Immune response to parasitic diseases
The immune response to parasitic diseases is a complex interaction involving the human immune system's attempts to combat various multicellular organisms, including helminths (worms). Upon infection, the immune system identifies parasites and initiates a defense mechanism aimed at expulsion and isolation. This response often includes the activation of helper T cells, particularly the T helper 2 (TH2) subtype, which is common in mucosal areas like the gastrointestinal tract. The immune reaction typically leads to the production of cytokines, immunoglobulin E (IgE), and the activation of eosinophils and mast cells, resulting in inflammation and physical reactions such as diarrhea.
However, the immune response can become muted over time due to continuous exposure to parasite antigens, allowing some parasites to establish chronic infections. These organisms have evolved various evasion strategies, such as disguising themselves or suppressing the host's immune functions. In some cases, the immune response itself can lead to tissue damage or complications, creating a dual challenge of managing the infection while minimizing harm to the host. Despite the prevalence of parasitic diseases affecting billions globally, ongoing research aims to develop effective vaccines and therapeutic approaches, potentially offering insights into broader health issues like allergies and autoimmune diseases.
Immune response to parasitic diseases
Definition
Parasites are large multicellular organisms that undergo multiple stages of development, inhabit a variety of biological niches, and produce a range of antigens and metabolic secretions; thus, the human body’s immune response to these organisms is necessarily complex.
Immune Response
Information on the human immune system’s reaction to parasites is based largely on laboratory models. In general, once parasites (such as helminths, or worms) are identified, the immune system works to expel or isolate the organisms and to minimize their harmful effects. Although the response varies by invading species, it typically involves binding and inactivation of antigens, the release of cytotoxic agents, regulated hypersensitivity reactions, and tissue repair.
In mucosal areas (such as the gastrointestinal tract), a strong helper T cell (T lymphocyte) type 2 (TH2) response is common, although the exact route has not been identified and likely depends on the invading organism. In many cases, helminth antigens are recognized by T cells in the human gut’s lymphoid tissues, a recognition that sparks the production of cytokines (interleukins), mucus-producing cells, and immunoglobulin E (IgE). IgE antibodies then react with parasite antigens, leading to the release of mediators from mast cells and of eosinophils and basophils; inflammation soon follows. The gastrointestinal environment becomes toxic, and the smooth muscles contract, causing diarrhea and inducing the worms to leave or be expelled. The larval stages of some nematodes are damaged by toxic proteins released by eosinophils only after they leave the gut and migrate through the body.
Tissue-dwelling trematodes and filarial nematodes also trigger a TH2 response that includes the destruction of larvae by eosinophils, the formation of granulomas around Schistosoma eggs, and the production of nodules around the adult Onchocerca volvulus. Mast cells may play a larger role in expelling nematodes from tissue, possibly by making blood vessels more permeable. Neutrophils also work with eosinophils and macrophages to destroy parasites lodged in tissues. Nevertheless, the TH2 response appears to be less protective in these areas, in which chronic infections are the norm. The TH1 response (such as the secretion of interferon and activation of macrophages that destroy organisms) may be more important here, especially in early infections.
Although antigen-specific T cell responses are stimulated during the initial stages of an infestation, as the body is exposed to parasite antigens over time, the immune response often becomes muted, or down-regulated. This modified TH2 response has been noted in chronic infections with filarial worms, Schistosoma, and gastrointestinal tract nematodes, and it features an anti-inflammatory component that inhibits allergic responses. The actual mechanism behind the dampened response is unknown, but it appears that host macrophages may somehow be alternatively activated and recruited to the site of infection by parasites, creating an environment that favors the organisms’ survival. Interleukin 10, which is produced by regulatory T cells and helps to regulate the strength of TH1 and TH2 responses, also is likely involved. In addition to aiding in the suppression of inflammation, alternatively activated macrophages promote wound healing and damage repair (such as from hookworm bites).
Parasite Evasion
The persistence of parasites across species is a testament to their ability to successfully elude or neutralize host defense mechanisms. In many cases, the adult worm’s large size and motility make it difficult to eradicate through phagocytosis (ingestion). Some parasites also disguise themselves by adopting host antigens or by continually changing or turning down the expression of their own antigens. Other parasites evade destruction by shedding their outer coat, modulating their numbers to avoid detection, and accelerating growth and production of offspring when encountering hosts with potent immune systems.
Helminths also can interfere directly with the host’s immune response, doing so, for example, by secreting products that suppress T cell and B cell function, that interfere with the work of macrophages, that bind to immunoglobulins, and that dampen mast-cell signals. Some parasites also establish a relationship with the host known as premunition, in which an existing infection is allowed to continue, but new infestations by the same species are destroyed. This condition benefits both the host and the parasite because it avoids superinfection in the host and controls “overcrowding” by parasites.
Immunopathology
Occasionally, the body’s reaction to parasites causes self-injury or otherwise impairs functioning. Hypersensitivity reactions such as hives and swelling can be by-products of the immune response to worm antigens. During chronic infection, circulating antibodies and parasite antigens can coat cells or lodge in vessels or tissues and cause damage or blockages.
Immune responses to larval and egg stages of parasite development also can lead to pathology. For example, immune system attacks on migrating larvae can damage tissue inadvertently. In addition, many of the symptoms associated with onchocerciasis (such as rashes, lesions, severe visual impairment, and epilepsy) are attributed to antibody- and cell-mediated responses to dead or dying larvae. Similar cell-mediated pathologies can occur with granuloma formation in schistosomiasis. Over time, as the eggs die and the granulomas resolve, fibrosis can develop and obstruct blood flow to the liver or bladder. This scarring also can inhibit the liver’s ability to purify blood and can cause excessive bleeding.
Impact
According to the World Health Organization in 2023, soil-dwelling helminth infections, including those by roundworms, whipworms, and hookworms, affect roughly 1.5 billion people worldwide. Parasitic infections are associated with multiple disease states, delayed child development, and sometimes death. The World Health Organization added the control of morbidity from S. stercoralis as one of its 2030 objectives. In 2021, the organization helped treat over 500 million children in endemic nations with anthelminthic medicines.
Continued research on helminth biology and the body’s immune responses to the organisms can spur the development of effective vaccines. In addition, studies of the TH2 response and the parasite’s ability to suppress immunity may one day provide cures for infectious diseases and provide critical information about autoimmune and allergic disorders. The use of worms, eggs, and purified proteins of nematode parasites to promote protection from allergy and autoimmunity also has been investigated in preclinical and clinical trials.
Bibliography
Anthony, Robert M., et al. “Protective Immune Mechanisms in Helminth Infection.” Nature Reviews Immunology 7 (2007): 975-987.
Dunne, David W., and Anne Cooke. “A Worm’s Eye View of the Immune System: Consequences for Evolution of Human Autoimmune Disease.” Nature Reviews 5 (May, 2005): 420-426.
Maizels, R. M. “Exploring the Immunology of Parasitism: From Surface Antigens to the Hygiene Hypothesis.” Parasitology 136 (2009): 1549-1564.
Noble, Elmer R., and Glenn A. Noble. Parasitology: The Biology of Animal Parasites. Philadelphia: Lea & Febiger, 1982.
Roberts, Larry S., and John Janovy, Jr. Gerald D. Schmidt and Larry S. Roberts’ Foundations of Parasitology. 8th ed. Boston: McGraw-Hill, 2009.
"Soil-Transmitted Helminth Infections." World Health Organization, 18 Jan. 2023, www.who.int/news-room/fact-sheets/detail/soil-transmitted-helminth-infections. Accessed 3 Feb. 2025.