Most are free living Aerobic Heterotrophs Obtains carbons from organic matter Most are saprophytic Obtain nutrients from dead organic matter Some are normal human flora Candida, Malassezia Some are highly adapted mammalian or human parasites Dermatophytes, Pneumocytis

May be organized based on tissues infected: Cutaneous Subcutaneous Systemic or endemic Opportunistic

Varied routes of infection. _Includes:_ Respiratory Direct contact Soil-contaminated wounds

Some are pathogenic to normal hosts Have overt virulent factors Ex. Coccidioides Histoplasma Most are opportunists Minimal virulence Must have pre-disposing conditions to cause disease Loss of normal bacterial flora Iatrogenic immunosuppression Genetic or acquired immunodeficiencies DM Mechanical breach of skin/mucosal surfaces Indwelling catheter Serious disease is not common in immunocompetent host

Responses vary with type Innate immunity to most fungi is very high Neutrophil killing is the primary mechanism Esp. against hyphae Line up along hyphal surfaces and secrete lysosomal enzymes Conidia/spores requires Mφ ingestion Intracellular forms ⇒ yeast Requires cell mediated immunity for elimination CMI important in most fungal infections Impaired CMI / low T-cell counts ↑ susceptibility to invasive fungal infections Ab with minor role in resistance to fungi

of available treatments limited Due to common pathways and metabolic processes b/t fungi & mammalian cells Risk of toxicity high

Aspergillus fumigatus and Aspergillus flavus Most commonly associated with invasive disease Opportunistic fungi Disease usually associated with severe neutropenia Found ubiquitously in the environment Infection is acquired exogenously

Exam 2: Intro to Fungi and Parasites Flashcards by Quynh Tran

Fungi

Characteristics

Kingdom ⇒ Myceteae
Cell walls ⇒ chitin
Cell membrane ⇒ ergosterol
Classified as yeast or mycelium
- Yeast ⇒ unicellular
- Mycelium ⇒ multicellular

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Fungi cell walls are made mostly of…

chitin

(N-acetylglucosamine + glucan)

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Yeast

Unicellular
Replicate by budding, fission, or molds

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Mycelium

Multicellular
Formed from hyphae
- Each is unicellular
- Hollow or divided by crosswalls
  - Non-septate vs septate
Hyphae grow together forming a mat ⇒ mycelium

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Fungi

Reproduction

Occurs sexually or asexually.

Asexually
- Via production of various spores
  - Conidia
  - Sporangia
  - Ascospores
- Spores disperse and start new colonies
Sexual process not well understood

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Fungi

Metabolism

Most are free living
- Aerobic
Heterotrophs
- Obtains carbons from organic matter
Most are saprophytic
- Obtain nutrients from dead organic matter
Some are normal human flora
- Candida, Malassezia
Some are highly adapted mammalian or human parasites
- Dermatophytes, Pneumocytis

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Fungi

Classification

May be organized based on tissues infected:

Cutaneous
Subcutaneous
Systemic or endemic
Opportunistic

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Cutaneous Fungi

Cause infections of the keratinized layer of the skin, hair, and nails
Termed dermatophytes

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Subcutaneous Fungi

Infect the dermis, subcutaneous tissue, bone, or cornea
Ex. Sporothrix

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Systemic or Endemic

Fungi

Causes systemic disease
Confined to specific geographic regions
Dimorphic
- Two lifecycle forms
Usually cause primary infection in the lung with subsequent dissemination
- Transmission via inhalation of spores

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Opportunistic Fungi

Human commensals or fungi found in the environment
Affect immunocompromised individuals
Can cause serious disease
Ex. Candida

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Fungi

Transmission

Varied routes of infection.

Includes:

Respiratory
Direct contact
Soil-contaminated wounds

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Fungi

Pathogenesis

Some are pathogenic to normal hosts
- Have overt virulent factors
- Ex.
  - Coccidioides
  - Histoplasma
Most are opportunists
- Minimal virulence
- Must have pre-disposing conditions to cause disease
  - Loss of normal bacterial flora
  - Iatrogenic immunosuppression
  - Genetic or acquired immunodeficiencies
  - DM
  - Mechanical breach of skin/mucosal surfaces
  - Indwelling catheter
Serious disease is not common in immunocompetent host

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Fungal

Immunity

Responses vary with type
Innate immunity to most fungi is very high
- Neutrophil killing is the primary mechanism
  - Esp. against hyphae
  - Line up along hyphal surfaces and secrete lysosomal enzymes
- Conidia/spores requires Mφ ingestion
Intracellular forms ⇒ yeast
- Requires cell mediated immunity for elimination
- CMI important in most fungal infections
- Impaired CMI / low T-cell counts ↑ susceptibility to invasive fungal infections
Ab with minor role in resistance to fungi

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Fungi Propagation

Can be propagated on any nutrient medium
Mold forms ⇒ Sabaraud’s Dextros Agar (SDA)
- Growth of mold forms
- ID of spores (conidia)
- Low pH inhibits bacterial colonization
- Also includes some anti-bacterial agents
- Commonly takes 1-4 weeks to grow @ 25° C
Yeast forms cultivated at 37° C on specialized media
- Cutaneous forms frequently visualized in tissue specimens w/ KOH
- Can use lactophenol cotton blue to stain

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Fungal

Treatments

# of available treatments limited
- Due to common pathways and metabolic processes b/t fungi & mammalian cells
- Risk of toxicity high

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Aspergillus

Overview

Aspergillus fumigatus and Aspergillus flavus
- Most commonly associated with invasive disease
Opportunistic fungi
Disease usually associated with severe neutropenia
Found ubiquitously in the environment
Infection is acquired exogenously

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Aspergillus

Morphology

Exist as molds
Composed of septate hyphae
Branches @ 45° angles ⇒ dichotomous branching
- Characteristic of Aspergillus
Reproduce asexually by conidiaphore formation

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Aspergillus

Transmission

Spread by inhalation of conidiaspores

No person to person transmission

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Allergic Aspergillosis

Seen in people with chronic asthma or CF
Symptoms
- Episodic wheezing, fever, eosinophilia
- Transient pulmonary infiltrates
May become severe with age
Can lead to fibrosis

Aspergilloma

Usually seen in those with underlying lung diease
- Particularly those with pre-existing cavities in the lung
Non-allergic colonization
Chronic process with development of pathological changes in the lung
- Formation of Aspergillus containing granulomas
- Causes “fungus ball” formations on CXR
Granulomas must be surgically removed + antifulgal medications

Systemic or Invasive

Aspergillosis

Only in immunocompromised individuals
- Risk factor ⇒ neutropenia
May involve pulmonary, sinus, cerebral, or cutaneous sites
Pathogenesis involves angioinvasion, thrombosis, and dissemination to other organs
Damage caused by tissue infarcts, hemorrhage, and necrosis

Aspergillus

Diagnosis

Gomeri silver stain of tissue sections
- ID by dichotomously branched (45° angle) septate hyphae
Isolation in culture on Sabaraud’s Dextrose Agar (SDA)
Allergic aspergillosis
- Elevated specific IgE
- Eosinophilia
- Positive skin test (Type I) to Aspergillus Ag

Aspergillus

Immunology

Conidia (inhaled) ⇒ Mφ
Hyphae ⇒ neutrophils
- Line up along hyphal walls and secrete lysosomal enzymes
- Patrol blood vessels
  - Aspergillus is an angioinvasive organism
Neutropenia is the #1 risk factor for invasive aspergillosis

Aspergillus Treatment

**Amphotericin B** for invasive aspergilliosis Surgical removal of aspergilloma

Parasites Overview

* Refers specifically to **invertebrate animals that infest humans and other animals** * **Causes** **massive morbidity and mortality in developing countries** * Many have specific geographic distribution * Some with large distribution * Developed and undeveloped countries

Definitive Hosts

Species in which the parasite undergoes sexual reproduction.

Intermediate Host

Species in which a part or the whole process of asexual reproduction occurs.

Incidental Host

Unnatural host to which the parasite may not be adapted for replication. Leads to unusual pathology.

Vectors

Species capable of transmitting the parasite from one host to another.

Trophozoite

_Lifecycle form_ that **grows and replicates by binary fission** within the host.

Cyst

_Lifecycle form that is:_ * Dormant * Non-replicating * Resists environmental extremes * Frequently transmitted between hosts

Protozoa

* **Unicellular microbes** * Range in size from 2-100 microns * Have a cell membrane and numerous organelles * Organs of motility vary * Includes: * **Flagellates** * **Amoeba** * **Ciliates** * **Sporozoa**

Flagellates

* Cyst and trophozoite forms * Have flagella

Amoeba

* Cyst and trophozoite forms * Form pseudopods * Temporary arm-like projection of a eukaryotic cell membrane that are developed in the direction of movement

Ciliates

* Cyst and trophozoite forms * Have cilia

Sporozoa

* Frequently intracellular pathogens * Many forms: * Trophozoite * Sporozoite * Motile spore-like stage in the life cycle * Cysts * Gametes

Fungi

* Protozoa reclassified as degenerate fungi * Cell walls of chitin * Produces spores

Microsporidia

Obligate intracellular forms

Helminths

Multicellular worms

Nematodes

Round Teeth or plates for attachment

Trematodes

Flukes Oral and ventral suckers

Cestodes

Flat, segmented body (proglottids) Hooks or suckers for attachment Ex. hook worm

Parasite Epidemiology

More prominent in tropical/subtropical regions

Parasite Transmission

**Always acquired exogenously by multiple means:** * Direct penetration * Insect vector * Food borne

Parasite Pathogenesis

_Virulence factors:_ * Exotoxins * Hydrolytic enzymes * Proteinases * Migration through tissue * Mechanical blockage * Nutritional depletion

Host-Parasite Interactions

* **Most parasitic infections are chronic** * Some can live within a host for more than a decade * May induce pathology by **hypersensitivity** to parasite products and/or **autoimmunity** * May induce nutritional depletion

Parasite Host Defense Avoidance

* Ag variations * Camouflage * Acquisition of host Ag * Intracellular infection * Suppression or redirection of host immune response * Encystation * Escape from phagosomes or phagocytic mechanisms * Protective cuticles * Helminthes only

Parasitic Infection Diagnosis

* Most dx by ID of parasite or progency in clinical specimens * Cysts, eggs, larvae, worms * Understanding life cycle critical to effective dx