Immune Evasion Flashcards by Caroline Bong

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

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What are the properties of s. aureus

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What hydrolytic enzymes and cytotoxins does s.aureus have

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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

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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

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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

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S aureus toxin mediated sdiseased

Toxic shock syndrome

Scalded skin syndrome

Food poisoning

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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

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How can we detect bacteria

LPS in gram negative bacteria

LTA in gram positive bacteria

Flagella on certain bacteria

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Why must neutrophil responses be balanced

Balanced to prevent infection but to also prevent damage to the host

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How do neutrophils get activated

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Where is S aureus present

In nose 30% of the population

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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

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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

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What bacteria utilised capsule evasion

E coli

Pseudomonas aeruginosa

S pneumonia

S agalactiae

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S aureus SSL10 inform

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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

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**