Page 458 - Clinical Immunology_ Principles and Practice ( PDFDrive )

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Immune Responses to Helminth Infection

Subash Babu, Thomas B. Nutman

Parasitical helminths are complex eukaryotic organisms, character- nematode infection, or skin/subcutaneous tissue and draining
ized by their ability to maintain long-standing, chronic infections lymph nodes in onchocerciasis) or systemic (lymphatic filariasis
in human hosts, sometimes lasting decades. Hence, parasitical or schistosomiasis). Moreover, the migration patterns of the
helminths are a major health care problem worldwide, infect- parasite might elicit varied cutaneous, pulmonary, and intestinal
ing more than 2 billion people, mostly in resource-constrained inflammatory pathologies, as seen, for example, in Ascaris or
countries (Fig. 31.1). Common helminth infections include those Strongyloides infection during their migratory phase. This is
with intestinal helminths, and filarial and schistosome infec- further complicated by the fact that human hosts are often exposed
tions are a major medical, social, and economic burden to the to multiple lifecycle stages of the parasite at the same time. Thus
countries in which these infections are endemic. Chemotherapy, a patient with chronic infection with lymphatic filariasis harboring
although highly successful in some areas, still suffers from the adult worms and microfilariae might be exposed to insect bites,
disadvantages of the length of treatment, the logistics involved thereby transmitting the infective-stage parasite. The immune
in the distribution of drugs, and, in some cases, the emergence response that ensues will not only be a reaction to the invading
of drug resistance. Vector control measures are at best an adjunct organism but will also bear an imprint of the previous exposures
measure in the control of helminth infections but also suffer and the concurrent infection.
from the same social, logistic, and economic obstacles as those
for mass chemotherapy. Therefore the study of the immune KEY CONCEPTS
responses to helminth infections attains great importance both
in terms of understanding the parasite strategies involved in Helminth Infection
establishing chronic infection and in the delineation of a successful Divided into nematodes, trematodes, and cestodes
host immune response to develop protective vaccines against Produce chronic infections that can persist for decades
infection. Characteristically cause morbidity rather than mortality
Multicellular parasites that do not multiply in the definitive host but can
reproduce sexually to produce larval stages that ensure continued
SPECTRUM OF HOST–PARASITE INTERACTIONS transmission
Helminths have characteristically complex lifecycles with many
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developmental stages. Thus the host is exposed during the course Helminth infections can elicit a spectrum of clinical manifesta-
of a single infection to multiple lifecycle stages of the parasites, tions mirroring diversity in host immune responses. For example,
each stage with a shared as well as a unique antigenic repertoire. in lymphatic filariasis, most infected individuals remain clinically
Thus Schistosoma mansoni infection begins with penetration of asymptomatic despite harboring significant worm burdens; this
the skin of humans exposed to infested waters by the free- is thought to reflect the induction of parasite-specific tolerance
swimming cercariae, which then develop into tissue-dwelling in the immune system. Others exhibit acute manifestations,
schistosomula. In the liver and mesenteric veins, schistosomula including fever and lymphadenopathy, and this is thought to
differentiate into sexually dimorphic adult worms, which then reflect inflammatory processes induced by incoming larvae, dying
mate, and the resultant eggs produced migrate through tissues worms, or superadded infections. Individuals who mount a strong
into the lumen of the intestine or bladder for environmental but inappropriate immune response end up with lymphatic
release. Similarly, in lymphatic filarial infection, the host is exposed damage and subsequent immune-mediated pathology—hydrocele
to infective-stage larvae in skin, lymph nodes, and lymphatics; and elephantiasis. Finally, a group of infected individuals mount
to adult worms in lymph nodes and lymphatics; and finally to exuberant immune responses that often result in unusual pathol-
microfilariae in the peripheral circulation. Hence, the host– ogy, such as tropical pulmonary eosinophilia. Thus the clinical
helminth interaction is complex not only because of the multiple manifestations of lymphatic filariasis exemplify the spectrum of
lifecycle stages of the parasite but also because of the tissue host–parasite interactions that occur during helminth infections
tropism of the different stages. (Fig. 31.2).
Antigenic differences among the lifecycle stages can lead to Another hallmark of all helminth infections is their chronic
distinct immune responses that evolve differentially over the nature, with many helminths surviving in the host for decades.
course of a helminth infection. In addition, depending on the For example, adult schistosomes and filariae may survive in host
location of the parasite, the responses are compartmentalized tissues for as long as 30 years, producing eggs and larval stages
(intestinal mucosa and draining lymph nodes in intestinal throughout this time. Similarly, Strongyloides stercoralis, with its

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