Flashcards in Immunology and Microbiology Deck (35)
What are the functions of cytokines IL-1 to IL-6?
"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
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?
Inherited defects of the interferon-gamma signaling pathway!!
IL-12 receptor deficiency, for example.
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).
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?
invades intestinal mucosa
causes a PMN/neutrophil infiltration
What is the mechanism of Shigella's shiga toxin? What other organism uses a Shiga-like toxin?
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
How does Shigella invade? What is the more important factor for disease - mucosal invasion or toxin production?
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.
What does ingestion of 13C-labeled urea test for? How is the organism detected?
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
Difference in immunity between killed and live-attenuated polio vaccines?
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.
How does Giardia cause its characteristic foul-smelling, fatty diarrhea? What is the major defense?
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)
What cells kill cells with down-regulated expression of MHC I? What is the mechanism of the induced apoptosis?
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.
What chemotactic agents induces chemotaxis and/or phagocytosis in neutrophils?
leukotriene B4 (LTB4)
bacterial products (n-formylated peptides)
How does Strongyloides stercoralis enter the host? How is it detected? Treatment? When is hyperinfection seen?
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
Hyperinfection if cycle of autoinfection leads to massive worm burden and widespread dissemination into tissues - seen in immunocompromised or HTLV-1 pts.
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?
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).
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?
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.
56yo man with painful swallowing - biopsy shows budding cells and easily disrupted chains of elongated cells?
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.
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).
What factor is secreted by Neisseria species to facilitate mucosal penetration?
cleaves hinge region of IgA, which normally acts to bind pillae and other proteins that mediate bacterial adherence and penetration through the mucosa.
E. coli that does not ferment sorbitol? What toxin does it use?
produces Shiga-like toxin
inactivates the 60S ribosomal subunit leading to protein synthesis inhibition and death (same mechanism of Shiga toxin by Shigella)
Undercooked ground beef and bloody diarrhea?
EHEC E. coli
Week-long diarrhea that has now turned bloody with escalating fever, hepatosplenomegaly, and spots around abdomen? How is a carrier state established?
can cause bacteremia and sepsis, leading to colonization of the gallbladder and virtually limitless access to the gut lumen
Nausea and vomiting 2hrs after eating mayonnaise salad at picnic? Mechanism?
What is another organism that also causes rapid-onset food poisoning?
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)
Grows in alkaline media?
Oxidase positive, comma-shaped gram-negative rods? How to distinguish?
Campylobacter jejuni (grows in 42degreesC)
Vibrio cholerae (grows in alkaline media)
Heliobacter pylori (produces urease)
Mechanism of cholera toxin? What other organism shares a similar toxin? What kind of diarrhea in both?
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).
What are the anti-inflammatory cytokines?
IL-10 and TGFbeta
down-regulate local cytokine production and inflammatory rxns contributing to the systemic acute phase response
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?
HONEY = C. botulinum spores!!
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
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?
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
Mechanism of C.diff diarrhea? Diagnosis? Treatment?
- 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
Mechanism of C. perfringens toxicity? How acquired? Typical presentations?
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)
Watery diarrhea affecting apical ion transport?
Bloody diarrhea affecting protein synthesis?
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