Download 2008 AOA Review

2008 AOA Review
Infection and Immunity
Contact Information
Andrew R. Esterle
[email protected]
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.
USMLE 1 I & I
• 40% Bacteriology
– 20% Basic Science
– 20% Clinical
• 25% Immunology
• 25% Virology
– 10% Basic
– 15% Clinical
• 5% Parasitology
• 5% Mycology
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
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
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
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
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
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
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
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
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
A 38-year-old sexually-active woman developed symptoms of
lower abdominal pain with adjacent tenderness. No gramnegative 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
A 38-year-old sexually-active woman developed symptoms of
lower abdominal pain with adjacent tenderness. No gramnegative 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
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.
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.
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
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
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
Diarrhea
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•
•
•
•
•
•
•
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
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
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
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
Pneumonia
Children (6wks-18yr)
• Viruses (RSV)
• Mycoplasma
• Chlamydia
pneumoniae
• Streptococcus
pneumoniae
Adults (18-40)
• Mycoplasma
• C. pneumoniae
• S. pneumoniae
Pneumonia II
Adults (40-65)
•
•
•
•
•
S. pneumoniae
H. influenzae
Anaerobes
Viruses
Mycoplasma
Elderly (seasoned
citizens)
•
•
•
•
•
S. pneumoniae
Viruses
Anaerobes
H. influenzae
G- rods
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
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 catalasepositive 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
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 catalasepositive 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
Meningitis
Newborn (0-6mo.)
• Group B Strep
• E. coli
• Listeria
monocytogenes
Children (6mo. – 6yrs.)
•
•
•
•
S. pneumoniae
N. meningitidis
H. influenzae (type B)
Enteroviruses
Meningitis II
6 years – 60 years
•
•
•
•
N. meningitidis
Enteroviruses
S. pneumoniae
HSV
60 + years
• S. pneumoniae
• G- rods
• Listeria
monocytogenes
HIV: Cryptococcus, CMV, Toxoplasmosis (brain
abscess), JC virus (PML)
•Make note of CSF findings in different etiologies of
meningitis (pressure/cells/protein/glucose)
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)
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
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
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
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
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
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
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
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
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
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.
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
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)
• 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
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.
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.
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
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
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
Cytokines
• IL-1: Secreted by macrophages. Stimulates T cells,
B cells, neutrophils, fibroblasts, epithelial cells.
• IL-2: Secreted by Th cells. Stimulates growth of
helper and cytotoxic T cells.
• IL-3: Secreted by activated T cells. Supports the
growth and differentiation of bone marrow stem
cells. (similar to GM-CSF)
• IL-4: Secreted by Th2 cells. Promotes growth of B
cells. Enhances class switching of IgE and IgG.
• IL-5: Secreted by Th2 cells. Promotes differentiation
of B cells. Enhances class switching of IgA.
Stimulates production and activation of eosinophils.
• IL-6: Secreted by TH cells and macrophages.
Stimulates production of acute-phase reactants and
immunoglobulins.
• IL-8: Major chemotactic factor for neutrophils.
• IL-10: Secreted by Th2 cells. Stimulates Th2 while
inhibiting Th1.
• IL-12: Secreted by B cells and macrophages.
Activates NK and Th1 cells.
• γ-interferon: Secreted by Th1 cells. Stimulates
macrophages.
• TNF-α: Secreted by macrophages. Increased IL-2
receptor synthesis by Th cells. Increased B-cell
proliferation. Attracts and activates neutrophils.
Stimulates dendritic cell migration to lymph nodes.
Complement System
•
•
•
•
•
•
•
Alternative, Lectin, Classic Pathways
C1, C2, C3, C4: viral neutralization
C3b: opsonization
C3a, C5a: anaphylaxis
C5a: neutrophil chemotaxis
C5b-C9: cytolysis via MAC
Deficiencies:
– C1 esterase inhibitor = hereditary angioedema
– C3 = recurrent pyogenic sinus, resp. infections
– C6-C8 = Neisseria bacteremia
– Decay accelerating factor (DAF) = paroxysmal
nocturnal hemoglobinuria
Autoantibodies
•
•
•
•
•
•
•
•
•
•
Antinuclear antibodies (ANA) : SLE
Anti-dsDNA, anti-Smith: SLE specific
Antihistone: Drug-induced lupus
Anti-IgG: Rheumatoid arthritis
Antineutrophil (C-ANCA, P-ANCA) : Vasculitis
Anticentromere: Scleroderma (CREST)
Anti-Scl-70: Scleroderma (diffuse)
Antimitochondrial: 1º biliary cirrhosis
Antigliadin: Celiac disease
Anti-basement membrane: Goodpasture’s
syndrome
• Anti-microsomal: Hashimoto’s thyroiditis