Block V, Week VI
Terms
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- what is the "hygiene hypothesis?"
- the idea that at a young age we are exposed to nonpathogenic organisms and make antibidies to them. These antibodies can crossreact with pathogenic organisms encountered later in life. When a child grows up in a clean, hygenic house it is hypothesized that they are more prone to infection.
-
regarding AIDS:
1. what is the "top" viral opportunistic infection?
2. what is the "top" bacterial opportunistic infection? -
1. Cytomegalovirus (CMV) retinitis
2. MAC (mycobacterium avium-intracellular complex) -
regarding AIDS:
1. what is the "top" protozoal oppportunistic infection?
2. what is the "top" fungal opportunistic infection? -
1. Toxoplasmosis of the brain
2. PcP - Pneumocystis jirovecii pneumonia - which bacterial opportunistic infection is very similar to TB but only causes symptoms in the immunocompromised host?
- MAC (Mycobacterium avium-intracellular complex)
- what are 6 characteristics of fungi?
-
1. eukaryotic
2. non-photosynthetic
3. chitin cell walls
4. Spores (asexual or sexual)
5. can be single celled (yeast)
6. can be filamentous (molds, hyphae, mycelium) - what are the 4 classes of fungi?
-
1. Ascomycetes
2. Basidiomycetes
3. Zygomycetes
4. Deuteromycetes
(ABZD) - what are the sexual spores of Zygomycetes called and are they internal or external spores?
- Zygospores (external)
- what are the asexual spores of Zygomycetes called and are they internal or external spores?
- Sporangiospores (internal)
- what are the sexual spores of Ascomycetes called and are they internal or external spores?
- Ascospores (internal)
- what are the asexual spores of Ascomycetes called and are they internal or external spores?
-
Conidiospores (external)
"ascus" - "little sac" - what are the sexual spores of Basidiomycetes called and are they internal or external spores?
-
Basidiospores (external)
"basidio" = stick - what are the asexual spores of Basidiomycetes called and are they internal or external spores?
- Conidiospores (external)
- What are the asexual spores of Deuteromycetes called and are they internal or external spores?
- Conidiospores (external)
- In summary:which classes of fungi have asexual spores that are CONIDIOSPORES and are EXTERNAL?
-
Ascomycetes
Basidiomycetes
Deuteromycetes
(all but Zygomycetes) -
How would a fungal disease...
1. cause allergies?
2. manifest in the skin?
3. manifest in the respiratory system? -
1. airborne spores
2. athelete's foot, ringworm
3. similar to and often confused w/ TB - How does a KOH mount help us identify fungi?
- the acid disintegrates the tissue, leaving only the fungal hyphae to see.(this is due to acid resistance by their chitin walls)
- what is the name of the stain that causes fungi to fluoresce green or blue-green?
- Calcofluor white
- India Ink (nigrosin) is useful to identify which fungi in which fluid?
- THE CAPSULE OF Cryptococcus neoformans in CSF
- India ink is essentially what kind of stain? (what does it "pick out")
- India ink is a negative stain for fungal capsules.
- What does PAS (Periodic Acid Schiff) stain?
- PAS stains carbohydrates in the chitin cell wall
- What color do fungi stain in a Gomori-Silver stain?
- black or deep brown
- What are the 6 antifungal antibiotics available?
-
1. Amphotericin B (and derivatives)
2. 5-fluorocytosine
3. Azoles
4. KI
5. Topicals
6. Griseofulvin - What is the MOA of amphotericin B?
- destroys membrane function by binding sterols
-
What is the drawback of amphotericin B?
(be specific) -
nephrotoxicity
(kidneys have lots of sterols) - what are the two derivatives of amphotericin B?
-
1. ABLC (Amphotericin B Lipid Complex)
2. ABCD (Amphotericin C Colloidal Dispersion) - What are the advantages of using amphotericin B derivatives (ABLC, ABCD) instead of amphotericin B?
- less nephrotoxicity
- Which fungus is ABCD as effective as amphotericin B against?
- Aspergillus
-
1. what is the MOA of 5-fluorocystine?
2. what are the advantages and drawbacks? -
1. Inhibits DNA synthesis
2. less toxic,
only effective against a limited range of fungi. - Name 2 commonly used Azoles
-
fluconazole
ketoconazole - MOA of Azoles?
-
inhibits ergosterel synthesis
(ergosterel is specifically made in the fungal membrane) - What is the only organism KI is effective against?
- Sporotrichosis
-
1. Topicals are good against?
2. example of a topical? -
1. dermatophytoses
2. tolnaftate - What is the name of the oral drug used for severe systemic dermatophytoses?
- Griseofulvin
- MOA of Griseofulvin?
- interferes with microtubule function
-
1. which organism causes Pneumocystis pneumonia (PcP)?
2. what is significant about this organism? -
1. Pneumocystis jirovecii
2. It only causes pneumonia in immunocompromised persons. - what is a typical microscopic observation seen when diagnosing PcP?
-
dark black cysts in lung
(seen with Grocott silver stain) - what is the recommended treatment for PcP?
- cotrimoxazole or pentamidine
- which antifungal can be administered prophylactically to prevent PcP?
- cotrimoxazole
- Along with PcP, what is one of the most frequent fungal diseases?
-
Candidiasis
(Candida albicans ~60%) - Structural characteristics of Candidiasis?
-
dimorphic:
pseudomycelial form
"germ tube" formation at 37 deg.C - what is the normal habitat/reservoir for Candida?
-
mouth
large intestine
vagina - what three lab tests are used to diagnose Candidiasis?
-
1. germ tube test
2. cornmeal test
3. sugar assimilation -
what is the name of the Candidiasis infection in the...
1. mouth
2. Skin
3. Vagina
4. corners of mouth -
1. Thrush
2. Cutaneous Candidiasis (dermatocandidiasis)
3. Vaginitis
4. perleche -
What is the treatment for:
1. Thrush
2. Cutaneous candidiasis
3. Systemic candidiasis -
1. restore normal flora (lactobacilli in yogurt)
2. topical Tx: clotrimazole or nystatin
3. Amphotericin B - why is Candida albicans considered an opportunistic fungi?
- in the immunocompromised person it can cause systemic Candidiasis
- Cryptococcosis usually begins with _1__ and can spead to the __2__ or __3__ to cause __4__ or __5__.
-
1. lung infection
2. blood
3. lymph
4. meningitis
5. skin lesions -
what is the treatment regimen for cryptococcosis?
- what for lung inf. and meningitis
- what for skin lesions -
- Amphotericin B (lung infection and meningitis)
- fluconazole (skin lesion) - when cryptococcosis is seen in the clinic what kind of suspicion should be raised?
-
AIDS
80-90% of cases worldwide
>50% of cases in U.S. - where is Cryptococcosis more common than PcP as an opportunistic pathogen?
- Africa and Southeast Asia
- what is the habitat/reservoir of Cryptococcosis neoformans?
-
pigeon or other bird droppings
eucalyptus trees - describe the physical characteristics of Cryptococcus neoformans
-
dimorphic
filamentous mycelium at room temp.
at 37 deg. C yeast produces a VERY LARGE CAPSULE (this capsule is easily seen with India ink negative stain) -
1. What is the method of transmission for Cryptococcosis?
2. What contributes to its virulence? -
1. inhalation of spores
2. antiphagocytic capsule - How is Cryptococcosis diagnosed in the lab?
-
1. in meningitis cases: direct examination of CSF
2. in pneumonia cases: direct examination of sputum and tissue
3. brown colonies on birdseed (niger) agar - Which class of fungi (1) and specific genera (2) cause phycomycosis (mucormycosis)?
-
Fungi - Zygomycetes
Genera - Rhizopus, Mucor -
1. Which organism causes Aspergillosis?
2. Describe the organism structure
3. Which other fungal organism has a similar structure? -
1. Aspergillus fumigatis
2. structure - filamentous "bread mold"
3. Penicillin -
1. What is a potential complication of Aspergillosis?
2. How often does this occur in Aspergillosis cases? -
1. spread to heart and CNS
2. 25% of cases - what would you prescribe to treat Phycomycosis, Aspergillosis and Penicillinosis?
- Amphotericin B
- a systemic rash that is an allergic reaction (to circulating antigen that originated from a primary dermatophyte infection) is known as?
- dermatophytid (ID) reaction
- In diagnosing a dermatophytosis, which causative organism will show up on a PAS stain?
- Pityriasis versicolor
- Which species of fungi fluoresces under a Wood's light?
- Microsporum
-
fill in the following for the Microsporum species:
1. Infection site
2. # of Macroconidia
3. wall type of macroconidia
4. # of Microconidia -
1. skin, hair
2. lots
3. thick, rough
4. lots -
fill in the following for the Trichophyton species:
1. Infection site
2. # of Macroconidia
3. wall type of macroconidia
4. # of Microconidia -
1. skin, hair, nails
2. few
3. thin, smooth
4. few -
fill in the following for the Epidermophyton species:
1. Infection site
2. # of Macroconidia
3. wall type of macroconidia
4. # of Microcondia -
1. skin, nails
2. in 2's and 3's
3. thick, smooth
4. none - What are the three classes of dermatophytes?
-
1. Microsporum
2. Trichophyton
3. Epidermophyton - Describe the hallmark symptoms of Sporotrichosis
-
"Gardener's disease"
1. begins as a primary lesion, usually on hands or feet
2. chain of lesions move along the lymphatics up the arm - what is the etiologic agent of Sporotrichosis?
- Sporothrix shenckii
- Describe the morphology of Sporothrix shenckii
-
Dimorphic
filamentous hyphal form at room temp. ("floret" conidiospores)
"cigar" form yeast, often in "cigar packets" - Chromomycosis is often confused with what subcutaneous mycosis because they present similarly?
- Bacterial mycetoma
- what is the clinical presentation of both chromomycosis and bacterial mycetoma?
- large, distended swelling of the infected area
- What are the casuative agents of Chromomycosis (2) and what type of fungi are they?
-
1. Cladosporium
2. Phialophora
Both are "dematiaceous" (dark colored) fungi - What is the main diagnostic feature of chromomycosis?
- can see brown to black hyphae without using any tissue stain
- which organism is responsible for bacterial mycetoma (namely Madura foot and Lumpy jaw)
- Actinomyces israelii
- what are the diagnostic features of (A. israelii caused) bacterial mycetoma?
-
1. "sulfur granules" (bacterial colonies)are present in the exudate and visible to the human eye
2. dark filaments seen microscopically - which two stains are commonly used in diagnosis of (A. israelii caused) bacterial mycetoma?
-
1. Brown & Benn stain
2. Gomori methamanine silver stain - how can you tell the difference between a bacterial mycetoma caused by Actinomyces israelii or Nocardia asteroides?
-
A. isrealii - anaerobic
N. asteroides - aerobic
(both are Gram + branching rods) - what are the 2 fungal caused subcutaneous mycoses?
-
1. Sporotrichosis
2. Chromocycosis - what are the 3 fungal caused systemic mycoses?
-
1. Histoplasmosis
2. Blastomycosis
3. Coccidiomycosis - what are the general morphological characteristics of organisms causing systemic mycosis?
-
dimorphic
filamentous at room temp.
yeast form at 37 deg. C - what is the general method of transmission of systemic mycosis infections?
-
aerosol/respiratory
*no known human to human transmission* - which fungus causes Histoplasmosis?
- Histoplasma capsulatum
-
regarding H. capsulatum:
1. at room temp. it resembles?
2. at 37 deg. C it resembles a yeast that divides how? -
1. "tuberculate" macroconidia (looks like thing on the end of a mace)
2. with a narrow neck between daughters - what contributes to the virulence of Histoplasma capsulatum? (how does it infect the host cells)?
- it is an intracellular macrophage parasite
- what is the habitat/reservoirs of H. capsulatum?
-
bird droppings
guano - where is H. capsulatum geographically prevalent?
-
in the Midwestern U.S.
(around Mississippi and Ohio rivers) - Histoplasmosis often begins as __1___. It can then disseminate to which organs?
-
1. pneumonia or TB mimic (flu-like symptoms)
2. organs with macrophages (blood, bone marrow, spleen, liver, lung) - what is the recommended treatment for Histoplasmosis?
- Amphotericin B
- What is the organism that causes Blastomycosis?
- Blastomyces dermatitidis
- what is the dimorphic difference between blastomycosis and histoplasmosis?
-
at 37 deg. C:
histo-narrow neck between daughters
blasto-thick neck between daughters (Blasto=BroadBasedBuds) - how does blastomycosis present?
-
1. pulmonary, "flu-like" symptoms
2. acute pneumonia or TB mimic
3. dissemination (cutaneous or any other organ - bones, urogenital, CNS etc) - what is the organism that causes Coccidioidomycosis?
- Coccidioides immitis
- describe the morphology of C. immitis
-
dimorphic
filamentous arthrospores (barrel-shaped spores in hyphae) at room temp.
spherules (large spheres filled with spores)seen at body temp. - where is Coccidioidomycosis commonly seen and where is it prevalent?
-
commonly seen (free-living) in SW US deserts
prevalent in San Jaoquin Valley, CA (hence "San Joaquin Valley Fever") - what is the mode of transmission of coccidioidomycosis?
- VERY EASILY AEROSOLIZED, arthrospores are inhaled, cause spherules to grow in the lung.
- describe the clinical course of coccidiomycosis
-
1. "San Joaquin Valley Fever" - pneumonia, flu-like symptoms
2. can disseminate to any organ, VERY DANGEROUS - what is notable about coccidioidomycosis?
- it is the MOST RAPIDLY FATAL OF ALL SYSTEMIC FUNGAL INFECTIONS
- what is the diagnostic feature of coccidioidomycosis?
- spherules in sputum
- what is the preferred treatment for all the systemic mycoses?
- Amphotericin B
- define mycelium
- the mass of hyphae that make up the body of a fungus
- what is an arthrospore?
- a spore resulting from the fragmentation of a hypha
- define conidia
-
asexual spores produced by fungi
(have Micro- and Macro-) - What are the four forms of possible transplant rejection?
-
1. Hyperacute
2. Acute
3. Chronic
4. Graft-vs-host - which immunodeficiency disorder is caused by a failure of B cells to mature?
- Brutons agammaglobulinemia
- what is the heredity of Bruton's agammaglobulinema?
-
X linked recessive
Boys get it - what is the cause of Bruton's agammaglobulinema?
- mutation in tyrosine kinase - B cells never mature
- Hallmark of Bruton's agammaglobulinema?
- recurrent bacterial infections
-
In Bruton's agammaglobulinema: Describe B cell levels in
1. serum
2. bone marrow
3. What about T cells?
4. What about plasma cells? -
1. Decreased
2. B cell precursors are present
3. T cells are uneffected
4. Plasma cells are nonexistant - What is the treatment for Bruton's agammaglobulinema?
- Prophylactic IV Immunoglobulin
-
Describe symptoms seen in an IgA deficiency (4)
(remember most patients are asymptomatic) -
1. low levels of serum and secretory IgA
2. recurrent pulmonary infections, diarrhea
3. allergies
4. other autoimmune diseases - What is the thing to watch out for in patients with an IgA deficiency?
-
BE CAUTIOUS WITH TRANSFUSIONS
Many patients have serum Antibodies to IgA: this can cause a serious rxn. in tranfusion of blood with normal IgA antibodies in it. - What are the serum B cell levels in CVID?
-
normal
B cells just don't differentiate into plasma cells -
compare the pathology of lymphoid follicles seen in:
1. CVID
2. Bruton's agammaglobulinema -
1. hyperplastic lymphoid follicles
2. NO lymphoid follicles - describe the pathophysiology of hyper-IgM syndrome
-
- T cell disorder
- failure to isotype switch, therefore the only antibodies made are IgM
- results in immunodeficiency - what is the hallmark presenting symptom of hyper-IgM syndrome?
- Recurrent pyogenic infections
-
in hyper-IgM syndrome describe:
1. the serum B and T cell levels
2. Serum of the levels of different types of antibodies? -
1. B and T cells levels normal
2. Increased IgM
very little IgA, IgE, IgG - what is the cause of DiGeorge syndrome (Thymic aplasia)
-
Thymus and parathyroid glands fail to develop (because 2nd and 3rd pharyngeal pouches did not develop correctly)
Result: No T cells and hypocalcemia - what do patients with DiGeorge syndrome (thymic aplasia) present with?
- recurrent fungal and viral infections (due to loss of T cell mediated immunity)
- describe severe combined immunodeficiency (SCID)
-
NO T cells or B cells
therefore a defect in humoral and cell mediated response - What is the treatment for an individual with SCID?
- Bone marrow transplant
- describe the pathology of Wiscott-Aldrich Syndrome
-
X linked defect
- loss of cell mediated and humoral immunity
- still have a thymus -
in Wiscott-Aldrich Syndrome what are the levels of the following:
1. IgM
2. IgG
3. IgE
4. IgA -
1. low
2. normal
3. elevated
4. elevated - presenting symptoms of a patient with Wiscott-Aldrich Syndrome?
-
WIPE:
Wiscott-Aldrich
Infection
Purpura
Eczema
(also thrombocytopenia) - what are the symptoms of a person who has a deficiency of C5,6,7,8,9 (complement mediators)?
- Recurrent Neisserial infections
- what are the symptoms of a person who has a deficiency of C1 inhibitor?
-
Hereditary angioedema
(overactive complement) - compliment defends against what kind of bacteria?
- Gram negative
- which antibodies activate the classic pathway of compliment?
-
IgG
IgM
(GM makes CLASSIC cars) - what activates the alternate pathway of compliment?
- molecules on the surfaces of microbes (esp. endotoxin)
-
which type of transplant rejection am I?
* Occurs weeks after transplantation
*Cell mediated due to cytotoxic T cells reacting against foreign MHCs - Acute Rejection
-
Which type of transplant rejection am I?
* Antibody mediated vascular damage (fibrinoid necrosis)
*occurs months to years after transplant - Chronic rejection
-
which type of transplant rejection am I?
* antibody mediated due to already present anti-donor antibodies in the recipient.
*occurs within minutes of transplantation - Hyperacute Rejection
-
which type of transplant rejection am I?
* Grafted T cells reject host cells
* results in severe organ dysfunction - Graft-versus-Host disease
- What are some symptoms of Graft-versus-Host disease? (4)
-
jaundice
maculopapular rash
hepatosplenomegaly
diarrhea - what are the 5 groups at risk of contracting AIDS?
-
1. homosexuals
2. IV drug users
3. Blood recipients
4. hemophiliacs (recieve factor VII or IX)
5. heterosexuals making contact with high risk groups - How can vertical transmission of HIV occur? (3)
-
- transplacental
- via birth canal
- via breast milk