FUNGI HOST INVASION BY MICROORGANISMS IMMUNOLOGY

Introduction

Although there are over 50,000 identified species of fungi, only a few hundred are known to be pathogenic, causing infections known as mycoses (mycology being the study of fungi). Fungi are nonphotosynthetic organisms (lack chlorophyll) which are restricted to a parasitic or saphrophytic exsistence. They are abundant in soil, vegetation, water and on decaying vegetation and wood. Fungi have a eukaryotic cell structure and are able to grow as branching or filamentous forms (mycelia) or as single cells (yeasts).

Structure

Fungi are surrounded by a multi-laminate fibrous cell wall which provides rigidity, shape, determines the cellular volume and enables the cell to maintain turgor. The cell wall is composed of polysaccharides and carbohydrates (chitin and cellulose).

Inside the cell wall lies the thin, cytoplasmic cell membrane. The cell membrane is composed of lipid and protein and regulates the passage of substances into and out of the cell, such as metabolites and waste products. Important metabolites are taken up by active transport as the cell membrane is relatively impermeable. The cell membrane is also the first barrier to toxic materials entering the cell and is important in degredation of extra-cellular nutrients.

Reserve materials such as fats, glycogen and protein are stored as granules in the cytoplasm. As the cell ages, vacuoles appear which also contain reserves of metabolites and provide turgor to help keep the cell's shape and are important in growth of the organism.

Types of Fungi

There are two principle types of fungi, the moulds and the yeasts. The moulds are further divided into filamentous or dimorphic fungi.

Filamentous fungal hyphae are the branching tubular structures of moulds which become entwined as the fungi grows to form a mycelium. Hyphae grow by apical elongation as new wall material is laid down constantly at the tips of the terminal and lateral branches. Septate hyphae are divided by cross walls into septa. Each septum has a small central pore (dolipore) maintaining protoplasmic continuity throughout the hyphae allowing rapid nutrient transport and nuclear migration. Dead or damaged parts of septate hyphae are cut off by a plug blocking the septal pore. Non-septate hyphae only form cross walls to cut off dead or damaged parts of the hyphae and to delimit reproductive organs. There are arial (above the surface) and vegetative (surface) hyphae. The aerial hyphae produce spores which are reproductive fungal cells and vegetative mycelium have an assimilative function. There are two main types of spore produced, conidiospores and sporangiospores. These produce asexual spores called conidia which are relatively resistant to physical and chemical agents.

Dimorphic fungi develop as a mycelium or into another form depending on environmental conditions. There is usually as yeast like parasitic phase and a mycelial saprophytic phase. Dimorphic fungi show phenotypic duality and more than one physiological factors may be involved in dimorphic changes.

The yeasts range from 3µm to 5µm and are oval or spherical cells. Pseudohyphae are produced by some yeasts which are chains of irregular yeast cells. Dimorphic fungi change from the mycelial form into yeasts in certain conditions, e.g. 37°C or when inside animal tissue. Yeasts reproduce mainly by budding of the oval, unicellular or round thallus. The daughter cells may remain attach to the aprent yeast cells for several generations forming chains or colonies. To identify yeasts, the ability to assimilate sugar and nitrogen and the fermentation of various sugar compounds is studied.

Fungal Reproduction

Any fragment of hyphae can grow to form a new colony (if it is not too badly damaged). However, the main method of fungal reproduction is through spores which are produced in very large numbers. There are different types of spores: vegetative, asexual and sexual.

Vegetative spores can be divided into arthrospores and chlamydospores. Arthrospores are formed when septate hyphae disarticulate into seperate cells. Arthrospores are usually formed by dermatophytes. Chlamydospoes are formed by segmentation of mycelium. They are thick walled, enlarged, resting spores which contain reserve food material and can remain viable after the rest of the mycelium has died. Budding from the ends or sides of the parent cell forms blastospores, for example, in Candida yeast infections.

Asexual spores are either sporangiospores or conidiospores. Sporangiospores are formed when the cytoplasm cleaves within a sporangium (multinucleate segment of hyphae), producing either naked zoospores which have one or more flagella and are liberated through a hole in the sporangial wall or producing aplanospores. Aplanospores are non-motile and walled which are released when the sporangial wall breaks down. Conidiospores, such as Aspergillus can be formed directly from the mycelium, produced within a specialised fructification or can be formed externally by the abstriction of a conidiophore. Different types of conidia can be produced which differ in cell size and number and are called either microconidia (small and unicellular) or macroconidia (large and multicellular).

The sexual spores are divided into four categories dependent upon the spores produced and their morphology. Zygomycetes are primitive fungi with a non-spetate mycelium. The sexual spores are oospores or zygospores (the asexual spores are produced in a sporangium). Ascomycetes are higher fungi. They have a septate mycelium and the sexual spores are called ascospores (the asexual spores are conidia). Basidiomycetes are also higher fungi with a septate mycelium which has clamp connections. the sexual spores are basidiospores (the asexual spores are produced externally). Deuteromycetes are an artifical group of fungi which have an unknown sexual state.

Major pathogenic fungi

Superficial: These infections affect only the skin, hair, nails etc.

Generally not dangerous
Examples- Hortaea werneckii, causing tinea nigra, and Piedraia hortae, causing black piedra

Cutaneous: Also known as dermatophytoses

Only affect superficial keratinized tissue- skin, hair and nails
Again generally not dangerous
Examples- Candida albicans, causing candidiasis of the skin and nails, Microsporum species

Subcutaneous: Usually cause chronic localised infections of the skin and underlying dermis

Normally reside in soil and vegetation; they enter skin through cuts and grazes
Can occasionally affect the deep tissues, e.g. bones and muscles
Examples- Sporothrix schenkii, causing sporotrichosis, Madurella mycetomatis causing mycetoma

Systemic: Also known as deep, endemic or primary

Usually serious; sometimes fatal
Examples- Histoplasma capsulatum causing histoplasmosis, Blastomyces dermatitidis causing blastomycosis

Opportunistic: Ubiquitous fungi that affect only susceptible hosts; immunocompetent individuals are normally resistant

Examples- Aspergillus fumigatus, causing aspergilliosis, Cryptococcus neoformans, causing cryptococcosis

Immunity to fungi

Cutaneous and superficial fungal infections are normally self-limiting, with recovery associated with a resistance to re-infection. As hosts often develop delayed-type hypersensitivity, this resistance appears to be cell-mediated.

T cell immunity- it is thought that helper T cells release cytokines to activate macrophages to fight the infection
Neutrophils- there is now growing evidence for the role of neutrophils in some infections of the respiratory system, with defensin and the nitric oxide pathways implicated