IMMUNOLOGY - Host Defences Against Bacteria

Question 1

What are the most important immune defences against bacteria?

Answer 1

Phagocytes (macrophages and neutrophils)

Question 2

What are neutrophil extracellular traps (NETS)?

Answer 2

The neutrophils come into contact with an extracellular pathogen they extrude their nucleus to entrap and coat the pathogen with antimicrobial factors

Question 3

How does the host immune system defend against encapsulated bacteria? Describe briefly how this system works

Answer 3

Opsonisation - Opsonins are host molecules which attach to the surface of pathogens. Phagocytic cells have receptors which recognise these molecules allowing them to bind to both encapsulated and non-encapsulated pathogens

Question 4

Give an example of innate opsonin molecules

Answer 4

Complement

Question 5

Give an example of adaptive opsonin molecules

Answer 5

Immunoglobulins (antibodies)

Question 6

Describe the activation and resulting effects of the alternative complement pathway

Answer 6

The alternative complement pathway is activated in response to contact with bacterial surfaces and results in the synthesis of C5b6789 MAC (membrane attack complex) from the C3/C5 convertase. The C5b6789 MAC kills the bacteria

Question 7

Describe the activation and the resulting effects of the lectin complement pathway

Answer 7

The lectin complement pathway is activated by the binding of mannose binding lectin (MBL) to microbial capsules (microbial capsules contain mannose) which results in the synthesis of C3b, iC3b, C3dg and C4b from the C3/C5 convertase. The C3b, iC3b, C3dg and C4b act as opsonins to induce opsonisation and phagocytosis

Question 8

Describe the activation and the resulting effects of the classical complement pathway

Answer 8

The classical complement pathway is activated by the binding of complement proteins to antigen-antibody complexes resulting in the synthesis of C5a, C4a C3a from the C3/C5 convertase. C5a, C4a and C3a induce inflammation and phagocyte recruitment

Question 9

How does the host immune system recognise foreign invaders?

Answer 9

Pattern-associated molecular patterns (PAMPs) are present on the surface of pathogens and are recognised by pattern-recognition (toll-like) receptors

Question 10

List some examples of PAMPs present on bacteria and which toll like receptors recognise each of these structures

Answer 10

Lipid A (LPS) - TLR-4
Peptidoglycan - TLR-2
Bacterial DNA - TLR-9
Bacterial lipoproteins - TLR-2
Flagellin - TLR-5

Question 11

How does the function of toll-like receptors enhance the action of macrophages in response to pathogens?

Answer 11

Toll-like receptor recognition of PAMPs present on pathogens allows macrophages to secrete interleukins which enhance other innate and also acquired immune defences

Question 12

What are the three common helper T-cells?

Answer 12

TH1
TH2
TH17

Question 13

What is the main function of TH1 helper T-cells?

Answer 13

TH1 helper T-cells secrete mainly IFNγ which are involved in the attraction and activation of macrophages

Question 14

What is the main function of TH2 helper T-cells?

Answer 14

TH2 helper T-cells secrete mainly IL-4 which is involved in antibody production and defence against parasites

Question 15

What is the main function of TH17 helper T-cells?

Answer 15

TH17 helper T-cells mainly secrete IL-17 which is involved in the activation of epithelial cell defences

Question 16

What is classical activation of macrophages?

Answer 16

Classical activation of macrophages is the activation of macrophages in response to IFNγ produced by TH1 T-helper cells

Question 17

Many intracellular bacteria have evolved to evade, survive and grow within macrophages. Give three examples of these intracellular bacteria.

Answer 17

Mycobacteria
Brucella
Salmonella

Question 18

How does the host immune system respond to intracellular bacteria that has evaded macrophages?

Answer 18

1. TH1 cells recognises foreign proteins presented on the MHC class two protein present on the macrophage surface and binds to it. The macrophage undergoes classical activation in response to the secretion of IFNγ from the TH1 cell
2. This results in increased antimicrobial activity by increasing the production of reactive oxygen intermediates, nitric acid and phagolysosome fusion to destroy the intracellular bacteria

Question 19

Why do granulomas form in response to a bacterial infection?

Answer 19

If intracellular bacteria cannot be destroyed by macrophages and there is a prolonged inflammatory response, the macrophages will aggregate together to wall off the bacteria from the rest of the body

Question 20

How does the host prevent extracellular iron uptake by extracellular bacteria?

Answer 20

• Extracellular iron is complexed to high affinity host iron binding proteins known as transferrin (found in serum) and lactoferrin (found in mucosal surfaces)
• Hypoferraemia of infection occurs (the uptake of extracellular iron into cells) in response to pathogen recognition

Question 21

(T/F) In response to extracellular pathogens, the humoral immune response is the most appropriate immune response

Answer 21

TRUE

Question 22

(T/F) In response to intracellular pathogens, the humoral immune response is the most appropriate immune response

Answer 22

FALSE. The cell-mediated immune response and macrophage activation is the most appropriate defence against intracellular pathogens