Out Of The Past: Evolution Of Immune Mechanisms
From the humble amoeba searching for food (top
left) to the mammal with its
sophisticated humoral and cellular immune mechanisms (bottom right), all
cellular organisms can discriminate between self and non-self, and have
developed defence systems to prevent their cells and tissues being colonized by
parasites.
This figure shows some of the
important landmarks in the evolution of immunity. As most advances, once
achieved, persist in subsequent species, they have for clarity been shown only
where they are first thought to have appeared. It must be remembered that our
knowledge of primitive animals is based largely on study of their modern
descendants, all of whom evidently have immune systems adequate to their
circumstances.
All multicellular organisms,
including plants, have evolved a variety of recognition systems that respond to
common molecular patterns found on the surface of microbes (e.g.
lipopolysaccharides) by stimulating a variety of antimicrobial responses. This
broadly corresponds to vertebrate innate immunity. In contrast, only
vertebrates appear to have evolved
adaptive immunity (characterized by specificity and memory), mediated by lymphocytes and three
separate recognition systems (see Fig. 3): molecules expressed on B cells only
(antibody), on T cells only (the T-cell receptor) and on a range of cells (the
MHC), all of which look as if their genes evolved from a single primitive
precursor (for further details see Fig. 10). Why only vertebrates have evolved
adaptive immunity has never been totally explained, but there is a growing
appreciation that the adaptive immune system brings with it very significant
evolutionary costs. These include energy demands in maintaining the system (the
human immune system has at least as many cells as the human nervous system),
and also the potential danger that excess immunity will lead to tissue damage
(as out- lined in Figs 34–39). One of the consequences of the evolutionary
quest to balance the pros and cons of the immune system is reflected in the extraordinary
evolutionary diversity and genetic variability in many families of molecules
involved in immune function (see Fig.
47).
Bacteria We think of bacteria as parasites, but they
themselves can be infected by specialized viruses called bacteriophages and
have developed sophisticated systems to prevent this.
It is thought that the restriction endonucleases, so indispensable to the
modern genetic engineer, have as their real function the recognition and
destruction of viral DNA without damage to that of the host bacterium.
Successful bacteriophages have evolved resistance to this, a beautiful example
of innate immunity and its limitations.
Protozoa Lacking chlorophyll, these little animals must
eat. Little is known about how they recognize ‘food’, but their surface
proteins are under quite complex genetic control.
Research in this area is very
active, partly because it has become clear that some invertebrates make very
useful models for the study of vertebrate innate immunity, and partly because
of the importance of some invertebrates in carrying human diseases (e.g.
malaria transmission by mosquitoes).
Sponges and corals. Partly free-living, partly colonial, sponge and
coral cells use species-specific glycoproteins to identify ‘self’ and
prevent hybrid colony formation. If forced together, non-identical colonies
undergo necrosis at the contact zone, with accelerated break- down of a second
graft.
Worms Because of its relative simplicity and ease of
propagation, the nematode Caenorhabditis elegans has become one of the
most thoroughly studied animals on earth. Protection against infection is
achieved by behavioural responses (mediated by a Toll receptor; see Fig.
5), a thick outer coat or cuticle and production of a range of soluble
antimicrobial peptides and proteins.
Molluscs and arthropods are curious in apparently not showing graft rejection. However, both
cellular and humoral immunity are present. An important humoral system involves
the enzyme prophenyl oxidase, which is involved in production of toxic oxygen
radicals and melanin, both thought to play a part in defence against potential
pathogens. A common cellular response is encapsulation, in which invading
microorganisms are rapidly surrounded by blood cells and sealed off, thus
preventing spread of infection. A key feature of the insect immune response
(studied especially in the fruit fly Drosophila melanogaster) is the
production of an amazing number of different antimicrobial peptides. Two major
cellular signalling path- ways are involved in switching on the production of
these peptides, the Toll receptor pathway, which also plays an important part
in mediating innate immunity in vertebrates, and the Imd pathway, which
shares many features with the vertebrate tumour necrosis factor pathway.
Echinoderms The starfish is famous for Metchnikoff’s
classic demonstration of specialized phagocytic cells in 1882. Allografts
(grafts from one individual to another) are rejected, with cellular
infiltration, and there is a strong specific memory response.
Vertebrates
Jawless fishes (cyclostomes, e.g. hagfish, lamprey) These descendents
of the earliest vertebrates lack the immunoglobulin-based adaptive immune
system. In a remarkable example of parallel evolution, they were recently shown
to have two classes of lymphocytes, analogous to T and B cells, but to use a
different type of variable lymphocyte receptor based on the leucine rich domain
structure (see Fig. 5).
Cartilaginous fishes (e.g. sharks) The evolution of the jawed vertebrates
marks the first appearance of classic antibody, T-cell antigen receptors and
MHC, although details of isotype, isotype switching and somatic recombination
differ from higher vertebrates. Many molecules of the classic complement
pathway also make their appearance.
Bony fish Bony fish have most of the features of immunity
familiar to us from a study of humans and mice. The zebra fish has become an
attractive model species for the study of immunity and inflammation, because
its transparent body structure allows high resolution imaging, and its small
size facilitates the development of rapid screening assays for new
immunomodulatory drugs. Interest in fish immunology has also been driven by
economic considerations, as infectious diseases pose a major challenge for
farmed fish such as salmon.
Amphibians During morphogenesis (e.g. tadpole → frog)
specific tolerance develops towards the new antigens of the adult stage. Lymph
nodes and gut-associated lymphoid tissue (GALT) and haemopoiesis in the bone
marrow also appear for the first time.
Birds are unusual in producing their B lymphocytes
exclusively in a special organ, the bursa of Fabricius, near the cloaca. The
mechanisms for generating different antibody molecules also seem to be quite
different, involving a process known as gene conversion. They have a
large multilobular thymus but no conventional lymph nodes.
Reptiles have both T and B cells. As in birds, the major
antibody class is IgY rather than IgG, although both IgM, IgD and possibly IgA
may also exist.
Mammals are characterized more by diversity of Ig
classes and sub-classes, and MHC antigens, than by any further development of
effector functions. There are some curious variations; e.g. rats have unusually
strong innate immunity and some animals (whales, Syrian hamsters) show
surprisingly little MHC polymorphism. However, humans and mice, fortunately
(for the humans), are immunologically remarkably similar. Members of the
cammelid family (e.g. camels and llamas) have antibodies made up of a single
heavy chain and no light chain (see Fig. 14).
Plants
Plants, like animals, possess
sophisticated mechanisms to protect themselves against microbial pathogens.
These responses are triggered by plant receptors that recognize molecular
components of bacteria, fungi or viruses. The responses include secretion of a
variety of anti- microbial substances, some of which (e.g. nitric oxide) are
shared with vertebrate immunity. RNA silencing, in which short stretches of
double-stranded RNA can trigger sequence-specific mRNA degradation, and hence
gene silencing, forms part of another elaborate antiviral immune system in
plants.
