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An autopsy performed on a homeless middle-aged man demonstrates scattered small nodules within the apex of the right lung. On histologic examination, these nodules are composed of collections of large epithelioid macrophages and multinucleated giant cells, surrounded by lymphocytes and fibroblasts. Caseating necrosis is seen in some of these lesions, and acid-fast bacilli are demonstrated with appropriate staining. Which of the following mediators is responsible for the devleopment of epithelioid macrophages and multinucleated giant cells in this context?
Interferon-gamma
( Immunology General Principles: 63%): The lesion described in this case is a granuloma, more specifically a caseating granuloma due to mycobacterial infection. Granulomatous inflammation is a specialized immune-mediated form of chronic inflammation resulting from complex interactions between several inflammatory cells, including T lymphocytes and macrophages. The ultimate effect is the development of activated macrophages, which acquire an epithelial-like appearance (epithelioid macrophages) and may fuse to orm multinucleated giant cells. This process begins with the uptake of foreign antigens by macrophages, which process and present them to helper T lymphocytes. T lymphocytes recruit more T lymphocytes by secreting interleukin-2 and activate macrophages through interferon-gamma. Interferon-gamma instructs macrophages to become epithelioid and multinucleated giant cells, which are more apt to engulf and eliminate foreign antigens. In turn, epithelioid macrophages secrete IL-1 and TNA-alpha, which increases leukocyte recruitement locally and mediate the systemic acute-phase responses (e.g., fever, malaise). Macrophages release a large number of inflammatory mediators, which are responsible for tissue damage, necrosis of parenchymal cells, and subsequent reparative fibrosis. Macrophages also produce nitric oxide, which plays an important role in microbial killing but may also result in tissue damage through generation of NO-related free radicals.
A 30-year-old woman presents to a physician with a prominent rash over her nose and cheeks. She also has complaints of fever, malaise, and muscle soreness of several months duration. Serologic studies demonstrate positive ANA with autoantibodies to double-stranded DNA. This patient's probable condition is associated with which of the following HLA type(s)?
HLA-DR2 and HLA-DR3
( Immunology General Principles: 47%): The disease is systemic lupus erythematosus, which is an autoimmune disorder associated with HLA-DR2 and HLA-DR3. The presentation described in the question stem is classic; patients without the characteristic malar or "butterfly" rash are much harder to diagnose because their complaints are initially typically very vague. *HLA-A3: Associate HLA-A3 with primary hemochromatosis *HLA-B27: Associate HLA-B27 with psoriatic arthritis, ankylosing spondylitis, inflammatory bowel disease, and Reiter's syndrome. *HLA-DR3 and HLA-DR4: Type I diabetes is associated with both HLA-DR3 and HLA-DR4 *HLA-DR4: RHEUMATOID ARTHRITIS IS ASSOCIATED WITH HLA-DR4 (SLE:DR2 + DR3); (HLA-A3:PRIMARY HEMOCHROMATOSIS); (HLA-B27:PSORIATIC ARTHRITIS, ANKYLOSING SPONDYLITIS, INFLAMMATORY BOWEL DISEASE, AND REITER'S); (TYPE I DIABETES:DR3 + DR4); (RHEUMATOID ARTHRITIS:DR4)
A 16-year-old girl presents to her physician complaining of redness and a yellowish discharge from her left eye for the past 2 days. She reports minimal crusting upon awakening and denies eye pain or previous trauma. Upon examination, there is diffuse conjunctival hyperemia associated with a mucoid discharge. The pupils dilate normally, although there is mild photophobia in the affected eye. Gram's stain of the exudate shows pleomorphic, gram-negative bacilli. To culture this organism with whole blood agar, which of the following must be used?
Staphylococcus aureus
(Microbiology General Principles: 36%): The patient is suffering from conjunctivitis caused by Hemophilus, a fastidious organism requiring factors V (nicotinamide adenine dinucleotide) and X (hematin), which must be released from whole blood preparations to be accessible to the organism. This can be done by gentle heating, which lyses the red blood cells, or by co-culture with Staphylococcus aureus, which is beta hemolytic and lyses the red blood cells to provide factors Hemophilus needs for growth. This is called the satellite phenomenon. *ANTIBIOTIC TO INHIBIT NORMAL FLORA: ANTIBIOTIC WOULD NOT BE NECESSARY SINCE, WITH PROPER CULTURE TECHNIQUES, NO NORMAL FLORA SHOULD BE AVAILABLE TO CONFUSE THE DIAGNOSIS FROM THIS SITE. *Cold temperature: Cold temperature would not be necessary because Hemophilus grows at normal body temperature. LIsteria is the genus commonly mentioned for which a cold temperature is necessary. *Egg yolk cholesterol: Cholesterol is necesxsary for the growth of Mycobacteria, but not Hemophilus *Reduced oxygen tension: Low oxygen tension is necessasry for the growth of the microaerophiles (such as Campylobacter, Helicobacter, and Borrelia), but is not a condition for growth of Hemophilus.
A 22-year-old woman presents with a 1-week history of mild lower abdominal pain and a yellowish vaginal discharge. She describes the pain as dull in nature, relieved slightly by acetaminophen and worsened by intercourse. Pelvixc examination reveals a red, swollen cervix without motion tenderness. The mucosas is friable. Potassium hydroxide (KOH) mount is negative, and wet mount does not reveal clue cells. Gram's stain of the exudate reveals gram-negative cocci. Which of the following procedures would most likely lead to the correct diagnosis?
Order DNA probe assays of endocervical exudates
( Microbiology Reproductive: 23%): GO WITH TESTS THAT ARE THE MOST QUICK AND RELIABLE! The symptoms suggest infection with Neisseria gonorrhoeae; however, with Gram's stain results alone, it is not possible to distinguish the gonococcus from normal flora organisms such as Acinetobacter, unless gram-negative diplococci are found within polymorphonuclear leukocytes. The fastest and most reliable assay specific for diagnosis of gonorrhea is the use of commercial DNA probes, with results availabe in 2-4 hours. *CULTURE THE BLOOD ON THAYER-MARTIN AGAR: CULTURE ON THAYER-MARTIN MEDIUM IS INDEED THE CHOICE FOR CULTURE OF N. GONORRHOEAE, BUT WOULD YIELD SLOWER RESULTS, AND THEREFORE BE A SECONDARY CHOICE. *Order serologic tests to identify specific capsular antigens: Serology is not a good choice because N. gonorrhoeae does not have a significant capsule (the meningococcus does), and furthermore, serological tests for the gonococcus have proben insensitive and nonspecific. (GONORRHOEAE:NO SEROLOGY); (N. MENINGOCOCCUS:YES SEROLOGY) *Order the germ tube test: The germ tube test is one of the diagnostic tests for Candida albincans, but this case presentation is not characteristic of candidiasis. *Order the rapid plasma reagin (RPR) test: The RPR is a test for reaginic (heterophilic) antibodies formed early in infection with Treponma pallidum, but this case presentation is not suggestive of syphilis.
A new laboratory technologist receives an orientation on her first day of hospital employment. She is instructed on accepted procedures for biohazardous waste disposal. All reusable glassware is subjected to 20 minutes at 121 C at 15 pounds pressure. Which of the following would retain pathogenicity following this treatment?
Endotoxin
(Microbiology General Principles: 30%): The treatment described is the method necessary for sterilization using an autoclave. Sterilization is an absolute term, depicting the complete removal or killing of all viable organisms. Endotoxin is a molecule (not an organism) that is extremely heat-resistant. It is not destroyed by autoclaving, but is removed from surfaces by extensive scrubbing with detergents. The one exception to the rule that infectious agents are destroyed by autoclaving involves prions, the agents of slow viral diseases. These infectious proteins are extremely resistant to killing, and transmission of prion diseases have been proven using brain electrodes that were technically "sterile." *BACTERIAL FORMS CONTAINING DIPICOLINIC ACID: BACTERIAL FORMS CONTAINING DIPICOLINIC ACID DESCRIBES BACTERIAL SPORES. DIPICOLINIC ACID IS A UNIQUE MOLECULE THAT PROTECTS BACTERIAL SPORES FROM DESSICATION AND CHANGES IN PH. SPORES ARE KILLED BY AUTOCLAVING, ALTHOUGH THEY ARE NOT ALWAYS KILLED BY CHEMICAL DISINFECTANTS. *Botulinum toxin: Botulinum toxin is heat-sensitive and easily destroyed by boiling, so it would not withstand the temperature and pressure of an autoclave. *Mycobacterium tuberculosis: Mycobacterium tuberculosis, although resistant to most environmental pressures due to its extremely waxy cell coat, would not survive autoclaving. *Norwalk virus: Norwalk virus is a naked capsid virus with a shell that allows it to withstand the acidity of the stomach, but it would not survive autoclaving. (NORWALK:NAKED CAPSID)
An 8-month-old baby boy is evaluated because of repeated episodes of pneumococcal pneumonia. Serum studies demonstrate very low levels of IgM, IgG, and IgA. Flow cytometry of peripheral blood cells demonstrates a near absence of CD19+ cells, although levels of CD4+ and CD56+ cells are within normal limits. Studies of the bone marrow reveal abnormally high numbers of cells with cytoplasmic mu chains, but none bearing surface IgM molecules. This patient's condition is thought to be related to a deficiency of which of the following proteins?
tyrosine kinase
(Immunology General Principles: 37%): The patient in the question stem has X-linked (Bruton) agammaglobulinemia, which is due to a deficiency in a tyrosine kinase, leading to a B cell maturation arrest at the pre-B cell level.(BRUTON'S:TYROSINE KINASE); SCID:ADENOSINE DEAMINASE); (NO CD40L:HYPER-IGM); (NO MHC II + LESS CD4+ + NORMAL B CELLS:BARE LYMPHOCYTE SYNDROME); (NO GAMMA CHAIN OF IL-2 + NO B/T CELLS:SCID) *ADENOSINE DEAMINASE: ADENOSINE DEAMINASE DEFICIENCY IS A CAUSE OF SEVERE COMBINED IMMUNODEFICIENCY. IT CAUSES THE BUILD-UP OF TOXIC PRODUCTS IN LYMPHOCYTES, WHICH DEPRESS THEIR LEVELS IN THE PERIPHERAL BLOOD AND ELSEWHERE. *CD40 Ligand: CD40 ligand deficiency is the cause of hyper-IgM syndrome, in which there is an inability to switch immunoglobulin isotypes due to the absence of a stimulatory TH cell signal. The p[atient in this case history has depressed, not elevated levels of IgM. *Class II MHC: Absence of MHC class II is found in bare lymphocyte syndrome. IN this case, there would be depressed numbers of CD4+ cells, but normal maturation of B cells. *Gamma chain of the IL-2 receptor: Absence of the gamma chain of the IL-2 receptor is a cause of severe combined immunodeficiency. Its absence causes the failure of proliferative responses in both B and T lymphocytes, so both would be present at depressed levels.
A patient with colorectal cancer develops septicemia complicated by endocarditis. You would expect the blood cultures to grow:
Streptococcus bovis
( Microbiology Cardiovascular: 42%): Streptococcus bovis is a Group D streptococcus. There is a significant association between S. bovis bacteremia and endocarditis with carcinoma of the colon and other colonic diseases. Every patient with S. bovis bactermia should undergo gastrointestinal and cardiac evaluation. Up to 50% of patients with S. bovis bactermia are reported to have underlying colonic malignancies. In another study, 25-50% of cases of S. bovis bacteremia were assoicated with endocarditis, especially in patients with preexisting valvular lesions. *Streptococcus agalactiae: Streptococcus agalactiae is an important cause of maternal and neonatal bacteremia and neonatal meningitis. It is part of the normal flora of the gastrointestinal tract and the female genital tract. *Streptococcus pneumoniae: Streptococcus pneumoniae is a leading cause of community-acquired pneumonia, meningitis in adults, otitis media (especially in children), and sinusitis. Spontaneous peritonitis due to S. pneumoniae is reported in children with ascities from nephrotic syndrome. Asplenia predisposes patients to severe infections with S. pneumoniae and other encapsulated organisms. S. pneumoniae infections are also more frequent and unusually severe in patients with sickle cell anemia, multiple myeloma, alcoholism, and hypogammaglobulinemia. S. pneumoniae is now the leading cause of invasive bacterial respiratory diseasse in patients with AIDS. *Streptococcus pyogenes: Streptococcus pyogenes is the most common cause of bacterial pharyngitis. Complications include paratonsillar abscesses, otitis media, and sinusitis. Long-term sequelae include rheumatic fever and poststreptococcal glomerulonephritis. S. pyogenes is also responsible for many skin and soft tissue infections. The organism also produces many toxins that produce a variety of diseases. *STREPTOCOCCUS VIRIDANS: STREPTOCOCCUS VIRIDANS, OR THE VIRIDANS STREPTOCOCCI, ARE THE MOST COMMON CAUSE OF SUBACUTE BACTERIAL ENDOCARDITIS, WHICH SHOULD BE SUSPECTED IN CASES OF VIRIDANS STREPTOCOCCAL BACTEREMIA. ONE SPECIES OF VIRIDANS STREPTOCOCCI, STREPTOCOCCUS MILLERI, IS FREQUENTLY ASSOCIATED WITH PYOGENIC ABSCESSES, ESPECIALLY OF THE LIVER.
A 24-year-old male Asian immigrant presents with an ulcerative genital lesion. The lesion first appeared 1 month ago as a papule with an erythematous base, which eventually became ulcerated and painful. On physical examination, the man is afebrile. A tender ulcerative lesion is present on his prepuce, and inguinal adenopathy is evident. Which of the following would be the most likely microscopic finding in a scraping from the rash.
Pleomorphic gram-negative rods in parallel short chains
( Microbiology Reproductive: 31%): This is a typical case description of chancroid, caused by Haemophilus ducreyi, a pleomorphic gram-negative rod that displays a characteristic pattern ("school of fish") on Gram's stained slides. *Epithelial cells with intranuclear inclusion bodies: Epithelial cells with intranuclear inclusion bodies would be found with herpes simplex infections, but these lesions would not have the appearance described in this case history. *Iodine-staining intracelllular inclusion bodies: Iodine-staining intracellular inclusion bodies would be found with genital lesions of Chlamydia trachomatis, the causative agent of lymphogranuloma venereum, but this lesion is generally nonpainful. *LYMPHOGRANULOMA VENEREUM IS PAINLESS, AS IS SYPHILIS. SYPHILIS CHANCRES ARE HARD AND NON-TENDER, AS OPPOSED TO HAEMOPHILUS DUCREYI, WHICH ARE VESICULAR. *Koilocytotic squamous epithelial cells: Koilocytotic squamous epithelial cells would be found in infections with human papilloma virus (HPV), which is associated with venereal warts. *Neutrophils containing gram-negative diplococci: Neutrophils containing gram-negative diplococci would be found if this were gonorrhea, but the case symptoms are not consistent with this disease. *SPIROCHETES VISIBLE BY DARKFIELD MICROSCOPY: SPIROCHETES WOULD BE FOUND ON DARKFIELD MICROSCOPY IF THIS WERE A CASE OF SYPHILITIC CHANCRE, BUT THAT CHANCRE WOULD BE HARD AND NONTENDER.
What is the role of class II MHC proteins on donor cells in the process of graft rejection?
They are recognized by helper T cells, which then activate cytotoxic T cells to kill the donor donor cells.
(Immunology General Principles: 84%): Class II MHC proteins are expressed on the surfaces of macrophages, dendritic cells, and B cells; this complex of molecules is recognized by CD4+ helper T cells. The T cells of the transplant recipient recognize allogeneic MHC molecules on the surface of an antigen-presenting cell of the donor. It is thought that interstitial dendritic cells of the donor are the most important immunogens because not only do they express class I and II HLA molecules, but they are also endowed with co-stimulatory molecules. CD8+ cytotoxic T cells recognize the class I molecules. CD 4+ cells proliferate as Th1 cells and produce interleukin 2, which causes differentiation of the CD8 cells. The CD*+ cytotoxic cells of the recipient then cause lysis of the donor cells. *They are the receptors for interleukin-2, which is produced by macrophages when they attack the donor cells: Interleukin-2 activates T cells by binding to high-affinity IL-2 receptors (IL-2R). *THEY CAUSE THE RELEASE OF PERFORINS TO LYSE THE CELLS: PERFORINS ARE PRODUCED BY CD8+ CYTOTOXIC LY+MPHOCYTES AS THEY BIND TO CLASS I MHC MOLECULES. THE PERFORINS DAMAGE THE DONOR CELL MEMBRANES, RESULTING IN LYSIS. *They induce IgE, which mediates graft rejection: IgE-mediated reactions are not assoicated with graft rejection. *They induce the production of blocing antibodies that protect the graft: Blocing antibodies are employed as a form of immunosuppressive therapy. Antilymphocyte globulins and monoclonal anti-T cell antibodies (monoclonal anti-CD3) are used to inhibit rejection of the graft. This process does not involve class II MHC proteins on donor cells.
A psychotic, indigent man with a history of multisubstance abuse has been involuntarily hospitalized for 1 week. Because of persistent diarrhea, stools are sent for ova and parasites, revealing numerous granular, spherical, thin-walled cysts measuring 10-20 micrometeres in diameter. Trichrome stains show up to four nuclei in most of the cysts. These findings are consistent with an infection by which of the following organisms?
Entamoeba histolytica
(Microbiology Gastrointestinal: 35%): Entamoeba are relatively common enteric pathogens that can produce asymptomatic infection or more severe disease characterized by mucosal ulcerations and submucosal spread, causing abdominal distress and liquid stools. Stools may show either trophozoite forms or the typical spherical cysts. Several species of Entamoeba are seen, including Entamoeba coli and E. harmanni. E. histolytica cysts characteristically are spherical in shape, 10-20 micrometers in diameter, and have granular cytoplasm containing 1, 2, or 4 nuclei. *CRYPTOSPORIDIUM PARVUM: CYRPTOSPORDIUM PARVUM INFECTIONS OCCUR IN THE IMMUNOCOMPROMISED POPULATION AND MAY CAUSE SEVERE DIARRHEA. THE ORGANISM PRESENTS AS MINUTE (2-5 UM) INTRACELLULAR SPHERES OR ARC-SHAPED MEROZOITES UNDER NORMAL MUCOSA, AND CAN BE DIFFICULT TO APPRECIATE BY LIGHT MICROSCOPY. CYSTS IN THE STOOL ARE TOO SMALL (4-5 MICROMETERS) TO BE CONFUSED WITH ENTAMOEBA. *Dientamoeba fragilis: Dientamoeba fragilis is an intestinal amoeba that also may produce an infectious diarrhea. It does not have a cyst form, and only the trophozoite forms are seen in stools. *Giardia lamblia: Giardia lamblia is a flagellate protozoan that infects the stomach and small intestine when contaminated water is ingested. Diagnosis is usually made by examining duodenal contents; however, the stools may contain the oval or elliptical cysts, which are thick-walled and measure 8-14 micrometers in diameter. Spherical cysts are not seen in Giardia infection. *Isospora belli: Isospora belli produces self-limited intestinal infections mostly in the tropics, where fever and diarrhea may last weeks to months. The stool-borne cysts are much larger than Entamoeba (30 x 15 um), are asymmetrical, and are typically almond-shaped.
A 35-year-old woman presents to her gynecologist with complains of burning on urination for the past 2 days. Dipstick test of her urine demonstrates marked positivity for leukocyte esterase, but no reactivity for nitrite. Urine culture later grows out large numbers of organisms. Which of the following bacteria are most likely to be responsible for this patient's infection?
Enterococcus faecalis
(Microbiology Renal/Urinary: 24%): The positive leukocyte esterase test indicates the presence of neutrophils in the urine, suggesting a bacterial infection. The nitrite test exploits the fact that most Enterobacteria (gram-negative enteric rods) are able to form nitrite from nitrate; thus, the nitrite test is used to diagnose urinary tract inafections. One limitation of this method is the fact that enterococci (gut streptococci) do not produce nitrite from nitrate, but can nonetheless cause urinary tract infections. Enterococcal urinary tract infections are often nosocomial and classically acquixred in the intensive care unit, although they can occur in other settings. *ENTEROBACTER SP., ESCHERICHIA COLI, KLEBSIELLA PNEUMONIAE, AND PSEUDOMONAS AERUGINOSA: ENTEROBACTER SP., ESCHERICHIA COLI, KLEBSIELLA PNEUMONIAE, AND PSEUDOMONAS AERUGINOSA CAN CAUSE URINARY TRACT INFECTIONS AND WOULD USUALLY BE PICKED UP BY THE DIPSTICK FOR NITRITES. FALSE-NEGATIVE RESULTS MIGHT STILL BE SEEN WITH THESE ORGANISMS IF THE INFECTION WAS LIGHT, THE BLADDER HAD BEEN RECENTLY EMPTIED PRIOR TO COLLECTION, AND THE URINE WAS "NEW" AND HAD NOT YET GROWN ENOUGHT BACTERIA TO PRODUCE A POSITIVE RESULT.
A ten-year-old immigrant child from Haiti is brought to a free clinic complaining of shortness of breath, wheezing, exertional dyspnea, and occasional urticaria. A fecal examination for ova and parasites is positive for numerous golden-brown, oval, rough-shelleed nematode eggs. Sputum samples are positive for nematode larvae and eosinophilic infiltrates. What is the mechanism of this child's lung symptoms?
Type I hypersensitivity
(Immunology General Principles: 59%): This child is infected with Ascaris lumbricoides, a large nematode that migrates through the lung during its maturation to adulthood. Ascaris is known to possess one of the most potent allergens in nature, and it is common for infected individuals to suffer recurrent bouts of immediate hypersensitivity due to IgE production during the migration of the worms. The signs of uricaria, eosinophilia, and wheezing are all evidence of allergic hypersensitivity being manifested in the lung. *TYPE II CYTOTOXIC HYPERSENSITIVITY: TYPE II CYTOTOXIC HYPERSENSITIVITY INVOLVES AUTOANTIBODIES THAT BIND TO SPECIFIC TISSUES OR CELLS, ACTIVATE COMPLEMENT, AND CAUSE THE DESTRUCTION OF THE UNDERLYING TISSUE. *Type II non-cytotoxic hypersensitivity: Type II non-cytotoxic hypersensitivity is exemplified by Graves disease and myasthenia gravis. These diseases involve autoantibodies, but there is no complement or neutrophil mediated killing of the affected tissues. *Type III hypersensitivity: Type III hypersensitivity is also known as immune complex hypersensitivity. It is caused by the deposition of complexes of antigen and antibody causing complement activation in the small vasculature, where they become cleared from the circulation. The damage is mediated by complement activation, and is system-wide. *Type IV hypersensitivity: Type IV hypersensitivity is also known as T cell-mediated or delayed-type hypersensitivity. It is mediated by TH1 cells and macrophages and is manifested 48-72 hours following reintroduction of protein antigens.
A 7-month-old child is hospitalized for a yeast infection that does not respond to therapy. The patient has a history of multiple, acute pyogenic infections. Physical examination reveals that the spleen and lymph nodes are not palpable. A differential WBC count shows 95%$ neutrophils, 1 % lymphocytes, and 4% monocytes. A bone marrow biopsy contains no plasma cells or lymphocytes. A chest x-ray reveals the absence of a thymic shadow. Tonsils are absent. These findings are most consistent with:
severe combined immunodeficiency
(Immunology General Principles: 65%); NOTE! I SHOULD HAVE TRUSTED MY INSTINCT! Severe combined immunodeficiency (SCID) is associated with deficiencies in both B and T cells due to a defect in differentiation of an early stem cell. Over 50% of cases are caused by a gene defect on the X chromosome, resulting in a defective IL-2 receptor. The disease may exhibit a sex-linked or an autosomal recessive pattern of inheritance.. The autosomal recessive variant is characterized by a deficiency of adenosine deaminase, which results in accumulation of metabolites that are toxic to both B and T stem cells in the bone marrow. Children usually die within the first 2 years of life with severe infections unless they receive bone marrow transplants. *Bloom's syndrome: Bloom's syndrome jis an autosomal recessive disorder included in the chromosomal instability group of syndromes. It is associated with small body size, immunodeficiency, light-sensitive facial erythema, and a major predisposition to cancer. *Chronic granulomatous disease: Chronic granulomatous disease is caused by a deficiency of NADPH oxidase in neutrophils, resulting in loss of the first step of the myeloperoxidase system, and an absence of the respiratory burst. Patients are susceptible to staphyloccoal infections and granulomatous infections. *Waldenstrom's macroglobulinemia: Waldenstrom's macroglobulinemia is a monoclonal gammopathy characterized by high serum levels of IgM and hyperviscosity complications. *Wiskott-Aldrich syndrome: Wiskott-Aldrich syndorme is an immunodeficiency syndrome characterized by thrombocytopenia, eczema, and recurrent sinopulmonary infections. The patient has low levels of IgM and increased levels of IgG, IgA, and IgE.
A 23-year-old woman presents to the emergency room with pelvic pain. A Gram's stain of her cervical discharge reveals multiple polymorphonuclear leukocytes, but none contain gram-negaitve diplococci. Which of the following statements best describes the two organisms that most commonly cause this disorder?
Both induce endocytosis by epithelial cells
(Microbiology Reproductive: 39%): In young women, the most likely causes of cervicitis and pelvic inflammatory disease (PID) are Neisseria gonorrhoeae and Chlamydia trachomatis. Gram's staining alone may not be able to distinguyish between the two in women, so culture is warranted. Both organisms induce endocytosis by epithelial cells. *Both are unlikely to recur because of acquired cell-mediated immunity, both are unlikely to recur because of antibody-mediated immunity, BOTH ARE OGLIGATE INTRACELLULAR PARASITES, and both respond to beta-lactam antibiotics: Neisseria gonorrhoeae is a gram-negative diplococcus. It is endocytosed by mucus-secreting epithelia, and is exocytosed into subepithelial tissues leading to necrotizing acute inflammation and destruction of ciliated and non-ciliated cells. Through direct extension, it can lead to PID and infertility in women. It can be detected by visualizing the organisms in polymorphonuclear leukocytes (PMNs) in Gram's stained clinical material more easily in men than in women. Therefore, culture onto Thayer-Martin agar is usually required for diagnosis in women. SINCE THE ORGANISM CAN BE CULTURED, IT IS NOT AN OLBIGATE INTRACELLULAR PARASITE. The organism can be killed by PMNs, antibody, and complement; however, many of its outer membrane proteins undergo antigenic or phase variation or cause the production of blocking antibody that interferes with bactericidal activity. Immunity to the organism does not develop. Neisseria gonorrhoeae is resistant to penicillin, a beta-lactam antibiotic, because of a plasmid-mediated penicillinase and a chromosomally-mediated mutation that decreases the permeability of the outer membrane and decreases the affinity of penicillin binding proteins. It can be treated with ceftriaxone, a cephalosporin, which resists the penicillinase, or with quinolones and azithromycin. CHLAMYDIA TRACHMATIS IS AN OBLIGATE INTRACELLULAR PARASITE THAT INDUCES ENDOCYTOSIS AND RESIDES IN THE PHAGOSOME OF INFECTED EPITHELIAL CELLS. It possesses a gram-negative envelop but lacks peptidoglycan, and hence is intrinsically resistant to all antibiotics that inhibit peptidoglycan synthesis, such as the beta-lactam antibiotics. Antibodies are ineffective at controlliing infection. Cell-mediated immunity is probably the major means of controlling this infection, since a deficiency in cell-mediated immunity both increases susceptibility and sevwerity in animal modles. Chronic and clinically latent infections can cause serious morbidity, including pelvic inflammatory disease, fallopian tube dysfunction, and blindness. Chlamydia infection can be treated with macrolides, quinolones, and tetracyclines.
A 54-year-old HIV-positive homosexual is brought to the emergency department by his partner because of a sudeen detioration of mental acuity. He complains of headache, and at the time of examination, has nuchal rigidity, time-place disorientation, and marked confusion. Lumbar puncture reveals 100 white blood cells, 80% lymphocytes, protein = 85 mg/dL, and glucose = 45 mg/dL. A simultaneous blood glucose is 90 mg/dL. After the attending physician treats a drop of cerebrospinal fluid with a particulate dye, microscopic examination reveals the structures shown above. Which of the following would most likely confirm the diagnosis?
urease positivity
(Microbiology Nervous: 27%): This is a clear case of cryptococcal meningitis, caused by the monomorphic encapsulated yeast, Cryptococcus neoformans. It is a prfound problem in our HIV-positive population and the diagnosis is often associated by use of India Ink staining of CSF. This is not the best test, but one that is often mentioned on the USMLE because it demonstrates the capsule of the yeast. The preferred diagnositc is a latex particle agglutination test for capsular antigen. The other unusual attribute of this organism is that it is urease positive. *Growth on blood agar next to Staphylococcus aureus: Growth on blood agar next to Staphylococcus aureus would be a confirmatory finding in the diagnosis of Hemophilus influenzae meningitis, which is not common in this age group or patient population. This test is called the "setallite phenomenon" and it is used to demonstrate the requirement of Hemophilus for factors X and V. Also, the CSF findings given here are consistent with a fungal, not bacterial pathogen. *Growth on Thayer-Martin agar: Thayer-Martin agar would be the medium of choice for growth of Neisseria from sites with normal flora (not the CSF). To diagnose meningococcal meningitis, the medium of choice would be simple chocolate agar. Neisseria meningitidis is the most common agent of meningitis in young adults and does not necessarily require immunosuppression, as in the patient described here. *OWL'S EYE INCLUSIONS IN THE URINARY SEDIMENT: OWL'S EYE INCLUSIONS IN THE URINARY SEDIMENT WOULD BE CHARACTERISTIC OF CYTOMEGALOVIRUS INFECTION. ALTHOUGH CMV IS A PROBLEM IN THE HIV-POSITIVE POPULATION, THE CSF FINDINGS GIVEN IN THIS CASE ARE NOT CONSISTENT WITH A VIRAL INFECTION, AND CMV IS A CAUSE OF ASEPTIC ENCEPHALITIS, NOT MENINGITIS, IN THIS PATIENT GROUP. *Positive ELEK test: The ELEK test is the test for toxin production by Corynebacgerium diphteriae, which causes diptheria, a disease that does not produce signs of meningitis.
A perimenopausal woman elects to have her intrauterine device (IUD) removed. She has been experiencing unusual vaginal discharge for the past six months. When removed, the IUD is covered with yellowish flecks. Which of the following is most likely to be cultured from the IUD?
Actinomyces israelii
(Microbiology Reproductive: 46%): Actinomyces is an anaerobic normal flora organism that resides in gingival crevices and in parts of the gastrointestinal system and female reproductive tract. It is a filamentous gram-positive rod that produces yellow granular deposits (sulfur granules) in the areas of its tissue invasion. Presumably, small foci of tissue injury caused by IUDs can serve as a point for invasion of the organisms. *CANDIDA ALBICANS: CANDIDA ALBICANS CAUSES VULVOVAGINITIS, CHARACTERIZED BY A WHITE, CHEESY DISCHARGE. IT DOES NOT COMMONLY INVADE THE DEEPER PORTIONS OF THE FEMALE REPRODUCTIVE TRACT. *Chlamydia trachomatis: Chlamydia trachomatis is an intracellular bacterium associated with production of endocervicitis and pelvic inflammatory disease. It does not typically produce a vaginal discharge, but epithelial cells scraped from the area would show intracytoplasmic inclusion bodies. *Neisseria gonorrhoeae: Neisseria gonorrhoeae is an extracelllular gram-negative diplococcus, which is sexually transmitted. The infection typically presents as an endocervicitis or septic arthritis. The vaginal discharge would be leukorrheic and gram-negative diplococci would be found inside neutrophils in the fluids. *Nocardia asteroides: Nocardia asteroides is an aerobic, filamentous, gram-positive rod, which is partially acid-fast. It typically is introduced into the body from external sources. It is most commonly associated with lung infections in immunocompromised patients. It does cause the production of sulfur granules, but would not be expected to be found deep in the female reproductive tract.
A 54-year-old diabetic patient reports to his physician's office complaining of an unresolved skin lesion on his foot. The lesion began several weeks ago as a blister and has since become a painful, erosive, expanding sore. On examination, the affected site is now 5 cm in diameter, with a black necrotic center and raised red edges. Which of the following toxins has a mechanism of action most similar to the toxin responsible for tissue damage in this patient?
diptheria toxin
(Microbiology General Principles: 22%): This patient's wound is infected with Pseudomonas aeruginosa, and the characteristic lesion described is called ecthyma grangrenosum. The Pseudomonas alpha toxin, which is responsible for the tissue damage, inhibits protein synthesis by acting on EF-2 with a primary target cell in the liver. The diptheria toxin has a similar action, although its target cells are heart and nerve. *Anthrax toxin: Anthrax toxin: is an adenylate cyclase that causes fluid loss from cells. *Botulinum toxin: Botulinum toxin is a neurotoxin that decreases acetylcholine synthesis. *Cholera toxin: Cholera toxin acts to increasse adenylate cyclase activity by ribosylation of GTP-binding protein. *Clostridium perfringins alpha toxin: Clostridium perfringens alpha toxin is a lecithinase. *Escherichia coli labile toxin: Escherichia coli labile toxin works in a fashion similar to the cholera toxin. *Pertussis toxin: Pertussis toxin causes fluid loss by ribosylating Gi. *Shigatoxin: Shigatoxin decreases protein synthesis by inhibiting the 60S ribosomal subunit. *STREPTOCOCCAL ERYTHROGENIC TOXINS: STREPTOCOCCAL ERYTHROGENIC TOXINS ACTS SIMILARLY TO THE DIPTHERIA TOXIN, BUT DO SO BY INCREASING CYTOKINE PRODUCTION. *Tetanus toxin: Tetanus toxin is a neurotoxin that inhibits the inhibitory neurotransmitters glycine and GABA. (PSEDUOMONAS:ALPHA TOXIN); (PSEUDOMONAS:INHIBIT EF-2); (PSEUDOMONAS:TOXIN TARGET IN LIVER, MAINLY); (DIPTHERIA:PSEUDOMONAS); (DIPTHERIA:INHBIT EF-2); (DIPTHERIA:TARGET HEART AND NERVE); (ANTHRAX TOXIN:ADENYLATE CYCLASE); (ANTHRAX:FLUID LOSS FROM CELLS); (BOTULINUM TOXIN:DECREASE ACH SYNTHESIS); (CHOLERA TOXIN:INCREASE ADENYLATE CYCALSE VIA RIBOSYLATION OF GTP); (PERTUSSIS:FLUID LOSS); (PERTUSSIS:RIBOSYLATION OF GI); (SHIGA TOXIN:DECREASE PROTEIN SYNTHESIS); (SHIGA TOXIN:INHIBIT 60S); (STREPTOCOCCAL ERYTHROGENIC TOXIN:LIKE DIPTHERIA); (STREPTOCOCCAL ERYTHROGENIC TOXIN:INCREASE CYTOKINE PRODUCTION)
A 32-year-old woman consults her gynecologist because of fever and progressively severe pain in her left lower abdominal quadrant. The pain began several days ago, shortly after the onset of her menses. Pelvic examination demonstrates bilateral adnexal tenderness, much more marked on the left than the right. Which of the following is the most likely pathogen?
Neisseria
(Microbiology Reproductive: 64%): (NEISSERIA:ACUTE:PID); (CHLAMYDIA:SUBACUTE) This patient has pelvic inflammatory disease, which typically involves both right and left fallopian tubes, although one side may be more severely infected. The most common causative organisms are Neisseria gonorrhoeae and Chlamydia trachomatis. The condition may present acutely (as in this case) or insidiously. Timely diagnosis and treatment are important to prevent gynecologic morbidity that may include infertility, ectopic pregnancy, and chronic pelvic pain. *Escherichia: Escherichia is a bowel organism that is more likely to infect the urinary tract than the fallopian tubes. *STaphylococcus: Staphylococcus tends to colonize the nasopharynx and skin, and is more likely to cause infection in the skin or respiratory tract. *STreptococcus: STreptococcus tends to infect the respiratory tract and skin. *TREPONEMA: TREPONEMA CAUSES SYPHILIS, BUT DOES NOT CHARACTERISTICALLY PRODUCE PELVIC INFLAMMATORY DISEASE.
A 33-year-old G1P0 female at 6 months gestation returns from a visit to her parent's house in Arizona. Approximately 7 days following her return, she develops axillary lymphadenopathy and a low-grade fever. Her physician notices a small papule and healing scratch on her arm on the affected side. The patient states that she has pet birds at home, and there was a new kitten at her mother's house. She does not remember receiving the scratch. Which of the following organisms is most likely responsible for this illness?
Bartonella henselae
(Microbiology Heme./Lymph: 67%): Bartonella henselae is a gram-negative bacillus that is the causative agent of cat scratch disease. Cats, especially kittens, harbor the organism. It is usually inoculated through an easily forgotten scratch. A pustule forms at the site within days to weeks, accompanied by tender regtional adenopathy. Microscopically, granulomas with central necrosis and organisms are observed. Normally, treatement is not required because this disease is benign and self-limited, but immunosuppressed and pregnant patients are more susceptible to dissemination. Treatment is with ciprofloxacin or doxycycline. Aminoglycosides or erythromycin have also been employed. *COCCIDIOIDES IMMITIS: COCCIDIOIDOMYCOCIS IS A DISEASE CAUSED BY THE FUNGUS C. IMMITIS. SPORES OF THE ORGANISM ARE INHALED, USUALLY FROM THE SOIL. THOSE SPORES ENLARGE TO SPORANGIA, WHICH BURST AND SPREAD. THE DISEASE IS CHARACTERIZED BY PULMONARY SYMPTOMS, BUT IS USUALLY SELF-LIMITED. THIS ORGANISM IS COMMON IN ARID DESERT STATES LIKE ARIZONA, AND CAN AFFECT PEOPLE AFTER BRIEF VISITS. *Cyrptococcus neoformans: Cyrptococcus neoformans is a fungus found worldwide. The main reservoir is pigeon droppings. The small cryptococci are inhaled into the lungs, but do not usually cause disease in immunocompetent individuals,. In the immunosuppressed patient, Cyrptococcus can cause pulmona4ry and CNS disease, especially meningitis. *Histoplasma capsulatum: Histoplasma capsulatum is an infection acquired by breathing dust that contains bird/bat droppings that contain spores of the organism. The primary infection is in the lungs, and may be latent, or brief and self-limited. Symptoms include fever, cough, and sweats. In the United States, it is common in the Ohio-Mississippi valley. *Pasteurella multocida is a gram-negative rod spr4ead via dog and cat bites. The infection is characterized by rapidly evolving cellulitis starting at the site of the bite. There was no indication in this patient of an animal bite.
The mother of a 5-year-old girl claims that her stepfather may have had inappropriate sexual contact with the girl. Physical examination reveals an intact hymnen and no evidence of trauma. A vaginal swab is negative for acid phosphatase and reveals only normal flora. Which of the following organisms was most likely isolated?
Staphylococcus aureus
(Microbiology Reproductive: 26%): The vagina of prepubertal girls and post-menopausal women is colonized by colonic and skin bacteria, including Staphylococcus epidermidis, which is normally found on the skin. *LACTOBACILLUS, Candida, and Streptotoccus: THE VAGINA OF CHILD-BEARING AGE TNEDS TO BE COLONIZED BY LACTOBACILLUS SPECIES, yeasts such as Candida, and Streptococcus species. *Neisseria: The presence of Neisseria, such as N. gonorrhoeae (the cause of gonorrhea), in the vagina of a 5-year-old strongly suggests sexual abuse.
During the course of a pre-employment physical, a registered nurse receives an intradermal inoculation of tuberculin. During her employment in Pakistan, she was vaccinated with BCG (Bacille Calmet-Gueirn). At 48 hours, there is an 8 cm zone of erythema and induration over the injection site. Which of the following is the most important costimulatory signal involved in the elicitation of this response?
B7 molecules interacting with CD 28
( Immunology General Principles: 41%): The tuberculin response is the classic example of type IV hypersensitivity, which is mediated by TH1 cells and macrophages. The initial recognition signal involves interaction between MHC class II and the T cell receptor. The B7 molecule on the cell surface of the antigen-presenting cell reacts with the CD 28 molecule on the T cell surface for maximal costimulatory signals. *B7 molecules interacting with LFA-1: The B7 molecule on the surface of the antigen presenting cell reacts only with CD 28 and does not react with LFA-1 adhesion molecule. *ICAM-1 interacting with LFA-1: The ICAM-1 on the surface of an antigen presenting cell reacts with the LFA-I on the surface of a T cell for the purpose of cell-to-cell adhesion and does not function for costimulation. *LFA-3 interacting with CD 28: LFA-3 (CD 58) is an adhesion molecule on the surface of an antigen-presenting cell. It does not react with a CD 28 costimulatory molecule on the T cell surface. *MHC CLASS II INTERACTING WITH T CELL RECEPTOR: THE MHC CLASS II MOLECULE WITH ITS EPITOPE DOES INTERACT WITH A SPECIFIC T CELL RECEPTOR (TCR), BUT THIS IS NOT TERMED COSTIMULATORY. HOWEVER, THE INTERACTION DOES STIMULATE THE T CELL TO PRODUCE INTERLEUKINS FOR FURTHER CELL DIVISION. (B7:APC); (CD28:T CELL); (LFA-1:ICAM-1); (LFA-1:T CELL); (ICAM-1:APC); (LFA-1/ICAM-1:ADHESION); (LFA-3 = CD58); (LFA-3/CD58:APC); (LFA-3/CD58:ADHESION); (B7/CD28 = COSTIMULATORY BY DEFINITION)