Exam3Lec8MedicalMycology Flashcards
The impact of fungi
Immunosuppressive Drugs
note which species of fungi is being used to make the specifc immunosuppressive drugs
- Steroids: Rhizopuss
- Cyclosporin: Cordyceps spp and Tolypocladium spp
The impact of Fungi
Antobiotics
note which species of fungi is being used to make the specifc antibiotics
β-lactam antibiotics (Penicillin) – Penicillium chrysogenum
Although fungi can lead to human disease, fungi are used for what three things
antibiotic production, immunosuppressive drugs
production of food (like beer and cheese)
Cell Wall Structure of Fungi
The fungal cell wall itself is an important virulence factor
Cell well synthesis is the target of several anti-fungal drugs.
Name the components of the cell wall from surface to membrane
- Mannoprotein
- Beta-glucan
- Beta glucan + chitin
- Mannoprotein
- Membrane
Which component of the cell wall is unique to fungi and explain its role?
Chitin
interwoven within the B-Glucan layer and serves as structural support for the fungal cell wall. This is unique to fungi! (gives cell wall rigidity)
Morphology
What is a primary ex of single Celled Fungi?
Yeasts
How do single celled fungi reproduce?
Reproduce by budding
Incomplete budding leads to the formation of pseudohyphae
little piece comes off (bud) and recreating itself (making an exact daughter copy)
pseudohypahe is a long tail formed that comes off the cell
Morphology
What are examples of Multicellular Fungi
Hyphae and Mycelia
What is hyphae?
Septate
Nuclei are separated by cell walls (septum)
Non-Septate
Nuclei are not separated by cell walls (NO septum)
What is Mycelia?
slide 24 TA
Vegetative – Nutrient acquisition
Aerial – Growth and reproduction
As hyphae grow, they become a “tangled mass” known as Mycelia.
Vegetative mycelia develop a “root like system” that is responsible for nutrient acquisition. This kind of “borougs” into our tissues and act like diff anchors
Aerial mycelia produce spores which are critical for reproduction. ( these grow into the air and at the end we he have the spores which then can get disseminated)
What are three examples of spores that can be made?
Blastospores - Reproductive spores produced by yeast by budding.
Chlamydospores – Thick-walled survival spores produced by the yeast Candida.
Conidia – Asexual spores (e.g., in Aspergillus)
How is fungal morphology related to virulence?
Facilitate intracellular colonization (getting into cells and colonizing)
Linked with expression of virulence factors (causing disease)
Tissue penetration (Hyphae & Pseudohyphae)
Dissemination (Yeast)
Yeast is good fordissemniation bc its single celled and easily get into bkood stream and spread more easily. Hypahe anchored to tissue wont spread easily.
Morphology and VIrulence
The host has signals that trigger a change in fungal morphology. Explain this.
Fungi comes in contact with its ideal environment/cue (temperature, pH, serum components, starvation, etc) and It triggers the release of** Efg1p and/or Cph1p** which activate Hyphal Development.
Nrg1p + Tup1p and Rfg1p + Tup1p inhibit hyphal development
Efg1p and/or Cph1p = Hyphal Development
Nrg1p + Tup1p = Inhibition of Hyphal Development
Rfg1p + Tup1p = Inhibition of Hyphal Development
note that we always need tupp for inhibition
viruelnce factor
What is a primary example of Mycotoxins?
also note what is affects and what is can lead to
primary ex: Aspergillus flavus – Aflotoxin
Affects cereals, oilseeds, tree nuts, and peanut butter (negligible)
High-level of exposure can lead to acute hepatic necrosis and/or carcinoma (p53 mutations)
virulence factor
What is a primary example of Heat Shock protein?
also note what is affects and what is can lead to
primary ex: Histoplasma – HSP60 and HSP70
HSPs lead to adaptation in higher temperature environments such as Tropical Environments Host circulation
Less thermotolerant strain (less hsp) = less virulent
More thermotolerant strain (more hsp) = more virulent
basically it likes the heat, fungi with more hsp means that is thrives more in heat causing more disease
How are mycoses classified and what are the different types?
classified by the degree of tissue involvement and mode of entry into the host.
Superficial Mycoses
Subcutaneous Mycoses
Primary Pathogenic Mycoses
Opportunistic Mycoses
What are Superficial Mycoses?
Infection is localized to the skin, the hair, and the nails.
Does not infect the cell itself; remains on the surface.
infections of the keratin not the cell itslef
Whar are three examples of infections caused by superficial mycoses?
Tinea – Dermatophyte infection (i.e. tinea pedis “athletes foot”)
Thrush – Candida infection (candidiasis) of the mouth or vagina
Ringworm:
What are Subcutaneous Mycoses?
Infection confined to the dermis, subcutaneous tissue or adjacent structures.
Wounding of the skin allows for entry of fungus
Confined mainly to tropical regions
Slow onset and chronic duration (they are hard to treat and last a long time)
skin is infected
needs a door that is open for fungus to get inside
What is an infection caused by subcutaneous
mycoses?
Sporotrichosis
Thorn prick/scratch from a fish spine –>ulcerative lesion –> lymphangitis
Primary pathogenic mycoses typically infect via what? List examples
Infection typically via respiratory route
Lungs main site of infection but possible dissemination to other organs (liver, heart, and CNS)
Example:
Histoplasmosis
Blastomycosis
Coccidiomycosis
Opportunistic mycoses infection typically affects who? List some examples
typically affects immunocompromised individuals or those undergoing surgery, transplants, trauma, etc.
Examples:
Aspergillosis
Systemic Candidiasis
Cryptococcosis
For the Cryptococcus neoformans species of fungi what is it’s vector and what infections does it cause?
Vector: pigeon droppings
Doesn not cause infections UNLESS IMMUNOCOMPROMISED
can lead to pulmonary disease and Cryptococcocal meningitis
What is the Morphological form in diseased tissue of Cryptococcus neoformans
what is its virulence factor?
The polysaccharide capsule is the most prominent virulence factor
Induces alternate complement pathway
Capsule is immunogenic BUT makes fungus difficult to phagocytose
NOTE: Acapsular strains are avirulent
you are going to build an immune response but the capsule makes it hard to phag, so IS cant fight off easily
What is Candida albicans?
Commensal found on mucosal surfaces of oral, gastrointestinal, and urogenital tract.
naturally it is found here
What does Candida albicans do as a pathogen?
it is the most common causative agent of fungal-associated diseases such as:
Oral thrush
Fungal myocarditis
Fatal disseminated candidiasis
Biofilm formation (e.g. catheters)
Important** opportunistic pathogen** of hospitalized patients, immunocompromised individuals and burn victims
What is the Morphological form in diseased tissue of Candida albicans?
Yeast to hypahe transformation is critical for Candida pathogenicity prior to tissue invasion
What are the 4 VF of Candida albicans?
Adherence – Main adhesin = mannoproteins (outersurface)
Hyphal formation – Yeast-to-hyphae transformation
Protease secretion – Secrete aspartyl proteases and cytolysins
Thigmotropism – Enhances hyphal penetration by contact sensing
Aspartyl Proteases: Enzymes which enhance destruction of host tissue and fungal penetration
Cytolysins: After phagocytosis of fungus, this enzyme ensures release from phagolysosome to evade destruction.
Contact Sensing: Hyphae find intracellular junctions or microscopic breaks on mucosal surfaces
For Aspergillus fumigatus disease is caasued by what?
inhalation of conidia (asexual spores) which can result in a variety of diseases
condida are little spores that sits on the flower and is responsible for reproduction and spread. Think of it as pollen o on a flower
Conidia are inhaled into lung alveoli, attach to endothelial cells, and then hyphae penetrate microvasculature.
Exposire to conidia can lead to a variety of diseases dependong on the conditions of the host. What are 6 examples of this?
- Healthy → no sequel
- Cavitary lung disease → Aspergilloma
- Chronic lung disease → Chronic necrotizing aspergillosis
- Mildly immunocompromised → Chronic necrotizing aspergillosis
- Severely immunocompromised host → (Angio)invasive pulmonary aspergillosis (IPA)
- Asthma→ Allergic bronchopulmonary aspergillosis (ABPA)
Infects immunocompromised patients, especially neutropenic patients (!!!)
Laz said we will most likely be tested on either 5 or 6
Aspergillus fumigatus Virulence Factors
Mold only phase – no dimorphism (no change in morphology)
Adherence – Cell wall components
Cell wall pigments (melanin) – interferes with phagocytosis
Toxin & enzyme secretion – lead to hemorrhage and tissue necrosis
Angioinvasive properties – invasion of tissue and vasculature
Toxins include:
Haemolysin – leads to hemmorrhage and tissue necrosis
Gliotixin – slows ciliary beat frequency of human respiratory ciliated epithelium
Aspergillus fumigatus Pathology
Aspergillus growing in heart muscle, note the characteristic Y-shaped filaments
What type of infection is Sporothrix schenckii and what are its VF?
Primarily subcutaneous infection known as rose gardener’s disease
Virulence Factors:
Dimorph
Thermotolerance
Extracellular enzymes
Histoplasma capsulatum fungus causes what?
Histoplasmosis: pulmonary infection caused by inhalation of microconidia
Also known as “cave disease” because it associated with decaying bat guano or bird droppings
_____ of infections caused by Histoplasma capsulatum care mild and _____ are severe. Of the severe infections, what do we see in immuno competen/compromised people
> 95%, 5%
Immuno-competent → Lung lesions calcify
Immuno-compromised → Severe pneumonia leading to disseminating disease
Histoplasma capsulatum Virulence Factors
Dimorph – inhalation of fungal microconidia leads to transformation to **yeast **at 37 C
Survives/Multiplies within phagolysosome of non-activated macrophages
Escapes phagocytosis
starts at mold phase and when it enters host it enters the yeast phase where it sits inside macrophages and kupffer cells
Coccidioides immitis causes what?
Coccidiodomycosis: pulmonary infection caused by inhalation of fungal arthrospores (mold phase)
For the Coccidiodomycosis infection, what percent of infections are asynptomatic and what percent are mild to sever.
60% of these infections are asymptomatic
40% have mild to severe symptoms:
5% ->Erythema nodosum (painful inflammation of fat cells undern skin)
5%–> Disseminated disease (i.e. “valley fever”)
Erythema nodosum are painful subcutaneous nodules but a good sign of disease prognosis and outcome because the host’s immune system is responding to the infection.
Remember that Coccidioides immitis is dimorphic, explain its life cycle
- Mold Phase: Produce fungal arthrospores which are inhaled by host and cause disease. How?
Arthrospores have anti-phagocytic activity
Arthrospores swell to begin yeast phase
- Yeast Phase: Spherules are filled with endospores which are released
Spherules are too large for phagocytosis
mold phase with arthrospores
yeast phase with endospores
The two phases of the Coccidioides immitis life cycle make a dimorph
Innate and Adaptive Immune Response
Explain how dendritic cells produce an immune response to fungi
- Phagocytose fungi at the site of infection
- Transport to the lymph nodes for antigen
- presentation to lymphocytes
- Production of antibodies
- Activation of TH1/TH2 cells
Innate and Adaptive immune respone
Abs alone may not be able to control fungal infections, what must occur
T-cell + Antibody Inter dependency
An intact T-cell function is required for Ab-mediated protection. (without funcational T-cells we WILL NOT have proper IR against fungi, leading to disease)
Abs might have an influence over the Th1/Th2-type cytokine balance and the induction of regulatory T cells.
T-cells required as well. Thus activation of Th and T(reg) cells is crucial for proper immune response.
Remember:
1. TH1 Cells release IFN-gamma and TNF (Cytokines) which lead to macrophage activation
2. TH2 Cells release IL-3, IL-10, IL-13 (cytokines) which lead to inactivation of macrophages
Antifungal Medication
Azoles (e.g., Fluconazole) mechanism of action
bolded blue on Seyfang presentation
Cell membrane - inhibition of ergosterol synthesis
Antifungal Medication
Polyenes (e.g., Amphotericin B)
mechanism of action
bolded blue on Seyfang presentation
Direct cell membrane damage (binds to ergosterol)
Antifungal Medication
Flucytosine (nucleotide analogue)
mechanism of action
bolded blue on Seyfang presentation
Inhibition of nucleic acid synthesis
Antifungal Medication
Echinocandins
mechanism of action
bolded blue on Seyfang presentation
Cell wall - inhibition of glycan synthesis
Antifungal Medication
- Nikkomycin, 2. Griseofulvin, 3. Sordarins mechanism of action
The were NOT bolded blue on Seyfang presentation
Nikkomycin
Cell wall - inhibition of chitin synthesis
Griseofulvin
Inhibition of mitosis (disruption of microtubules)
Sordarins
Inhibition of protein synthesis
