Immunology and Microbiology

Question 0

Infant with fever, irritability, vomiting with Mycobacterium tuberculosis grown on blood culture and family history of brother who passed away from Mycobacterial infection during infancy. What disease? Inheritance? Normal mechanism?

Answer 0

Inherited defects of the interferon-gamma signaling pathway!!
IL-12 receptor deficiency, for example.
Autosomal recessive

Results in disseminated mycobacterial disease in infancy or early childhood. Pts require lifelong treatment with antimycobacterial agents.

Macrophages infected with mycobacteria produce IL-12, which stimulates T and NK cells to produce IFN-gamma which binds its receptor leading to dimerization, Janus kinase1&2 activation, STAT1 signaling, and transcription of IFNgamma-related genes that promotes mycobacterial killing by phagocytes and increases defenses (e.g., expression of MHC).

Question 1

What are the functions of cytokines IL-1 to IL-6?

Answer 1

“Hot T-bone stEAK”
IL-1: fever (hot)
IL-2: stimulates T cells (T)
IL-3: stimulates BM (bone)
IL-4: stimulates IgE production (enhances class switching to IgE)
IL-5: stimulates IgA production (enhances class switching to IgA)
IL-6: stimulates aKute-phase protein production, also fever

Question 2

Non-lactose-fermenting gram-negative rods with fecal leukocytes and occult blood tests positive. No gas on fermentation of glucose and no H2S on triple sugar agar. Mechanism?

Answer 2

Shigella
invades intestinal mucosa
causes a PMN/neutrophil infiltration

Question 3

What is the mechanism of Shigella’s shiga toxin? What other organism uses a Shiga-like toxin?

Answer 3

AB exotoxin
A subunit inactivates the 60S ribosome of the host, halting protein synthesis and causing cell death
(B subunits facilitate internalization of toxin into cells)

EHEC E. coli Shiga-like toxin / veratoxin

Question 4

How does Shigella invade? What is the more important factor for disease - mucosal invasion or toxin production?

Answer 4

accesses gut mucosal epithelium by entering M cells in Peyer’s patches
escapes phagosome, spreads laterally to other epithelial cells, and releases Shiga toxin

Mucosal invasion more important than toxin production - robust inflammatory response responsible for diarrhea seen.

Question 5

What does ingestion of 13C-labeled urea test for? How is the organism detected?

Answer 5

H. pylori

urease product degrades consumed urea into CO2 and ammonia
CO2 enters bloodstream and is exhaled in pt’s breath
pt blows into tube and 13C-labeled CO2 is detected in breath sample

Question 6

Difference in immunity between killed and live-attenuated polio vaccines?

Answer 6

Live-attenuated vaccine produces more prolonged synthesis and secretion of local mucosal IgA (offering immune protection at the normal site of viral entry) vs. killed vaccine.

Local secretory antibody synthesis best promoted when specific mucosal surfaces are directly stimulated by antigen!

Live vaccines colonize natural site of viral entry to produce a more robust and prolonged immune response.
Killed vaccines are usually intramuscular and unable to stimulate mucosal production.

Question 7

How does Giardia cause its characteristic foul-smelling, fatty diarrhea? What is the major defense?

Answer 7

trophozoites (pear-shaped) adhere to intestinal brush border in the duodenum and jejunum and cause injury to the mucosa by inducing an inflammatory response

Secretory IgA impairs adherence (major adaptive immunity)

Question 8

What cells kill cells with down-regulated expression of MHC I? What is the mechanism of the induced apoptosis?

Answer 8

Natural killer (NK) cells
target cells with decreased MHC I expression (e.g., virus-infected or tumor cells)

Perforins (put holes in target membrane) and granzymes (induce apoptosis) are contained in cytoplasmic granules.

Question 9

What chemotactic agents induces chemotaxis and/or phagocytosis in neutrophils?

Answer 9

leukotriene B4 (LTB4)
C5a
IL-8
bacterial products (n-formylated peptides)

Question 10

How does Strongyloides stercoralis enter the host? How is it detected? Treatment? When is hyperinfection seen?

Answer 10

Larvae (infectious/filariform) in soil contaminated by human feces penetrate the skin
Migrate hematogenously to lung, coughed up and swallowed, larvae develop into adults, lay eggs for more larvae which are excreted.

Diagnosis: detection of larvae (noninfectious/rhabtidiform) in stool

Treatment: Ivermectin

Hyperinfection if cycle of autoinfection leads to massive worm burden and widespread dissemination into tissues - seen in immunocompromised or HTLV-1 pts.

Question 11

What portion of an IgG antibody is attached tot he surface of macrophages, neutrophils, and B-lymphocytes? What part of the antibody attaches to complement?

Answer 11

the Fc region of the immunoglobulin molecule near the carboxy terminal is the attachment site to Fc receptors on macrophages, etc.
(This binding is essential for the process of opsonization/promotion of phagocytosis.)

The complement-binding site of an IgG molecule is proximal to the hinge region of the molecule (toward the C-terminal of the heavy chain).

Question 12

Describe the classical pathway of complement activation. What antibodies are involved? What are the other pathways of complement activation? What factor do all these pathways converge on?

Answer 12

IgG or IgM bound to antigen binds/activates C1
(“GM makes classic cars”)

Alternative pathway: microbial products directly activate complement

Mannose-binding lectin (MBL) pathway: MBL binds to mannose on microorganisms and activates complement

ALL pathways result in production of C3 convertase (C3 to C3a&C3b), which turns on C5 convertase (C5 to C5a&C5b), which leads to C5b complexing with C6-C9 to form the MAC.

Question 13

56yo man with painful swallowing - biopsy shows budding cells and easily disrupted chains of elongated cells?

Answer 13

Esophageal candidiasis

Question 14

What type of cells provide defense against local/superficial Candida infections? What type of cells provide defense against systemic/disseminated Candida?

Give examples of each type of infection.

Answer 14

T-lymphocytes (particularly Th cells) prevent superficial Candida infection.
Local/superficial: oral thrush, cutaneous candidiasis, vulvovaginitis
Common in HIV-positive pts but they rarely get disseminated form!!

Neutrophils prevent hematogenous spread (disseminated/systemic forms).

Question 15

What factor is secreted by Neisseria species to facilitate mucosal penetration?

Answer 15

IgA protease
cleaves hinge region of IgA, which normally acts to bind pillae and other proteins that mediate bacterial adherence and penetration through the mucosa.

Question 16

E. coli that does not ferment sorbitol? What toxin does it use?

Answer 16

EHEC

produces Shiga-like toxin
inactivates the 60S ribosomal subunit leading to protein synthesis inhibition and death (same mechanism of Shiga toxin by Shigella)

Question 17

Undercooked ground beef and bloody diarrhea?

Answer 17

EHEC E. coli

Question 18

Week-long diarrhea that has now turned bloody with escalating fever, hepatosplenomegaly, and spots around abdomen? How is a carrier state established?

Answer 18

Salmonella typhi

can cause bacteremia and sepsis, leading to colonization of the gallbladder and virtually limitless access to the gut lumen

Question 19

Nausea and vomiting 2hrs after eating mayonnaise salad at picnic? Mechanism?
What is another organism that also causes rapid-onset food poisoning?

Answer 19

Staphylococcus aureus
enterotoxin-mediated rapid-onset food poisoning
PREFORMED, heat-stable enterotoxin not destroyed by cooking

Bacillus cereus also causes rapid-onset food poisoning
also with preformed heat-stable enterotoxin
characteristically starchy foods like rice (reheated fried rice classic)

Question 20

Grows in alkaline media?

Answer 20

Vibrio cholerae

Question 21

Oxidase positive, comma-shaped gram-negative rods? How to distinguish?

Answer 21

Campylobacter jejuni (grows in 42degreesC)
Vibrio cholerae (grows in alkaline media)
Heliobacter pylori (produces urease)

Question 22

Mechanism of cholera toxin? What other organism shares a similar toxin? What kind of diarrhea in both?

Answer 22

increases activity of adenylate cyclase in intestinal mucosal cells
increased cAMP causes increased efflux of sodium and chloride from intestinal epithelial cells and decreased reabsorption (disrupted apical ion transport = massive water loss and watery diarrhea)

ETEC (E. coli) produces heat-labile toxin that is cholera-like!!
Also produces heat-stabile toxin that targets GC to increase cGMP and also promote watery diarrhea.

Watery diarrhea with NO invasion or enterocyte death, so NO blood and NO pus (leukocytes/neutrophils).

Question 23

What are the anti-inflammatory cytokines?

Answer 23

IL-10 and TGFbeta

down-regulate local cytokine production and inflammatory rxns contributing to the systemic acute phase response

Question 24

Infant with poor feeding, weakness, and complete loss of extremity muscle tone. Vaccinations up to date with formula his sole source of nutrition other than occasional fruit juice and honey? Mechanism and diagnosis?

Answer 24

HONEY = C. botulinum spores!!
Infant botulism

ingestion of spores, germination in GI tract, intracellular toxin production and bacteriolytic release
(in adults, preformed toxins accumulate in canned food)

Diagnose via bacterial toxins in stool

Question 25

What type of antibody is present in colostrum? Where else is this form present? What form does it and other antibodies take in the serum?

Answer 25

IgA in dimer form (two IgAs, J chain protein, secretory component protein)
Colostrum = first breast milk after birth
tears, saliva, mucus

IgA is a monomer in serum
IgG and IgE also monomers in serum
IgM exists as a pentamer in serum

Question 26

Mechanism of C.diff diarrhea? Diagnosis? Treatment?

Answer 26

Two toxins:

• Toxin B (cytotoxin) causes actin depolymerization leading to cell death and necrosis
• Toxin A (enterotoxin) binds to brush border and causes mucosal inflammation via neutrophil attraction

Diagnosis: stool PCR for toxin genes

Treatment: Metronidazole or oral Vancomycin

Question 27

Mechanism of C. perfringens toxicity? How acquired? Typical presentations?

Answer 27

produces alpha toxin lecithinase (phospholipase)
causes membrane destruction and cell death

Infection: spores abundant in soil – penetration injury leads to inoculation

Presentation: gas gangrene (myonecrosis) most commonly, but also causes transient watery diarrhea (due to ingestion of spores)

Question 28

Watery diarrhea affecting apical ion transport?

Bloody diarrhea affecting protein synthesis?

Answer 28

Watery: Cholera or cholera-like toxin
V. cholerae or ETEC E.coli
increased AC activity, increased cAMP
increased transport out, decreased reabsorption = watery loss

Bloody: Shiga or Shiga-like toxin
Shigella or EHEC E.coli
blocks 60S ribosomal subunit = death

Question 29

Describe traveller’s diarrhea and its toxins/mechanisms.

Answer 29

ETEC E.coli
toxins: LT (heat-labile) and ST (heat-stable)

LT – increases AC to increase cAMP
Cholera-like toxin!!

ST – increases GC to increase cGMP

Both cause water/electrolyte loss = watery diarrhea

Question 30

How are peptides loaded onto MHC I processed? How are peptides loaded onto MHC II processed? Which relies on acidified lysosomes?

Answer 30

MHC I: proteins in cytoplasm degraded by proteasome
transported into ER to be loaded onto MHC I

MHC II: exogenous proteins degraded after uptake by endosome fusion with lysosome
MHC II enters lysosome with invariant chain in binding site - invariant chain degraded and exogenous peptide loaded

MHC II thus relies on acidification of lysosomes.

Question 31

Low inoculum/infectious dose organisms?

Answer 31

BACTERIA:
Shigella (as low as 10)
Campylobacter jejuni (500)

PARASITES:
Entamoeba histolytica (as few as one)
Giardia lamblia (as few as one)

Question 32

Name the Picornaviridae. Which are enteroviruses?

Answer 32

PERCH
Poliovirus
Echovirus
Rhinovirus
Coxsackie virus
Hepatitis A

All but Rhinovirus are enteroviruses (relatively acid stable so pass through the stomach to colonize/infect GI tract)

Question 33

Pt with diarrhea and white/yellow membrane-like plaques on colonic mucosa composed of fibrin and inflammatory cells? How do diagnose?

Answer 33

White/yellow membrane-like plaques virtually pathognomonic for C. diff.

Diagnosis: toxin genes in stool by PCR

Question 34

What toxins are produced by Pseudomonas?

Answer 34

endotoxin (fever, shock)

exotoxin A (inactivates EF-2; similar to diphtheria toxin)