[Immunology] Re: What causes maternal antibodies to break down in a newborn?

Mike Clark via immuno%40net.bio.net (by mrc7 from cam.ac.uk)
Mon Dec 15 07:59:15 EST 2008


[Posted and mailed]

In message <mailman.1085.1229101530.29717.immuno from net.bio.net>
          "Alan Bradbury" <abradbury from taptonschool.co.uk> wrote:

> I hope somebody can help with this.
>  
> A recent exam question for A level (16-18 year olds) in the UK had a
> question asking why passive immunity in newborns is short lived.  The
> answer expected was that a newborn will recognise the maternal
> antibodies as foreign and have an immune response to them.  This just
> didn't sound right to me. I have tried to do some internet research on
> the question and it seems that the half-life of maternal antibodies is
> about 30 - 45 days. But I have not been able to find out what causes
> the removal of the maternal antibodies. I had assumed that it was just
> due to the natural turnover and breakdown of the antibodies that the
> infant might receive from its mother.
>  
> Am I right, or is the exam answer right?
>  
> Alan Bradbury (A level Biology teacher, UK).
> 

I would say that there is little evidence for the exam answer and that
the observations are consistent with your answer.

Human babies acquire IgG class antibodies from their mother by transport
across the placenta in the third trimester of pregnancy. The
transport receptor implicated for this is known variously as the
Brambell receptor (after the academic who first postulated its
existence) or the neonatel Fc receptor (FcRn). Thus young human infants
acquire a polyclonal IgG reponse from their mothers.

Once the baby is born the only immunoglobulin that the baby can acquire
is in the colostrum and later the milk. Milk contains mainly IgM and IgA
so this immunoglobulin will mainly pass through, and offer some passive
immunity to, the digestive system. In some species such as ruminants and
rodents there is little, if any, transplacental transport of IgG and
most of the IgG immunoglobulin is transported across the gut by FcRn and
is acquired from the colostrum. At present it has not been demonstrated
that this is a major mechanism in humans for acquring IgG.

Once the baby is born and stops acquring maternal IgG, the
immunoglobulin will start to decline for two reasons. [1] Any
immunoglobulin that encounters antigen will form an immune complex and
be removed from the system via the complement and the Fc receptor
mediated processes. [2] Immunoglobulin like any other protein is likely
to be destroyed by natural catabolism and so will decline in
concentration over time. Interestingly FcRn plays a major role for IgG
in reducing the rate of catabolism and thus increasing the half-life of
that particular class of antibodies.

The examination answer suggests a third possibility. That the infants
own anti-globulin response is responsible for removal of maternal IgG.
This appears to be invoking an idea related to the Jerne anti-idiotype
network hypothesis. That anti-idiotypes (acquired from the mother) will
bind to the idiotypes of the infants new B-cells and stimulate them to
produce antibody against the mothers antibody. Whilst this is
theoretically a possibility I doubt whether it is the major cause of
loss of maternal IgG, particularly since the observed decay is mainly
consistent with [2] above.

Cheers,

Mike
-- 
M.R. Clark PhD,  Reader in Therapeutic and Molecular Immunology
Cambridge University, Department of Pathology
Tennis Court Road, Cambridge CB2 1QP
Tel +44 (0)1223 333705    Web  http://www.path.cam.ac.uk/~mrc7/


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