Immune Evasion Flashcards
How does S.aureus cause disease
Localised pyogenic or pus producing disease characterised by tissue destruction mediated by hydrolytic enzymes and cytotoxins
Diseases mediated by toxins function as superantigens producing systemic disease
What are the properties of s. aureus
What hydrolytic enzymes and cytotoxins does s.aureus have
What toxins does S.aureus have
Enterotoxins - heat stable and acid resistant toxins responsible for food poisoning
Exfoliative toxins A and B causing the superficial layers of skin to peel off (scalded skin syndrome)
Toxic shock syndrom toxin - heat and protease resistant toxin that mediates multiorgan pathology
What is the epidemiology of S aureus
Common cause of infection in community and hospital because bacteria easily spread person to person and through direct contact or exposure
What are the symptoms of S aureus
Impetigo - localised skin infection characterized by pus filled vesicles on a reddened or erythematous base
Folliculitis - involving hair follicles
Furuncles and carbuncles - large, puss filled skin nodules, progress to deeper layers of the skin and spread into blood
Woud infections
Pneumonia
Endocarditis- endothelial lining of heart
Osteomyelitis
Septic arthritis
S aureus toxin mediated sdiseased
Toxic shock syndrome
Scalded skin syndrome
Food poisoning
Treatment, prevention and control of S aureus
Localised infections managed by incision and drainage
Antibotic therapy
Vancomycin - intravenous
Oral therapy - trimethoprim-sulfamethoxazole, clindamycin, doxycycline
Cleansing of wounds
Thorough hand washing
T
How can we detect bacteria
LPS in gram negative bacteria
LTA in gram positive bacteria
Flagella on certain bacteria
Why must neutrophil responses be balanced
Balanced to prevent infection but to also prevent damage to the host
How do neutrophils get activated
Where is S aureus present
In nose 30% of the population
What is antibody opsonisation
Antibodies bind bacterial antigens allowing
- deposition of complement in classical complement pathway
- Neutrophils and other pagocytes the ability to detect invading microbes
How does s aureus evade antibody opsinisation
S.aureus express capsule on its surface - polysaccharide
SpA binds to IgG Fc region not FAB, prevents deposition of complement, prevent bacteria being recognised by Fc receptors. Also portein Sbi
SSL10 - binds to Fc region, prevent complement and detection. Also Sak
What bacteria utilised capsule evasion
E coli
Pseudomonas aeruginosa
S pneumonia
S agalactiae
S aureus SSL10 inform
What are other bacteria that bind to Fc region
Streptococcus dysgalactiae - protein G binds IgG
Peptostreptococcus magnus - protein L binds IgG
Streptococcus agalactiae - beta protein binds IgA
Which bacteria cleaves proteases
Group B streptococcus (cleaves IgG class)
Porphyromonas gingivalis
Streptococcus pyogenes
Neisseria gonorrhoeae
Haemophilus influenzae
What is antigenic variation
Surface structure cahnges
N gonorrhoeae (Opa and lOS antigens)
S pneumoniae (Cap)
What are the key steps of the complement cascade
Initiation
Formation of C3 convertase
Formation of C5 convertase
MAC formation
What is the significance of SCIN S.aureus
SCIN protein binds C3bBb and inhibits formation of C3 convertase and C5 convertase
Prevents C3B deposition - presents opsonisation , unabel to detect S aureus
Prevent C3a and C5a formation
What is the significance of S aureus Efb
Binds to C3d in C3, induces conformational change
Factor B cannot bind to C3 - no formation of C3 convertase C3bBb
No conversion of C3 by C3 convertase required for the formation of C5 convertase
C3dg is unable to be recognised by CR2 by phagocytes
Other bacteria release proteins binding C3 - m catarrhalis
What proteases cleave complement components
S pyogenes (SpeB)
P gingivalis (Kgp)
N meningitidis (MalP)
P aeruginosa (AprA)
What bacteria can acquire host derived complement regulators
C3b inactivated by fH on bacterial surface - s aureus, s agalactiae, h influenzae, salmonella, a baumannii, n meningitids
C4BP degrades C2a from C3 convertases - b pertussis
Examples of immune receptors on neutrophils
TLR receptors - conserved microbial structures
CLEC receptors - microbial carbohydrates
FPR receptors - formylated peptides
Fc receptors - (SIGNAL THROUGH ITAM)
Complement receptors
Cytokine receptors
Chemoattractant receptors
LAIR receptors - ITIM - inhibitary to ITAM
SIGLEC receptors
LILR
CEACAM
How does S aureus inhibit chemotaxis
How does S aureus inhibit phagocytosis
FLIPr inhibitors Fc y receptors (IgG)
SSL5 innhibits Fc a receptors (IgA)
What are additional methods of neutrophil evasion
Kill neutrophils with toxins
Bind and inhibit functions of activating receptors
What are other bacteria neutrophil evasion
Bind inhibitory receptors
Inhibit effects of antimicrobials - upon phagocytosis or granulation
Manipulate intracellular signalling
Modify bacterail surface
What are some other ways of immune evasion
Antigenic variation
Inactivating antibodies or complement
Resisting phagocytosis
Suppressing the host adaptive immune response - interfering with cytokines or inhibiting MHC expression
Establishing latency
Antibody response to viral evasion
How do you resolve infection
Oo
How do viruses escape antibody recognition
Rhinovirus - Antigenically distinct serotypes
HIV - multiple clades or quasi-species
HBV and Ebola - surface antigens which mop up antibody stopping it reaching infected cell
Dengue virus - exists as 4 serotypes
How is interferon induced
How do interferons work
Facts about IFN - Beta and IFN - alpha
Secreted by all cells
One gene for IFN-beta
Facts about IFN - gamma
Produced by activated T cells and NK cells
Signals through a different receptor IFN-gamma R
Type 2 IFN
Facts about IFN - lambda
Signals through recepotrs IL28R and IL10- ebta that are mainly present on epithelila cells surfaces
Why is it significant that viruses like hep B and influenza can block production of IFN
Inhibition of IFN transcription(HBV) or influenza
What do natural killer cells do
Activated by IFN-a and interleukin 12 which activates macrophages with IFN - gamma
NK kill virus infected cells
Finds a cell displaying fewer than normal MHC (cytomegalovirus or herpes smiple virus), released toxic substances which kill cell
What do macrophages and dendritic cells do
Macrophages filter viral particles from blood
Macrophages inactivate opsonized virus particles
Immature and plasmactyodi DC produce IFN-alpha and other cyotkines
DC initiate and determine nature of CD4 and CD8 T cell response
What is the role of T cells
Essential for controlling enveloped and noncytolytic viral infections
Recognise viral peptides by MHC molecules on cell surfaces
Antigenic viral peptides come from any viral protein
CD8 cytotoxic T cells respond to viral peptide - class 1 MHC protein
CD4 TH2 response may be detrimental if they prematurely limit TH1 inflammatory and cytolytic responses
Viruses encode proteins (herpes and cytomegalovirus) that interfere with MHC anitgen processing pathway
HIV kills CD4 and alters macrophag efunction
Herpes prevent CD8 killing
