PMI02-2003 Innate immunity

Question 1

What is innate immunity?

Answer 1

It is a non-specific response so it recognises all types of antigen
It provides an immediate response

Question 2

How is innate immunity induced?

Answer 2

The pathogen initially adheres onto the surface epithelium

It then breaks through the epithelium and enters the tissues and induces local responses within the tissue

Question 3

What is mucosal epithelia?

Answer 3

They include any secretory and absorptive surfaces

Question 4

Where is mucosal epithelia found?

Answer 4

In the lining of the gut and lungs

Question 5

How does mucosal epithelia affect microbes?

Answer 5

They secrete mucus which coats microbes and makes it harder for microbes to adhere to the surface
Mucus also traps the microbes so they can be cleared out

Question 6

What are antibacterial peptides?

Answer 6

Small peptides
They include alpha defensins and beta defensins
Usually secreted by epithelial cells

Question 7

How do antibacterial peptides kill microbes?

Answer 7

Damaging the cell wall or membrane

Question 8

Where do alpha defensins of antibacterial peptides come from?

Answer 8

neutrophils

Question 9

Where do beta defensins of antibacterial peptides come from?

Answer 9

epithelial cells

Question 10

What are the three pathways of the complement cascade?

Answer 10

Classical pathway
MB-Lectin pathway
Alternative pathway

Question 11

What is the classical pathway activated by?

Answer 11

C1q component

Question 12

Describe the classical pathway that results in C3b production

Answer 12

C1 proteins (c1q, c1r, c1s) bind to the antibody
This pathway is activated by the binding of C1q to the antigen-antibody complexes
Binding of C1q activates C1r
C1r then cleaves and activates C1s
C1s then cleaves C4 into C4a and C4b, and C2 into C2a and C2b
C4b and C2a come together to form C4b2b complex
C4b2b is an active C3 convertase which cleaves C3 into C3a and C3b
C3b binds to the bacterial surface
One molecule of C4b2b can cleave upto a 1000 molecules of C3 to C3b
Many C3b molecules bind to the microbial surface

Question 13

What is mannose-binding lectin?

Answer 13

MBL is a lectin that binds mannose

Lectin is a carbohydrate- binding protein produced by the liver

Question 14

Describe MB-Lectin pathway

Answer 14

It works in a similar way to the classical pathway

Except the initial trigger is not C1Q, but mannose-binding lectin

Question 15

Why is the alternate pathway truly innate?

Answer 15

It occurs in the absence of antibodies

Question 16

What is the alternate pathway initiated by?

Answer 16

Initiated by the hydrolysis of C3 which forms C3b and ultimately the MAC

Question 17

Describe the alternate pathway that forms C3a and C3b?

Answer 17

The spontaneous hydrolysis of C3b forms C3b(H2O)
C3b(h2O) binds Factor B and D
C3b(h2O) is then cleaved by Factor D into C3b(H2O)Ba and C3b(H2O)Bb
C3b(H2O)Bb is a C3 convertase which converts more C3 into C3a and C3b

Question 18

How does the presence of a pathogen affect C3b?

Answer 18

If there is no pathogen present, the C3b will be degraded and destroyed as C3b must bind to the surface to stabilise

Question 19

What molecules do all pathways of complement pathway lead to the activation of?

Answer 19

C3 and C5

Question 20

What are anaphylatoxins?

Answer 20

They are inflammatory mediators

Question 21

Which molecules are anaphylatoxins?

Answer 21

C3a, C4a and C5a

Question 22

How does C5b differ from C4b and C3b?

Answer 22

C5b doesn’t covalent bind to the pathogen surface unlike C4b and C3b

Question 23

How is C5b formed?

Answer 23

C3b binds to C4b2b and C3bBb to form an active C5 convertase

C5 binds to the C3b component of the convertase and forms C5a and C5b

Question 24

How do anaphylatoxins work?

Answer 24

They act on blood vessels to increase vascular permeability allowing increased fluid leakage
Immunoglobulins and complement molecules also leak out from these vessels
Macrophages, lymphocytes and neutrophils also leak out

Question 25

Why is opsonisation needed?

Answer 25

Many micro-organisms have evolved to develop capsules to hide from phagocytic cells

Question 26

How does opsonisation work?

Answer 26

Phagocytic cells have receptors for active complement proteins such as C3b
These receptors improve binding and recognition of the pathogen and subsequent phagocytosis

Question 27

How does the Membrane Attack Complex (MAC) form?

Answer 27

C5b from the breakdown of C5 will bind with C6 and C7
This forms C5b67 which binds to the pathogen surface
This provides a docking surface for C8 which binds to the complex and inserts itself into the cell membrane
C9 molecules then bind to this whole complex and begin to polymerise
Roughly 16 molecules of C9 polymerise to form a ring-shaped MAC pore

Question 28

What are neutrophils also known as?

Answer 28

Polymorphonuclear cells (PMNs)

Question 29

What are the two main types of phagocytes that patrol the body?

Answer 29

Neutrophils and monocytes