Lecture 2

Question 1

What are the first and earliest of elements of the vertebrate immune system?

Answer 1

The first and the earliest element was antimicrobial peptides such as defences that are secreted by insects snails, Emily and leucocytes ( and eight) and plants.
Along with this compliment mediated sell killing as a rapid Recognition system operates on a restricted range of pathogens such as sea urchins (innate)

Question 2

Is cell mediated killing innate or adaptive?

Answer 2

Both

Question 3

What type of immunity is the production of soluble antibodies?

Answer 3

Adaptive

Question 4

Describe a defence strategy that exists in bacteria to defend from bacteriophages

Answer 4

Restriction endonucleases are enzymes able to cut beige DNA at specific recognition sites. Crisper cast is a system that targets and Cleves foreign DNA. The system can also be exploited to create mutants for experimental work.

Question 5

Name an example of Organisms with limited differentiation and their immune system.

Answer 5

Jellyfish possess a collection of undifferentiated cells with toll like receptors. Sponges grow in colonies of relatively under differentiated cells also. Limited Functions such as food gathering waste disposal and host defence are carried out by the same cells.

Question 6

What is significant about Cnidaria she (jellyfish and corals)?

Answer 6

Components of the innate immune system are found in them, as one of the earliest branches of the animal tree.the endodermal epithelium acts as a chemical barrier with anti microbial peptides embedded. Nonself recognition is mediated by PRRs like toll and nod like receptors.

Question 7

Describe a case study for antimicrobial peptides

Answer 7

• found in plants and animals
• defending made at the epithelial surface is an example
• arabidopsis make 13, drosophila make 15, human paneth cells in gut crypts make 21
• human and radish defensins are quite structurally related
• all three are active against gram negative and positive bacteria and likely existed before the plant ad animal divergence

Question 8

Describe a case study for the complement system and innate immunity.

Answer 8

Jules. Order (just after elli metchniko) found a component in plasma that augmented antibody killing that ‘complemented’ antibacterial activity of the antibody
Complement proteases require activation by proteolytic cleavage, these enzymes are known as zymogens

Question 9

What are the three biochemical pathways of the complement system

Answer 9

Classical pathway, MB-Lectin pathway, Alternative pathway

Question 10

What are the three principal outcomes of complement activation?

Answer 10

Lysis of pathogens,
opsonisation (coating) of foreign entities to enhance phagocytosis, the generation of peptide by-products that are involved in the inflammatory response

Question 11

What is thought to be the most primitive function of the complement system?

Answer 11

To increase efficiency of uptake of pathogens by phagocytic cells mediated by C3 - Complement components discovered in echinoderms. A homolog of C3 s produced by amoeboid coelytes (phagocytic cells in thecoelemic fluid). This expression is seen to increase in the presence of bacteria.

Question 12

Which of the three paths does the echinoderm complement system resemble?

Answer 12

Alternative pathway.
Echinoderms have factor B and C3. C3 binds to pathogens, then binds to factor B, which is cleaved by factor D, which creates C3 convertase, which then acts to cleave more C3 molecules.

Question 13

In what creature were PRR discovered?

Answer 13

drosophila

Question 14

What are PRRs?

Answer 14

invariant cell-surface receptors called pattern recognition receptors. They recognise common molecular patterns of pathogens ad the signalling pathways leading to the activation of the transcription factor NF -kB. THe activation of NF-kB is the original and central signalling pathway in innate immunity.

Question 15

What was the first mammalian TLR discovered? name an animal model proving this

Answer 15

TLR-4, mice lacking TLR-4 were found susceptible to infection with gram negative bacteria. TLRs can recognise bacterial components, viral RNA and bacterial DNA.

Question 16

How do we know TLRs are evolutionarily conserved?

Answer 16

They are conserved across metazoans that develop from an embryo, 3 germ layers. TLR diversity is greatest in echinoderms, and decreases in diversity toward human. This is likely because the development of adaptive immunity shifted the function of PRRs to initiate downstream immune responses e.g. increase in cytokine receptor diversity

Question 17

Drosophila vs mammalian TLR

Answer 17

INtracellular TLR signalling pathway is quite conserved between both. IC Signalling results in the activation of NF-kB transcription factor. One significant difference between the fl and the mammalian TLR system is that the mammalian receptors can directly recognise pathogen products. Fly can only recognise a cleaved self product called a spatzle.

Question 18

What is the Imd pathway in drodophila?

Answer 18

A second recognition system that is used to detenct gram-negative bacteria. The Imd pathway is strikingly similar to the mammalian TNF receptor pathway. Relish (Rel) activates the expression of several immune response genes such as those which encode some antimicrobial peptides including defensins.

Question 19

How is Imd analagous to TNF receptor pathway?

Answer 19

TNFRR signalling path can lead to gene expression or cell death. RIP (receptor interacting protein) or FADD (Fas-associated death domain protein). Imd, DmFADD< DREDD, RIP homologs, FADD and caspase 8. Both TLR adn Imd pathways activate equivalent effector mechanisms to eliminate infection.

Question 20

Describe the background behind the phrase ‘immunological big bang’ and the evolution behind adaptive immunity.

Answer 20

adaptive immunity seemed to emerge very suddenly. The evolution of adaptive immunity seems to have been made possible by the invasion of immunoglobulin-like genes by a transposable element. This conferred on the ancestral immunoglobulin genes the ability to undergo somatic gene rearrangement and thus generate diversity. The excising of the mobile DNA element from a piece of DNA altered the original DNA sequence. It was then introduced into the host DNA when the cut ends are rejoined. This is the origin of diversity of antigen receptors in the adaptive immune system.

Question 21

Explain how adaptive immunity appeared abruptly in cartilaginous fish.

Answer 21

In jawed fish and higher vertebrates, adaptive immunity is possible because of a transposon carrying the ancestral RAG recombinase inserting itself into a gene similar to an immunoglobulin or T-cell receptor V gene region. Original transposon thought to have been an a

Question 22

Explain the theorised relationship between jaws and adaptive immunity (RAG)

Answer 22

Jaws, ability to eat a wider variety of foodstuffs e.g. hard shells and chitinous exoskeletons, exposes animal to damage to the gut tissue and a wider risk of infection, immunological memory evolves as well as antigen-receptor diversity suggesting a repeated exposure to pathogens as opposed to a greater exposure key for selection pressure

Jaw adaptation was one change, but longer life times and slower development would have been another

Question 23

Describe an alternative adaptive immune system in jawless vertebrates (VLR)

Answer 23

the most primitive vertebrates are the jawless vertebrates comprising hagfish and lampreys. They assemble antigen recognition receptor genes through genomic rearrangement of leucine-rich repeats (LRRs). the different recombinatorial system from RAG-mediated recombination. Multiple short stretches encoding LRRs are situated next to the incomplese CONSTANT part of the variable lymphocyte receptor locus. gene conversion generates one complete VLR gene which gets many possibilities. they have some unknown function, but exist membrane bound and in secreted forms.

Question 24

How might 2 forms of adaptive immune systems have emerged?

Answer 24

The VLR based recombinatorial system may have evolved in an ancestor shared by only the two agnathans. Meanwhile the VLR would have likely existed preceding both agnathans and gnathostomes. The subseuent acquisition of V(d)J recombinatorial system may have ld initially to the coexistance of VLR and V(d)J recombinatorial mechanisms.