Immune evasion Flashcards
How do neutrophils get from blood to pathogen in tissue?
Pathogen triggers release of C3a and C5a. Endothelial cells express ICAM allowing for neutrophil adhesion. Neutrophil transmigration occurs. Gradient of C3a and C5a detected by neutrophils via their C3aR and C5aR receptors. Neutrophils move towards gradient of complement and bacteria proteins.
What can neutrophils do to kill pathogen?
Phagocytosis. Degranulation (release of antimicrobial molecules). Regulate Inflammation (recruiting other immune system cells).
What type of bacterium is staphylococcus aureus?
Gram positive.
Where is staphylococcus aureus found?
Human nose.
Why is staphylococcus aureus regarded as an opportunistic pathogen?
Lives in our microbiota and is harmless however can become harmful in certain situations (immunocompromised or unhealthy individuals).
What can staphylococcus aureus cause?
Skin infections and can also lead to life threatening sepsis.
What kind of bacterium is streptococcus pyogenes?
Gram positive.
Where is streptococcus pyogenes found?
Human throat.
What can streptococcus pyogenes cause?
Pharyngitis, skin infection, scarlet fever and sepsis.
How does a capsule polysaccharide evade the immune system?
Hides antigenic structures. Antibodies or complement proteins can’t bind.
What surface protein does s.aureus express?
Protein A
What surface protein does S.pyogenes express?
M protein.
What do surface proteins expressed by bacteria do to evade immune system?
Binds antibodies by the fc region (constant region) rather than the fab region (variable region). This prevents normal opsonization and so neutrophils can’t detect.
What do proteases that are released do to evade immune system and what proteases does s.pyogenes release?
They cleave antibodies. Prevents normal opsonisation and so neutrophils can’t detect. S.pyogenes = Ides.
How does antigenic variation help evade immune system?
Prevents pathogen from being detected by immune cells.
What do complement proteins do?
Opsonisation, membrane attack complex, enhance inflammation.
What does a membrane attack complex do?
Forms cytotoxic pores on the surface of microbes.
What does C3 convertase do?
Cleaves C3 into C3a and C3b.
What does C3a and C5a do?
Enhances inflammation. Chemoattraction by forming complement protein gradient.
What does C3b do?
Opsonisation and formation of C5 convertase (produces c5a and c5b).
What does C5b do?
Formation of MAC complex.
How does the degradation of C3 by bacteria allow them to evade immune system?
Prevents c3a and c3b deposition. Prevents c5a formation.
3 ways in which bacteria evade complement system?
Cleave complement factors. Inhibit complement convertases. Recruit negative regulators of complement cascade to bacterial surface.
How does the bacterial protease ‘aur’ evade the immune system?
Cleaves C3. Prevents c3a and c3b deposition. Prevents c5a formation. This result in less inflammation, less recruitment of immune cells, less opsonisation and no MAC formation.
What do s.aureus and s.pyogenes produce that degrades complement protein C3?
Aur and SpeB.
Explain how s.aureus inhibits C3 and C5 convertases?
S. aureus produces SCIN protein which binds to C3bBb and inhibits formation of C3 convertase and C5 convertase.
What does inhibition of C3 or C5 convertases result in?
Prevents C3b deposition, C3a formation, C5a formation. This result in less inflammation, less recruitment of immune cells, less opsonisation and no MAC formation.
What complement factor do bacteria cleave?
C3.
What does recruitment of complement negative regulators result in?
Inhibits formation of C3 convertase and C5 convertase. Prevents C3b deposition, C3a formation, C5a formation. This result in less inflammation, less recruitment of immune cells, less opsonisation and no MAC formation.
What are pathogen recognition receptors?
They directly detect microbes.
What happens once pathogen recognition receptors detect microbe?
Neutrophils are activated.
Types of pathogen recognition receptors?
TLR, CLEC and FPR.
What do TLR detect?
Microbial structures.
What do CLEC receptors detect?
Microbial carbohydrates.
What do FPR detect?
Microbial peptides.
How can neutrophils indirectly detect microbes?
Detect opsonised microbes through their Fc receptors or complement receptors.
What do Fc receptors on neutrophils detect?
Antibody opsonised microbes.
What do complement receptors detect?
Complement opsonised microbes.
What is C5aR?
Chemotactic receptor present on neutrophils.
What is CXCL8?
Chemokine.
What does S.aureus do to inhibit chemotaxis?
Releases CHIPs which binds to C5aR and prevents binding of C5a. This prevents neutrophils moving to the area of infection.
What does S.pyogenes do to inhibit chemotaxis?
Releases SpyCEP which cleaves CXCL8. CXCL8 can’t bind to CXR1/2 and so migration to site of infection doesn’t occur.
How does S.aureus prevent antibody mediated phagocytosis?
They release molecules that bind to Fc receptors on neutrophils and prevent detection of opsonised bacteria. FLIPR targets IgG Fc receptor and SSL5 target IgA Fc Receptor.
How do bacteria kill neutrophils?
They release toxins.
What toxins does s.aureus release to kill neutrophils?
PVL Toxin, LukAB, LukDE
What toxins does s.pyogenes release to kill neutrophils?
SLS and SLO
What less common ways can bacteria evade immune system?
Inhibit effects of antimicrobials. Manipulate
intracellular signalling.
What s.aureus protein inhibits C3 or C5 convertases?
SCIN protein.
What complement negative regulator does s.aureus recruit?
Factor H.
What complement negative regulator does s.pyogenes recruit?
Factor H and C4BP.
What does S.auerus protein CHIP’s do?
CHIPs binds to C5aR and prevents binding of C5a. Neutrophils do not migrate to sites of infection
What does s.pyogenes protease SpyCEP do?
Cleaves CXCL8 and so prevents binding to CXCR1/2. Neutrophils do not migrate to sites of infection.
What toxins cause food poisoning? What bacteria produces these?
Enterotoxins. S.aureus
What toxins cause skin peeling? What bacteria produces these?
Exfoliative toxinsA and B. S.aureus
What toxin can mediate multiorgan pathology? What bacteria produces these?
Toxic shock syndrome toxin. S.aureus
What are some diseases s.aureus can cause?
Pneumonia, Endocarditis and Septic arthritis.
What antibody class is an indicator of recent or current infection.
IgM
Antiviral antibody?
IgG
How do antibodies neutralise extracellular virus?
It blocks viral attachment proteins. It destabilises viral structure.
Why does a new influenza vaccine need to be created each year?
Antigenic drift. Influenza viruses mutate and evolve to change year on year. A new influenza vaccine is required each year to reflect the circulating virus types.
How do influenza viruses undergo antigenic shift?
Acquire completely new antigens by reassortment with animal viruses.
How do rhinoviruses evade antibody recognition?
Exist as hundreds of antigenically distinct serotypes.
How do Hepatitis B virus (HBV) and Ebola virus evade antibody recognition?
Secrete surface antigens that mop up antibody, stopping it reaching virus particles or infected cells.
What does previous infection with one serotype of Dengue Virus followed by infection with a different serotype lead to?
Leads to antibody dependent enhancement of disease as virus enters immune cells via antibody and the Fc-Receptor. This triggers Dengue Haemorrhagic Fever.
What are the Type I IFNs?
IFN-α and IFN-β
What cells are specialised for secreting IFN-α?
Plasmacytoid dendritic cells.
What cells secrete interferon gamma?
Activated NK cells, CD4+ Th1 cells and CD8+ cytotoxic T cells.
What proteins block viral replication?
2’5’ oligoadenylate synthetase and protein kinase R.
What are type II IFN’s?
IFN-γ
What molecules activates NK cells?
IFN-α and interleukin-12.
How does NK detect infected cells?
If a is cell displaying fewer than normal MHC molecules.
How does herpes simplex HSV and cytomegalovirus CMV evade immune system?
Encode proteins that interfere with the MHC antigen processing pathway.
