Immune evasion Flashcards
Name the four mechanisms where immune evasion can occur
Opsonisation
chemotaxis
Phagocytosis
straight up murder
What are the two groups that diseases caused by S. aureus can be divided into?
- localized pyogenic or “pus-producing” diseases that are characterized by tissue destruction mediated by hydrolytic enzymes and cytotoxins
- diseases mediated by toxins that function as superantigens producing systemic diseases.
What are the properties of s. aureus bacteria that allow it to grow efficiently?
- Ability to grow aerobically and anaerobically, over wide range of temps
- Have a polysaccharide capsule that protects the bacteria from phagocytosis
- Cell surface proteins (protein A , clumping factor proteins) that mediate adherence of the bacteria to host tissues
- Catalase that protects staphylococci from peroxides produced by neutrophils and macrophages
- Coagulase converts fibrinogen to insoluble fibrin that forms clots to protect s. aureus from phagocytosis
What hydrolytic enzymes and cytotoxins does S. aureus produce?
Lipases, nucleases, and hyaluronidase that causes tissue destruction
Cytotoxins (alpha, beta, delta, gamma, leukocidin) that lyse erythrocytes, neutrophils, macrophages, and other host cells
What toxins does S. aureus produce and what does it cause?
Enterotoxins - many antigenically distinct that are heat and acid resistant so cause food poisoning
Exfoliative toxins A and B cause superficial layers of skin to peel off (scalded skin syndrome)
Toxic shock syndrome toxin is a heat and protease resistant toxin that mediates multiorgan pathology
List some S. aureus Pyogenic Diseases.
Impetigo : localized skin infection characterized by pus-filled vesicles on a reddened or erythematous base; seen mostly in children on their face and limbs
Folliculitis : impetigo involving hair follicles, such as the beard area
Pneumonia : abscess formation in the lungs; observed primarily in the very young and old and frequently following viral infections of the respiratory tract
Endocarditis : infection of the endothelial lining of the heart; disease can progress rapidly and is associated with high mortality rate
Wound infections : characterized by erythema and pus at the site of trauma or surgery; more difficult to treat if a foreign body is present (e.g., splinter, surgical suture); majority of infections both in the community and hospital are caused by MRSA; recurrent bouts of infections are common
List some S. aureus toxin-mediated diseases Diseases.
Food poisoning : consumption of food contaminated with the heat-stable enterotoxin
the onset of severe vomiting, diarrhea, and stomach cramps is rapid (2 to 4 hours) but resolves within 24 hours.
intoxication is caused by the preformed toxin present
Scalded skin syndrome : bacteria in a localized infection produce the toxin that spreads through the blood and causes the outermost layer of the skin to blister and peel off; almost exclusively seen in very young children
Toxic shock syndrome : bacteria in a localized infection produce the toxin that affects multiple organs; characterized initially by fever, hypotension, and a diffuse, macular, erythematous rash.
There is a very high mortality rate associated with this disease unless antibiotics are promptly administered and the local infection managed.
How are localised S. aureus infections controlled?
Managed by incision and drainage
How are systemic S. aureus infections treated?
Antibiotic therapy indicated for systemic infections; empiric therapy should include antibiotics active against MRSA
Oral therapy can include trimethoprim-sulfamethoxazole, clindamycin, or doxycycline
Vancomycin is the drug of choice for intravenous therapy
Treatment is symptomatic for patients with food poisoning although the source of infection should be identified so other individuals will not be exposed
How can you prevent S. aureus infections?
Proper cleansing of wounds and use of disinfectant help prevent infections
Thorough hand washing and covering exposed skin helps medical personnel prevent infection or spread to other patients
No vaccine is currently available
What cells are included in our innate immune response?
Neutrophils, Eosinophils, Basophils, dendritic cells and macrophages
Why must neutrophil responses be balanced?
Must be balanced to prevent infection, but also prevent damage by excessive inflammation to the host
List basically what neutrophils do.
Recruitment of neutrophils Adhesion Transmigration Priming Chemotaxis Activation Opsonisation Phagocytosis & Inflammation & degranulation
What is staphylococcus aureus?
Gram-positive bacterium
Commensal and livesharmlessly in the nose of 30% of human population.
S. aureusis an opportunistic pathogen; minor skininfections to severe and life-threatening diseases.
S. Aureus has many ways to avoid neutrophils
What is opsonisation?
Antibodies (opsonins) bind to bacterial antigens tagging them.
This allows:
1. deposition of complement in the classical complement pathway
2. neutrophils and other phagocytes the ability to detect invading microbes
How does S. aureus evade opsonisation via capsules?
Polysaccharide capsule which hides antigenic structures that can be detected by innate and adaptive immune components such as complement/antibodies
Which other bacteria evade opsonisation through polysaccharide capsules?
E. coli S. pyogenes pseudomonas aeruginosa S. pneumonia S. agalactiae
List the three ways S. Aureus evades detection by antibodies
- Polysaccharide capsule
- Incorrect opsonisation due to presence of Spa protein which binds to the incorrect region of the antibody (Fc instead of Fab)
- Secretes SSL10 which binds to Fc region of the IgG antibody
How does S. aureus evade opsonisation via SpA?
S. aureus protein binds to the IgG fc region stopping the antibody binding to the bacteria from its Fab region
Normal opsonisation is prevented so neutrophils cannot detect S. aureus - deposition of complement via the classical complement pathway is prevented
Also prevents bacteria being recognised via Fc region by the Fc receptors on neutrophils/phagocytes
How does S. aureus avoid opsonisation by SSL10?
Secretes SSL10 protein which binds to Fc region of the IgG antibody, this prevents the Fc receptors on neutrophils from detecting IgG on the surface of S. aureus
What methods can be used to avoid opsonisation?
Hide antigens Disrupt function of antibodies Prevent detection of opsonised bacteria Degrade antibodies Modify antigenicity Many bacteria use multiple
What is complement opsonisation ?
The complement system is composed of a large number of proteins that react with one another to opsonise pathogens or to directly kill them by membrane attack complex (MAC) formation.
What are the four key steps of the complement cascade?
- Initiation
- Formation of C3 convertase
- Formation of C5 convertase
- MAC formation
What are the three triggers which initiate the complement cascade?
Classical pathway > antigen-antibody complexx
Lectin pathway > Mannose-binding lectin (MBL)
Alternate pathway > bacterial surfaces (not dependent on antibodies)
