Fungi, parasites, prions Flashcards
How are fungi similar to our cells?
Fungi are eukaryotes, have membrane bound organelles, they have DNA in chromosome form. This makes them hard to target and differentiate from our cells.
4 types of fungi and their characteristics
Yeast:
- More virulent
- Unicellular
- Budding
- Facultative anaerobes
Molds:
- Less virulent
- Multicelular
- Sexual reproduction
- Spore forming
- Aerobic
- Filamentous hyphae
Dimorphic (change back and forth between yeast and mold forms)
Sapryphytes: Live in decaying matter. Break down organic material.
How are fungal infections transmitted and what is the most commonly transmitted fungal type
Saprophytes are most commonly transmitted. By open wound inoculation or inhalation of spores.
Who is at risk for infection by fungal commensals
Old and young
Immunocompromised (AIDS, chemo, post transplant)
Diabetic
healthy individuals are usually able to fight off.
What makes fungi ubiquitous
They are able to adapt well to any host environment.
They have a wide range of temps
Can eat keratin
Low 02 requirements
Fungi and cytokine effects
They down regulate immune release of pro-inflam cytokines. Ex; TNF-a
They up regulate immune release of anti-inflam mediators.
3 ways that fungi can invade and evade
- Capable of morphological change. From avirulent (mold) to virulent (yeast) by changing gene expression.
- Survive phagocytosis
- Capsule makes them slippery
- Gliotoxin inhibits phagocytosis
- Reproduce inside phagolysosome. - Immunosuppressoin
- Capsule blocks recognition by macrophages
- Gliotoxin suppresses mast cell activation
Dual function of toxin released by fungi
Gliotoxin can inhibit phagocytosis and it suppress mast cell activation
Dual function of capsule on fungi
Can provide resistance to phagocytosis bc slippery and can block regognition from macrophages.
Key to clearance of many infections
Mast cell activation. Suppressed by gliotoxin of fungi
Fungi cellular damage by direct
Enzymes: proteases, phospholipase, elastase
Mycotoxins: Cause loss of muscle coordination, weight loss, tremors. Ex: aflatoxin aspergillus
Fungi cellular damage by indirect
Cell mediated immune response: collateral damage caused by t cells, MO, and neutrophils
Granuloma formation: due to not being able to break down fungi. can settle in lungs, nervous system or blood vessels.
Mycoses
Fungal infection in an animal
Three type of mycoses infections (broad)
Superficial/cutaneous
-Skin and hair
Subcutaneous
-usually due to penetrating trauma.
Systemic
-Inhalation or spores cause pulmonary or chronic granuloma
Type of fungi that causes cutaneous mycoses
Dermatophytes. Require keratin for metabolic process.
Dermatophytes
- transmission
- Mechanism of action
- 2 infections
- Person to person, animal to person, soil to person.
- Elicit host inflammatory response
- Pityriasis versicolor (patches on skin. Hypopigemented. Appear after UV exposure.)
And
Dermophytosis: Fungal infection of the skin. Lesion with central clearning. Ex: ringworm/tinea.
Where are these ring worm locations?
- Tinea capitis
- Barbae
- Pedis
- Curries
- Unguium
- Scalp
- Beard
- Foot
- Groin
- Nials
Commensal yeast
Candida albicans
Most common fungal infection in humans
Most common fungal infection in humans
Candida albicans. Commensal.
Where is candida albicans likely to cause infection
Mouth
Vagina
GI tract
Two types of infections caused by candida albicans (commensal)
Candidiasis (Thrush)
-Antibiotic treats
Candidosis
- 30-40% mortality
- spread throughout body. Infection.
Opportunistic fungi (4)
Aspergillus causes aspergillosis and aspergilomas in the lungs/inner ear/sinuses/eye.
Cryptococcus neoformans causes cryptococcosis in pulmonary. Causes meningitis and granulomas.
Pneumocystis jirovecii is an AIDs defining infection.
pneumocystis pneumonia. cough, fever, shortness of breath.
ASpergillus (opportunistic fungi)
Ubiquitous, Spore forming mold that causes aspergillosis in the lungs/inner ear/sinuses/eyes. Can cause aspergilloma- fungus ball that colonizes in a healed lung scar from previous disease.
Cryptococcus neoformans (opportunistic fungi)
Encapsulated yeast found in pigeon droppings.
Causes cryptococcosis that can be in the lungs and spread to CNS to cause meningitis or cutaneous granulomas.
Granulomas occur only in severely immunocompromised patients.
Pneumocystis jirovecii (opportunistic fungi)
Ubiquitous yeast.
AIDS defining infection.
Only in severely immunocompromised pts: maybe pt has Cancer or is taking a Chronic immunosuppressant medication
Pneumocystis pneumonia (opportunistic fungi)
Cough, fever, rapid breathing, shortness of breath
Primary pathogenic fungi
Infection may occur in healthy people.
Usually inhaled into lungs.
Histoplasmosis
Histoplasmosis
Dimorphic
Found in ohio and mississippi river valleys. Soil and bird/bat feces.
Causes pulmonary granulomas. Travels to liver, heart, CNS, and eyes.
How many people have positive skin test to histoplasmosis? (cell mediated immunity)
70%. Of those 70%, 4.4 people have ocular histoplasmosis.
Characteristics of presumed ocular histoplasmosis
- Punched out lesions. “Histo spots.” most common
- Juxtapapillary atrophy. Atrophy around nerve
- Rare, but could have choroidal neovascularization. Most severe form.
- NO vitritis.
Protozoa
- cell type
- 2 forms
- Most common Protozoa infection in US
Unicellular eukaryotes
Trophozoite form and cyst form (really resistant to clearance)
Giardia lamblia is the most common- associated with fecally contaminated water. Long lasting diarrhea disorder.
Helminths (3 types)
- Cell type
- How do you get it?
Nematodes, flukes, and tapeworms.
Multicellular eukaryotes
Fecally contaminated food/water. May be able to penetrate healthy skin.
How do Protozoa and helminths invade and evade immune system?
- Prevent phagolysosome formation
- Change antigen surface proteins
- Coat themselves and host-antigens (fibrin) Helminths.
- IgA and IgG proteases
- Soluble antigen release. Diffuse immune response, not targets at infection.
- Inactivation of complement.
How do Protozoa and helminths cause direct cellular damage?
Bulk properties- ability to reproduce and block lumen. Ex: bile duct, lymphatics
Toxins cause direct damage to tissues
How do Protozoa and helminths cause indirect cellular damage?
Prolonged inflammatory response causes collateral damage
Granulomas
How do Protozoa and helminths elicit a host immune response?
Cell mediated
ADCC
Eosinophils (helminths)
Primary host of malaria
Humans
What type of cell is malaria
Unicellular eukaryote. Protozoa.
Malaria
- What type of illness
- How does it affect body?
- How many species?
Mosquito borne
Hemolytic, febrile illness (increase in body temp)
-Cyclic chills. Certain time of day due to protozoa causing lysis of red blood cells= release intracellular contents= fever
-Fever
-Anemia bc lyses RBC
-Splenomegaly: Bc the spleen clears damaged RBCs
four main species.
Most common is plasmodium falciparum
Events that cause malaria once bitten by mosquito
Protozoa are put into the body and reproduce in the liver and red blood cells. Causes RBC to lyse and makes them sticky. They may adhere to basement membranes and vessels to cause blocked lumen.
Two examples of protozoa
Malaria: Plasmodium falciparum Toxoplasma Gondii (cat is the final host) May cause toxoplasmosis
Toxoplasma gondii
- Final host
- Sources?
- Causes what
Protozoa infection with a complex life cycle. Final host is the cat.
Sources: undercooked meat, contaminated water, handling cat feces.
Toxoplasmosis: Most infections are asymptomatic, but can be fatal for fetus or immunocompromised. Can cross placenta and cause fetal encephalitis.
Toxoplasmosis of the eye due to toxoplasma gondii
Caused by protozoa: toxoplasma gondii.
results in necrotizing retinitis due to immune system responding to infection. Causes vitritis, retinitis, and vasculitis (inflammation of vessels).
Looks like headlines in the fog.
Headlights bc it erodes retina and causes sclera to shine through (white)
Fog because the vitreous is cloudy due to immune cells.
usually unilateral.
Toxocara Canis
Helminth (Nematode) infection
Dog is primary host
Human is dead end.
Can result in toxocariasis (ingestion of T canis eggs) or visceral larva migrans (worms in internal organs)
Visceral larva migrans
Worms in internal organs due to toxocara canis infection (roundworm nematode helminth)
Abdominal pain HA weakness Fever Coughing/asthma/pneumonia if in lungs
Ocular larva migrans
Due to round worm/nematode/helminth in eye.
Usually found in macula due to increased blood flow there.
Vision loss can be severe
Usually unilateral
Clinical signs:
- Uveitis
- Vitritis
- Neuroretinitis
- Papillitis
- Chronic endopathalmitis
- **White, elevated granuloma of retina or optic disc.
Oncocera volvulus
- how is it transmitted?
- What does it cause
Helminth transmitted only by black fly vector (cannot transmit human to human)
causes subcutaneous nodules (chronic pruritic dermatitis)
Onchocerciasis. Small worms moving through body to the eye (surface of cornea and anterior chamber). Chronic exposure without treatment causes inflammatory response and eventual scarring –> vision loss.
2nd most common cause of infectious vision loss
Onchocerciasis (small worms moving to eye) from onchocerca volvulus.
Most common is chlamydia.
Riverblindness.
Onchocerciasis. Parasitic disease caused by tiny worms, microfilariae. Transmitted by black fly.
How to treat helminths
Interfere with their NT
Inhibit arachidonic and microtubule synthesis (problematic bc we use these. Side effects will occur)
How to treat protozoals
Inhibit protein and RNA synthesis
Inhibit cell division
Disrupt generic material
What are prions
Misformed proteins that are nonliving, but pathogenic and transmissible by person to person.
They cause infection and induce conformational changes in proteins. No DNA or RNA.
Prion pathogenesis
Gradual.
- Causes neuronal loss –> Expressive astrocytes.
- Amyloid plaque formation. Accumulates and we can’t break down.
- No immune response bc self molecule
prion appearance in neural tissue
Sponge-like with amyloid plaques and astrocytosis
Prion disease in animals
Bovine spongiform ecephalopathy- mad cow
Scrapie in sheep
Chronic wasting disease in deer
Can also affect squirrels and travel to humans via kentucky burgoo.
3 types of prion diseases in humans
- Creutzfeldt Jakob disease (CJD)
- Variant CJD
- Kuru
Creutzfeldt-Jakob disease
85% sporadic (random mutation)
5-10% inherited
Very rare
Variant CJD
Transmitted by person to person by:
Human growth hormone
Contaminated surgical instruments (v hardly and can persist thru autoclaving)
Infected corneal graft
Consumption of infected tissue
Kuru
Consumption of human CNS tissue. Culture in papua new guinea.
Prion disease clinical manifestations
Long incubation period (slow infection) Loss of muscle coordination Dementia- loss of cognitive function Progressive insomnia NO signs of inflammation or fever 90% fatal in 1 year
Prion disease diagnosis
Brain or tonsil biopsy- looking for amyloid plaque
Usually done after death as confirmatory
Blood test is under development
Treatment of prion disease
There is none. Palliative.
