Immune evasion Flashcards
What are the two groups of diseases caused by staphylococcus aureus?
- 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.
Give 5 properties of s.aureus
- Ability to grow aerobically and anaerobically, over a wide range of temperatures, and in the presence of a high concentration of salt; the latter is important because these bacteria are a common cause of food poisoning.
- 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 and can protect S. aureus from phagocytosis
What are the 3 types of enzymes released by s.aureus?
lipases, nucleases and hyaluronidase
What are the 3 types of toxins released by s.aureus and what do they do?
o Enterotoxins (many antigenically distinct) are the heat-stable and acid-resistant toxins responsible for food poisoning
o Exfoliative toxins A and B cause the superficial layers of skin to peel off (scalded skin syndrome)
o Toxic shock syndrome toxin which is a heat- and protease-resistant toxin that mediates multi-organ pathology
Name 4 pyogenic diseases caused by s.aureus
Pneuomonia, endocarditis, osteomyelitis, wound infections
Name 3 toxin-mediated diseases caused by s.aureus
Food poisoning, scalded skin syndrome, toxic shock syndrome
Name 3 drugs used in oral therapy for s.aureus treatment
Trimethoprim-sulfamethoxazole, clinamycin, doxyvycline
What is the drug of choice for intravenous therapy?
Vancomycin
How do s.aureus avoid antibody opsonisation? (3 ways)
- The S.aureus expresses a capsule on its surface helping to hide antigenic structures that can be detected by the innate and adaptive immune components
- The s.aureus protein A binds to antibodies via their Fc region instead of their Fab region. This prevents normal opsonisation.
- S.aureus secretes protein SSL10 which binds to the Fc region of IgG antibodies preventing the Fc receptors on neutrophils from binding to the same Fc receptors therefore the neutrophils cannot detect IgG on the surface of s.aureus
What are the 5 main antibody opsonisation evasion strategies?
- Hide antigens
- Disrupt functions
- Prevent detection
- Degrade antibodies
- Modify antigenicity
What does s.aureus SCIN protein do?
Binds to C3bBb and inhibits the formation of C3 and C5 convertase. This prevents:
- C3b deposition on cell surfaces
- C3a formation
- C5a formation
Explain the classical complement pathway
A c1 complex contains one molecule of c1q and 2 molecules of c1r and c1s. The c1 complex can bind to one IgM antibody or 6 IgG antibodies in an immune complex or the c1q can directly bind to a pathogen which activates c1r. C1r is a serine protease and cleaves c1s. The C1r2s2 complex cleaves c4 and c2. C4b and C2b bind to form c3 convertase which cleaves c3 to form c3a and c3b. C3b that binds to the c3 convertase complex forms c5 convertase.
Explain the alternative complement pathway
C3b formed by the cleavage of c3 with c3 convertase or the random hydrolysis of c3 due to the breakdown of the internal thioester bond is rapidly inactivated by factor H and factor I.
However when the internal thioester bond reacts with an amino or hydroxyl group on cell surfaces or pathogens, the c3b covalently bound to the cell is now protected from factor H inactivation.
The surface bound C3b then binds to factor B to form C3bB. This complex in the presence of factor D will be cleaved to form C3bBb which is the alternative pathway c3 convertase. This complex is stabilised by the binding of factor P.
The stabilised c3 convertase complex can now cleave much more c3, some of this c3b gets covalently bound to the same pathogen surface as the c3 convertase molecule. The binding of more c3b recruits more factors B, D and P amplifying the cascade. On self cells there will be regulatory proteins preventing the formation of this cascade however pathogens in general do not have these complement regulatory proteins.
If the c3 convertase complex binds to another c3b it forms c5 convertase which cleaves c5 into c5a and c5b.
Explain the lectin pathway
Same as classical except MBL protein is used instead of c1q to cleave c4 and c2.
What does s.aureus Efb protein do?
Binds to C3d in C3 which changes the shape of the C3 complex preventing the binding of factor B to C3.
