MadSci Network: Immunology
Query:

Re: Why does our body not mount an immune response against our own antbodies.

Date: Sun Oct 22 10:50:47 2006
Posted By: Cenk Sumen, Post-doc/Fellow, Immunology, Memorial Sloan-Kettering Cancer Center
Area of science: Immunology
ID: 1138688592.Im
Message:

The process that is invoked here (anti-antibody antibodies) is referred to as "anti-idiotype networks". This is an old idea that has been floating around since the 50s but has gone in and out of fashion through the intervening decades. The theoretical underpinnings contributed to Niels Jerne's sharing the Nobel prize and prominent immunologists such as Eli Sercarz have made some headway, but data has been scarce as to whether these networks actually exist in normal immune systems and labs have regularly abandoned the field for greener pastures.

So, currently it is not clearly understood why these networks don't form as often as predicted theoretically (except in highly engineered model mouse systems, for example). In order to make antibodies, B cells almost always require "licensing" from helper (CD4+) T cells, and perhaps this "help" is in short supply when it comes to antibodies directed against self-antigens. The "idiotypic determinants" of an antibody, namely small regions of the polymorphic variable regions at the tips of the "Y" shaped molecules, are the only really "novel" parts of the molecules to the immune system. The bulk of the antibody are constant regions which are conserved throughout the species and to which B cells would be tolerized as with any self-antigen. Lastly, I need to point out that just having a foreign protein in the body does not guarantee production of antibodies against that antigen. In what used to be termed "the immunologists' dirty little secret", stimulatory substances collectively referred to as "adjuvants" need to be included with any foreign protein in order to elicit a potent antibody response; for example in human vaccines aluminium compounds are often included, and lipopolysaccharides (LPS) such as those found in Freund's adjuvant are currently used in almost all mouse immunology experiments. The reason for this "second-signal" requirement in addition to the primary signal directed to the specific protein antigen, sometimes referred to as the "danger signal" championed by immunologist Polly Matzinger, appears to rest with pattern-recognition receptors called "Toll-like receptors (TLRs)" originally discovered in flies as a key determinant for resisting invasion by fungi and other microorganisms. TLRs are one of the most significant recent discoveries in biology and in my opinion warrant the next Nobel in Physiology or Medicine. Unfortunately for science, the Yale professor famed for directing research into the discovery of these receptors, the superb teacher Charlie Janeway, has passed away, but his acolyte Ruslan Medzhitov at Yale (as well as Shizuo Akira from Osaka U.) would clearly be worthy of the prize.

In summary, anti-idiotype networks may exist in special experimental situations and perhaps in disease states such as high tumor burden, but it is uncommon to find antibodies directed to self in healthy mammals.


Current Queue | Current Queue for Immunology | Immunology archives

Try the links in the MadSci Library for more information on Immunology.



MadSci Home | Information | Search | Random Knowledge Generator | MadSci Archives | Mad Library | MAD Labs | MAD FAQs | Ask a ? | Join Us! | Help Support MadSci


MadSci Network, webadmin@madsci.org
© 1995-2006. All rights reserved.