Immune Evasion

Question 1

What are the innate immune cells?

Answer 1

Neutrophils
Eosinophils
Basophils
Dendritic cells
Macrophages

Question 2

Main features of neutrophils

Answer 2

Most abundant leukocyte
Recruited to are of infection
Detect microbes
Perform effector functions

Question 3

Why must neutrophil responses be balanced?

Answer 3

Prevent infection 
Prevent damage (inflammation)

Question 4

What do neutrophils do?

Answer 4

Recruitment
Transmigration
Adhesion 
Priming
Chemotaxis
Activation
Phagocytosis/ Degranualtion

Question 5

What are the three things Bacteria evade?

Answer 5

Antibody opsonisation
Complement opsonisation
Neutrophil Functions

Question 6

What is Staphylococcus aureus?

Answer 6

Gram-positive bacterium
Lives harmlessly in nose
Opportunistic pathogen
Many mechanism to evade neutrophils

Question 7

What is antibody opsonisation?

Answer 7

Antibodies bind antigens allowing:

1. Deposition of complement in the classical pathway
2. Neutrophils and other phagocytes the ability to detect invading microbes

Question 8

How can Bacteria suppress opsonisation I?

Answer 8

Expresses capsule on its surface

Hides antigenic structure that can be detected by innate and adaptive immune components

Question 9

Name some bacteria that express capsules

Answer 9

E. coli

S. aureus

Question 10

How can Bacteria suppress opsonisation II?

Answer 10

S. aureus protein A binds IgG Fc region
Prevents normal opsonisation
Neutrophils cannot detect S.aureus

Question 11

How can Bacteria suppress opsonisation III?

Answer 11

S. aureus SSL10 bind IgG to inhibit detection

Prevents the Fc receptors on neutrophils from detecting IgG on the surface of the bacteria

Question 12

What are the three mechanism of suppressing opsonisation?

Answer 12

Capsule expression
Inhibit antibody opsonisation:
-SpA
-SSL10

Question 13

What are other mechanism of suppressing opsonisation?

Answer 13

Proteases cleave antibodies: no stimulation of immune response
Antigenic variation

Question 14

What are all the mechanisms to evade opsonisation?

Answer 14

Hide antigens
Disrupt functions
Prevent detection
Degrade antibodies
Modify antigenicity

Question 15

What is complement opsonisation?

Answer 15

Complement system is compose of a large no of proteins that react to opsonise pathogens or directly kill them by MAC formation

Question 16

What are the key steps of the complement cascade?

Answer 16

Initiation
Formation of C3 Convertase
Formation of C5 Convertase
MAC Formation

Question 17

What does MAC do?

Answer 17

Produces pore on bacterial cell membrane

Causes lysis

Question 18

What is the mechanism of evading complement opsonisation I?

Answer 18

SCIN binds C3bBb and inhibits convertase production

Question 19

What is the mechanism of evading complement opsonisation II?

Answer 19

Efb binds C3d and inhibits fB binding C3 as it causes a conformational change

Question 20

What are the three complement evasion mechanisms?

Answer 20

Inhibit complement convertases
Inhibit C3 processing
Inhibit MAC formation

Proteases cleave complement components
Acquired host derived complement regulators- inactivate proteins

Question 21

How do neutrophils sense and respond to their environment?

Answer 21

Express 100s of receptors allows detection within environment

Question 22

What are pathogen recognition receptors?

Answer 22

Directly detect microbes or microbial products

Neutrophils are primed or activated

Question 23

What do immune receptors do?

Answer 23

Generate and modulate a balanced immune response

Question 24

What are the two types of immune receptors?

Answer 24

Activatory- enhance immune cell activity

Inhibitory- suppress immune cell activity

Question 25

How do bacteria evade neutrophil response I?

Answer 25

Bacterial CHIPs inhibits chemotaxis and activation CHIPS binds C5aR and FPR1 and prevents binding of antagonist Prevents recognition of neutrophils

Question 26

How do bacteria evade neutrophil response II?

Answer 26

Bacterial FLIPr binds Fc(gamma) receptors preventing the detection of IgG opsonised bacteria Reduced antibody mediated phagocytosis

Question 27

How do bacteria evade neutrophil response III?

Answer 27

Kills neutrophils by releasing toxins

Question 28

How do bacteria evade neutrophil response (other)?

Answer 28

Bind inhibitory receptors, prevents activation of cells Inhibit the effects of antimicrobials present in granules Manipulate intracellular signalling Modify bacterial surface

Question 29

How do bacteria evade neutrophil response (summary)?

Answer 29

``` Inhibit chemotaxis Inhibit detection of bacteria Kills neutrophils Stimulate inhibitory receptors Disrupt intracellular signalling ```

Question 30

What are the two types of diseases caused by S. aureus?

Answer 30

localised pyogenic "pus-producing" | disease mediated by toxins

Question 31

Under what conditions can S. aureus grow?

Answer 31

Can grow aerobically and anaerobically Over a wide range of temperatures High salt conc.

Question 32

Give some features of S. aureus?

Answer 32

Polysaccharide capsule to protect from phagocytosis | Cell surface proteins that mediate adherence of the bacteria to host tissues

Question 33

What enzymes do S. aureus use?

Answer 33

Catalase that protect from peroxides produced by neutrophils and macrophages Coagulase converts fibrinogen to insoluble fibrin that forms clots and can protect S. aureus from phagocytosis Hydrolytic enzymes and cytotoxins Lipases, nucleases, and hyaluronidase that causes tissue destruction

Question 34

What toxins do S. aureus produce?

Answer 34

Enterotoxin- food poisoning Exfoliative toxins A and B- scaled skin syndrome Toxic shock syndrome toxin- mediates multi-organ pathology

Question 35

How can localised infections of S. aureus be managed?

Answer 35

Incision and Drainage

Question 36

How can systemic infections of S. aureus be managed?

Answer 36

Antibiotic therapy | Empiric therapy should include antibiotics against MRSA

Question 37

What is the drug of choice for IV therapy?

Answer 37

Vancomycin