Microbes Flashcards
Immune evasion, Microbial therapies
What is pyogenic s.aureus disease?
Pus producing - hydrolytic enzymes and cytotoxins cause tissue destruction
What is systemic s.aureus disease?
Mediated by toxins functioning as super antigens
How does s.aureus protect itself from phagocytosis?
Polysaccharide capsule and coagulase which causes fibrinogen to convert to insoluble fibrin causing blood clots
How does catalase protect the s.aureus?
Breaks down peroxides produced by neutrophils and macrophages
What do cytotoxins produced by s.aureus do?
Lyse erythrocytes, neutrophils, macrophages plus other host cells
What do hydrolytic enzymes does s.aureus produce and what are their function?
Lipases, nuckeases, hyaluronidase causing tissue destruction
What is a key property of s.aureus linked with food poisoning?
Grow aerobically & anaerobically
Over a wide range of temps
In the prescence of high salt concentration
What toxins does s.aureus produce and what are their properties?
Enterotoxins - heat stable + acid resistant -> food poisoning
Exfoliative toxins A&B - superficial layers of skin peel off
Toxic shock syndrome - heat & protease resistant mediates multiorgan pathology
List the 7 pyogenic diseases caused by S.Aureus
Impetigo Folliculitis Furuncles (boils) and carbuncles Wound infections Pneumonia Endocarditis Osteomyelitis Septic arthritis
List 3 S aureus toxin mediated diseases
Food poisoning
Scalded skin syndrome
Toxic shock syndrome
Describe impetigo and folliculitis
Localized skin infection characterized by pus-filled vesicles on reddened/erythematous base
Folliculitis is impetigo involving hair follicles
Describe furuncles (boils) and carbuncles
Large, pus filled skin nodules, can progress deeper and spread
Describe wound infections
Erythema and pus at site. MRSA common
Describe pneumonia
Abscess in lungs
Common in very young and old
Usually follows viral infection of R tract
Describe endocarditis
Infection of endothelial lining of heart, progresses rapidly and high mortality
Describe osteomyelitis
Destruction of bones, particularly in highly vascularized areas in children
Describe septic arthritis
Infection of join spaces (swollen, reddened joint)
How is food poisoning caused and what are the symptoms and progression?
Heat stable enterotoxin, 2-4 hours cramps, vomiting, diarrhoea. Resolved in 24 hours
Describe scalded skin syndrome
Localized infection causing outermost layer of skin to peel off caused by exfoliative toxins A&B
Describe toxic shock syndrome
Localized infection but toxins affect multiple organs (fever, hypotension, erythematous rash, high mortality rate unless ABs promptly administered and local infection managed)
What is the treatment for localised infection?
Incision and drainage
What is the treatment for systemic infection?
IV - Vancomycin
Oral therapy- trimethoprim- sulfamethoxazole, clindamycin, doxycycline
Food poisoning - identify source
Prevention methods for s.aureus
Proper cleansing of wounds
Use of disinfectant
Hand washing and covering exposed skin
No vaccine currently available
What are the main mechanisms bacteria use to evade opsonisation by antibodies?
- Hide antigens
- Disrupt functions
- Prevent detection
- Degrade antibodies
- Modify antigenicity
Give 1 ways s.aureus hides from antibodies
Capsule hides antigens on surface and less complement is deposited
Name and describe 2 proteins s.aureus uses to prevent antibody detection
S.aureus surface protein A (SpA) binds IgG Fc region so Fc receptors on immune cells can’t detect
Secreted SSL10 binds IgG to inhibit detection
Name 2 antigen evasion strategies not specific to S.aureus
Proteases cleave antibodies (group B strep [IdeS])
Antigenic variation ( n.gonorrhoaea [Opa and LOS antigens])
What happens when neutrophils are recruited?
- C5a binds to C5aR and C3a binds to C3aR
Endothelial cells express ICAM
Adhesion occurs and neutrophils roll along endothelial surface of blood vessels
- Priming
- Chemotaxis - down gradient of complement components and bacterial proteins
- Activation
- Opsonisation
- Phagocytosis, inflammation, degranulation - reactive O2 species, antimicrobial molecules
What happens during inflammation and which complement components are proinflammatory agents?
C3a and C5a
Which pathogen specific receptors (PRRs) do neutrophils express and what do they do?
They prime and activate neutrophils
TLR receptors detect conserved microbial structures eg. Lipopolysaccharides (LPS, gram -ve cell wall) and lipoteichoic acid (LTA, gram +ve cell wall), flagella
CLEC detect microbial carbohydrates
FPR detect formulated peptides released by bacteria
How do neutrophils detect osonised microorganisms?
Fc receptors, complement receptors
What is an opsonin?
An opsonin is any molecule that enhances phagocytosis by marking an antigen for an immune response or marking dead cells for recycling.
Describe two chemotaxis receptors of neutrophils
C5aR detects C5a
FPR1 detects fMLP (formulated peptides released by bacteria)
How does s. Aureus inhibit chemotaxis and activation?
Secretes CHIPs which binds C5aR and FPR1 with a higher affinity than C5a and fMLPs
How does a.aureus interact with receptors, thus preventing phagocytosis?
FLIPr binds Fcg receptors (IgG) preventing detection of IgG opsonised bacteria
SSL5 binds Fca receptors (IgA) preventing detection of IgA opsonised bacteria
How does s. Aureus evade neutrophils?
Produces toxins to kill them
Expresses molecules that are receptor antagonists, binding an inhibiting the function of activatory receptors
What happens during the classical complement pathway?
- Immunoglobulins bind to pathogen surface
- C1q binds to Fc region and activates C1r which activates C1s
- C1s activates a serine protease which cleaves C4 into C4a and b, c4b binds to pathogen surface
- C1s cleaves C2 to C2a and b
- C2b binds C4b forming C4b-2b complex (C3 convertase)
- C3 convertase cleaves C3 to C3a and C3b which binds to C3 convertase forming C4b-2b-3b complex (C5 convertase) OR C3b binds to surface of pathogen
- C5 binds to C3b part of C5 convertase and is cleaved into C5a and C5b
- Opsonisation is complete!
Which components is the membrane attack complex (MAC) composed of?
C5b, C6, C7, C8, C9
Which are the proinflammatory fragments of the complement cascade?
C3a and C5a
What are the two types of C3 convertase?
C4b-2b - classical and MBL
C3bBb - alternative
Which fragments label the target pathogen for elimination by phagocytosis?
C3b and C4b
Which protein does s.aureus produce that inhibits MAC formation?
SSL7 binds C5
What does the Efb protein do and what produces it?
S.aureus
Binds C3d part of C3, inducing a conformation change which prevents binding of factor B to C3, and C3dg binding CR2. It essentially prevents C3 being cleaved to C3b
Which protein does SCIN bind to?
C3bBb - inhibits formation of C3 convertade and C5 convertase, preventing C3b deposition, C3a formation, C5a formation.
Describe 2 complement evasion strategies not covered by SCIN, SSL7 or Efb
Proteases cleave complement components
Aquired host derived complement regulators eg. fH on bacterial surface inactivates C3b and C4BP is associated with FI and degrades C2a from C4b2a (C3 convertases)
