Lecture 3 Flashcards
How was Toll-Receptors role in immunity discovered?
The receptors were initially discovered due to the role they play in dorsoventral patterning and then found to have a role in immunity when mutations in its signalling pathway affected the production of drosomycin
What was the first mammalian toll-like receptor discovered?
TLR4 which recognises lipopolysaccharide of gram negative bacteria (determined as mice lacking this receptor were particularly susceptible to infection from gram negative bacteria)
Why are the toll receptors considered to be the most primitive pathogen recognition system?
The genes are highly conserved being similar between humans and drosophila
What immune signalling pathway, other than the toll-receptor pathway was discovered in drosophila?
The tumour necrosis factor receptor pathway which can provide protection against gram negative bacteria through the relish (NFkB) signal activating immune response genes including those for antimicrobial peptides
This was discovered through Imd (Immunodeficient) drosophila
What is the suspected relationship between the TLR and Imd mechanisms?
These activate equivalent effector mechanisms to eliminate infections suggesting they may have arose through gene duplication
What are the features of complement proteins?
Proteins are often zymogens activated through proteolytic cleavage
These proteins mark pathogens for destruction by phagocytes
The major mechanism through which pathogen recognition is converted into an effective host defense against initial infection
What are the three activation pathways of complement?
The classical pathway where activation is triggered by antigen:activation complexes
The MB-Lectin pathway Lectin binding to pathogen surfaces
The alternative pathway where activation occurs through contact with the pathogen surface
What are the effects of complement activation?
Recruitment of inflammatory cells
Opsonization of pathogens
Killing of pathogens
Where might the complement system originate from?
It appears to be an ancient host defense system with the most primitive function likely to use C3 to increase the efficiency of pathogen phagocytosis
This is due to its presence in echinoderms which resembles the alternative complement pathway
How has the adaptive immune system developed/
The origins are considered obscure as it seemed to rapidly emerge as a complete biological system at roughly the same time as vertebrates until the jaw theory arose
What is the jaw theory of immune system evolution?
The fact that many of the major features of the adaptive immunity appeared shortly after the appearance of vertebrates and are found in all jawed vertebrates has lead to the suggestion that the development of jaw resulted in an ability of an organism to increase the variety of its diet and therefore the variety of microbes to which it was exposed creating a selection pressure to have a more complex immune system
However other changes such as slower development and longer lifespans in vertebrates may have been important
What are the immunoglobulins in jawed vertebrates?
IgM is thought to be the most primordial and stable Ig isotype in vertebrate evolution as it is present in all living jawed vertebrates
IgD is present in mammals, absent in birds so it is thought to be a recently evolved isotype
IgW is also found in skates, sharks and lungfish so it is now thought that IgD and IgW have played varied roles in different vertebrate groups since the inception of immune system
Where have some of the major features of adaptive immunity evolved?
The IgH class switch arose in lobed-fin fish or early amphibians Cartilaginous fish and birds have evolved distinctive arrangements of their Ig loci and mechanisms for generating antibody diversity Lamprey and hagfish have evolved rearranging antigen-specific receptors from leucine-rich repeat structures rather than Ig domains
What has made the evolution of an adaptive immune response possible?
A transposon carrying the ancestral RAG recombinases inserted itself into a gene similar to an immunoglobulin or T-cell receptor V gene region
This allowed for the somatic recombination which generates the variety required by an adaptive immune system
