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Momtezuma Tuatara
03-04-09, 03:23 PM
As many of you know, I've long written about the affect that vaccines have on two of the arms of the immune system, and have long expressed concern that vaccinated children appear to have a "paralysed" Th1 arm.

A recent animal experiment bears this out:

http://www.eurekalert.org/pub_releases/2009-04/uom-nee040109.php


Public release date: 1-Apr-2009
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Contact: Christian Basi
BasiC@missouri.edu (BasiC@missouri.edu)
573-882-4430
University of Missouri-Columbia (http://www.missouri.edu/)

New evidence explains poor infant immune response to certain vaccines, says MU researcher



COLUMBIA, Mo. ¬— For years, researchers and physicians have known that infants' immune systems do not respond well to certain vaccines, thus the need for additional boosters as children develop. Now, in a new study from the University of Missouri, one researcher has found an explanation for that poor response. In the study, the MU scientist found evidence that the immune systems of newborns might require some time after birth to mature to a point where the benefits of vaccines can be fully realized.

Habib Zaghouani, a professor of molecular microbiology and immunology and child health at the MU School of Medicine, recently found that a slowly maturing component of the immune system might explain why newborns contract infections easily. In his work, Zaghouani studied newborn mice and how their immune systems reacted when they were repeatedly exposed to an antigen that simulates a virus.

Zaghouani found that while the antigen would prompt a response of the immune system, it was not the expected response. In the adult immune system, two major types of cells, known as T-helper 1 (Th-1) and T-helper 2 (Th-2) cells, are instrumental in the development of an effective immune response. Typically, Th-1 cells respond when dangerous microbes enter the body. The Th-1 cells then work to help destroy the foreign microbes. When an antigen from a vaccine enters a body with a mature immune system, Th-1 cells respond and, after destroying the invader, the Th-1 cells "remember" how to fight the antigen for future battles. Th-2 cells typically develop when the body is exposed to allergens. The responses of Th-2 cells are usually strong and manifest in the form of allergic reactions.

When Zaghouani gave the newborn mice an antigen shortly after birth, he noticed the presence of both Th-1 and Th-2 cells. However, when he gave the antigen a second time, he noticed an abundance of Th-2 cells that responded to the antigen instead of Th-1 cells. Zaghouani was surprised to notice that the Th-2 cells worked to destroy the small contingent of Th-1 cells that had responded to the antigen given at birth.

"Perhaps we should test vaccines at a very early age in animals to establish a regimen with the most effectiveness," Zaghouani said.

When a baby first gets an infection, the immature immune system responds with both types of T cells. Unfortunately, Th-1 cells have an unusual receptor that binds to a specific hormone, which is deadly to the Th-1 cells. Ironically, this particular hormone is produced by the Th-2 cells. This results in an overabundance of Th-2 cells during the first few days of life.

"We found that after six days, the immune systems in the mice matured enough to stop the death of the Th-1 cells," Zaghouani said. "After those initial days, the immune system is producing Th-1 cells with diminished hormonal receptors, thus surviving the effect of the compound that the Th-2 cells make."


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Zaghouani's publication, "Delayed maturation of an IL-12-producing dendritic cell subset explains the early Th2 bias in neonatal immunity," was published in The Journal of Experimental Medicine.

NOTE: To hear an interview with Zaghouani about this study, please visit: http://jem.rupress.org/biobytes/biobytes_Sept_22_2008_gen.shtml (http://jem.rupress.org/biobytes/biobytes_Sept_22_2008_gen.shtml) and click on the "listen now" link near the bottom of the page.

Now, before someone jumps up and down, and says, but wouldn't we know this already? Dont' they test vaccines in animals?

Yes, and No.

They have not yet worked out an animal model, which can be extrapolated to humans. http://www.fda.gov/cber/minutes/tox120202.htm
When they do, they first have to be sure that the immune system works, the same and can be applied to humans, then they have to work out which age in the animal equates to what age in humans.

As yet, that has not been done, so all we are left with, is guesses.

deesalie
04-04-09, 11:59 AM
Interesting. Thanks MT

Momtezuma Tuatara
08-04-09, 01:30 PM
Immunity. (javascript:AL_get(this, 'jour', 'Immunity.');) 2004 Apr;20(4):429-40.
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IL-4 utilizes an alternative receptor to drive apoptosis of Th1 cells and skews neonatal immunity toward Th2.

Li L (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Li%20L%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Lee HH (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Lee%20HH%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Bell JJ (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Bell%20JJ%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Gregg RK (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Gregg%20RK%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Ellis JS (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Ellis%20JS%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Gessner A (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Gessner%20A%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Zaghouani H (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Zaghouani%20H%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract).

Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, M616 Medical Sciences Building, Columbia, MO 65212 USA.

Primary neonatal Th1 cells develop alongside of Th2 upon priming of the newborn but undergo apoptosis upon recall with antigen. These Th1 cells were isolated, and their death was correlated with elevated IL-13Ralpha1 chain expression. Strikingly, neutralization of Th2s' IL-4 reduced apoptosis, sustained recall responses, and the live Th1 cells displayed a decrease in IL-13Ralpha1 expression. Blockade of IL-13Ralpha1 or IL-4Ralpha also restores recall and secondary Th1 responses. Adult T cells primed within the neonatal environment did not upregulate IL-13Ralpha1 chain or undergo apoptosis and developed recall Th1 responses. These observations indicate that developmental expression of IL-13Ralpha1 along with IL-4Ralpha provides a receptor through which IL-4 induces death of Th1 cells and skews neonatal immunity toward Th2.

Publication Types:

Research Support, Non-U.S. Gov't (javascript:AL_get(this, 'ptyp', 'Research Support, Non-U.S. Gov\'t');)
Research Support, U.S. Gov't, P.H.S. (javascript:AL_get(this, 'ptyp', 'Research Support, U.S. Gov\'t, P.H.S.');)

PMID: 15084272 [PubMed - indexed for MEDLINE]