Innate Immunity

Question 1

What is innate immunity?

Answer 1

Evolutionary old
Exists in plants, invertebrates and fungi as well as all vertebrates - not unique to animals
As a mark of its importance, most pathogens have evolved mechanisms to either subvert and avoid it.

Question 2

What is the difference between humoral and cellular response?

Answer 2

Humoral response- down to secreted factors e.g. acids

Cellular response - factors due to cells acting and targeting

Question 3

When does the adaptive immune response kick in?

Answer 3

After the pathogen is flooded in.

After a few days.

Question 4

Explain the significance of mucosal epithelia

Answer 4

They are the main site of infection. Most pathogens gain entry across them.
They are secretory and absorptive surfaces that line externally exposed cavities.
They secrete mucus so mucus-coated microbes find it harder to adhere and to draw microbes away as it flows.

Question 5

Give some details on anti-bacterial peptides found in the stomach

Answer 5

• small peptides (20-60aa)
• include alpha and beta defensins
• have proteins including lysozyme and histatins
• secreted by epithelial cells naturally or upon stimulation
• most kill by damaging the microbial cell wall/membrane

Question 6

What is the complement cascade?

What is the first protein involved in the classical pathway?

Answer 6

A series of 20+ proteins which circulates the blood and tissues. When in contact with a micro-organism molecule, they can get activated in a cascade where one protein cleaves the next.

First involved is the c1, activated by c1q, component which interacts with the antigen-antibody complex. This gives it a conformational change and gets activated as an enzyme.

Question 7

What happens in the classical pathway once c1q activates c1?

Answer 7

C1 divides into c1q, c1s and c1r.
C1s cleaves C4 into C4a and C4b.
C4b binds to the antigen surfaces and associates with the complement.

C4b binds to C2 and cleaves it into C2a and C2b forming C4b2b.
C4b2b then cleaves c3 into c3a and c3b making c4b2b3b.

C4b2b3b can activate c3 alone to make c3b and this binds directly to the pathogen surface to opsonise it.

C4a, c2a and c3a are inflammatory molecules and make endothelial walls leaky so increased tissue fluid production.

Question 8

What happens in all pathways once c3b is activated?

Answer 8

C3b cleaves c5 into c5a and c5b. c5b associates with the immune surface (cannot bond like c4b and c3b can).

Question 9

How is the Mannose-binding Lectin pathway different?

Answer 9

• it is initiated by manose binding lectin instead of c1q

Question 10

How is the alternative pathway different?

Answer 10

No antigen-antibody complexes needed.
Occurs in the absence of antibody.
Initiated by spontaneous cleavage of c3.
This hydrolysis of c3 allowed factor d and b to bind to it.
Factor b is cleaved into Ba and Bb. 
Bb cleaves more c3 into c3a and c3b.

Question 11

How does opsonisation with c3b work?

Answer 11

Many microorganisms have evolved coats or capsules to hide from phagocytic cells.
However, phagocytic cells such as macrophages and neutrophils have receptors for active complement proteins e.g. C3b
These receptors improve binding and recognition of the pathogen and subsequent phagocytosis..

Question 12

What do all pathways lead to after c3b is made?

Answer 12

C3b cleaves c5 into c5a and c5b.

C5b is associated with c6, c7, c8 and c9.

Question 13

What are the 3 main things that complement does for the body?

Answer 13

1. Recruitment of immune cells
2. ‘Opsonisation’ of pathogens
3. Killing of pathogens

Question 14

What immune cells make up the most of the population?

Answer 14

Neutrophils (75%)

Question 15

What are the two main types of phagocytic cells?

Answer 15

1. Neutrophils

2. Monocytes/macrophages

Question 16

What are the 2 ways of pathogen recognition?

Answer 16

• opsonisation

- pathogen recognition receptors

Question 17

What are pathogen recognition receptors?

Answer 17

They recognise pathogen associated molecular patterns.
They recognise types of molecules.

The effects of it lead to phagocytosis, secretion of inflammatory mediators and cytokine secretion.

Question 18

Give basic details on cytokines

Answer 18

• small glycoproteins
• similar to hormones
• secreted by a variety of cells
• involved in cell communication
• innate and adaptive immunity

Question 19

What are the categories of cytokines and explain?

Answer 19

1. Pro-inflammatory cytokines
2. Anti-inflammatory cytokines
3. Growth factors/Colony Stimulating Factors
4. Chemokines
5. Type I Interferons

Pro inflammatory - induce many of the effects associated with inflammation e.g. activation of macrophage stimulation of inflammatory mediator release

Anti- inflam cytokines -
Not necessarily anti-inflammatory
Antagonistic to pro-inflammatory cytokines.
Can mediate the adaptive immune response.

Growth factors
Important in development of immune cells. Can stimulate differentiation and cell growth.

Chemokibes
Produced by all cells in response to a viral infection. They render surrounding cells non-permisive to viral replication and activate immune cells to destroy the infected cell.