Term
| What are the 2 major strategies on immune evasion utilized by various pathogens? |
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Definition
1) Disguised antigens resulting in inadequate immune response to the pathogen (N. meningitidis, S. pyogenes, S. aureus)
2) Production of cross-reactive antigens that result in pathological immune response against host (S. pyogenes, C. jejuni, T. cruzi) |
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Term
| How does S. aureus utilize molecular mimicry? |
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Definition
Disguise- Coating without phagocytosis
Protein A binds to Fc on IgG, coating membrane without phagocytosis. |
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Term
| How does S. pyogenes utilize molecular mimicry? |
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Definition
1) Pharyngitis, bacteremia and TSS
- Disguise with hyaluronic acid capsule (human ground substance) and M protein (binds Factor H)
2) Rheumatic Fever
- Autoantigen with M protein inducing autoantibodies that react with cardiac tissue. |
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Term
| How does N. meningiditis utilize molecular mimicry? |
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Definition
Meningitis
1) Disguise with serotype B capsule (same as human neuronal sialic acid) |
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Term
| How does C. jejuni utilize molecular mimicry? |
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Definition
Guillain-Barre Syndrome
Auto-antigen- Ganglioside sugars that mimic neuronal tissue and are associated with GBS |
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Term
| How does T. cruzi utilize molecular mimicry? |
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Definition
Neuronal Damage
Autoantigen: Cross-reactive peptides lead to auto-reactive B-cells. |
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Term
A gram stain comes back and shows gram (-) diplococci that are oxidase (+) and non-motile.
What bug is this and what is its pathogenesis? |
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Definition
N. meningiditis
1) Attaches to mucosal epithelium of pharynx via Pili and multiply to form "plaque."
2) Use IgA protease to avoid immune response and then invade epithelium.
3) Once inside vascular space, they release LOS, which disseminates to brain (meningitis), skin (purpura), joints (arthritis), and bones (osteomyelitis) |
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Term
| How can you tell between different Neisseria species? |
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Definition
Capsule, Pili and OpA
1) meningitidis colonizes respiratory tract with Carbohydrate capsule and Pili and makes Acid from maltose
2) gonorrhoeae colonizes the genital tract. It lacks a capsule, but uses pili and Opa for attachment and disease (cannot metabolize maltose)
3) Commensual colonize oral and GI, but have no capsule and no pili, and NO DISEASE. |
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Term
| What is the Reservoir and Transmission of Neiserria meningitidis? |
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Definition
1) Human reservoir
2) Usually colonizes pharynx w/o disease, leading to a lot of carriage in young adults.
3) Recent colonization, new strains to region/patient and immune deficiencies are all risk factors for disease |
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Term
| What are the primary risk factors for N. meningitidis infection? |
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Definition
Global Health Issue in Africa
1) Recent colonization
2) New strains to region/patient
3) Immune deficiencies are all risk factors for disease |
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Term
| What are the Virulence factors of N. meningitidis? |
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Definition
Capsule, OpA, Pili, LOS, IgA-protease, Complement-binding protein
1) Serotype B Capsule- branching carbs avoid immune system because homology to neuronal sialic acid
2) OpA for attachment and antigenic variation
3) Pili for attachment, invasion and antigenic variation
4) LOS for inflammation and can spread hematologically (levels correlate with level of sepsis).
5) IgA protease to avoid immune response in respiratory epithelia
6) Complement-binding proteins (binds Factor H to prevent complement activation). |
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Term
| What is the relationship between complement-deficiency states and meningococcal infection? |
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Definition
| Strong positive correlation (complement is important for protection) |
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Term
| How do you diagnose a case of N. meningitidis? |
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Definition
Clinical
1) High fever and low BP with stiff neck and headache
2) Rash with ***petechiae or purpura***
Lab
1) Blood and CSF gram stain
2) DONT IDENTIFY CARRIERS
3) **Oxidase-positive**, maltose fermenters
4) Serotype for epidemiology |
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Term
| What treatment/prevention methods are available for N. meningiditis? |
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Definition
1) Reduce contact
2) Treat with high-dose PCN or Ceftriaxone (can also use FQ) IMMEDIATELY
3) Reduce carriage with vaccination (capsular vaccine covers all but group B) |
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Term
| What vaccine options are available for N. meningitidis? |
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Definition
Get vaccinated by 11-12, and can after 2 years old.
**Nothing to serotype B, which is problem in infants!**
1) MPSV4 (Menomune) polysacharide capsular for A, C, Y and W135
2) MCV4 (Menactra) is conjugate that covers the same |
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Term
A gram stain comes back with gram (+), non-motile, non-spore-forming, catalase (-) pairs of cocci that are sensitive to Bacitracin.
What bug is this and what is its pathogenesis? |
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Definition
Strep pyogenes
Causes 4 Things
1) Mucosal infections (pharyngitis)- can progress to pyogenic or immunogenic
2) Pyogenic infections (Nec Fasc.)- only solution is surgical
3) Toxigenic infections (TSS)
4) Non-suppurative or immunologic (Rheumatic fever and poststreptococcal glomerulonephritis) |
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Term
| What is the molecular pathogenesis of Mucosal and Pyogenic GAS infections? |
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Definition
If invasive, will require antibiotics!
-M protein-and LTA-mediated attachment to host tissue
- Hyaluronidase digests matrix,
- Hemolysins lyse RBCs
- Streptokinase prevents clotting after leak |
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Term
| Where would you find S. agalactiae? |
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Definition
Beta-hemolysis
In vagina and causes neonatal sepsis and meningitis |
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Term
| What symptoms are Viridans streptococci associated with? |
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Definition
No Lancefield group
Colonizes UR, colon and female genital tract causes dental caries, endocarditis and abscesses |
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Term
| Explain Streptococcal taxonomy. |
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Definition
S. pyogenes most common agent responsible for disease!
1) Lancefield group is cell wall carbohydrate
2) Hemolysis |
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Term
| How does PYR testing contribute to identifying S. pyogenes? |
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Definition
| Only S. pyogenes and Enterococci hydrolyze this compound. |
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Term
| What is the Reservoir and Transmission of S. pyogenes? |
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Definition
1) Disease confined to humans and results from novel strain altering normal flora
2) Aerosole (fomites) or by direct contact- worst in late winter/early spring in school-age children |
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Term
| What are the major Cell Wall virulence factors associated with S. pyogenes? |
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Definition
M protein (disguise and autoantigen)
LTA (Adhesion)
Hyaluronic acid (Disguise/Mol. mimicry)
C5a peptidase
1) M protein- Disguise antigens complexes with Factor H to avoid phagocytosis and Autoantigens cause Rheumatic fever and Poststreptococcal glomerulonephritis
2) Lipoteichoic acid (LTA) attaches to fibronectin on oropharyngeal epithelial cells (Adhesion)
3) Hyaluronic acid capsule (disguise molecular mimicry)
4) C5a peptidase cleaves C5a |
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Term
| What are the major Exotoxin virulence factors associated with S. pyogenes? |
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Definition
1) Hemolysins (Beta hemolysis)
2) Streptokinase/Stepdornae (Fibrinolysis and DNA damage)
3) Hyaluronidase (Spreading)
4) Erythrogenic Toxin (T-cell mediated vascular damage in TSS)
1) Hemolysins- Streptolysin O and S (SLO and SLS) responsible for Beta-hemoylsis of RBC
2) Streptokinase/steptodornase
- SKA converts plasminogen to plasmin (fibrinolysis)
-Steptodornae (DNAse B) digests dsDNA
3) Hyaluronidase
- Digests GAS capsule and connective tissue hyaluronic acid (SPREADING)
4) Erythrogenic toxin
-Phage-mediated causes superantigen effects to activate T cells in a TCR-indenpendent manner causing small vessel damage in TSS |
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Term
| How does Rheumatic fever arise in GAS? |
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Definition
Disease of children with fever, arthritis, carditis, with (RARE) chorea, rash and nodules
- Molecular mimicry (Autoantigen) causes autoimmune reaction to M-protein
- Early antibiotic therapy is effective against Rheumatic fever. |
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Term
| How does Poststreptococcal glomerulonephritis (PSGN) occur? |
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Definition
PSGN is a Non-suppurative GAS reaction that involves hematuria (coca cola urine), Edema and Hypertension.
- Can follow strep pharyngitis (1-2 weeks later) or soft tissue/skin infections (3-4 weeks)
- May involve deposition of antigen-antibody complexes in glomeruli (95% resolve with supportive care) |
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Term
| How do you diagnose GAS infections? |
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Definition
1) Microscopy (cocci in pairs and chains- Gram stain is not informative because there are TOO MANY OTHER STREPS)
2) Culture at 37 on blood agar in 10% CO2 environment and follow up with hemolysis (beta), PYR test (positive) and bacitracin sensitivity (sensitive)
3) Rapid (60-90% as sensitive as culture) and Serologic (Ab testing) |
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Term
| How is treatment/prevention of GAS achieved? |
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Definition
Treat is easy, Prevent is challenging
1) PCN and all beta-lactams (some Macrolide resistance
Treat as EARLY AS POSSIBLE
2) Prevention involves prophylactic PCN for rheumatic fever (no Vaccine) |
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