The evolution of innate immunity

Question 1

What are the core concepts of immunity?

Answer 1

1. to discriminate self from non-self

2. to kill or disable an infecting agent

Question 2

What is innate immunity?

Answer 2

The non-specific immediate response once a pathogen has been detected. Typically defined with having no memory - this is challenged though

Question 3

What are the different components of innate immunity?

Answer 3

Barriers:
- physical (skin)
- physiological (low pH, killing things before they get to your gut)
Humoral:
- pattern recognition receptors (PRRs)
- opsonins (complement and antibodies)
- anti microbial peptides (AMPs)
- cytokines
Cellular:
- phagocytes
- natural killer cells

Question 4

What drives the evolution of immunity?

Answer 4

> constant evolutionary arms race
stay in the same place
strong selective pressure to find immunity against the pathogen, leading to the host developing some sort of pattern-triggered immunity, which leads to increased pressure being put on the bacteria, which then develops a mechanism to fight the defence.

Question 5

What did having a huge variety of pathogens enable our ancestors to develop?

Answer 5

Our first ancestors needed to respond to everything and therefore needed:

• a broad spectrum
• non-specific barrier

Question 6

How can immunity traits be developed?

Answer 6

Over time or introduced individually. Can be direct or convergent evolution

Question 7

What is an ancient component of the innate immune system that is present in all living organisms?

Answer 7

Antimicrobial peptides

Question 8

What are antimicrobial peptides (AMPs) and how do they work?

Answer 8

Small peptides that have a very broad spectrum. They use the slight difference in the charge in the membrane to recognise the difference from self & non-self. They have cationic and amphiphilic characteristics. Generally secreted by white blood cells & epithelial cells.
- Bacteria membranes are slightly more negative than ours
○ Once attached to the membrane, a pore will be formed (hole punch mechanism)
○ A leak of the cell will occur
○ Cell will DIE

Question 9

How did antimicrobial peptides (AMP) evolve?

Answer 9

Through convergent evolution throughout the lineages

Question 10

Name examples of AMPs.

Answer 10

cathelicidin subfamily; LL-37, BMAP-27

defensin subfamily; α-defensin 4, β-defensin 2

Question 11

What is the most ancient pathogen recognition system?

Answer 11

Toll-like receptors (TLRs) & NOD-like receptors (NLRs).

Question 12

What are toll-like receptors (TLRs)?

Answer 12

• proteins that recognise pathogen associated molecular patterns (PAMPs)
• can be extracellular or intracellular (can be patrolling in membranes or outward facing)
• recognises all pathogens
• induce inflammation via NF-kappaB

Question 13

What are NOD-like receptors (NLRs)?

Answer 13

• proteins that recognise bacterial peptidoglycan (or Strep, stays in the bacterial pathogens)
• solely intracellular

Question 14

Where can TLRs & NLRs be found in the TREE?

Answer 14

All eukaryotes

Question 15

What are PAMPs?

Answer 15

Pathogen associated molecular patterns

• molecular structure that is pathogen specific and not found in our cells
• e.g. bacterial lipopolysaccharide (LPS) (a diverse set of microbial molecules that share a number of different general “patterns,”)
• e.g. flagellin found in bacterial flagella, porins in the outer membrane of the Gram-negative cell wall

Question 16

What are DAMPs?

Answer 16

Damage associated molecular patterns (DAMPs)
- endogenous danger molecules that are released from damaged/ dying cells and activate the innate immune system by interacting with pattern recognition receptors (PRRs)
- e.g. heat-shock proteins;
altered membrane phospholipids

Question 17

How do TLRs and NLRs work together to form an apoptotic response?

Answer 17

Inducing inflammation via NF-kappaB response

• recruits other parts of the immune system
• initiates the immune response

Question 18

How is nucleic acid recognition useful in the innate immune system?

Answer 18

recognises foreign nucleic acids therefore can differentiate between self and non-self

Question 19

What nucleic acid recognition mechanism does Bacteria & Archae have?

Answer 19

Through the driving force of being attacked by phages, the memory allows bacteria and archae to evolve to having: 
>CRISPR
Archae has an enzyme called  
> Argonaute
- Archae does not have a full RNAi mechanism, but has the major enzyme Argonaute that does the cutting/ splicing 
> Restriction enzymes
- comes from bacteria
- self vs non self
- recognises invading phage

Question 20

What nucleic acid recognition mechanism do Eukaryotes have?

Answer 20

> RNAi

• recognises foreign nucleic acids
• has been adapted in research for knockdowns (not knock outs)

Question 21

How have nucleic acid recognition mechanisms evolved?

Answer 21

Through convergent evolution

Question 22

Where is the complement system in the evolutionary TREE?

Answer 22

present in most animals

- difficult to pinpoint where it first appeared

Question 23

What is the complement system?

Answer 23

part of the immune system that enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells, promote inflammation and attack the pathogen’s cell membrane.

• large no. of distinct plasma proteins that react with each other to opsonise pathogens and activate an inflammatory response
• circulate in the blood as inactive precursors - stimulated by one of several triggers, proteases in the system cleave and activate the cascade

Question 24

Where are reactive oxygen species (ROS) in the evolutionary TREE?

Answer 24

All eukaryotes

- Archae can protect itself from ROS but there is no evidence that it produces it itself

Question 25

What are reactive oxygen species (ROS) ?

Answer 25

• highly reactive molecules
• variant species of superoxide (contains oxygen)
• a natural by-product of metabolic processes
• can by synthesised deliberately for as defensive molecules
  ○ Phagosome maturation
  ○ Killing the cargo
• recent studies have shown that it functions as a second messenger of signal transduction

Question 26

Where is phagocytosis in the evolutionary TREE?

Answer 26

In some eukaryotes (Protists and animals)

Question 27

Why is phagocytosis not seen in plants or fungi?

Answer 27

Phagocytosis became an impossibility due to the cell wall

Question 28

What is the common homologue of phagocytosis present between us and archae? Suggest a reason as to how this came about?

Answer 28

• common homologue of actin & Arp2/3
• When symbiosis was occurring, a simple ancestral cell had an actin cytoskeleton that wasn’t as regulated as it is now. The membrane could push forward. Randomly, a protrusion engulfed something from the extracellular matrix
  ○ engulfed bacterial
  ○ That became our mitochondria

Question 29

Where is programmed cell death in the evolutionary TREE?

Answer 29

Restricted to multicellular eukaryotes

Question 30

Why would a cell undergo programmed cell death?

Answer 30

selective suicide is used as an immunity mechanism to prevent disease spread

• hope that the pathogen dies with you
• origin is unclear

Question 31

What can trigger apoptosis/ programmed cell death?

Answer 31

DAMPS, DNA damage, viral infection, mitochondrial signals, receptor activation

Question 32

What is behavioural immunity?

Answer 32

individual organisms detect the potential presence of disease-causing parasites in their immediate environment, and engage in behaviours that prevent contact with it

• seen in ants and humans (such as ebola etc outbreak, common practice to isolate the patient to stop spreading)
• self-medication such as herbal treatment (limitation of symptoms by behaviour)

Question 33

What are the major steps in the evolution of innate immunity? (Antisocial Trying Nuggets Caress Round Pink Burgers)

Answer 33

• antimicrobial peptides (AMPs)
• TLRs and NLRs
• Nucleic acid recognition
• complement system
• reactive oxygen species
• programmed cell death
• behavioural immunity