Normally when we hear the word immunity, we think of defense against infections, graft rejection, inflammation, etc. But, what if this defense may cause more damage than the infection itself ? In this case, the immune system shows a certain privilege through acting smarter where it deviates its mechanisms in a way to down-regulate its own damaging mechanisms. This whole process is known as Anterior Chamber-Associated Immune Deviation (ACAID).

                                                                                            image credit: http://research.opt.indiana.edu/

        

           ACAID is endogenous to specific sites such as the anterior chamber of the eye and the brain. The process is considered as saving in cases of ocular infections where the visual axis is easily deflected by inflammation leading to blindness. Also ACAID is considered beneficial in case of allografting as it downregulates the immune processes responsible for allograft rejection. The process was discovered by Medwar in 1940, when he first noticed that surprisingly certain tumors proliferate more rapidly in the anterior chamber of the eye than anywhere else. Medwar’s further studies demonstrated the role of the process in transplantation immunology.

          As an example of ACAID, upon antigenic inoculation of anterior chamber of the eye, the immune deviation presents itself as follows: Instead of Natural Killer T-cells perform certain functions attributed to T-Helper & T-Cytotoxic cells, the antigen injected into the eye APCs (Antigen Presenting Cells) that carry antigen to the spleen. These APCs activate NKT cells which in turn produce certain cytokines as TGF-ß that induce the generation of CD8+Tr cells which by production of cytokines such as TGF-ß and IL-10, can downregulate subsequent Th1-mediated DTH reactions against the same antigen.

 

 

 

 

 

 

 

 

image credit : http://www.nature.com

 

Thus, regarding the beneficial effects that can be drawn from ACAID, current research is being conducted for inducing ACAID to avoid graft and transplant rejection. ACAID can be induced by animal injection with non-ocular APCs, e.g., peritoneal exudate cells (PECs) that have been precultured with TGF-ß and antigen in vitro. Such procedure is believed to be a step forward toward the success of transplantation.

Tags: Anterior Chamber Associated Immune Deviation, APC, cytokines, graft, immunity, Medwar, ocular, T cells, Visual axis

Researchers at Yale & the University of Chicago were faced with a surprising conclusion based on their scientific experimentation on mice. Unlike the common belief that microbes are in fact “bad” & possess a harmful threat to our health, some of these bacteria prove their innocence. Mice, that were exposed to common bacteria in the normal gut flora, were protected against the development of Type I diabetes. Previous research had shown that mice, exposed to killed Mycobacterium tuberculosis, were also protected. So, this means that mice that grow in their natural habitat are better off than the ones raised in the much improved sanitary conditions of the lab.

This comes to support the hypothesis many scientists have lately adopted. They tend to believe in a directly proportional realtionship between a person’s exposure to parasites, bacteria, worms, etc.. within the surrounding evironment and his immunity. The more, the better..that is within limits of course.

This actually makes perfect sense to me. It is really obvious when you see, for example, people living in third world countries with mosquitoes hovering around and considered normal. But when they travel abroad for a while and come back, they get different sorts of allergies & rashes from those previously “harmless” mosquitoes. What parasites and microbes do for you is not all bad. Unfortunately, I had to experience this dilemma.

Source: ScienceDaily

Tags: bacteria, diabetes, flora, immunity, mice, tuberculosis, Yale

Nothing made the world highly concerned about the immune system, what are its components? How does it work?, better than the emergence of HIV in the 80s. It’s a disaster, but made us know more about the immune system.

HIV’s target is CD4 receptors, which are present mostly on T-helper cells. It has glycoprotein 120 (Why do they call it 120 any way?! Is it the UV absorption again?! Or maybe it has 120 amino acids?!) It’s on its envelope. By recognition & binding to the CD4 receptors, it kills the T-helper which result in suppression of the whole cell-mediated immunity mechanism. It’s like cutting the snack’s head off. T-helper cells are responsible for giving signals (Interleukins) to other members of the IS so they can kill the viruses. By the whole suppression idea, the IS is turned off, the human body will be opened like your friend’s heart to you, to all possible invaders of m.o.

When we talked about HIV, the professor told us:” You wanna fight HIV, young docs full of enthusiasm, block its binding site, so it can’t bind to CD4 anymore.” I remembered the wise man’s words when I surveyed this article “Antibodies to the CD4-binding site of HIV-1 gp120 suppress gp120-specific CD4 T cell response while enhancing antibody response” about studying the effect of monoclonal anti-bodies against only the highly conserved part of the gp 120 (The binding site). We know that after exposure to HIV, the IS produces Ab against gp 120 to neutralize it, but the HIV tends to change the gp 120, so it can’t fit with the neutralizing Ab, moving on to more destruction. With those highly specific binders, I thought it’ll be the ultimate success.

Unfortunately, the research group made in vivo (in mice) & in vitro studies using the normal virus & another recombinant one with no CD4bs. They called it CD4bs+ Env & CD4bs- Env (Like with or without cheese). They found that the Anti-CD4bs mAb have high neutralizing activity, they raised the Ab titer (mainly IgG but not IgM). But they hinder the ability of the proteolytic enzymes/ the degrading mechanisms of phagocytes/ T-helper response to the envelope Ag/ the ability of Antigen presenting cells & MHC II to present the Ag. Let’s think about it…. They can only present the virus’s Ag, not the gp120/anti-CD4bs complexes. This is too long in writing, how about presenting? Just kidding, It’s about that the Ag is already covered, so it’s useless to be presented.

This is so awful, even the last approach to bind HIV didn’t work. What are the researchers gonna do? What’s the next move? We’ll find out soon.

Image credits:
Anatomy of AIDS virus: http://www.roshanpakistan.com/

Tags: HIV, immunity