Early to Late Innate Immune Response

Question 1

What do pathogens express? Hint; not found on human cells

Answer 1

Pathogen associated molecular patterns (PAMPs)

Question 2

What do innate immune cells express? Hint; partner receptors for PAMPs

Answer 2

Pattern-recognition receptors (PRRs)

Question 3

Where are low levels of inactive Complement System proteins found?

Answer 3

Extracellular fluids

Question 4

What does an activated Complement System create?

Answer 4

A cascade (downstream) of chemical reactions that promotes: opsonisation of pathogens, direct pathogen killing, acute inflammation and leukocyte recruitment

Question 5

What is the inactive precursor of the Complement System?

Answer 5

C3 (–> C3b + C3a)

These products activate the cascade

Question 6

What triggers C3’s conversion into its active products?

Answer 6

Mannose binding lectin (nb mannose is not found in the human body) activates C3 convertase - there is a whole cascade of reactions that occur before C3 convertase is activated c

Question 7

What does active C3b do?

Answer 7

Associates with other complement system proteins producing C5 convertase - cleaves inactive C5 into C5a and C5b

Question 8

What does active C5b do?

Answer 8

Associates with other complement system proteins to produce a pore-forming channel which inserts into the pathogen membrane/cell = MAC (membrane attack complex)

Question 9

When is the downstream complement pathway activated?

Answer 9

Only in the presence of a pathogen (is what should prevent destruction of a human cell membrane 0 they have special receptors to avoid being destroyed)

Question 10

What does the MAC do?

Answer 10

Extracellular salts and water enter the pathogen via the pore, causing the pathogen to swell and burst

Question 11

Other than C5 conversion what else does C3b do?

Answer 11

It is an opsonin - involved in opsonisation for pathogen phagocytosis and killing

Question 12

What are C3a and C5a?

Answer 12

Anaphylatoxins

Question 13

What do anaphylatoxins do?

Answer 13

Promote changes in the local vasculature, acute inflammation and leukocyte recruitment by activating mast cells or acting directly on local blood vessels

Question 14

What are some features of healthy tissues?

Answer 14

No inflammatory mediators, normal vasculature and circulating neutrophils

Question 15

What does inflammation promote?

Answer 15

Vascular changes, and recruitment/activation of neutrophils (transendothelial migration)

Question 16

What vascular changes occur in infected/damaged tissue?

Answer 16

Dilation of post capillary venues (leads to vasodilation/increased blood flow), tight junctions between endothelial cells are lost (increased vascular permeability/swelling) and expression of specific adhesion molecules on the surface of endothelial cells and activation of adhesion receptors on circulating neutrophils

Question 17

What do neutrophils do?

Answer 17

1. Phagolysosomal killing and ROS-mediated killing (reactive oxygen species) as they are toxic to pathogens (double the effectiveness).
2. Degranulation/releasing residual enzyme and toxins - direct killing of pathogens (causes tissue damage/systemic inflammation)

Question 18

What do neutrophils do?

Answer 18

1. Phagolysosomal killing and ROS-mediated killing (reactive oxygen species) as they are toxic to pathogens
2. Degranulation/releasing residual enzyme and toxins - direct killing of pathogens (causes tissue damage/systemic inflammation)
3. Neutrophil Extracellular Traps (NETs) - neutrophils kill themselves and release nets to stick to pathogens and hold them until macrophages come and ‘mop’ up the damage

Question 19

What are the components of pus?

Answer 19

Neutrophils, NETs, dead bacteria and cellular debris

Question 20

Why does fever help infection?

Answer 20

Raising the body temperature outside of bacteria’s narrow temperature niche helps their replication rates to drop drastically

Question 21

What does C reactive protein (CRP) do?

Answer 21

Primes certain bacteria for destruction by the complement system (it is prognostic- rapidly increased during inflammation and very short 1/2 life so disappears once inflammation is gone)

Question 22

How do virally infected cells attempt to respond to attack?

Answer 22

1. Signal neighbouring cells to stop translation and transcription.
2. Signal neighbouring cells to undergo apoptosis
3. Activates immune cells - eg Natural Killer Cells
   (signalling done by interferons which are host specific but not virus specific)

Question 23

What do Natural Killer cells?

Answer 23

Specifically kill infected/abnormal cancer cells but ignore healthy tissues and cells.

Question 24

What are natural killer cells?

Answer 24

Lymphocytes that recognise and destroy viral or cancer cells