Immunity To Worms
Parasitic
worms of all three classes (roundworms, tapeworms and flukes) are responsible for numerous human
diseases, including three of the most unpleasant (upper left): onchocerciasis,
elephantiasis and schistosomiasis. These worms are transmitted with the aid of
specific insect or snail vectors, and are restricted to the tropics, while the
remainder (lower left) can be picked up anywhere by eating food contaminated
with their eggs, larvae or cysts. A feature of many worm infections is their
complex life cycles and circuitous migratory patterns, during which they often
take up residence in a particular organ (see figure).
Another striking feature is the
predominance of eosinophils and of IgE; as a result,
hypersensitivity reactions in skin, lung, etc. are common, but whether they are
ever protective is still controversial. As they do not replicate in the human
host (unlike protozoa, bacteria and viruses),
individual worms must resist the immune response particularly well in order to
survive and, as with the best-adapted protozoa (compare malaria), immunity
operates, if at all, to keep down the numbers of worms rather than to eliminate
them. The outlook for vaccination might seem very dim, but it is surprisingly
effective in certain dog and cattle infections.
Mystifying, but provocative, is the
finding that several drugs originally used against worms (niridazole,
levamisole, hetrazan) turn out to have suppressive or stimulatory effects on T
cells, inflammation and other immunological elements, bringing out the point
that worms are highly developed animals and share many structures and pathways
with their hosts. Some very effective drugs against worms act against their nervous system.
Eosinophils may have three effects in worm infections: phagocytosis of the copious antigen–antibody complexes,
modulation of hypersensitivity by inactivation of mediators and (in vitro at
least) killing of certain worms with the aid
of IgG antibody. Eosinophilia is partly due to mast-cell and T-cell chemotactic
factors; T cells may also stimulate output from the bone marrow via cytokines
such as IL-5.
Nematodes may be filarial (in which
the first-stage larva, or micro-filaria, can only develop in an insect, and
only the third stage is infective to humans) or intestinal (in which full
development can occur in the patient).
Filarial nematodes Onchocerca
volvulus is spread by Simulium
flies, which deposit larvae and collect microfilariae in the skin.
Microfilariae also inhabit the eye, causing ‘river blindness’, which may be
largely due to immune responses. In the Middle East, pathology is restricted to
the skin; parasitologists and immunologists disagree as to whether this
reflects different species or a disease spectrum (compare leprosy). Loa loa (loasis)
is somewhat similar but less severe. Wuchereria ban- crofti and Brugia
malayi are spread by mosquitoes, which suck microfilariae from the blood.
The larvae inhabit lymphatics, causing enormously enlaged limbs and/or scrotum
(elephantiasis), partly by blockage and partly by inducing cell-mediated immune
responses; soil elements (e.g. silicates) may also be involved. In some animal
models, microfilaraemia can be controlled by antibody.
Intestinal nematodes (Ascaris, Strongyloides, Toxocara
spp.). Travelling through the lung,
larvae may cause asthma, etc., associated with eosinophilia. Trichinella
spiralis larvae encyst in muscles. In some animal models, worms of this
type stimulate good protective immunity. Strongyloides sp. has become an
important cause of disease in immunosuppressed patients, suggesting that in
normal individuals it is controlled immunologically. Toxocara sp.,
picked up from dogs or cats, is an important cause of widespread disease in
young children, and eye damage in older ones.
Flukes (trematodes)
Trematodes spend part of their life
cycle in a snail, from which the cercariae infect humans either by penetrating
the skin (Schistosoma sp.) or by being eaten (Fasciola, Clonorchis spp.).
The latter (‘liver flukes’) inhabit the liver but do not induce protective
immunity.
Schistosomes (‘blood flukes’) live and mate harmlessly in
venous blood (Schistosoma mansoni, S. japonicum: mesenteric; S.
haematobium: bladder), causing trouble only when their eggs are trapped in
the liver or bladder, where strong granulomatous T-cell-mediated reactions
lead to fibrosis in the liver and nodules and sometimes cancer in the bladder.
The adult worms evade immune attack by covering their surface with antigens
derived from host cells, at the same time stimulating antibody that may destroy
subsequent infections at an early stage. Eosinophils, macrophages, IgG , IgE
and the TH2 cytokines IL-4, IL-5 and IL-13, have all been implicated.
Schistosomes also secrete a variety of molecules that destroy host antibodies
and inhibit macrophages, etc., making the adult worm virtually indestructible. Nevertheless,
there is evidence for the development of partial immunity, mainly directed at
the skin and lung stages of the cycle. The combination of adult survival with
killing of young forms is referred to as ‘concomitant immunity’. An irradiated
cercarial vaccine is effective in animals, but purified antigens are also being
tried.
Fasciola spp. are chiefly a problem in farm animals,
where they live in the bile duct. What immunity there is appears to lead mainly
to liver damage and vaccines have been disappointing.
Clonorchis sp. infects humans but otherwise resembles Fasciola
spp. It may lead to cancer of the bile duct.
Tapeworms (cestodes)
Cestodes may live harmlessly in the
intestine (e.g. Taenia spp.), occasionally invading, and dying
in, the brain (‘cysticercosis’), or establish cystic colonies in the liver,
etc. (e.g. the hydatid cysts of Echinococcus spp.), where the
worms are shielded from the effects of antibody. Antigen from the latter, if
released (e.g. at surgery) can cause severe immediate hypersensitivity
reactions (see Fig. 35). An experimental vaccine has proved effective in dogs
and sheep, the primary and intermediate hosts.
