I am thinking of why some patients do not have natural immunity after exposure to the A-B toxin of diphthria. I think the A-B exotoxin is the key factor causing this disease and should trigger memory cells to form.
DT has both local and systemic effects. Locally, its action on epithelial cells leads to necrosis and inflammation, forming a pseudomembrane composed of a coagulum of fibrin, leukocytes and cellular debris. Absorption and circulation of DT allow binding throughout the body. Local effects produce pseudomembrane.
The major impact of transduction in pathogens is the introduction and stable inheritance of virulence genes such as those coding for toxins. C diphtheriae is lysogenic with a phage containing the diphtheria toxin gene. Diphtheria toxin is produced by C diphtheriae only when infected with a bacteriophage that integrates the toxin-encoding genetic elements into the bacteria
The toxicity for intact cells depends on toxin binding and uptake. In other words, the net effect of the toxin depends on the function of the target protein and the function of the cell. B subunit binds to receptors that regulate cell growth and differentiation, thus exploiting a normal cell function. A subunit inhibits protein synthesis. B subunit binding determines cell susceptibility. Absorption and circulation of DT allow binding throughout the body. I think this uptake does not occur sufficiently with patients without natural immunity stimulation.
I think the reason for no natural immunity for some patients after toxin exposure is that the host does not stimulate enough adaptive immunity and no memory cells are built. Again, this is because the bacteria has little invasive capacity. Diphtheria is due to the local and systemic effects of DT with potent cytotoxic features. The uptake of the toxin varies also among some patients. So other patients have probably more local effects. This would explain partially why the adaptive immunity is not triggered.
Diphtheria toxin is antigenic itself. So it can stimulate the production of protective antitoxin antibodies during natural infection. In those patients without development of natural immunity, A subunit fails to bind EF-2, probably.
One reason is that the toxin does not get into bloodstream in 6-8% cases, and so natural immunity is developed. So there is too low effective dose of diphtheria for some patients to invade the epithelium and trigger the adaptive immune response and create memory cells.
Sources: Murray Microbiology, Sherris Microbiology and Jawetz Microbiology.
Why do 6-8% of diphtheria patients not develop natural immunity after being infected?