MEDICALLY IMPORTANT FUNGI AND PROTOZOA Flashcards
(10 cards)
Mycosis: Fungal disease. Five major groups of infections.
Superficial infections: Little or no reaction to infection. Essentially no pathology. No cellular response, remote from living tissue.
Malassezia furfur and M. ovalis: Common inhabitants of skin, restricted to the stratum corneum.
Causes discolored (depigmented) areas of skin on the chest, abdomen, back and arms (tinea versicolor).
Exophiala werneckii: Causes tinea nigra. Brown to black scaly macules on palms and feet.
Cutaneous infections: Dermatophytosis- Fungal infections with specific groups of fungi (Dermatophytes). Microsporum spp., Trichophyton spp., and Epidermophyton spp.
Colonize keratinized tissues (nails, hair, and stratum corneum). Non-invasive pathogens that produce an allergic, inflammatory response to metabolic products. Normally found in man, animals and soils.
Subcutaneous infections: Infections beneath the skin, but usually limited to the site of inoculation. Primary mode of entry is traumatic implantation of fungus through the skin. Little tendency to spread. Causative agents are usually normal soil inhabitants.
Chromoblastomycosis- Caused by dematiaceous (pigmented) fungi, commonly found in rotting wood and decaying forest litter. Phialophora spp., Fonsecaea spp., and others.
Sporotrichosis- Sporothrix schenckii- causes a wide spectrum of chronic diseases. Most are nodules and ulcers, limited to local area. Occasionally: spreads to bones and meninges, or (rarely) lungs.
Systemic infections: (True pathogenic fungi)
-Route of infection almost always respiratory. Primary infection is asymptomatic in 90-95% of all cases.
Strong immunity develops. Less than 5% of infections result in a respiratory disease, and a few cases result in disseminated disease, which is rare but very severe.
-Disease can result any time the inoculum is of sufficient size.
-The saprophytic (mycelial) form occurs in nature and is highly infectious.
The yeast form grows in infected individuals and is not-infectious (unless directly inoculated). -Usually geographically restricted.
Histoplasma capsulatum- (Causes Histoplasmosis.) A soil inhabitant, endemic to Midwestern US. Infection is by inhalation of conidia. Appears in tissue as intracellular yeast (in macrophages).
Blastomyces dermatitidis- (Blastomycosis) Seen in North and Central America, and in Africa. Infective form is conidia. Seen in tissue as budding yeasts.
Systemic spread may result in chronic granulomatous lesions of the skin and other organs.
Paracoccidioides brasiliensis- (South American blastomycosis). Infection is by inhalation of spores from soil. Appears in tissues as thick walled yeast cells with multiple buds.
Coccidioides immitis- (Coccidioidomycosis). Soil fungus, endemic to southwestern US. Infectious form is arthrospores from fractured hyphae. Appears in tissues as spherules. Initial respiratory infection may be followed by flu-like disease, hypersensitivity reactions and pulmonary lesions (“valley fever” syndrome).
Opportunistic infections: May be systemic, but these are not true pathogens.
-Causative agents are of low inherent virulence. Patient’s defenses must be abrogated before infection is
established. Formerly very rare, but now much more common due to AIDS, use of antibiotics, and
immunosuppressive drugs. Most opportunistic fungal infections can be attributed to a few species. -Some are present in small numbers as normal gut inhabitants and proliferate rapidly when the balance of
bacterial flora is upset. Some may gain entry to the body when a “barrier break” occurs.
-Opportunistic pathogens tend to have a very wide distribution, but dimorphism is not seen.
-Recovery does not give specific immunity. If defenses are weakened again, another outbreak can occur. Candida albicans- (Candidiasis). Oval budding yeasts. Normal flora of mucous membranes of respiratory,
GI, and female GU tracts. May become dominant and cause disease locally. May become systemic in
debilitated or immunosuppressed patients. Causes a wide variety of inflammations.
Cryptococcus neoformans- (Cryptococcosis). Thick carbohydrate capsule. Occurs widely in nature, often
associated with pigeon feces. Highly opportunistic in humans. Infection via respiratory tract.
Pneumocystis jerovecii (P. carinii)- Agent of PneumoCystis Pneumonia (PCP). Most common infectious cause
of death in AIDS patients. An extremely immunosuppressive yeast infection.
Fungi:
Single- or multi-cellular eucaryotic organisms that require organic compounds for nutrition.
Saprophytic Primarily soil dwellers and plant pathogens; a few medically important parasites. Aerobes, facultative anaerobes, and a few anaerobes.
Morphology: Yeast or mold. Classified on basis of gross and macroscopic appearance.
Yeasts: Non-filamentous, unicellular fungi. Round or oval shape. Reproduce by fission or budding. Molds: Thallus (body) consists of long filamentous cells (hyphae) that may or may not have septae
(crosswalls). A growing, intertwining mass of hyphae is a mycelium. Reproduce by forming spores (sexual or asexual) or by fragmentation of hyphae.
Dimorphism: Multiple forms. A few medically important fungi can grow as a mycelium or as yeast, depending on temperature and/or nutrition.
PROTOZOA- Kingdom Protista. (~20000 species)
Single-celled eukaryotes.
Mostly aerobic, water-dwelling heterotrophs.
Some are normal microbiota; a few cause disease. Parasitic forms must get from host to host. Reproduction: asexual (fission, budding, schizogony) or sexual (conjugation, gametocyte formation).
Encystment- Form a protective capsule (cyst); allows survival under adverse conditions. Trophozoite is the vegetative (actively feeding and reproducing) form.
Classification has undergone significant change recently (still not completed). Traditionally, the primary basis of classification of medically important species was means of locomotion. Recently, rRNA sequencing has provided a more accurate picture of evolutionary relationships, but has shuffled previously recognized groups.
Archaezoa- Lack true mitochondria (mitosomes). Flagellates.
Trichomonas vaginalis- vaginitis, urethritis. Host to host transfer, no cyst form. Giardia lamblia- enteritis from ingestion of cysts in contaminated water.
Microspora- Obligate intracellular parasites that lack mitochondria and microtubules. Nosema- Diarrhea and keratoconjunctivitis in AIDS patients
Amoebozoa- Amoebas. Move by extension of pseudopodia
Entamoeba histolytica- amoebic dysentery from ingestion of cysts
Acanthamoeba- primarily corneal infections. Central nervous system in the immunocompromised.
Apicomplexa- May be highly invasive, but mature forms are non-motile, intracellular parasites. Plasmodium- malaria, transmitted by mosquitoes (the definitive host) to man (the intermediate host). Toxoplasma gondii- invade and reproduce in tissues after ingestion of oocysts.
Associated with domestic cats; very dangerous to pregnant women
Cryptosporidium- potentially lethal respiratory and gall bladder infections in the immunosuppressed.
Oral transmission (feces or contaminated water). Phylum Ciliophora- ciliates
Balantidium coli- Ingestion of cysts leads to dysentery. Organism is occasionally invasive.
Euglenozoa- (hemoflagellate sub-group)
Trypanosoma brucei and T. rhodesiense (Euglenozoa)- African sleeping sickness (Trypanosomiasis). Transmitted by tsetse fly.
T. cruzi- Chagas disease, (American trypanosomiasis). Transmitted by kissing bug.
Naegleria fowleri (dinoflagellate and amoeboid forms)
HELMINTHS (worms- Kingdom Animalia)
Most are free-living, with well-developed systems.
These are absent or reduced in parasitic forms (except reproductive system).
Life cycle can be complex, with definitive and intermediate hosts.
Sexual reproduction only occurs in the definitive host asexual reproduction may occur in the intermediate host.
May be dioecious (separate sexes) or hermaphroditic (reproductive organs of both sexes in one body). Most parasitic forms are transmitted by ingestion of eggs (gastrointestinal route).
Phylum Platyhelminthes- flatworms; incomplete digestive system. 2 medically important classes. Trematodes (“flukes”)- Leaf-shaped bodies. Oral and ventral suckers for attachment and obtaining food.
Clonorchis sinensis- Asian liver fluke.
Paragonimus westermani- lung fluke. Man- definitive host. Snail and crayfish- intermediate hosts Schistosoma spp.- blood flukes. Intermediate forms penetrate skin
Cestodes- Tapeworms. Intestinal parasites.
Obtain nutrients by absorption.
Scolex- head with suckers or hooks
Proglottids- Body segments. Gravid (mature) are most distal.
Taenia saginata- beef tapeworm. Human is definitive host. Eggs shed in feces are ingested by cattle.
Larvae hatch from eggs, migrate to muscle and encyst. Human eats infected meat and cannot digest scolex.
Taenia solium- pork tapeworm. Human-pig life cycle similar to T. saginata, but rare in U.S. Human to human transmission- Eggs hatch and larvae encyst in the brain, causing cysticercosis.
Echinococcus granulosus- Dogs and coyotes are definitive hosts. Humans become infected by the oral route.
Eggs hatch, migrate to liver or lungs and develop to hydatid cysts. X-rays detect cysts, but diagnosis usually at autopsy.
Eggs are infective form
Enterobius vermicularis- pinworms. Ingested eggs hatch, worms mature in the colon, mate, and eggs are deposited near the anus or passed in feces.
Diagnosis by “tape” or “flashlight” methods.
Ascaris lumbricoides- Eggs excreted in feces survive in soil.
Ingested eggs hatch in intestines, mature in lungs, and migrate to intestine. Diagnosis by finding eggs (in stool sample) or appearance worms.
Larvae are infective form
Necator americanus- Hookworm. Adult worms inhabit the intestine.
Eggs are excreted in feces; larvae hatch and develop in soil.
Larvae penetrate the skin, and travel through the blood or lymphatics to the lungs.
From there they are coughed up and swallowed. Eventually they attach to the lining of the intestine.
Diagnosis is by finding eggs by microscopic examination of feces.
Trichinella spiralis- Causative agent of trichinellosis (trichinosis).
Transmission is usually by ingestion of encysted larvae in poorly cooked pork or bear meat.
Larvae mature to adults in intestine and reproduce.
Second generation larvae hatch, migrate throughout the body, and become encysted in muscle tissue. Diagnosis is by microscopic examination of encysted larvae in muscle tissue.
VIRUSES
Characteristics
One type of nucleic acid: RNA or DNA, surrounded by a protein coat. Some have an envelope (lipid membrane) around the protein coat Obligate intracellular parasites-
Multiply only within living cells. Has few enzymes of its own.
Lacks ability to make proteins or ATP. Takes over the cell’s “synthetic machinery”. The host range of viruses is very specific.
Structure
Virion- a complete virus particle
Nucleic acid (NA)- A single type (DNA or RNA, never both). Single stranded (ss) or double stranded (ds).
Linear, circular, or segmented (multiple strands) ssRNA virus may be + or -.
Plus sense RNA (+RNA, or sense) can be used directly as mRNA and translated to protein.
Minus sense RNA (-RNA, or anti-sense) cannot be used as mRNA. It is complementary to mRNA. Capsid- the protein coat. Protects the nucleic acid.
Capsomeres- Protein subunits that make up the capsid.
Some types are enveloped; others are non-enveloped (naked viruses).
The envelope is derived from the host cell plasma membrane or nuclear membrane as virus “buds out”. Consists of lipid, polysaccharide, and plasma membrane proteins (host and viral encoded).
Morphology
Size- ranges from ~20 nm to 14 μm (14000 nm). Largest are about the size of the smallest bacteria
Shape
Helical- Rod-shaped capsid with a hollow core (for NA), rigid or flexible. May be enveloped. Icosahedral- 20-sided, triangular faces, 12 corners. May be enveloped.
Complex viruses- bacteriophage
CLASSIFICATION - Roughly on the basis of NA type, morphology, and envelope. DNA viruses:
DNA viruses:
Adenovirus: ds; icosahedral, naked capsid with spikes (Fig. 13.1). Respiratory diseases, animal tumors. Papovavirus: (papilloma, polyoma, and vacuolation viruses) ds, icosahedral, naked.
Papilloma viruses may cause warts, epithelial abnormalities, and cancer. Parvovirus: ss, icosahedral, naked. Mostly animal infections.
May cause fetal deaths and gastroenteritis in humans. Needs Adenovirus co-infection.
Herpesvirus: ds, icosahedral, enveloped.
Cold sores and genital herpes, chickenpox (and shingles), infectious mononucleosis, Burkitt’s lymphoma.
Hepadnavirus: the Hepatititis B Virus (HBV)- ds, icosahedral, enveloped.
Has an RNA dependent DNA polymerase (reverse transcriptase). Causes Hepatitis B and liver cancer.
Poxvirus: ds, complex (brick-shaped), enveloped. Skin lesions (pus filled)
RNA viruses:
Picornavirus: ss(+), icosahedral, naked. Smallest viruses (pico-rna).
Rhinovirus (common cold) and Enterovirus (enteric diseases, including polio and hepatitis A) Togavirus- ss(+), icosahedral, enveloped. Arthropod borne equine encephalitis; rubella.
Flavivirus- ss(+), icosahedral, enveloped. Hepatitis C, yellow fever, dengue, West Nile encephalitis. Coronavirus- ss(+), icosahedral, enveloped. Common cold and severe acute respiratory syndrome (SARS). Rhabdovirus- ss(-), helical (bullet-shaped) with spikes; enveloped. RNA dependent RNA polymerase.
Rabies and other animal diseases.
Filovirus- ss(-), helical, enveloped. Ebola, Marburg and other hemorrhagic fevers.
Orthomyxovirus- segmented ss(-), helical, envelope spikes (hemagglutinin and meuraminidase). Influenza. Retrovirus- ss(+), icosahedral, enveloped. Reverse transcriptase.
Provirus- becomes integrated in host genome. Tumors, animal leukemias, AIDS. Reovirus- dsRNA, icosahedral, naked. Respiratory enteric orphans.
Viral propagation
Bacteriophage: A. Lytic cycle
Attachment: Receptor mediated, hydrogen bonding of phage tail fibers and bacterial cell wall Penetration: Virus enzyme makes a hole, tail penetrates and DNA is directly injected. Biosynthesis: Host synthesis is blocked or stopped and synthesis of viral protein and NA occurs.
Early genes code for enzymes to replicate the genome; late genes code for capsid proteins Maturation: Assembly of virus particles. Appears to be spontaneous
Release: Lysis of cell. Plasma membrane erupts and virus is released
B. Lysogenic cycle: host cell is not lysed. Virus integrates in bacterial chromosome (Prophage).
Host cell is resistant to further infection by the same phage. Virus may remain inactive for a long time. Host cell may exhibit new characteristics. Transduction may occur. Can return to lytic cycle
Animal cell viruses- Similar to bacteriophage. An additional step is required.
Attachment- Viral surface proteins bind cell plasma membrane proteins and glycoproteins (receptors) Penetration- Endocytosis of the entire virion (non-enveloped), or fusion of the virus envelope with the host
cell’s plasma membrane occurs. The virus capsid is then released into the host cell’s cytoplasm.
Uncoating- NA is not injected, so the capsid must be removed. May be accomplished by viral or host enzymes. Biosynthesis: There are variations, depending on the type of viral NA.
DNA viruses: DNA synthesis usually occurs in the nucleus, with viral enzymes. Protein synthesis is in the cytoplasm, with host enzymes. (Fig.13.15)
RNA viruses: A variety of unique strategies and enzymes for replicating genome (Fig.13.17) +RNA viruses: Synthesize -RNA to serve as a template to make new genomes and mRNA -RNA viruses: Synthesize +RNA which is mRNA and a template for -RNA genomes
Retrovirus: Synthesizes DNA from RNA and must integrate to host chromosome (13.19) Maturation: Capsid assembly is usually spontaneous.
In nucleus for most DNA viruses; in cytoplasm for RNA viruses
Release: By rupture of plasma membrane (lysis) or by budding, host cell may survive a long time.
Latent infections may be observed (Herpesvirus)
B. Lysogenic cycle: host cell is not lysed. Virus integrates in bacterial chromosome (Prophage).
Host cell is resistant to further infection by the same phage. Virus may remain inactive for a long time. Host cell may exhibit new characteristics. Transduction may occur. Can return to lytic cycle
Animal cell viruses- Similar to bacteriophage. An additional step is required.
Attachment- Viral surface proteins bind cell plasma membrane proteins and glycoproteins (receptors) Penetration- Endocytosis of the entire virion (non-enveloped), or fusion of the virus envelope with the host
cell’s plasma membrane occurs. The virus capsid is then released into the host cell’s cytoplasm.
Uncoating- NA is not injected, so the capsid must be removed. May be accomplished by viral or host enzymes. Biosynthesis: There are variations, depending on the type of viral NA.
DNA viruses: DNA synthesis usually occurs in the nucleus, with viral enzymes. Protein synthesis is in the cytoplasm, with host enzymes. (Fig.13.15)
RNA viruses: A variety of unique strategies and enzymes for replicating genome (Fig.13.17) +RNA viruses: Synthesize -RNA to serve as a template to make new genomes and mRNA -RNA viruses: Synthesize +RNA which is mRNA and a template for -RNA genomes
Retrovirus: Synthesizes DNA from RNA and must integrate to host chromosome (13.19) Maturation: Capsid assembly is usually spontaneous.
In nucleus for most DNA viruses; in cytoplasm for RNA viruses
Release: By rupture of plasma membrane (lysis) or by budding, host cell may survive a long time.
Latent infections may be observed (Herpesvirus)
CANCER: A multi-step process. Initiation
Promotion
Progression.
Result is an inability of cells to recognize signals telling them to stop growing.
The uncontrolled growth leads to tumor formation.
Transformation- Alteration of genetic material to make a normal cell cancerous
Proto-oncogenes are host genes that are sites of transforming alterations. These genes are typically necessary for
normal cellular function. Most code for proteins involved with signal transduction or programmed cell death. Certain virus infections may result in alterations of proto-oncogenes to oncogenes. Expression of oncogenes may lead to the unregulated cell division characteristic of cancer.
Virus groups associated with cancer
DNA: Adenovirus, Herpesvirus, Poxvirus, Papovavirus, Hepadnavirus; RNA: Retrovirus
