【正文】 line of defense. 2. Tcell stimulated PMNs kill Blastomyces cells by oxidative mechanisms. 3. Conidia are more sensitive to killing by PMNs because yeast are too big. 4. TH1 response is of primary importance Blastomycosis Treatment 48 第四十八頁，共八十一頁。 a large number also have granulomatous pulmonary lesions. ? Risk Factors: Occupational contact with soil。 but can spread to other ans. Most prevalent in males 4060 years of age and children. Blastomyces dermatitidis Dimorphic anism originates in the soil and infection ensues by inhalation of spores. Converts to yeast in animal hosts or at 37o in vitro. 46 第四十六頁，共八十一頁。 Even More Histoplasmosis F. Treatment ? Amphotericin still mainstay of therapy vs. disseminated and severe pulmonary histoplasmosis. ? Ketoconasole or itraconasole is effective as therapy for selflimited disease (used in AIDS). Ocular Histoplasmosis A small fraction of individuals form scar tissue in the retina many years after the original histoplasmosis infection. Live anisms cannot be recovered from these specimens. The scarring can obscure the macula and lead to loss of central vision. The first signs are small ―histo spots〞 . Advanced disease is treated with laser photocoagulation to limit the proliferation of blood vessels. 45 第四十五頁，共八十一頁。 More Histoplasmosis 1. 90% of cases are asymptomatic, but in rare cases flu like respiratory symptoms occur 2. Disseminated histoplasmosis occurs in 1:200 cases and is diagnosed frequently in patients with AIDS living in the central . 3. In these cases, the anism spreads via blood from the lung to involve bone marrow, adrenal glands, heart valves and CNS 4. Spread can also be associated with underlying lung disease (., emphysema). B. Spread C. Immune Response 1. Cellmediated responses are of primary importance 2. Activated macrophage can kill yeast cells D. Evasion of Defenses 1. Survival in macrophages— elevates pH of phagosomes 2. Yeast cells absorb iron (siderophore) and calcium from host 3. Alteration of cell surface 43 第四十三頁，共八十一頁。 Histoplasmosis (also called cave disease) Caused by the dimorphic fungus Histoplasma capsulatum Tuberculated macroconidia, grown at 25C Intracellular yeast at 37C Histoplasmosis is characterized by intracellular growth of the pathogen in macrophages and a granulomatous reaction in tissue. These granulomatous foci may reactivate and cause dissemination of fungi to other tissues. 41 第四十一頁，共八十一頁。 Coccidioidomycosis: A. Encounter: Mycelium found in dry, dusty soil. Contact by inhalation of arthroconidia B. Spread: Most monly an asymptomatic self limited pulmonary disease, but may spread via the blood to skin, soft tissues, bones, joints and meninges. C. Immune Response: Tcell mediated (Th1) D. Evasion of Defenses: Resistant to killing by phagocytes protein rich, hydrophobic outer wall alkaline halo associated with urease E. Damage: secreted proteinases break down collagen, elastin hemoglobin, IgG IgA 39 第三十九頁，共八十一頁。 Characteristics of systemic dimorphic mycoses ? Are unmon, often occurs in endemic areas ? Most infections are asymptomatic or selflimiting ? in immunepromised hosts, infections are often fatal ? The pattern of infection are similar – Route of acquisition is inhalation – Pulmonary infection – Disseminated infection (Blood, Bone marrow, Brain and CSF, Joint) 37 第三十七頁，共八十一頁。 ? Eumycetoma – Dark grains – Madurella mycetomatis – Le