Lecture 2: Evolution of the immune system Flashcards
Describe the immune system in its present state;
The immune system is a coherent system of interacting cells and molecules
Describe the origin of the human immune system;
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
What are the main elements that are likely to have come together from the immune system?
The four main elements that likely have evolved separately and come together are;
- Compliment mediated cell killing
- Antimicrobial peptides
- Cell mediated killing
- Antibodies
Describe the origin of compliment mediated cell killing
First and earliest origin,
- Rapid recognition system
- Restricted range of pathogen recognition
- Innate
Describe the origin of antimicrobial peptides;
antimicrobial peptides and defensins
- Secreted by mammalian leucocytes
- Innate
Describe the origin of cell mediated killing;
- Mechanism to distinguish self from non-self results in cell mediated killing
- Innate + adaptive
What sort of response is the production of soluble antibodies/
Adaptive
What is an important component of the immune system and these four elements?
Cross talk (considerable amount)
What is the first line of defence against common microorganisms that have passed the physical barriers?
Macrophages and neutrophils of the innate immune system provide the first line of defence
These cells cannot always eliminate microbes
How have lymphocytes evolved?
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
How do innate cells influence the adaptive response?
The innate immune system initiates and directs the adaptive immune response
Innate immune system also removes pathogens
Describe the time scale of infection and immune response;
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”
During the evolution of the immune system what sort of process’ are conserved in the phyologenetic tree?
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
What is consistent across multicellular organisms?
Processes to identify self from non self i.e MHC proteins
The process to thus protect self from pathogens or competition for nutrients
What also occurred as mutlicellular organisms evolved regarding immune cell differentiation/
As tissues differentiated their populations of immune cells also differentiated to function and serve that specific tissue
What molecules developed in the immune system to identify pathogens?
Pattern Recognition Molecules (PRM)
i.e Toll Like Receptors (TLRs)
This is preserved across species.
Do other organisms have the same extent of immune system as mammals?
No trues lymphocytes, TCRs, BCR’s, antibodies or MHC molecules are found in vertebrates
What distinguishes the innate immune response from adaptive?
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
What are the general principles of the innate immune system?
- Front line of host defence
- Pattern recognition in the innate immune system
- The compliment system and innate immunity
- Induced innate responses to infection
Why does the innate immune system exist?
- Early defence against pathogen
- To alert the adaptive immune system to pathogen invasion
How does the innate and adaptive immune system communicate?
Operate through ancient communication system known as the Toll Pathway (predates adaptive immune system)
Does the toll system exist beyond mammals?
Yes it is also found in invertebrates and vertebrates
What were the first defence molecules in immune evolution?
Antimicrobial peptides
How old is the compliment system?
Predates vertebrates
What are the four case studies looked at for immune system evolution?
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
How does the innate immune system recognise pathogens?
- Pattern recognition receptors recognise patterns of repeating structural motifs.
i. e mannose binding lectin - Toll like receptors also recognise the strucutre of many pathogens
Once a pathogen is recognised by an innate immune cell what may happen?
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
What was the innate immune system originally discovered in?
Drosophilia
What is found in drosophilia and humans?
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
What is NFkB?
The activation of NFkB is the original and central signalling pathway in innate immunity
What may represent the most primitive pathogen recognition system?
Toll like receptors
Write brief notes on TLRs;
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
What do TLRs tend to recognise?
Bacterial components, flagella, viral RNA and bacterial DNA
Why is there variation in the quantity of TLR subtypes in species?
Humans and other higher organisms have less TLRs because we possess alternative immune defences
Compare drosophilia and mammalian TLRs;
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
What is another system in drosophilia that recognises gram negative bacteria that is similar to a human system;
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.
How is Imd in drosophila similar to TNF?
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
What is the compliment system?
A component in plasma that augmented the killing of pathogens.
What are compliment proteins;
Compliment proteins are proteases that have to be activated by proteolytic cleavage - these enzymes are known as zymogens
What do compliment proteins do?
They mark/tag pathogens ready for destruction by pahgocytes
What are the three pathways of compliment activation?
1) Classical pathway (Antigen;Antibody complexes)
2) MB Lectin Pathway (Lectin binding to pathogens surface)
3) Alternative Pathway ( Pathogen surfaces)
What are the three effects of compliment activation?
1) Recruitment of inflammatory cells
2) Opsonization of pathogens
3) Killing of pathogens
Describe the ancestral origin of compliment system;
First discovered in echinoderms
Comprised of factor B and C3
Describe the simple compliment system in echinoderms;
C3 binds pathogen then binds factor B
Cleavage by factor D
Creates C3 converts which then cleaves and activates more downstream molecules.
Describe antimicrobial peptides
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
What is observed regarding the immune system timeline?
It suddenly emerged i.e like the big bang, roughly at the same time as vertebrates
Appeared abruptly in cartilaginous fish
Describe jawed fish and immune system relationship
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.
What did the insertion of RAG recombinase allow for?
The capacity for t cell and immunoglobulins to undergo somatic recombination (thus leading to diversity)
What do Jaws have to do with RAG recombinase?
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.
What’s important of hagfish?
Through the rearrangement of leucine-rich repeat modules they assembled lymphocyte antigen recognition receptor genes. (This lead to diversity in receptors(rearrangement)) (adaptive immunity)
