Exam3Lec8MedicalMycology Flashcards

1
Q

The impact of fungi

Immunosuppressive Drugs

note which species of fungi is being used to make the specifc immunosuppressive drugs

A
  1. Steroids: Rhizopuss
  2. Cyclosporin: Cordyceps spp and Tolypocladium spp
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2
Q

The impact of Fungi

Antobiotics

note which species of fungi is being used to make the specifc antibiotics

A

β-lactam antibiotics (Penicillin) – Penicillium chrysogenum

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3
Q

Although fungi can lead to human disease, fungi are used for what three things

A

antibiotic production, immunosuppressive drugs
production of food (like beer and cheese)

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4
Q

Cell Wall Structure of Fungi

A

The fungal cell wall itself is an important virulence factor

Cell well synthesis is the target of several anti-fungal drugs.

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5
Q

Name the components of the cell wall from surface to membrane

A
  1. Mannoprotein
  2. Beta-glucan
  3. Beta glucan + chitin
  4. Mannoprotein
  5. Membrane
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6
Q

Which component of the cell wall is unique to fungi and explain its role?

A

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)

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7
Q

Morphology

What is a primary ex of single Celled Fungi?

A

Yeasts

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8
Q

How do single celled fungi reproduce?

A

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

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9
Q

Morphology

What are examples of Multicellular Fungi

A

Hyphae and Mycelia

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10
Q

What is hyphae?

A

Septate
Nuclei are separated by cell walls (septum)

Non-Septate
Nuclei are not separated by cell walls (NO septum)

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11
Q

What is Mycelia?

slide 24 TA

A

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)

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12
Q

What are three examples of spores that can be made?

A

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)

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13
Q

How is fungal morphology related to virulence?

A

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.

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14
Q

Morphology and VIrulence

The host has signals that trigger a change in fungal morphology. Explain this.

A

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

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15
Q

viruelnce factor

What is a primary example of Mycotoxins?

also note what is affects and what is can lead to

A

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)

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16
Q

virulence factor

What is a primary example of Heat Shock protein?

also note what is affects and what is can lead to

A

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

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17
Q

How are mycoses classified and what are the different types?

A

classified by the degree of tissue involvement and mode of entry into the host.

Superficial Mycoses
Subcutaneous Mycoses
Primary Pathogenic Mycoses
Opportunistic Mycoses

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18
Q

What are Superficial Mycoses?

A

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

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19
Q

Whar are three examples of infections caused by superficial mycoses?

A

Tinea – Dermatophyte infection (i.e. tinea pedis “athletes foot”)

Thrush – Candida infection (candidiasis) of the mouth or vagina

Ringworm:

20
Q

What are Subcutaneous Mycoses?

A

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

21
Q

What is an infection caused by subcutaneous
mycoses?

A

Sporotrichosis
Thorn prick/scratch from a fish spine –>ulcerative lesion –> lymphangitis

22
Q

Primary pathogenic mycoses typically infect via what? List examples

A

Infection typically via respiratory route
Lungs main site of infection but possible dissemination to other organs (liver, heart, and CNS)

Example:
Histoplasmosis
Blastomycosis
Coccidiomycosis

23
Q

Opportunistic mycoses infection typically affects who? List some examples

A

typically affects immunocompromised individuals or those undergoing surgery, transplants, trauma, etc.

Examples:
Aspergillosis
Systemic Candidiasis
Cryptococcosis

24
Q

For the Cryptococcus neoformans species of fungi what is it’s vector and what infections does it cause?

A

Vector: pigeon droppings

Doesn not cause infections UNLESS IMMUNOCOMPROMISED
can lead to pulmonary disease and Cryptococcocal meningitis

25
Q

What is the Morphological form in diseased tissue of Cryptococcus neoformans

what is its virulence factor?

A

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

26
Q

What is Candida albicans?

A

Commensal found on mucosal surfaces of oral, gastrointestinal, and urogenital tract.

naturally it is found here

27
Q

What does Candida albicans do as a pathogen?

A

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

28
Q

What is the Morphological form in diseased tissue of Candida albicans?

A

Yeast to hypahe transformation is critical for Candida pathogenicity prior to tissue invasion

29
Q

What are the 4 VF of Candida albicans?

A

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

30
Q

For Aspergillus fumigatus disease is caasued by what?

A

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.

31
Q

Exposire to conidia can lead to a variety of diseases dependong on the conditions of the host. What are 6 examples of this?

A
  1. Healthy → no sequel
  2. Cavitary lung disease → Aspergilloma
  3. Chronic lung disease → Chronic necrotizing aspergillosis
  4. Mildly immunocompromised → Chronic necrotizing aspergillosis
  5. Severely immunocompromised host → (Angio)invasive pulmonary aspergillosis (IPA)
  6. Asthma→ Allergic bronchopulmonary aspergillosis (ABPA)

Infects immunocompromised patients, especially neutropenic patients (!!!)

Laz said we will most likely be tested on either 5 or 6

32
Q

Aspergillus fumigatus Virulence Factors

A

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

33
Q

Aspergillus fumigatus Pathology

A

Aspergillus growing in heart muscle, note the characteristic Y-shaped filaments

34
Q

What type of infection is Sporothrix schenckii and what are its VF?

A

Primarily subcutaneous infection known as rose gardener’s disease

Virulence Factors:
Dimorph
Thermotolerance
Extracellular enzymes

35
Q

Histoplasma capsulatum fungus causes what?

A

Histoplasmosis: pulmonary infection caused by inhalation of microconidia
Also known as “cave disease” because it associated with decaying bat guano or bird droppings

36
Q

_____ of infections caused by Histoplasma capsulatum care mild and _____ are severe. Of the severe infections, what do we see in immuno competen/compromised people

A

> 95%, 5%
Immuno-competent → Lung lesions calcify
Immuno-compromised → Severe pneumonia leading to disseminating disease

37
Q

Histoplasma capsulatum Virulence Factors

A

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

38
Q

Coccidioides immitis causes what?

A

Coccidiodomycosis: pulmonary infection caused by inhalation of fungal arthrospores (mold phase)

39
Q

For the Coccidiodomycosis infection, what percent of infections are asynptomatic and what percent are mild to sever.

A

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.

40
Q

Remember that Coccidioides immitis is dimorphic, explain its life cycle

A
  1. 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

  1. 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

41
Q

Innate and Adaptive Immune Response

Explain how dendritic cells produce an immune response to fungi

A
  1. Phagocytose fungi at the site of infection
  2. Transport to the lymph nodes for antigen
  3. presentation to lymphocytes
  4. Production of antibodies
  5. Activation of TH1/TH2 cells
42
Q

Innate and Adaptive immune respone

Abs alone may not be able to control fungal infections, what must occur

A

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

43
Q

Antifungal Medication

Azoles (e.g., Fluconazole) mechanism of action

bolded blue on Seyfang presentation

A

Cell membrane - inhibition of ergosterol synthesis

44
Q

Antifungal Medication

Polyenes (e.g., Amphotericin B)
mechanism of action

bolded blue on Seyfang presentation

A

Direct cell membrane damage (binds to ergosterol)

45
Q

Antifungal Medication

Flucytosine (nucleotide analogue)
mechanism of action

bolded blue on Seyfang presentation

A

Inhibition of nucleic acid synthesis

46
Q

Antifungal Medication

Echinocandins
mechanism of action

bolded blue on Seyfang presentation

A

Cell wall - inhibition of glycan synthesis

47
Q

Antifungal Medication

  1. Nikkomycin, 2. Griseofulvin, 3. Sordarins mechanism of action

The were NOT bolded blue on Seyfang presentation

A

Nikkomycin
Cell wall - inhibition of chitin synthesis

Griseofulvin
Inhibition of mitosis (disruption of microtubules)

Sordarins
Inhibition of protein synthesis