Immune response to fungal infections
The immune response to fungal infections is a vital mechanism through which the body identifies and combats fungal pathogens. This process begins with the skin and mucous membranes serving as the first line of defense. If these barriers are breached, specialized white blood cells called lymphocytes (including T cells and B cells) become active. T cells directly attack antigens from the fungi, while B cells produce antibodies that facilitate the destruction of these antigens. Although many healthy individuals encounter numerous fungal spores daily, most infections remain mild due to a robust immune response. However, certain fungi, like Histoplasma capsulatum and Cryptococcus neoformans, can evade immune defenses and cause more severe infections.
In contrast, individuals with compromised immune systems, such as those with leukemia or HIV/AIDS, face a heightened risk of invasive fungal infections. Conditions and treatments that weaken immune function significantly increase susceptibility to severe fungal diseases. As the prevalence of immunocompromised individuals rises, understanding the immune response to fungi becomes crucial for managing these infections effectively.
Immune response to fungal infections
- ALSO KNOWN AS: Mycoses
Definition
The immune response is the mechanism by which the body recognizes and defends itself against invading microbes, including fungi. The more effective the body’s immune response, the more successfully it combats the development and severity of infection. A breakdown of the immune response can have dire consequences.
Basic Immune System Components
Skin and mucous membranes are the first line of defense against microbes. If these are penetrated, the body’s immune response becomes active. Lymphocytes, specialized white blood cells, react to the presence of substances called antigens on the surface of invading fungal spores or molds. The two major types of lymphocytes are T cells (T lymphocytes) and B cells (B lymphocytes). T cells attack antigens directly. B cells produce antibodies, circulating proteins that bind to specific antigens and make it easier for immune cells to destroy the antigens.
Other contributors to the immune response to fungal infections include macrophages and other phagocytes, which are blood cells that surround and digest foreign bodies; complement, which are specialized proteins in the blood that act in sequence to mediate inflammation and the immune response; and neutrophils, which are circulating white blood cells that play a major role in destroying fungal pathogens.
Lymphocytes may develop a “memory” of invading antigens they encounter. This allows the immune system to respond faster and more efficiently to future exposure to the same antigens. For superficial, noninvasive infections, this memory is not long-lasting, so a recurrence of infection often occurs after treatment has been discontinued.
Immune Response to Fungi in Healthy Persons
Humans inhale or ingest thousands of fungal spores every day. Of the more than 200,000 species of fungi, fewer than 100 are associated with human infection. In healthy persons, most potentially pathogenic fungi produce mild, even subclinical, transitory infection, if any infection. In these situations, the body’s immune system has responded quickly and effectively to the pathogens.
Some fungal pathogens, however, challenge the body’s immune response, even in healthy persons. Histoplasma capsulatum, in its yeast form, can be resistant to killing by macrophages. H. capsulatum can actually multiply within macrophages. Progressive pulmonary infection or disseminated disease may result. Candida albicans may bind to complement, and by doing so can short-circuit the immune response. Coccidioides immitis contains a substance in its wall that resists its destruction, a critical step in the immune response. Cryptococcus neoformans, unlike other pathogenic fungi, is an encapsulated yeast. The capsule helps to impair destruction of the fungus by phagocytes. Despite setbacks from such challenges, in most healthy persons the immune response recoups, with T-cell-mediated responses and a proliferation of neutrophils playing a major role.
With most fungal pathogens, antibodies do not contribute significantly to the immune response. C. neoformans is an exception, so much so that rising titers of antibodies against C. neoformans are evidence of recovery from illness. In contrast, high titers of C. immitis-specific antibodies are associated with dissemination and a worsening clinical course.
Immune Response to Fungi in Immunocompromised Persons
Invasive fungal infections are a major threat to immunocompromised persons. Both underlying disease and therapy can compromise the immune response and cause it to malfunction, resulting in an increased risk for severe and systemic fungal infections. Leukemia, diabetes ketoacidosis, sarcoidosis, chronic granulomatous disease, and acquired immunodeficiency syndrome (AIDS) are examples of diseases that have a direct impact on the functioning of the immune response. Leukemia can severely deplete neutrophils, resulting in neutropenia, a low level of circulating neutrophils. Diabetic ketoacidosis has a negative impact on lymphocytes by increasing serum acidity. The lesions caused by sarcoidosis and chronic granulomatous disease interfere with the functioning of macrophages. Human immunodeficiency virus (HIV), the virus that causes AIDS, attacks and destroys helper T cells. Consequently, T-cell-mediated immunity is compromised.
Agents used to treat cancer and AIDS or to suppress rejection of solid or stem-cell transplants and high-dose, long-term therapy with corticosteroids increase the risk for severe and systemic fungal infections by suppressing the immune response. In particular, they cause neutropenia and depression of the T-cell-mediated immune response. Neutropenia is a major contributor to the emergence of disseminated candidiasis and severe aspergillosis, zygomycosis, and hyalophomycosis (caused by Fusarium species). High-dose, long-term use of corticosteroids impairs both macrophage and neutrophil function. This contributes to the development of severe aspergillosis, cryptococcosis, and zygomycosis (also called mucormycosis).
Impact
As the number of immunocompromised persons increases, both from disease (such as AIDS) and from treatment (such as immunosuppressive chemotherapy), fungal infections are emerging as a major cause of morbidity and mortality. These infections include particularly virulent strains and fungi rarely observed as pathogenic in the past. Greater understanding of the factors contributing to the breakdown of the immune response in these situations has become critical to controlling these opportunistic infections.
Bibliography
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