Quiz 2 Flashcards
What is ergosterol?
A substance similar to cholesterol found in fungal cell walls
What enzyme in the fungal cell wall is responsible for synthesizing ergosterol?
14-a-demethylase
What drug classes are used to target 14-a-demethylase in fungal cell walls?
Azoles
Do the following descriptors better match a yeast or mold?
Yeast
Do the following descriptors better match a yeast or mold?
Mold
Does the pictured agar resemble a yeast or a mold?
Yeast
Does the pictured agar resemble a yeast or a mold?
Mold
A multicellular, filamentous organism would most likely be a yeast or a mold?
A mold
In molds, what word is used to describe thread-like filaments?
Hyphae
What name is given to hyphae interweaves in molds?
Mycelium
What is the makeup of over 90% of the fungal cell wall?
Polysaccharides
Are yeasts multicellular?
Yeasts grow by budding. What is another name for a bud?
A blastoconidia
True hyphae (not pseudohypha) begin as what transient structure from the parent yeast cell?
A germ tube
What is an example of a yeast that makes psuedohyphae and true hyphae?
Candida albicans
Is candida albicans germ tube + or germ tube -?
Germ tube +
What descriptor of pseudohyphae differentiates it from true hyphae?
Pseudohyphae resembles sausage-links (septate/non-septate hyphae will resemble branches)
What are the correct names for asexual and sexual sporulation?
Asexual state- anamorph
Sexual state- teleomorph
How do yeast reproduce?
Budding
How do molds reproduce?
Production of conidia (conidiospores, or separation of hyphal elements)
How do yeasts/molds undergo sexual sporulation?
Halpoid nuclei of donor and recipient fertile cells/spores fuse
What are the temperature constraints of dimophic fungi?
Mold at 25-30 C
Yeast at 35- 37 C
Define endemic fungi:
Fungi geographically restricted in the environment
Define opportunistic fungi:
Fungi that only cause disease in compromised hosts
Define dermatophytes:
Fungi causing superficial skin infections
Define dematiaceous fungi:
Dark brown-black pigmented molds
Is Candida albicans dimorphic?
Yes, but for the purpose of H&D, think of it as a yeast
What are 2 pros and 2 cons for Direct microscopy lab testing for yeasts/molds (KOH +/- Calcofluor)?
What are pros and cons for a culture in testing for yeasts/molds?
What are the pros and cons for PCR in testing for yeasts/molds?
What laboratory test is the gold standard for invasive disease?
Histopathology
What is the moa of terbinafine?
Inhibition of squalene epoxidase
What drug class inhibits glucan synthase?
Echinocandins
What four criteria are required for fungal pathogens to cause disease?
1) Growth at or above 37 C
2) Penetrate host barriers
3) Digest/absorb nutrients
4) Evade immune system
What is a definite host in the context of parasitism?
Where sexual maturity & reproduction occur for completion of transmission cycles
What is an intermediate host in context of parasitism?
Where asexual or developmental stages occur (larvae, excystation, etc), but not competent for development to final lifecycle stages
What is a reservoir host in context of parasitism?
A host which harbours only immature stage; used for further trasmission
What is a dead-end or accidental host in context of parasitism?
Various levels of life cycle can occur, but cycle cannot complete and gametes fail to perpetuate or fully mature
What are two significant histological features of Plasmodium falciparum?
Is induction immunosuppression necessary before surgery?
Not necessarily, but it is often used to optimize patient outcomes
What are the three chief roles of induction immunosuppression therapy?
1) Potent acute immunosuppression in peri-operative period
2) Minimize risk of acute rejection in early post- transplant period
3) Allow for delay in initiation of CNI/allows medications to reach therapeutic levels
What are the two primary roles of maintenance immunosuppression therapy?
1) Prevent chronic organ transplant rejection
2) Minimize drug toxicity
What primary immunodeficiency is caused by a loss of the common gamma chain (IL-2R-gamma)?
X-linked Severe Combined Immunodeficiency (SCID)
What is the status of the T cells, NK cells, B cells, and antibodies of a patient diagnosed with X-linked SCID?
Absent T & NK cells
B cells may be present
No functional antibodies
Would a patient diagnosed with X-linked SCID have germinal centers in their lymph nodes/spleen? Why not?
No, the absence of Tfh cells prevents naive B cells from being activated
What are common symptoms of X-linked SCID?
Failure to thrive
Recurrent infections
Chronic diarrhea
What is the role of Bruton’s tyrosine kinase in developing B cells?
Successful heavy chain rearrangement of developing B cells culminates in an intraceullular signal mediated by Btk promoting cell survival
Failed heavy chain rearrangement culminates in apoptosis of the developing cell
85% of X-linked agammaglobulinemia cases are due to a deficiency in what?
Bruton’s tyrosine kinase (Btk)
Why do patients with X-linked agammaglobulinemia lack the capacity to produce Ig?
B cells cannot mature due to lack of Btk -> developing B cells will apoptose
What are clinical symptoms of X-linked agammaglobulinemia?
Recurrent sinusitis, otitis media, pneumonia starting at least 6mo after birth with chronic enteroviral meningoencephalitis
What is a granuloma?
What is the MoA of Calcineurin inhibitors (Tacrolimus, Cyclosporin)?
CNIs bind to immunophilins -> Immunophilin complex binds calcineurin & prevents NFAT activation -> Reduced T-cell activation & proliferation
What is the mechanism of X-linked Hyper IgM?
A defect in CD40L -> poor AID activity -> defective affinity maturation and isotype switching (i.e. Tfh and Th1 cannot effectively influence B cells)
What blood abnormalities are consistant with X-linked hyper IgM?
High IgM, with low IgG and IgA, as well as neutropenia
What is the clinical presentation of Hyper IgM syndrome?
Onset 6 months after birth, with recurrent bacterial and opportunistic infections (Pneumocystis jirovecii pneumonia)
What is the mechanism of IgA deficiency?
Defect in IgA production, usually associated with autoimmune disease or anaphylatic reaction to blood transfusion
*Can progress to CVID
What is the clinical presentation of IgA deficiency?
80-90% asymptomatic, but can present with sinopulmonary infections, Giardiasis
What is the mechanism of CVID?
Mostly unknown etiology, but about 10% if TACI
Defects in antibody production, low IgG and/or IgA and/or IgM
What is the clinical presentation of CVID?
Usually adult onset (2nd or 3rd decade)
Recurrent sinopulmonary infections (i.e. Giardia)
What is the etiology of chronic granulomatous disease? What is the clinical test that can be administered?
Defects in NADPH oxidase
CT: Phagocytes fail to reduce nitro blue tetrazolium (NBT)
Granulomatous disease poses an extra risk of infection by what type of organisms?
Catalase-expressing organism infections (Staph Aureus, Pseudomonas, Candida, etc)
What is the etiology of Leukocyte adhesion deficiency (LAD)?
Defect in subunit of LFA-1 (CD18)
What is the clinical presenation of LAD?
-Neutrophilia
-Failed Rebuck test
- Low CD18
-Delayed separation of umbilical cord
-Poor wound healing w/ no pus
What two disorders are primarily due to defects in complement?
Hereditary angioedema
PNH
What is the etiology of Hereditary angioedema?
Defect in C1 INH -> increased bradykinin -> vascular permeability leads to diffuse edema
When does Hereditary angioedema typically increased in severity?
Late childhood or adolescence
What is the etiology of PNH? What particlar organism does this condition increase susceptibility to?
PIG-A can’t add GPI anchors to cells -> poor surface expression of DAF, CD59 -> sporadic RBC lysis
Neisseria meningitidis
What is the etiology of DiGeorge syndrome (complete)?
22q11 deletion
Defects in 3rd/4th pharyngeal pouches lead to thymic hypoplasia -> deficient T cell maturation
What is the clinical presentation for DiGeorge syndrome?
Absent parathyroid, abnormal development and facial abnormalities, as well as small or absent thymus
What is the MOA, CU, and TOX for Acetaminophen?
MOA: Inhibition of peroxidase in CNS?
CU: Analgesic, antipyretic (NOT anti-inflammatory)
TOX: Hepatotoxicity and liver failure in overdose
What is the MOA, CU, and TOX for Aspirin?
MOA: Irreversible inhibition of COX 1 & 2
CU: Analgesic, antipyretic, anti-inflammatory, anti-platelet agent
TOX: Tinnitus, nephrotoxicity, GI pain & ulcer risk, prolonged bleeding time, increased risk of MI/stroke w/ long term use
Which NSAID has a unique risk of Reye’s syndrome in children?
Aspirin
What is the MOA, CU, and TOX of ibuprofen and naproxen?
MOA: Inhibition of COX 1 & 2
CU: Analgesic, antipyretic, anti-inflammatory
TOX: Acute interstitial nephritis, nephrotoxicity, GI pain & ulcer risk, prolonged bleeding time, increased risk of MI/stroke w/ long term use
Which NSAIDs have a unique risk of Stevens-Johnson syndrome?
Ibuprofen and naproxen
What are the MOA, CU, and TOX for celecoxib & meloxicam?
MOA: COX 2 inhibition
CU: analgesic, antpyretic, anti-inflammatory
TOX: CV risk similar to ibuprofen or naproven, may increase in risk with dose
What are the MOA, CU, and TOX for corticosteroids (prednisone, hydrocortisone, dexamethasome)?
MOA: Inhibition of phospholipase A2, cyclooxygenase, and cytokines
CU: Immune suppression, pain management (reduction of inflammation)
TOX:
acute- mood changes, hyperkalemia, hyperglycemia
chronic- HPA-axis suppression, muscle wasting, cushingnoid cataract, glioma
What are the broad MOA, CU, and TOX for calcineurin inhibitors (CNIs)?
MOA: Binds to immunophilin -> immunophilin complex binds calcineurin to block NFAT activation -> decreased T-cell activation and proliferation
CU: Maintenance immunosuppression
TOX: Nephrotoxicity (caution with NSAID & ACEI use) and CYP3A4 and PgP substrate interactions
What are the two most pertinent CNIs?
Cyclosporin and tacrolimus
What is the specific MOA and TOX for cyclosporin?
MOA: Binds cyclophilin
TOX: Hypertension, hyperlipidemia
What is the specific MOA and TOX for tacrolimus?
MOA: Binds FK binding protein (FKBP-12)
TOX: Neurotoxicity, hyperglycemia
What are the two most pertinent TOR inhibitors?
Sirolimus and Everolimus
What are the MOA, CU, and TOX for TOR inhibitors?
MOA: Binds to FKBP-12 and inhibits MTOR -> bloackage of IL2 -> cell cycle arrest in G1-S phase -> suppression of T and B cell proliferation
CU: Used during CNI minimization or withdrawal, adjunct immunosuppressive therapy, CAV, CLAD, or cancer
TOX: Proteinuria, hyperlipidemia, edema, oral ulcers
BBW (lung): impaired wound healing
BBW (kidney and liver): thrombosis
BBW (heart): increased mortality
What are the two most pertinent proliferation/metabolic inhibitors?
Azathioprine and mycophenolate mofetil
What is the general MOA of proliferation/metabolic inhibitors?
6-MP and MPA inhibit purine nucleotide synthesis -> impaired DNA synthesis -> inhibition of T and B cell proliferation
What are the specific MOA, CU, and TOX of azathioprine?
MOA: Prodrug of 6-mercaptopurine (6-MP)
CU: Immunosuppressive therapy
TOX: Hemolytic anemia, pancreatitis, drug interactions
BBW: malignancy
What are the specific MOA, CU, and TOX of mycophenolate mofetil?
MOA: Converted to mycophenolic acid
CU: Decreased organ rejection rates compaired to azathioprine
TOX: BM suppression, N/D, drug interactions w/ magnesium containing products & antacids, teratogen
What are pros and cons of using azathioprine for immunosuppression vs. mycophenolate mofetil?
Pros:
-1x daily dosing
- less GI SE than mycophenolate mofetil
Cons:
-worse rejection rates in kidney, liver, and heart transplant pts
What are the most common causes of infectious esophagitis?
Candida spp.
HSV
CMV
What are the most common causes of infectious gastritis?
H. pylori
CMV
Others (Candida, mucor, histoplasma, mycobacteria, giardia, strongyloides)
What are the most common causes of infective ileitis?
Mycobacterium tuberculosis
Yersinia enterocolitica
Salmonella spp.
C. diff
MAC
Histoplasma
What are the most common causes of infective colitis?
Diarrheal pathogens
CMV
adenovirus
C. diff
MAC
Entamoeba histolytica
What are common symptoms of diverticulitis?
LLQ pain, fever, N/V, leukocytosis
What are common symptoms of peritonitis?
Abodminal pain, fever, encephalopathy
What are the most common infectious causes of peritonitis?
E. coli
Klebsiella spp.
Streptococcus spp.
