Fungal Immunology
Most of the fungus are harmless, but some of them can induce disease in human, called mycoses. The diseases vary from typical relatively surface infections to harmful systemic diseases particularly in immunodeficient hosts, depending on various factors including indigestible capsule (cryptotic), resistance against phagocytosis (histoplasm) and polymorphonuclear cell destruction (coccidiosis). Several fungus activate complement through alternative pathway, but the effect on their survival is not yet known. Antibodies can also be observed and are thought play role in immune response against fungus.
Fungus have 2 types, yeast that is unicellular and mold that develop with branches called hyphe. The most pathogenic is the genus of aspergillus and genera of dimorphyic cryptotic and the histoplasm developed as fungus in nature or cell in culture but capable of developing with branches in human tissues.
Diseases caused by fungus can be classified into 3 clinical classes: superficial, subcutaneous and systemic mycoses. The superficial mycoses are often infect the skin (ringworm), hair and nail. This fungus infection is chronic, and is relatively mild. This group also include mucose membran infection with Candida albicans. Although Candida albicans can normally be found in mouth, vagina and digestion pathway, but the excess growth can also occur in immunocompromised individuals and those receive antibiotic. Subcutaneous mycoses can be induced by injury from needle prick and characterized by abscess.
The most severe fungus infection is systemic infection such as histoplasmosis, cryptocosis and coccidiomycosis which are usually begin as pulmonary infection and acquired by inhalation of spores from fungus that not free living. Most of infections are asymptomatic or indicate only mild influenza symptoms, but sometimes invade to other tissues and are often fatal if not treated. Systemic fungus disease tend to occur in immunodeficient subject because of, but not limited to, the high steroid dosage, chemotherapy for cancer, patient with AIDS and prolonged implanted cathether.
A. Effector cells in fungal infection
Natural resistance against many pathogenic fungus depends on phagocytes. Although intracellular elimination can occur, fungus are primarily attacked extracellularly because of their large size. Neutrophile is the most effective cell, particularly against candida and aspergillus.
Fungus also stimulate cytokine production such as IL-1 and TNF-α upregulating the expression of adhesion molecule in local endothelial, increasing the neutrophile infiltration to infection site. Neutrophile kills the toxic oxygen-dependent and oxygen-independent fungus.
Alveolar macrophages play role in first line defense against inhaled fungus spores. Aspergillus is usually digestible by alveolar macrophage, but Coccidioides imunitis and Histoplasm capsulatum can be found in normal individual and those resistant to macrophage. In this case, macrophage still can assume its role through activation of Th1 cell forming granuloma.
NK cell can also fight against the fungus. First through the release of granules containing sytosolin. NK cells can also directly kill the fungus when stimulated fungus derived substance that induce macrophage to produce cytokine such as TNF and IFN-γ activating NK cell.
B. Nonspecific immunity
Skin physical barrier and mucose membran, the chemical factors in serum and skin secretion play role in nonspecific immunity. Primary effectors of nonspecific immunity on fungus are neutrophile and macrophage. Patients with neutropenia are highly susceptible to opportunistic fungus. Neutrophile is though release fungicidal substances such as ROI and lysosome enzyme and digest the fungus for intracellular destroy. Virulent groove such as Cryptococci neoformans inhibit cytokine production TNF and IL-12 by macrophage and stimulate the production of IL-10 inhibiting the macrophage activation.
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