2008 AOA Review

1. 2008 AOA Review Infection and Immunity

2. Contact Information Andrew R. Esterle aesterle@neoucom.edu

3. Helpful Hints • Do not let yourself get stressed out. • Make a study plan that works for you. Make it realistic and allow for time to catch up if you get off track. • Use questions for self-assessment throughout your preparation. • Maintain balance in your life.

4. USMLE 1 I & I • 40% Bacteriology • 20% Basic Science • 20% Clinical • 25% Immunology • 25% Virology • 10% Basic • 15% Clinical • 5% Parasitology • 5% Mycology

5. Exotoxin G+ or G- Secreted polypeptide Plasmid, bacteriophage Highly antigenic Toxoids as vaccines Lower heat stability (cooking) Examples: tetanus, botulism, diphtheria Endotoxin Most G- (cell wall) Lipopolysaccharide Chromosomally based Induces TNF, IL-1, etc. leading to fever and potential shock Poorly antigenic (no vaccines) Greater heat stability

6. Exotoxins • Super-Antigen • S. aureus; TSST-1 (toxic shock), enterotoxin • S. pyogenes; erythrogenic toxin (scarlet fever) • ADP ribosylating A-B (B=binding, A=active) • Cornebacterium diphtheriae • Vibrio cholerae • E. coli • Bordetella pertussis

7. Exotoxins • Clostridium perfringens; α toxin (gas gangrene) • C. tetani; blocks neurotransmitter inhibition • C. botulinum; blocks Ach = anticholinergic • B. anthracis; three toxin complex • Shigella (E. coli O157:H7); shiga toxin

8. A 25-year-old female executive presents with edema, hematuria, proteinuria, and decreased urination indicative of glomerulonephritis. Three weeks ago she had impetigo on her chest which resolved without treatment. Which of the following organisms is the most likely cause of her renal disease? (A) E. coli (B) S. aureus (C) S. saprophyticus (D) Streptococcus agalactiae (E) S. pyogenes

9. A 25-year-old female executive presents with edema, hematuria, proteinuria, and decreased urination indicative of glomerulonephritis. Three weeks ago she had impetigo on her chest which resolved without treatment. Which of the following organisms is the most likely cause of her renal disease? (A) E. coli (B) S. aureus (C) S. saprophyticus (D) Streptococcus agalactiae (E) S. pyogenes

10. A 22-year-old Hispanic man worked for a company that processed animal products and provided no medical coverage benefits. One week after working with wool imported from a Caribbean island, he developed a small lesion on his arm resembling an insect bite. One week later, the lesion was 2.5 cm in diameter with a central, black sloughed-skin area. Two weeks later, he presented at an emergency room with early stages of sepsis. Which of the following microbes is responsible for the infection? (A) Bacillus anthracis (B) Bacteroides melanogenicus (C) Hemophilus ducreyi (D) M. scrofulaceum (E) Treponema pallidum

11. A 22-year-old Hispanic man worked for a company that processed animal products and provided no medical coverage benefits. One week after working with wool imported from a Caribbean island, he developed a small lesion on his arm resembling an insect bite. One week later, the lesion was 2.5 cm in diameter with a central, black sloughed-skin area. Two weeks later, he presented at an emergency room with early stages of sepsis. Which of the following microbes is responsible for the infection? (A) Bacillus anthracis (B) Bacteroides melanogenicus (C) Hemophilus ducreyi (D) M. scrofulaceum (E) Treponema pallidum

12. Endotoxin G- cell wall component (lipopolysaccharide) Macrophages IL-1: fever TNF: fever, tissue necrosis Nitric Oxide: Hypotension Complement system (alternate pathway) C3a: hypotension, edema C5a: neutrophil chemotaxis Coagulation cascade (Hageman factor) Coagulation to DIC

13. Bacterial Classification Classification and significance to lead thinking. • Gram +, Gram – • Obligate Aerobes • Intracellular Bacteria (Obligate v. Facultative) • Encapsulated Bacteria • α, β-hemolytic • Catalase, Coagulase producers

14. A 38-year-old sexually-active woman developed symptoms of lower abdominal pain with adjacent tenderness. No gram-negative cocci were observed or isolated. The obligate intracellular organism causing the infection is unable to perform which of the following metabolic functions? (A) form ATP (B) form the intracellular, metabolically active, reticulate body (C) produce polypeptides (D) reproduce by binary fission (E) synthesize DNA gyrase

15. A 38-year-old sexually-active woman developed symptoms of lower abdominal pain with adjacent tenderness. No gram-negative cocci were observed or isolated. The obligate intracellular organism causing the infection is unable to perform which of the following metabolic functions? (A) form ATP (B) form the intracellular, metabolically active, reticulate body (C) produce polypeptides (D) reproduce by binary fission (E) synthesize DNA gyrase

16. Severe septic infections caused by bacteria possessing capsules often occur following splenectomy. Which of the following statements most accurately explains why this medical complication is able to occur? (A) The spleen is a source of IgM and IgG antibodies needed to opsonize encapsulated bacteria. (B) The spleen is the main source of stem cells. (C) The spleen is uniquely equipped to process capsular polysaccharides. (D) The spleen rapidly inactivates many antimicrobial agents. (E) The spleen readily metabolizes therapeutic doses of antibiotics.

17. Severe septic infections caused by bacteria possessing capsules often occur following splenectomy. Which of the following statements most accurately explains why this medical complication is able to occur? (A) The spleen is a source of IgM and IgG antibodies needed to opsonize encapsulated bacteria. (B) The spleen is the main source of stem cells. (C) The spleen is uniquely equipped to process capsular polysaccharides. (D) The spleen rapidly inactivates many antimicrobial agents. (E) The spleen readily metabolizes therapeutic doses of antibiotics.

18. A 37-year-old man was immunologically competent but presented to his physician with malaise, fever, lethargy, and back pain. Examination also revealed vertebral osteomyelitis, splenomegaly, and hepatomegaly. He was a PPD-negative farm worker who consumed unpasteurized goat milk. Which of the organisms listed below is the most likely etiological agent? (A) Actinomyces israelii (B) Aspergillus fumigatus (C) Brucella melitensis (D) Candida albicans (E) Mycobacterium tuberculosis

19. A 37-year-old man was immunologically competent but presented to his physician with malaise, fever, lethargy, and back pain. Examination also revealed vertebral osteomyelitis, splenomegaly, and hepatomegaly. He was a PPD-negative farm worker who consumed unpasteurized goat milk. Which of the organisms listed below is the most likely etiological agent? (A) Actinomyces israelii (B) Aspergillus fumigatus (C) Brucella melitensis (D) Candida albicans (E) Mycobacterium tuberculosis

20. Food Poisoning • Contaminated seafood • Vibrio parahaemolyticus, V. vulnificus • Reheated rice, fried rice • Bacillus cereus • Mayonnaise, custard, preparer with cut on finger • S. aureus • Reheated meat dishes • Clostridium perfringens • Improperly canned food • Clostridium botulinum • Undercooked meat, food contaminated with feces • E. coli • Poultry, meat, eggs • Salmonella

21. Bloody Campylobacter Salmonella Shigella Enterohemorrhagic E. coli Enteroinvasive E. coli Yersinia enterocolitica C. Difficile Entamoeba histolytica Watery Enterotoxigenic E. coli Vibrio cholerae C. perfringens Protozoa Giardia, Cryptosporidium Viruses Rotavirus, adenovirus, Norwalk virus Diarrhea

22. After extraction of a wisdom tooth, an 18-year old male student was diagnosed as having subacute bacterial endocarditis. He has a congenital heart disease which has been under control. Which of the following is the most likely organism causing his infection? (A) Enterococcus faecalis (B) S. aureus (C) S. epidermidis (D) S. pneumoniae (E) S. viridans

23. After extraction of a wisdom tooth, an 18-year old male student was diagnosed as having subacute bacterial endocarditis. He has a congenital heart disease which has been under control. Which of the following is the most likely organism causing his infection? (A) Enterococcus faecalis (B) S. aureus (C) S. epidermidis (D) S. pneumoniae (E) S. viridans

24. Normal flora • Skin - Staphylococcus epidermidis • Nose – Staphylococcus aureus • Oropharynx – viridans streptococci • Dental plaque – S. mutans • Colon – Bacteroides fragilis > E. coli • Vagina – Lactobacillus, E. coli, group B strep

25. Children (6wks-18yr) Viruses (RSV) Mycoplasma Chlamydia pneumoniae Streptococcus pneumoniae Adults (18-40) Mycoplasma C. pneumoniae S. pneumoniae Pneumonia

26. Adults (40-65) S. pneumoniae H. influenzae Anaerobes Viruses Mycoplasma Elderly (seasoned citizens) S. pneumoniae Viruses Anaerobes H. influenzae G- rods Pneumonia II

27. Pneumonia by Group • Nosocomial – Staphylococcus, G- rods • Immunocompromised – Staph, G- rods, fungi, viruses, PCP (HIV) • Aspiration – Anaerobes • Alcoholic/IV – S. pneumoniae, Klebsiella, Staphylococcus • Post viral – Staphylococcus, H. influenzae • Neonate – GBS, E. coli • Atypical – Mycoplasma, Legionella, Chlamydia

28. A newborn boy appears to be lethargic and septic. A spinal tap was performed, and a Gram stain of the spinal fluid revealed gram-positive bacilli. Cultures of the spinal fluid on sheep blood agar plates, at a temperature of 22–25°C, yielded catalase-positive hemolytic rods that had a tumbling motion. Penicillin cleared the infection. Which of the following is the most likely organism that caused this disease? (A) Bacillus cereus (B) Bordetella pertussis (C) Corynebacterium diphtheriae (D) Listeria monocytogenes (E) Neisseria meningitidis

29. A newborn boy appears to be lethargic and septic. A spinal tap was performed, and a Gram stain of the spinal fluid revealed gram-positive bacilli. Cultures of the spinal fluid on sheep blood agar plates, at a temperature of 22–25°C, yielded catalase-positive hemolytic rods that had a tumbling motion. Penicillin cleared the infection. Which of the following is the most likely organism that caused this disease? (A) Bacillus cereus (B) Bordetella pertussis (C) Corynebacterium diphtheriae (D) Listeria monocytogenes (E) Neisseria meningitidis

30. Newborn (0-6mo.) Group B Strep E. coli Listeria monocytogenes Children (6mo. – 6yrs.) S. pneumoniae N. meningitidis H. influenzae (type B) Enteroviruses Meningitis

31. 6 years – 60 years N. meningitidis Enteroviruses S. pneumoniae HSV 60 + years S. pneumoniae G- rods Listeria monocytogenes Meningitis II • HIV: Cryptococcus, CMV, Toxoplasmosis (brain abscess), JC virus (PML) • Make note of CSF findings in different etiologies of meningitis (pressure/cells/protein/glucose)

32. Osteomyelitis ESR, CRP are elevated, trend down with treatment. Most common in children. • Most common – S. aureus • Sexually active – N. gonorrhoeae (rare, usually septic joint questions) • Diabetes/addicts – Pseudomonas • Sickle cell – Salmonella • Endoprosthesis – S. aureus, S. epidermidis • Vertebrae – M. tuberculosis (Pott’s disease)

33. A 42-year-old woman had a catheter placed in her urethra. One week later she is experiencing suprapubic flank pain with urinary urgency and frequency. She has also chills and fever. After examining the patient and evaluating the sediment of her centrifuged urine, she is informed by her physician that she has acute ascending pyelonephritis. If the diagnosis is accurate and the patient’s urine is cultured, which of the following organisms will most likely be isolated? (A) Clostridium difficile (B) Escherichia coli with pili (C) Pseudomonas aeruginosa (D) Staphylococcus aureus (E) streptococci—group B

34. A 42-year-old woman had a catheter placed in her urethra. One week later she is experiencing suprapubic flank pain with urinary urgency and frequency. She has also chills and fever. After examining the patient and evaluating the sediment of her centrifuged urine, she is informed by her physician that she has acute ascending pyelonephritis. If the diagnosis is accurate and the patient’s urine is cultured, which of the following organisms will most likely be isolated? (A) Clostridium difficile (B) Escherichia coli with pili (C) Pseudomonas aeruginosa (D) Staphylococcus aureus (E) streptococci—group B

35. UTI UTI: dysuria, frequency, suprapubic pain Pyelonephritis: fever, chills, flank pain, CVA • E. Coli (50-80%), Staphylococcus saprophyticus (10-30%, young women), Klebsiella (8-10%) • Proteus mirabilis – produces urease, association with struvite stones (staghorn calculi) • Pseudomonas aeruginosa – often nosocomial, drug resistant • Asymptomatic bacteruria in a healthy adult is not a UTI and does not need antibiotics

36. Classic Test Parasites • Taenia solium (cysticercosis); brain cysts, seizures • Echinococcus granulosus; liver cysts • Diphyllobothrium latum; B12 deficiency • Clonorchis sinensis; billiary tract disease • Paragonimus westermani; hemoptysis • Schistosoma mansoni; portal hypertension • Schistosoma haematobium; hematuria, bladder cancer • Ancylostoma, Necator; microcytic anemia • Enterobius; perianal pruritus

37. Viruses It will be worth your effort to have a good grasp on viruses in terms of DNA vs. RNA, family, and medical significance. For example: Picronaviruses - No envelope, SS+ linear RNA • Poliovirus - polio • Echovirus – aseptic meningitis • Rhinovirus – “cold virus” • Coxsackievirus – aseptic meningitis, herpangina, hand/foot/mouth, myocarditis • HAV – Hepatitis A

38. A 3-year-old child presents at the physician’s office with symptoms of coryza, conjunctivitis, low-grade fever, and Koplik’s spots. The causative agent of this disease belongs to which group of viruses? (A) adenovirus (B) herpesvirus (C) orthomyxovirus (D) paramyxovirus (E) picornavirus

39. A 3-year-old child presents at the physician’s office with symptoms of coryza, conjunctivitis, low-grade fever, and Koplik’s spots. The causative agent of this disease belongs to which group of viruses? (A) adenovirus (B) herpesvirus (C) orthomyxovirus (D) paramyxovirus (E) picornavirus

40. A 30-year-old previously healthy patient has all the gastrointestinal symptoms of infection with hepatitis A virus (HAV), yet all the tests for HAV-IgG and HAV-IgM are negative. Which of the following is the most likely cause of this infection? (A) hepatitis B virus (B) hepatitis C virus (C) hepatitis D virus (D) hepatitis E virus (E) rotavirus

41. A 30-year-old previously healthy patient has all the gastrointestinal symptoms of infection with hepatitis A virus (HAV), yet all the tests for HAV-IgG and HAV-IgM are negative. Which of the following is the most likely cause of this infection? (A) hepatitis B virus (B) hepatitis C virus (C) hepatitis D virus (D) hepatitis E virus (E) rotavirus

42. Hepatitis Transmission • HAV: (RNA picornavirus) Fecal-oral. 3 week incubation. No carriers. • HBV: (DNA hepadnavirus) Parenteral, sexual, maternal/fetal. 3 month incubation. Carriers. • HCV: (RNA flavivirus) Blood; IV drug users. Carriers. *Both HBV, HCV predispose to chronic active hepatitis, cirrhosis, and hepatocellular carcinoma. • HDV: (Delta agent) Requires HBsAg envelope. Carriers. • HEV: (RNA calicivirus) Enteric transmission- water borne epidemics. *High mortality rate in pregnant women.

43. Hepatitis Serologic Markers • IgM HAVAb: Detect active hepatitis A. • HBsAg: continued presence = carrier • HBsAb: HBsAg antibody, provides immunity • HBcAg: HBV core antigen • HBcAb: window period (5-6 months) • HBeAg: core antigen, indicates transmissibility • HBeAb: antibody to e antigen, indicates low transmissibility state

44. Hypersensitivity Reactions • Type I: Anaphylactic and Atopic • Ag cross-links IgE on presensitized mast cells and basophils (antibody preformed = rapid) • Triggers release of vasoactive amines (histamine) • Type II: Antibody Mediated • IgM, IgG bind to antigen on cell, leading to lysis or phagocytosis • Lysis mediated by complement system – Membrane Attack Complex (MAC)

45. Type III • Immune Complex: antigen-antibody complexes activate complement  neutrophils  lysosomal enzymes • Serum Sickness: Antibodies to foreign proteins are produced (days). Complexes deposited in membranes  fix complement  tissue damage • Arthus Reaction: Local, subacute, intradermal. Antigen-antibody complexes  edema, necrosis, activation of complement. • Type IV: Delayed (T-cell mediated) • Sensitized T lymphocytes encounter antigen  release lymphokines  macrophage activation

46. While on a wilderness vacation, a banker develops extensive skin lesions noted for their varying degrees of erythema, edema, and vesiculations. His physician tells him that these lesions are due to delayed type hypersensitivity. If this is actually the case, which of the following statements is accurate? (A) Delayed-type hypersensitivity can be transferred passively to volunteers by sensitized lymphocytes. (B) Delayed-type hypersensitivity is suppressed by antihistaminic drugs. (C) This allergy does not cause tissue damage. (D) This allergy is due to IgE absorbed on mast cells. (E) This type of allergy usually occurs after inhalation of grass pollens.

47. While on a wilderness vacation, a banker develops extensive skin lesions noted for their varying degrees of erythema, edema, and vesiculations. His physician tells him that these lesions are due to delayed type hypersensitivity. If this is actually the case, which of the following statements is accurate? (A) Delayed-type hypersensitivity can be transferred passively to volunteers by sensitized lymphocytes. (B) Delayed-type hypersensitivity is suppressed by antihistaminic drugs. (C) This allergy does not cause tissue damage. (D) This allergy is due to IgE absorbed on mast cells. (E) This type of allergy usually occurs after inhalation of grass pollens.

48. Which of the following will be observed in a person who is deficient in interleukin-1 synthesis? (A) difficulty with immunoglobulin isotopic switching (B) dependence on endotoxin for the induction of febrile responses (C) effective mediation of acute phase responses (D) effective regulation of vascular shock (E) tendency to develop intense inflammatory reactions

49. Which of the following will be observed in a person who is deficient in interleukin-1 synthesis? (A) difficulty with immunoglobulin isotopic switching (B) dependence on endotoxin for the induction of febrile responses (C) effective mediation of acute phase responses (D) effective regulation of vascular shock (E) tendency to develop intense inflammatory reactions

50. Cell Surface Proteins • Helper T cells: CD4, TCR, CD3, CD28, CD40L • Cytotoxic T cells: CD8, TCR, CD3 • B cells: IgM, B7, CD19, CD20, CD40, MHC II • Macrophages: MHCII, CD14, receptors for Fc and C3b • NK cells: Receptors for MHCI, CD16, CD56 • All cells (except RBC) : MHCI