Date:   12/19/2008 9:24:52 AM ( 17 y ago)
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URL:   https://www.curezone.org/forums/fm.asp?i=1319198

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“What people learn in textbooks often is in contradiction with the facts.”

This may be true. I suppose it depends on the textbook. I recommended Janeway’s Immunobiology because it is relatively basic (one can understand some of it with little scientific preparation, and most of it with just a basic understanding of biochemistry and genetics) and yet thorough, and it gives references to the articles on which each section is based (I also recommended it because it is available online for free. If you’re willing to spend a bit of money, I can recommend a more advanced text). I agree that a solid review of the literature will give a more complete and complex account on the functions of CD4 cells, but without a strong foundation in basic immunology (the sort of survey that one can only really get from a textbook or an introductory course), one is liable to either not understand the experiments, or misinterpret the results. A good textbook will give you a good foundation to understand the kinds of experiments conducted by immunologists. Most importantly, a good textbook includes some primary data and gives references to primary sources, so that you can look up any experiment discussed and make sure that the authors’ conclusions are in line with the known data.

“I have been working with AIDS patients since AIDS appeared. We used to see people all the time with zero to near zero CD4 counts that showed no ill effects.”

I find this hard to believe. I have been infected with HIV for more than 20 years, and prior to the advent of antiviral therapy, once a person reached zero or single-digit T-cell counts, they were good as dead (although the time to death varied between different individuals). Over time, the medications that were developed to treat and prevent certain opportunistic infections improved the prognoses of some, but not a single person I know was able to live for years with zero T-cells without contracting severe opportunistic infections and, in every case that I can think of, dying.

Just out of curiosity, in what capacity was your work with AIDS patients?


“Why? Because there are numerous components to the immune system, and CD4s do not govern all of them.”

Yes, although CD4+ T-cells do have effects on just about every aspect of the immune system.

“ The immune system is comprised of various white blood cells, various cytokines (some of which are also generated by B cells), antibodies, monokines, peroxide, SOD, adrenal steroids, the intestinal flora, etc.”

That’s an, uh, interesting list of the components of the immune system (this is where some formal knowledge from a textbook might help).

“To think that CD4s are going to govern the immune system is like saying that removing one kidney is going to kill the person because they will no longer be able to remove water and waste. IN such as case the other kidney will enlarge and the body will continue to remove water and waste through sweating, stool, the other kidney, etc. The body has redundancies built in just in case one system fails.”

Nope: saying a person can live healthily without CD4 T-cells is like saying they can live healthily without either kidney. You can remove half of a healthy person’s CD4 T-cells and for the most part, they will be fine. Remove all of them and it’s like trying to live without either kidney. Analogies only work if they actually fit the scenario.

You appear to be starting from the (unproven) assumption that the immune system is so full of redundancies that you can knock out any cell type, cytokine, or effector function and that the rest of the immune system is capable of picking up the slack. The best way to know whether this is true is to look for the proof in the pudding: what happens to people when they lose particular immune functions?
In some cases, not much! For example, deficiencies in certain complement proteins lead to few, if any, negative effects.
In other cases, the rest of the immune system CAN’T compensate and, once again, the proof is in the pudding:
In the case of CD4 T-cells, look at the people without CD4 T-cells in the periphery due to MHC-II deficiency (I notice that you did not respond to this article, which was probably the most important part of my post) – they are very sick and, without treatment, die young. The other components of the immune system do NOT jump in and cause their immune systems to function at an adequate level. The same is true with many other immunodeficiencies – e.g. people with certain deficiencies in phagocyte number or function are prone to infection with pyogenic bacteria. The rest of their immune system does not compensate to sufficiently fight off these bacteria.

The question is not: can a healthy person have a less-than-optimal immune system? The answer to that would be: Of course! The question is: are CD4 cells so necessary to proper immune function that people lacking them are unable to fight common pathogens. And the answer to this is also, of course!

All it takes to know this is to look at people with genetic defects leading to an absence of CD4 cells outside the thymus. Or look at CD4 KOs, or studies where CD4 cells have been depleted with mAbs. (to study the effects of pure CD4 deficiency, it is usually better to look at these populations than at people with AIDS, because HIV wreaks direct havoc on parts of the immune system other than CD4+ T-cells)

I’m not sure how the article you cited was supposed to support your case. It’s well known that CTLs can be activated (at least in a primary response) against many pathogens in a CD4-independent manner, and that in many cases, this is sufficient to beat off the bug.

However, there are just too many common pathogens that absolutely require CD4 cells for an effective immune response – when it comes to these pathogens, no attempts at compensation from other cells are sufficient. Just a few examples:

Just a few examples of infections where CD4 cells are required:

Tuberculosis: http://www.ncbi.nlm.nih.gov/pubmed/11739519


M. avium: http://iai.asm.org/cgi/content/abstract/73/5/2621


PCP: http://jem.rupress.org/cgi/content/abstract/172/3/937


Cryptococcus: http://jem.rupress.org/cgi/content/abstract/173/4/793



Some of the references that YOU cited me to (21, 37-40) from that article really don’t help your case:

Reference 27: “CD4+ T cells are required to sustain CD8+ cytotoxic T-cell responses during chronic viral infection”.
“We show that CD4+ T cells are not necessary for resolving an acute LCMV infection. CD4+ T-cell-depleted mice were capable of generating an LCMV-specific CD8+ cytotoxic T-lymphocyte (CTL) response and eliminated virus with kinetics similar to those for control mice. The CD8+ CTL response was critical for resolving this infection, since beta 2-microglobulin knockout (CD8-deficient) mice were unable to control the LCMV Armstrong infection and became persistently infected. In striking contrast to the acute infection, even a transient depletion of CD4+ T cells profoundly affected the outcome of infection with the macrophage- and lymphocyte-tropic LCMV variants. Adult mice given a single injection of anti-CD4 monoclonal antibody (GK1.5) at the time of virus challenge became lifelong carriers with high levels of virus in most tissues. Unmanipulated adult mice infected with the different LCMV variants contained virus for prolonged periods (> 3 months) but eventually eliminated infection from most tissues, and all of these mice had LCMV-specific CD8+ CTL responses. Although the level of CTL activity was quite low, it was consistently present in all of the chronically infected mice that eventually resolved the infection. These results clearly show that even in the presence of an overwhelming viral infection of the immune system, CD8+ CTL can remain active for long periods and eventually resolve and/or keep the virus infection in check. In contrast, LCMV-specific CTL responses were completely lost in chronically infected CD4-depleted mice. Taken together, these results show that CD4+ T cells are dispensable for short-term acute infection in which CD8+ CTL activity does not need to be sustained for more than 2 weeks. However, under conditions of chronic infection, in which CD8+ CTLs take several months or longer to clear the infection, CD4+ T-cell function is critical. Thus, CD4+ T cells play an important role in sustaining virus-specific CD8+ CTL during chronic LCMV infection.

This not only shows a case where CD4+ T-cells are necessary, but also disproves your belief that no type of immune cell is truly necessary to resolving a certain type of infection, because others will compensate. When they knocked out B2m (necessary for the expression of MHC-I on cell surfaces, and therefore CD8 development), the mice couldn’t even clear the acute infection!

Two of the other references were all about how CD4 cells were necessary for CD8 memory! Again, it doesn’t seem that any of this really supports your case.

"CD8+ T cells can respond to antigen in the absence of CD4+ T cell help (21, 37–40)."

Again, undeniable. I’m unsure why you felt the need to point it out to me.

"Our data support the previous studies showing that CD8 cells can generate a strong response in the absence of CD4+ T cells, but we have determined that the CD4 molecule is required for this to occur optimally."


“The cells do not have to function optimally to do their job well enough.”

The fact that some cells, in some situations, can still do their jobs well enough without optimal function does not lead to the conclusion that any non-optimal response is sufficient. The immune responses of individuals without CD4 cells are NOT sufficient against many common and ubiquitous pathogens.

“In fact many AIDS patients, around 30%, have been found to be HIV free.”

Can you cite some evidence of this? I know of none.

“Apparently there is something else causing the immune collapse.”

The data on individuals with genetic CD4 deficiencies should show you that CD4 depletion alone is capable of causing overwhelming opportunistic infection and inevitable death.

“Unfortunately they have not looked beyond HIV because too many ignorant scientists still falsely believe presence of means cause of.”

What are you suggesting they look for?


I actually have a whole bunch of questions for you because I'm really not clear on where you're coming from, but they'll have to wait for later. Also, my only free internet time right now is right when I'm at my most sleepy, so I apologize if this shows.
 

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