How do macrophages know what to eat?

Mike Clark mrc7 at cam.ac.uk
Thu Feb 12 08:29:22 EST 1998

In article <xzqafbxz9s1.fsf at dali.uni-paderborn.de>, Axel Boldt
<URL:mailto:axel at uni-paderborn.de> wrote:
> Hi,
> I've asked this question here before, I didn't quite understand the
> answers, was advised to read a good immunology book and did just
> that. However, every book I get my fingers on seems to gloss over the
> (from my perspective) most important point about the whole immune
> system.

It's a good question and one which can only partly be answered at the
moment. Some text books such as the latest Janeway and Travers,
"Immunobiology" do better than others. My own view is that it comes down to
that grey area between the innate and the adaptive immune responses.
Certainly macrophages have complement receptors and complement can be
activated by the alternative pathway by many pathogens. Thus during
evolution the complement system has developed specificities for antigens on
pathogens which you commonly encounter in the environment. Secondly
macrophages have Fc receptors so they can identify immune complexes
containing antibody and of course antibody can also activate the complement
cascade as well. So where does the antibody come from? Well there are some
specificities of antibody which seem to be easily inherited and which form
part of the repertoire of everyone, eg antibodies to blood group antigens
and other carbohydrates and glycolipids. I think that these inherited
specificities help to bootstrap the immune system into recognising
pathogens and other antigens. In turn the adaptive responses to these
antigens then form a part of the repertoire which can cross react on new

> Neither B- nor T-cells nor anybody else will take any action unless a new
> antigen has been engulfed, processed and presented by a macrophage (let's
> talk about thymus-dependant antigens only for now);

I think it's wrong to try and separate too clearly T-dependent and
T-independent responses (see above). Certainly pathogens like parasites,
viruses and bacteria are likely to present both types of antigen to the
immune system. Of course immunologists can conduct experiments where they
give carefully selected and purified antigens which fall into one or other
category but this isn't likely to be true for pathogens.

> so the most central question of all should be: how do macrophages know
> what to engulf? Which soluble proteins, which free viruses, which
> bacteria? How do THEY distinguish self from non-self?  And, given this
> huge evolutionary pressure, why are there not more pathogens who can
> circumvent this macrophage detection mechanism and thereby bypass the
> whole immune defense?

Why is the immune system so complex and difficult to understand? Doesn't
that address this problem?

> Why does everybody talk about the wonders of gene rearrangement and
> somatic mutation which account for the specificity of antibody, when the
> genes that tell macrophages what to do are much more important?

Ah yes, but as I point out above the innate and adaptive immune responses

Another issue is maternally aquired immunoglobulin. Mammals are born and
inherit antibody from their mother. The antibody they acquire is
representative of the Ig immune responses which their mother was making at
the time of birth. Thus if you encounter the same antigens shortly after
birth the maternally acquired antibody might form immune complexes and
target the appropriate antigens to your macrophages and hence get the cycle

> Thanks for any reply that could help clear this up for me.
> Cheers,
>   Axel
In addition to the above there are many other contributory factors which we
are only just beginning to understand eg NK recognition, non-classical
T-cell receptors, presentation of antigens by heat-shock proteins,
inflammation as a result of infection and tissue damage etc. etc. etc.

Hope this is of partial help

Mike Clark,

Antibody Structure and Function Web Site                  
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