Immune Evasions Flashcards
S. Aureus facts
Can cause localised pyogenic diseases by enzymes and cytotoxins
Can cause systemic diseases by toxins (superantigens)
Anaerobic/Aerobic growth
Capsule keeping safe from phagocytosis
Catalase + Coagulase test positive
What is Scalded skin syndrome?
Superficial layers of skin peel off due to S.Aureus Exfoliative toxins A and B spread from localised area into blood
Toxin - mediated
What disease is Impetigo?
localised pus filled nodule infection, reddened skin usually on children’s face and limbs.
Pyogenic
What is Impetigo involving hair follicles?
Folliculitis
Pyogenic
Why can Furuncles and Carbuncles become dangerous?
The large, pus filled nodules can progress into deeper layers of skin and spread in blood - secondary infections
Pyogenic
What is frequently followed by viral infections of the respiratory tract?
Pneumonia - abscess formation in the lungs
Pyogenic
What is Endocarditis?
infection of endothelial heart lining - high mortality
Pyogenic
What is Osteomyelitis?
Infection / destruction of bones, usually long bones with highly vascularised areas
Pyogenic
What is the name of the infection of joint spaces characterised by swelling, redness, puss accumulation at joint?
Septic Arthritis
Pyogenic
what is Food poisoning?
Heat-stable enterotoxin contaminates food = vomiting, diarrhea, stomach cramps.
Why does Food poisoning rapidly get better after 24 hours?
Because intoxication is due to toxin on food, not bacteria growing and producing toxin in intestine
What is Toxin shock syndrome?
Localised infection of bacteria, toxin affects multiple organs. Fever, hypotension, rash. High mortality rate unless local infection managed
Oral therapy examples?
Trimethoprim, sulfamethoxazole, clindamycin, doxcycyline
What is Vancomycin for?
Drug of choice for intravenous therapy
What are common features bacteria share despite diversity
Lipopolysaccharides (LPS) in Gram - Lipoteichoic acid (LTA) in Gram + Flagella
How does Antibody Opsonisation lead to Neutrophil activation?
Gradient of C3a and C5a + bacterial proteins created from area of antibody opsonisation
C5a binds C5aR
C3a binds C3aR
Endothelial cells express ICAM and so when neutrophils roll along inner surface, they adhese
Transmigration out of vessel, Priming and chemotaxis towards complement + bacterial protein componants
Activated Neutrophil then can cause phagocytosis, inflammation or degranulate
How does S.aureus hide its antigens?
Capsule on surface.
E.coli, S.Pneumonia, S.agalactiae, Spyogenes also do this
What is SSL10?
S.aureus secreted protein that binds to Fc region of IgG, preventing Fc regions of neutrophils from detecting IgG on surface of s.aureus
What is SpA?
S.aureus surface protein which binds to antibodies via Fc region.
preventing normal opsonisation which needs binding via Fab region.
Other bacteria expressing surface proteins that bind to antibodies and prevent opsonisation?
Streptococcus dysgalactiae - Protein G binds IgG
Peptostreptococcus magnus - Protein L binds to IgG
Streptococcus agalactiae - Beta protein binds IgA
What are proteins Sbi and Sak?
Sbi like Spa inhibits antibody opsonisation
Sak like SSL10 inhibits detection of antibody
What are PRRs?
Pathogen recognition receptors
are proteins capable of recognising molecules frequently found in pathogens directly and can prime/activate neutrophils
TLR receptor?
A PRR, detects conserved microbial structures
CLEC receptor?
A PRR, detects microbial carbohydrates
FPR receptor?
A PRR, detects Formylated peptides
What is ITAM ?
Activatory motif on Neutrophils enhance immune cell activity so Neutrophil receptors can detect opsonised microbes through Fc receptors on antibodies or
through complement receptors
How do immune receptors modulate function?
Cytokine receptors Chemoattractant receptors LAIR receptors (inhibitory - prevent wrong activation) SIGLEC receptors. (inhibitory) LILR receptors CEACAM receptors
How does CHIPs? inhibit chemotaxis and activation
(Chemotaxis inhibitory protein of Staphylococcus aureus)
binds to C5aR and FPR1 (detects formylated peptides - fMLP) preventing binding of agonists C5a and formylated peptides.
Do neutrophils do not migrate and do not become activated by C5aR FPR1
How does FLIPr and SSL5 prevent phagocytosis
FLIPr inhibits Fc gamma receptors - IgG
SSL5 inhibits Fc alpha receptors - IgA
prevents detection of IgG/IgA opsonised bacteria
Which S.Aureus toxins that kill/inactivate neutrophils?
PVL
PSM
Bacterial Immune Evasions?
Express proteins which bind to inhibitory receptors and switches off neutrophil activity.
Protein examples: S.agalactiae B protein
N.gonorrhoeae opa protein
H. pyolri Hop Q protein
E.Coli
How to neutrophils inhibit effects of bacterial proteins?
Granules have anti-microbial compounds inhibiting: SPIN protein S.pneumoniae SP-1749 Y pestis YOPE P.aeruginosa EXOS protein
What do IFN initiate?
Interferons initiate antiviral state: transcription of genes to block replication and activates NK cells
How does the body remove free virus?
Antibody agglutination
How can viruses evade antibody recognition?
Rhinovirus exists as 100s of distinct serotypes
HIV as multiple clades and quasi species
Multiple Serotypes
Antigenic drift
Antigen shift
How are NK cells activated?
activated by IFN 2 and IL 12 which activate macrophages with IFN Gamma
What do Macrophages do in response to viruses?
Filter viral particles from blood, inactivate opsonized viral particles.
Which Interferon is secreted by every cell?
IFN-Beta
Which IFN receptor is in all tissues?
IFN- alpha R
Which cells secrete IFN - alpha
Plasmacytoid dendritic cells
What produces typeII IFN Gamma?
Activated T and NK cells
What is type III IFN?
IFN Lambda (λ) signals through IL28 R and IL10-Beta
receptors on epithelial surfaces
