Expert: Florence M Rollwagen - 5/24/2009

Question
QUESTION: I would like a detailed description, including sources(preferably Internet or possibly literature), of how the immune system fights Cholera. I would like it to be described in each "line of defence" also (first, second and third)

Thank you for your help, please respond A.S.A.P.

ANSWER: Hi Jack:  Thanks for your question.

When you ask for detailed responses and scholarly articles from the literature you are asking for highly technical information.  Since I don’t know your level of education, I’ll give you what you asked for, but you can write back for a more detailed explanation.

Vibrio cholerae is a gram negative curved bacterium that secretes a toxin.  The toxin is responsible for the clinical effects of cholera (diarrhea and loss of electrolytes).  The disease can kill within a day or so, mostly from electrolyte imbalance, which can be corrected with oral rehydration therapy.

For most infectious diseases, the first response is the “innate immune response”.  This is a nonspecific response to any pathogen, usually including the signs of inflammation (heat, redness, swelling, pain).  Along with this response comes the secretion of natural defense mediators, such as the prostaglandins, arachadonic acid metabolites, etc.  This is a general response and is not specific for any pathogen.  That’s why we call it the innate response.  Here is a link for natural responses in the intestine:
http://www.medscape.com/viewarticle/551795

The acquired immune response is later than the innate response and involves the production of secretory IgA in the intestine.  The antibody binds to the bacteria, agglutinating them and making them more attractive to macrophages which ingest them.  The antibodies also fix complement, which destroys the bacteria by inserting holes in the cell membrane.

Here is a paper dealing with the immune response to cholera in the presence of concomitant helminth infection.:
http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000403

An important part of the immune response to cholera lies in the production of antibodies against the toxin (CT).  Here is a paper which looks at this response:
http://iai.asm.org/cgi/reprint/55/9/1997.pdf

You also should read something on the mucosal immune response, since V cholerae is an intestinal bacteria:
http://www.brown.edu/Courses/Bio_160/handouts/feb23.pdf
http://www.medscape.com/viewarticle/414702_1


Hope this helps, please write back if you have more questions.

FM Rollwagen, PhD



---------- FOLLOW-UP ----------

QUESTION: Thank you, for your quick, precise and well-sourced response. This is a big help and very informative.

I was wondering if you could go into more detail on the topic of the "second and third lines of defence" against Cholera, the action of phagocytes and natural killer cells on the bacteria, as well as B and T cells. This is an area I am a little hazy on. I'm not sure whether they would be involved in this particular immune response.

What I really would like is a sequential description of detection, signal transferrence, response etc. for the second AND third lines of defence, this would be utterly fantastic.

Now I know how good your help is, I await it with even more anticipation. Thank you again and I hope I am not asking too much of you. Again please respond A.S.A.P.

Jack.

Answer
Hi again, Jack:  I'm not sure what you mean by "second and third" lines of defense.  Phagocytes and NK cells are part of the innate immune response, since they are not antigen specific.  The acquired immune response consists of T-cells, B-cells, macrophages and their secretions.  Macrophages form a link between the innate and acquired immune responses.  In terms of kinetics, as I said before, the innate immune system responds immediately with the signs of inflammation.  After that, if the subject is immune, then the memory recall response is initiated and within a couple of days the specific immune response is activated.  If the subject is immunologically naive, then it can take up to 2 weeks for the specific (acquired) immune response to reach a peak.

Immunologists usually classify the first line of defense as the unbroken skin and mucosa.  These organs provide an excellent barrier to invasion by bacteria and viruses.

Perhaps you're thinking of the second line as the innate response and the third line of defense would be the antibody and killer T cells (not NK cells).

Is this more or less what you're thinking?

FMR