Lecture 2: Evolution of the immune system

Question 1

Describe the immune system in its present state;

Answer 1

The immune system is a coherent system of interacting cells and molecules

Question 2

Describe the origin of the human immune system;

Answer 2

Each component has been selected through evolutionary pressures and physiologically adapted to protect against threats today.

Many components came from different origins i.e different ancestors

Origins can be traced on phylogenetic trees

Question 3

What are the main elements that are likely to have come together from the immune system?

Answer 3

The four main elements that likely have evolved separately and come together are;

• Compliment mediated cell killing
• Antimicrobial peptides
• Cell mediated killing
• Antibodies

Question 4

Describe the origin of compliment mediated cell killing

Answer 4

First and earliest origin,

• Rapid recognition system
• Restricted range of pathogen recognition
• Innate

Question 5

Describe the origin of antimicrobial peptides;

Answer 5

antimicrobial peptides and defensins

• Secreted by mammalian leucocytes
• Innate

Question 6

Describe the origin of cell mediated killing;

Answer 6

• Mechanism to distinguish self from non-self results in cell mediated killing
• Innate + adaptive

Question 7

What sort of response is the production of soluble antibodies/

Answer 7

Adaptive

Question 8

What is an important component of the immune system and these four elements?

Answer 8

Cross talk (considerable amount)

Question 9

What is the first line of defence against common microorganisms that have passed the physical barriers?

Answer 9

Macrophages and neutrophils of the innate immune system provide the first line of defence

These cells cannot always eliminate microbes

Question 10

How have lymphocytes evolved?

Answer 10

Lymphocytes of the adaptive immune system have evolved to provide versatile defence and provide protection form subsequent reinfections of the same pathogen

i.e

• Versatile application against microbes
• Generates immunological memory

Question 11

How do innate cells influence the adaptive response?

Answer 11

The innate immune system initiates and directs the adaptive immune response

Innate immune system also removes pathogens

Question 12

Describe the time scale of infection and immune response;

Answer 12

The adaptive immune response can take 4-7 days to be effective. This is because of the process of APC activating T,B cells and subsequent proliferation in lymph nodes.

The innate immune system keeps the infection in check until the adaptive response can eliminate. “controls infection”

Question 13

During the evolution of the immune system what sort of process’ are conserved in the phyologenetic tree?

Answer 13

Intracellular processes in the immune response are conserved across species and through evolution as these were less exposed to selective pressures.

Extracellular processes and receptors were influenced by environmental pressures

Question 14

What is consistent across multicellular organisms?

Answer 14

Processes to identify self from non self i.e MHC proteins

The process to thus protect self from pathogens or competition for nutrients

Question 15

What also occurred as mutlicellular organisms evolved regarding immune cell differentiation/

Answer 15

As tissues differentiated their populations of immune cells also differentiated to function and serve that specific tissue

Question 16

What molecules developed in the immune system to identify pathogens?

Answer 16

Pattern Recognition Molecules (PRM)

i.e Toll Like Receptors (TLRs)

This is preserved across species.

Question 17

Do other organisms have the same extent of immune system as mammals?

Answer 17

No trues lymphocytes, TCRs, BCR’s, antibodies or MHC molecules are found in vertebrates

Question 18

What distinguishes the innate immune response from adaptive?

Answer 18

The innate immune response mechanisms act immediately and are followed by early induced responses which can be activated by infection but do not generate a traditional immunological memory

Question 19

What are the general principles of the innate immune system?

Answer 19

• Front line of host defence
• Pattern recognition in the innate immune system
• The compliment system and innate immunity
• Induced innate responses to infection

Question 20

Why does the innate immune system exist?

Answer 20

• Early defence against pathogen

- To alert the adaptive immune system to pathogen invasion

Question 21

How does the innate and adaptive immune system communicate?

Answer 21

Operate through ancient communication system known as the Toll Pathway (predates adaptive immune system)

Question 22

Does the toll system exist beyond mammals?

Answer 22

Yes it is also found in invertebrates and vertebrates

Question 23

What were the first defence molecules in immune evolution?

Answer 23

Antimicrobial peptides

Question 24

How old is the compliment system?

Answer 24

Predates vertebrates

Question 25

What are the four case studies looked at for immune system evolution?

Answer 25

1) Drosophila toll-like receptors and signalling
2) Simple compliment system in Echinoderms
3) Antimicrobial peptides
4) Jaws(bone structure) and the adaptive immune system

Question 26

How does the innate immune system recognise pathogens?

Answer 26

• Pattern recognition receptors recognise patterns of repeating structural motifs.
  i. e mannose binding lectin
• Toll like receptors also recognise the strucutre of many pathogens

Question 27

Once a pathogen is recognised by an innate immune cell what may happen?

Answer 27

The receptor triggers an intracellular signalling cascade that results in the production of proinflammatory cytokines and the activation, recruitment of innate cells to the site of infection and possible adaptive response.

The proinflammatory response is highly conserved

Question 28

What was the innate immune system originally discovered in?

Answer 28

Drosophilia

Question 29

What is found in drosophilia and humans?

Answer 29

Pattern Recognition receptors (innate immune system component)

Recognizes common molecular patterns of pathogens and the signalling pathways to the activation of the transcription factor NFkB

Question 30

What is NFkB?

Answer 30

The activation of NFkB is the original and central signalling pathway in innate immunity

Question 31

What may represent the most primitive pathogen recognition system?

Answer 31

Toll like receptors

Question 32

Write brief notes on TLRs;

Answer 32

TLRs have an array of variations and thus function

TLR-4 was first discovered and responds in mice to lipopolysacchardies of gram negative bacteria membranes

mice lacking TLR4 are particularly susceptible to gram negative infection

Question 33

What do TLRs tend to recognise?

Answer 33

Bacterial components, flagella, viral RNA and bacterial DNA

Question 34

Why is there variation in the quantity of TLR subtypes in species?

Answer 34

Humans and other higher organisms have less TLRs because we possess alternative immune defences

Question 35

Compare drosophilia and mammalian TLRs;

Answer 35

One distinct difference is that mammals TLR systems can directly recognise pathogen products whereas drosophilia recognise a cleaved self product called spatzle

Otherwise the signalling processes are conserved

Question 36

What is another system in drosophilia that recognises gram negative bacteria that is similar to a human system;

Answer 36

A system similar to tumor necrosis factor in humans provides protection from gram negative bacteria

Known as the Imd (immunodificiency) pathway (very similar receptors and signals to human tumor necrosis factor.

Question 37

How is Imd in drosophila similar to TNF?

Answer 37

Relish activates the expression of several immune-response genes such as those which encode some antimicrobial peptides including defensins

Those potential arose by duplication in an evolutionary fork

Question 38

What is the compliment system?

Answer 38

A component in plasma that augmented the killing of pathogens.

Question 39

What are compliment proteins;

Answer 39

Compliment proteins are proteases that have to be activated by proteolytic cleavage - these enzymes are known as zymogens

Question 40

What do compliment proteins do?

Answer 40

They mark/tag pathogens ready for destruction by pahgocytes

Question 41

What are the three pathways of compliment activation?

Answer 41

1) Classical pathway (Antigen;Antibody complexes)
2) MB Lectin Pathway (Lectin binding to pathogens surface)
3) Alternative Pathway ( Pathogen surfaces)

Question 42

What are the three effects of compliment activation?

Answer 42

1) Recruitment of inflammatory cells
2) Opsonization of pathogens
3) Killing of pathogens

Question 43

Describe the ancestral origin of compliment system;

Answer 43

First discovered in echinoderms

Comprised of factor B and C3

Question 44

Describe the simple compliment system in echinoderms;

Answer 44

C3 binds pathogen then binds factor B

Cleavage by factor D

Creates C3 converts which then cleaves and activates more downstream molecules.

Question 45

Describe antimicrobial peptides

Answer 45

Ancient and conserved

I.e defensins made at the epithelial surface

activate against gram -ive and +ive bacteria

Found in plants and mammals, similar structure

Question 46

What is observed regarding the immune system timeline?

Answer 46

It suddenly emerged i.e like the big bang, roughly at the same time as vertebrates

Appeared abruptly in cartilaginous fish

Question 47

Describe jawed fish and immune system relationship

Answer 47

A specific event where a transposon carrying the ancestral RAG recombinase inserted itself into a immunoglobulin, T cell gene. Thus giving jawed fish and vertebrates adaptive immunity.

Question 48

What did the insertion of RAG recombinase allow for?

Answer 48

The capacity for t cell and immunoglobulins to undergo somatic recombination (thus leading to diversity)

Question 49

What do Jaws have to do with RAG recombinase?

Answer 49

It is believed the development of jaws allowed for a greater range of consumption and thus the evolution of a better immune system to fight off the new introduction of diseases.

Question 50

What’s important of hagfish?

Answer 50

Through the rearrangement of leucine-rich repeat modules they assembled lymphocyte antigen recognition receptor genes. (This lead to diversity in receptors(rearrangement)) (adaptive immunity)