Disease, Causative Agent, Spread, and Pathogenesis - Kirby 32-33 PDF

Disease Causative Agent Spread Pathogenesis Ingestion of contaminated Cysts ingested → trophozoites bind to epithelial Amebiasis Entamoeba histolytica water or food; sewage leaks cel...

Disease Causative Agent Spread Pathogenesis Ingestion of contaminated Cysts ingested → trophozoites bind to epithelial Amebiasis Entamoeba histolytica water or food; sewage leaks cells → cytotoxin secretion → ulcers in the colon → into water supply. bacterial invasion. Ingestion of fecally contaminated water or food; Trophozoites attach to intestinal villi → Giardiasis Giardia lamblia direct contact with faeces inflammation → malabsorption. containing viable cysts. Inflammation and erosion of vaginal/urethral Trichomoniasis Trichomonas vaginalis Not provided. epithelium. Sporozoites released in the duodenum → circulate Ingestion of oocysts from cat Toxoplasmosis Toxoplasma gondii in the body → invade nerve cells → tissue cysts faeces. form → cellular death. African Introduced by the bite of the Trypanomastigote multiplies in blood, lymph, CNS Sleeping Trypanosoma brucei tsetse fly. → toxins cause systemic reactions. Sickness Insect faeces rubbed into the Intracellular amastigote multiplies → destroys Chagas Disease Trypanosoma cruzi conjunctiva or skin breaks. cells. Larvae burrow through skin Schistosomiasis Schistosoma spp Larvae enter circulatory system. from contaminated water. Beef tapeworm: ingestion of undercooked beef. Taenia saginata, T. Pork tapeworm: ingestion of Cysticerci develop in muscles, skin, eyes, CNS → Tapeworms solium, Echinococcus undercooked pork or contact neurocysticercosis in the brain. granulosus with human faeces. Dog tapeworm: contact with dog faeces or saliva. Virulence Factor Role in Pathogenesis Examples Candida albicans adheres using HWP1 (cell wall protein), Ability to evade physical clearing mechanisms. Adherence to ALS gene family (surface glycoproteins), and INT1; Adherence to host cells helps establish infection Host Cells Blastomyces dermatitidis uses adhesin WI-1 to bind by avoiding being washed out of niches. macrophages. Capsule Capsules resist phagocytosis by immune cells, C. neoformans produces a capsule that increases when Formation allowing the fungi to survive in the host. iron is limited. Thermal Ability to grow at elevated temperatures (37– Saccharomyces cerevisiae can infect mice if it can grow at Dimorphism 42°C), which is crucial for systemic infections. 42°C and form pseudohyphae. Ability to acquire iron, which is essential for C. albicans acquires iron from red blood cells; production Iron Acquisition fungal metabolism and growth. of siderophores to bind and mobilize iron. Enzymatic Fungi secrete enzymes to degrade host tissue, A. fumigatus secretes elastase to degrade lung tissue; C. Secretion penetrate barriers, and facilitate dissemination. albicans secretes phospholipases and proteinases. Fungi resist being killed by phagocytic immune Resistance to cells, enhancing their survival and ability to cause Dimorphic fungi exhibit resistance to phagocytes. Phagocytes infection. Mycotoxin Fungi secrete toxins that contribute to disease Secretion severity and evasion of host defenses. Pathogenic fungi can grow in multiple forms C. albicans exists as both yeast and hyphal forms at Morphological (yeast, hyphae, mycelial), allowing them to adapt infection sites; Histoplasma and Blastomyces grow as Versatility to different environments in the host and cause yeast in parasitic forms. infection. Epigenetic changes in colony morphology can C. albicans switches between “white” (yeast) and Phenotypic alter virulence, biofilm formation, and immune “opaque” (bean-shaped) colony forms, influencing Switching evasion. virulence. Hydrophobicity enhances the ability of spores to Hydrophobic Aspergillus spores are hydrophobic, helping them disperse in the air and resist clearance in the Surface colonize the alveoli in the lungs. host. Tissue Ability to penetrate host tissues, break down A. fumigatus grows along blood vessels; C. albicans Penetration barriers, and spread the infection systemically. hyphae penetrate host cell walls. Blocking Immune Fungi can block or evade cell-mediated immune - Defenses responses, preventing effective host defense. Enzymes that cause tissue damage and necrosis, A. fumigatus secretes proteases; C. albicans secretes Necrotic Factors enabling fungi to overcome structural barriers. phospholipases and proteinases. Nutritional and Fungi require certain nutrients (e.g., iron) for C. neoformans increases capsular synthesis when iron is Metabolic growth and survival in the host, often utilizing limited; pathogenic fungi produce siderophores to bind Factors host resources. iron. Ability to switch between mould and yeast forms Dimorphic Histoplasma, Blastomyces, and Coccidioides convert from based on environmental conditions, aiding Pathogens moulds to yeasts/spherules in the host. survival and virulence. Stimulation of host cytokines, such as GM-CSF, Cytokine suppresses complement receptor production, C. albicans stimulates GM-CSF production. Stimulation weakening the immune response. Risk Factors for Fungal Infections Some factors that can predispose someone to fungal infections include: Diabetes Obesity Drug addiction Occupation Stages of a Microbial Infection Microbial infections can include some or all of these steps: Acquisition Colonisation Penetration Dissemination Damage Resolution Virulence Factors Virulence is the degree of pathology or disease caused by an infection. Virulence factors are tools that microorganisms use to cause disease processes in the body. Because pathogenesis is a complex interaction between the infecting organism and the host, very few factors are absolutely required for fungal virulence. Possession of a single putative virulence factor is unlikely to make a fungus pathogenic. A complex mix of properties is usually required. Here are some examples of fungal virulence factors: Ability to adhere to host cells using cell wall glycoproteins. Production of capsules, which resist phagocytosis. Stimulation of cytokine production (e.g., GM-CSF), which can suppress the production of complement receptors by monocytes and macrophages. (Example: C. albicans) Growth at elevated temperatures (37 °C) - exhibiting thermal dimorphism (25– 37 °C). Ability to acquire iron from red blood cells. (Example: C. albicans) Having a unique enzymatic capacity that allows the fungus to damage the host by secreting enzymes such as keratinase, elastase, and collagenase. Ability to resist killing by phagocytes, as seen in dimorphic fungi. Ability to secrete mycotoxins. Ability to block the cell-mediated immune defenses of the host. Surface hydrophobicity. Penetration and dissemination factors Nutritional and metabolic factors Necrotic factors Morphological versatility Phenotypic switching Opportunistic and Primary Pathogens Fungal pathogens can be divided into two general classes: 1. Primary pathogens Primary pathogens usually have an environmental reservoir and can cause disease in a host regardless of the host's normal flora or immune status. Many primary pathogens are dimorphic fungi. (Examples: Coccidioides, Histoplasma, Blastomyces, Sporothrix spp.) Infection by a primary pathogen often leads to subclinical disease (asymptomatic--without signs of disease); there may be a significant delay between infection and the onset of infection. Some species can be both a primary and an opportunistic pathogen. These infections will have different clinical manifestations. o For example, Cryptococcus neoformans is a model opportunistic pathogen but sometimes causes disease in healthy individuals. o Infections caused by Coccidioides immitis are much more virulent in immunocompromised patients. 2. Opportunistic pathogens Opportunistic pathogens are organisms that take advantage of debilitated or immunocompromised hosts to cause infection. They may have an environmental reservoir (e.g., Cryptococcus neoformans, Aspergillus fumigatus) or exist as commensals in healthy organisms (e.g., Candida species). Examples of opportunistic fungi include: Cryptococcus neoformans, Aspergillus fumigatus, Candida species Opportunistic pathogens incite disease in hosts whose local and/or systemic immune system is impaired, damaged, or innately dysfunctional. The pathogenesis of opportunistic infections involves the production of virulence factors, which allows an organism to be commensal when humans have normal immune systems but allows the organism to initiate an infection when the host’s immune system is suppressed.