Fungi, Parasites, and Prions Flashcards
Fungi
- eukaryotes
- yeasts
- molds
- dimorphic
- saprophytes
yeasts
- unicellular
- budding
- facultative anaerobes
molds
- multicellular
- filamentous hyphae
- spore-forming
- aerobic
transmission of fungal infections (mainly of saprophytes)
- open wound
- inhalation (spores)
at risk for fungal infection (commensals)
- young
- old
- diabetic
- immunocompromised (severely): HIV/AIDS, chemotherapy, post-transplant
fungi ____ to host environment
adapt well;
- wide range of temps
- digest keratin
- low O2 requirements
fungi- cytokine effects
- inhibit pro-inflammatory cytokines (TNF-a)
- induce production of anti-inflammatory cytokines
fungi- invasion and evasion:
morphological change
- from avirulent to virulent (ex: mold to yeast)
- variable gene expression
fungi- invasion and evasion:
survive phagocytosis
- capsule: provides resistance to phagocytosis
- gliotoxin: inhibits phagocytosis
- reproduce inside the phagosome
fungi- invasion and evasion:
immunosuppression
- capsule: blocks recognition by macrophages
- gliotoxin: suppression of mast cell activation (much less of an inflammatory response)
fungi- direct cellular damage
- enzymes: proteases, phospholipase, elastase
- mycotoxins: loss of muscle coordination, weight loss, tremors, ex: aflatoxin (aspergillus)- carcinogenic
fungi- indirect cellular damage
- cell-mediated immune response: T cells, macrophages, and neutrophils
- granuloma formation: lungs, nervous system, blood vessels
mycoses
-fungal infection in an animal
superficial/cutaneous mycoses
- limited to skin and hair
- dermatophytes: require keratin as part of their metabolic process
- transmission: person to person, animal to person, soil exposure
- mechanism of action: host inflammatory response
- pityriasis versicolor (patches on skin, appear after UV exposure)
- dermophytosis: fungal infction of the skin
- characteristic lesion with central clearing
- tinea/ringworm
subcutaneous mycoses
- subcutaneous fascia, muscle, and deeper epidermal layers
- penetrating trauma
systemic mycoses
- inhalation of spores (pulmonary infection)
- chronic granulomatous disease
tinea capitis
scalp
tinea barbae
beard
tinea pedis
foot
tinea cruris
groin
tinea unguium
nails (also called onychomycosis)
candida albicans
- commensal yeast: most common fungal infections in humans*
- mouth (30-50% of pop), GI tract, vagina (20% of pop)
- candidiasis/”thrush”: impaired immunity, antibiotic treatment
- candidosis: disseminated infection, 30-40% mortality
aspergillus
- opportunistic fungi
- ubiquitous, spore-forming
- mold
- aspergillosis: lungs, inner ear, sinuses, eye
cryptococcus neoformans
- opportunistic fungi
- ubiquitous, encapsulated yeast
- often isolated from pigeon droppings
- cryptococcosis: pulmonary, meningitis, cutaneous (granulomas)
pneumocystis jirovecii
- opportunistic fungi
- ubiquitous yeast
- AIDS-defining infection
- also at risk: cancer, chronic immunosuppressant medication
- pneumocystis pneumonia: cough (often mild and dry), fever, rapid breathing, shortness of breath
primary pathogenic fungi
- infection may occur in healthy people
- respiratory route
- examples: histoplasmosis, blastomycosis, coccidiomycosis, paracoccidiodomycosis
histoplasma capsulatum
- dimorphic
- endemic to the Ohio and Mississippi River valleys
- found in soil, bird, and bat excreta
- histoplasmosis: pulmonary granulomas, dissemination to liver, heart, and CNS
presumed ocular histoplasmosis
- 4.4% of exposed
- punched out lesions
- juxtapapillary atrophy
- choroidal neovascularization
- no vitritis
protozoa
- unicellular eukaryotes
- trophozoite and cysts forms
- Giardia lamblia: #1 protozoal infection in US
- 3 main groups: GI, UG, and blood
helminths
- multicellular
- nematodes
- flukes
- tapeworms
helminths and protozoa invasion and evasion
- prevent phagoloysosome formation (surviving phagocytosis)
- variable surface glycoproteins (antigens changing)
- host antigen coating (ex: fibrin)
- IgA and IgG proteases
- soluble antigen release (diffuse immune response, not targeted at infection)
- inactivation of complement
protozoa and helminths: direct cellular damage
- bulk properties: block lumens throughout the body
- toxins
protozoa and helminths: indirect cellular damage
- prolonged inflammatory response
- granulomas
protozoa and helminths: host immune response
- cell-mediated
- ADCC
- eosinophils (helminths)
malaria
- mosquito-borne disease (protozoa)
- 400 million infected/yr
- 1 million deaths/yr
- hemolytic, febrile illness: cyclic chills, fever, anemia, splenomegaly (clears RBCs)
- four main species
- plasmodium falciparum*
toxoplasma gondii
- protozoa
- complex life-cycle
- final host is the cat
- toxoplasmosis: most infections are asymptomatic, may be fatal for fetus or immunocompromised (encephalitis)
- sources: undercooked meat, contaminated water, handling cat feces
toxocara canis
- dog roundworm (nematode)
- ~10k infections/yr (700 ocular cases)
- toxicariasis: ingestion of T. canis eggs
- visceral larva migrans: abdominal pain, headache, weakness, fever, coughing/asthma/pneumonia
ocular larva migrans
- vision loss can be severe
- usually unilateral
- clinical signs: uveitis, vitritis, neuroretinitis, papillitis, chronic endophthalmitis, white elevated granuloma of retina or optic disc
onchocerca volvulus
- transmitted by black fly
- subcutaneous nodules
- chronic pruritic dermatitis
- onchocerciasis: “river blindness”, 2nd most common cause of infectious vision loss, microfilariae migrate to surface of the cornea and anterior chamber, eventual scarring of the cornea
antihelminthics
- interfere with helminth neurotransmission
- inhibit arachidonic acid metabolism (present in humans too)
- inhibit microtubule synthesis (present in humans too)
antiprotozoals
- inhibit protein and RNA synthesis
- inhibit cell division
- disrupt genetic material
prions
- misformed protein
- non-living but pathogenic and transmissible
- “infection”: no DNA or RNA, induce conformational change in other proteins
- pathogenesis: gradual; neuronal loss (astrocytosis), amyloid plaque formation, no immune response*
- sponge-like appearance of neural tissue
animal prion diseases
- bovine spongiform encephalopathy (mad cow)
- scrapie (sheep)
- chronic wasting disease (deer)
Creutzfeldt-Jakob disease (CJD)
- 200 cases per year in US
- 85% sporadic/5-10% inherited
Variant CJD
- ~1% of cases
- harvested human growth hormone
- contaminated surgical instruments
- infected corneal grafts
- consumption of infected tissues
Kuru
consumption of human CNS tissue
clinical manifestation of prion disease
- long incubation period (slow infection)
- loss of muscle coordination
- dementia
- progressive insomnia
- no signs of inflammation or fever
- 90% fatal in 1 year of being diagnosed
diagnosis and treatment of prion disease
diagnosis:
- brain biopsies
- tonsilar biopsies
- blood test under development
treatment: palliative
