Immunity To Fungi And Ectoparasites
The vast majority of fungi are free-living, but
a few can infect larger animals,
colonizing the skin or entering via the lung in the form of spores (centre
left). Fungal infections are normally only a superficial nuisance (e.g.
ringworm, top), but a few fungi can cause serious systemic disease,
particularly if exposure is intense (e.g. farmers) or the immune system is in
some way compromised (e.g. AIDS); the outcome depends on the degree and type of
immune response, and may range from an unnoticed respiratory episode to rapid
fatal dissemination or a violent hypersensitivity reaction.
In general, the survival mechanisms
of successful fungi are similar to those of bacteria: antiphagocytic capsules
(e.g. Cryptococcus), resistance to digestion within macrophages (e.g. Histoplasma)
and destruction of polymorphs (e.g. Coccidioides). Some yeasts activate
complement via the alternative pathway, but it is not known if this has any
effect on survival. Perhaps the most interesting fungus from the immunological
point of view is Candida albicans (upper left), a common and
harmless inhabitant of
skin and mucous
membranes which readily
takes advantage of any
weakening of host resistance. This is most strikingly seen when polymorphs
(PMN) or T cells are defective, but it also occurs in patients who are
undernourished, immunosuppressed, iron deficient, alcoholic, diabetic, aged or
simply ‘run down’ (see Fig. 33). Organisms that thrive only in the presence of
immunodeficiency are called ‘opportunists’ and they include not only fungi, but
also several viruses (e.g. CMV), bacteria (e.g. Pseudomonas), proto- zoa
(e.g. Toxoplasma) and worms (e.g. Strongyloides), and their
existence testifies to the unobtrusive efficiency of the normal immune system.
The most important ectoparasites
(‘outside living’; skin dwelling) are mites, ticks, lice and fleas. The last
three are vectors for several major viral and bacterial diseases. The evidence
for immunity, and the
feasibility of a
vaccine, are currently
under intense study.
PMN Polymorphonuclear leucocyte (‘neutrophil’), an
important phagocytic cell.
Recurrent fungal as well as bacterial infections may be due to defects in PMN
numbers or function, which may in turn be genetic or drug-induced (steroids,
antibiotics). Functional defects may affect chemotaxis (‘lazy leucocyte’),
phagolysosome formation (Ché- diak–Higashi syndrome), peroxide production
(chronic granulomatous disease), myeloperoxidase and other enzymes.
Deficiencies in complement or antibody will of course also compromise
phagocytosis (see also Fig. 33).
Hypersensitivity reactions are a feature of many fungal
infections, especially those infecting the lung. They
are mainly of type I or IV (for an explanation of what this means see Fig. 34).
Dermatophytes Filamentous fungi that metabolize keratin and
there- fore live off skin, hair and nails (ringworm). Sebaceous secretions help
to control them, but CMI may also play an ill-defined part.
Candida albicans (formerly Monilia) A yeast-like fungus
that causes severe spreading infections of the skin, mouth, etc. in patients
with immunodeficiency, especially T-cell defects, but the precise role of T
cells in controlling this infection is not understood. Dissemination may occur
to the heart and eye.
Cryptococcus A capsulated yeast able to resist phagocytosis
unless opsonized by antibody and/or complement (compare pneumococcus, etc.). In
immunodeficient patients, spread to the brain and meninges is a serious
complication. The organisms can be killed, at least in vitro, by NK
cells.
Actinomycetes spp. and other sporing fungi from mouldy hay,
etc. can reach the lung alveoli, stimulate antibody production and subsequently
induce severe hypersensitivity (‘farmer’s lung’). Both IgG and IgE may be
involved. Aspergillus sp. is particularly prone to cause trouble
in patients with tuberculosis or cellular immunodeficiency. Dissemination may
occur to almost any organ. The toxin (aflatoxin) is a risk factor for liver
cancer.
Histoplasma (histoplasmosis),
Coccidioides (coccidioidomycosis)
and Blastomyces (blastomycosis)
spp. are similar in causing pulmo- nary disease, particularly in America, which
may either heal spontaneously, disseminate body-wide or progress to chronic
granulomatosis and fibrosis, depending on the immunological status of the
patient. The obvious resemblance to tuberculosis and leprosy emphasizes the
point that it is microbial survival mechanisms (in this case, resistance to
digestion in macrophages) rather than taxonomic relationships that determine
the pattern of disease.
Pneumocystis jirovecii (formerly P. carinii) is mentioned here because
although it was originally assumed to be a protozoan, studies of its RNA
suggest that it is nearer to the fungi. Pneumocystis pneumonia has
become one of the most feared complications of AIDS (see Fig. 28), which
suggests that T cells normally prevent its proliferation, although the
mechanism is so far unknown.
Ectoparasites
Mites are related to spiders. Sarcoptes scabei (scabies)
burrows and lays eggs in the skin and induces antibody, but such protective immunity
as there is appears to be cell-mediated (TH1). The house dust mite Dermatophagoides
pteronyssinus is an important cause of asthma. It induces high levels of
IgE, and sublingual desensitization has had some success, probably by switching
the T-cell response away from TH2 and towards the TH1 pattern. A DNA-based
vaccine has been tried in mice.
Ticks, like mites, are arachnids, living on the skin and feeding on blood. They
are vectors of several diseases, including Lyme disease, typhus and relapsing
fever. A vaccine has had some success in cattle.
Lice (Pediculosis spp.) feed on skin, clinging to hairs. There
are three main species, P. capitis (head lice), Phthirius pubis (pubic
lice) and P. corporis (body lice). A vaccine has proved successful in
salmon.
Fleas Pulex irritans is an important vector for plague, tularemia
and brucellosis.
Mosquitoes and other vectors. Although not strictly
parasites, mosquitoes should be mentioned as vectors for malaria, dengue,
yellow fever and some forms of filariasis. Other important vectors are the
sandfly (leishmaniasis), tsetse
fly (trypanosomiasis), simulium
fly (onchocerciasis) and
reduviid bug (Chagas’ disease).
