I pray.

Obstacles to final eradication remain largely human and political.’s Hayes Brown reports that, “Pakistan has been the epicenter of attacks on vaccination programs, following the revelation that the CIA in 2010 used a fake vaccination campaign to hide their intelligence gathering efforts to locate Osama bin Laden. Since then, the Pakistani Taliban have now come to see all health workers as suspect and prime for targeting”

War, especially civil war, has led to countries such as Somalia, Pakistan and The Gaza Strip of Israel becoming reservoirs for disease and expanding the number of countries with wild polio.

ImageNevertheless, Even as polio does Rage against our efforts, it is still much reduced and there is no reason to give up hope that a combination of political and medical interventions will be sufficient to add polio to that short list of diseases that are ‘forever gone.’

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Posted by on May 6, 2014 in Uncategorized


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Immunology’s ‘dihybrid cross’ : Antibody response to different antigens

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.

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Posted by on November 25, 2013 in Uncategorized


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B Cell Activation (The Basics)

B cells, along with T cells, are lymphocytes that bear antigen receptors that have been randomized for their binding specificity during development (see my earlier post). On the B Cell, the antigen receptor is aptly named: B Cell Receptor, or more commonly, BCR.

Like the T cell Receptor (TCR) on T Cells, the BCR is a transmembrane protein expressed on the plasma membrane, where it can bind by antigen. Unlike the TCR, B Cells are not ‘presented’ antigen by other cells in the context of an MHC molecule. Instead, B Cells ‘see’ antigens in their native state – imagine these as soluble toxins or cell-surface antigens on bacteria of viruses.

APC : T Cell Interaction   vs  Native Antigen : B Cell


Another difference between T Cell and B Cell activation is that T Cells become activated, but do not change their expression of their antigen receptor. B Cells, on the other hand, may react in one of several different ways.  In general terms, this means differentiation into either Memory Cells or Plasma Cells.

Memory B Cells proliferate, but retain their membrane-bound receptors. This makes sense because the purpose of these cells is to lie in wait until antigen is seen again, so they need their receptors to ‘see’ it.

c18Plasma cells lose their membrane-bound receptors, but continue to express the same molecule in a soluble form called Antibody. In fact, they grow in size and fill with ER and Golgi Apparatus to handle the extreme output of protein that they begin producing (~2000 molecules / sec according  to  Molecular Biology of the Cell. 4th edition. Alberts B, Johnson A, Lewis J, et al. New York: Garland Science; 2002. ).

ImageAntibody comes in a number of varieties, but all share a similar core structure as the one pictured to the right. It consists to two heavy chains and two light chains, creating two unique binding sites for antigen.

Events following B Cell Activation

Once cells become activated, they may either immediately become short-lived plasma cells (SLPCs) that secrete antibody identical to the BCR for a short time and then die off, or they may enter into Germinal Center (GC) Reactions. In the GC, B cells get T Cell help and compete for antigen in a poorly understood manner whilst undergoing hypermutation of the BCR’s antigen-binding site.  This results in BCR / Antibodies with higher affinity (greater binding ability) for antigen that may then differentiate into either Long-Lived Plasma Cells (LLPCs) of memory cells. These several differentiation paths can be seen in the illustration below.


To Summarize:

1. B Cells are activated as a result of crosslinking BCRs by native antigen

2. B cells do require help from T Cells to enter germinal center reactions and produce LLPCs and memory cells (although getting help was not discussed here)

3. B cells become activated and either start producing antibody right away as SLPCs or enter genrminal center reactions.

4. Once in a germinal center, B cells undergo hypermutation of the antigen-binding section of  their BCR/Antibody.

5. Following the GC reaction, B cells bearing high-affinity BCR/antibody will differentiate into LLPCs or memory cells.


Posted by on May 12, 2013 in Uncategorized


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