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).
T As severe fungal infection in both the skin and mucous membranes (Candida spp.) and in the lung (Pneumocystis spp.) are common in T-cell deficiencies, T cells evidently have antifungal properties, but the precise mechanism is not clear. Some fungi (see below) can apparently also be destroyed by NK cells.
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.
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).