Download CHAPTER 42 Pathogenesis of Fungal Infections

CHAPTER 42
Pathogenesis of Fungal Infections
We all have regular contact with fungi. They are so widely distributed in our environment
that thousands of fungal spores are inhaled or ingested every day. Other species are so
well adapted to humans that they are common members of the normal flora. Despite this
ubiquity, clinically apparent systemic fungal infections are quite uncommon, even among
persons living within the geographic habitat of the more pathogenic species. However,
progressive systemic fungal infections pose some of the most difficult diagnostic and
therapeutic problems in infectious disease, particularly among immunocompromised
patients to whom they are a major threat.
GENERAL ASPECTS OF FUNGAL DISEASE
I. EPIDEMIOLOGY
1. Environmental conidia are inhaled or injected
2. Endogenous yeasts may invade
II. PATHOGENESIS
1. Fungal pathogenesis is similar to bacteria
2. Most fungi are opportunists
A. Adherence
1. Adherence is mediated by fungal adhesins and host cell receptors
2. Mannoprotein is an adhesin, and fibronectin a receptor
B. Invasion
1. Traumatic injection is linked to trauma
2. Small conidia may pass airway defenses
3. Invasion across mucosal barriers may involve digestive enzymes
C. Injury
1. No classic exotoxins are produced in vivo
2. Injury is due to inflammatory and immunologic responses
III. IMMUNITY
A. Innate Immunity
1. Normal persons have a high level of innate immunity to most fungal infections
2. Important receptors include a lectin-like structure on phagocytes and Toll-like
receptors
3. Most fungi are readily killed by phagocytes
4. Tissue phases of dimorphic fungi resist phagocytic killing
B. Adaptive Immune Response
1. T cell–mediated responses of primary importance
2. Progressive fungal diseases occur in the immunocompromised
a. Humoral Immunity
1. Antibodies can be detected but for most fungal diseases there is little evidence
that they contribute to immunity
2. Opsonizing antibody is effective in some yeast infections
b. Cellular Immunity
1. Systemic disease associated with deficiencies in neutrophils and TH1 cellmediated immunity
2. Fungi that escape neutrophils grow slowly in macrophages
3. Growth is restricted when macrophages activated by cytokines
4. Immune defects lead to progressive disease
5. Defective TH1 responses are often specific to the fungal pathogen