Topic 6 Flashcards
What are the features of the innate immune system?
It is very old, as every organism has some form of innate defense
However this system is unable to adapt and instead relies on unique molecular features of pathogens that are relatively well conserved
What are the features of the adaptive immune system?
This has only existed since the development of jawed vertebrates approx. 500 million years ago
It makes use of VDJ recombination to use a small number of similar receptors to generate a vast repertoire of binding molecules
TcR is unique in its ability to bind MHC
What are the two arms the adaptive immune system is frequently divided into?
Humoral immunity which includes B cells and the production of soluble Ig of 5 different classes which vary dependent on the situation and function of the cell
Cellular Immunity which is made up of alpha/beta T cells which includes helper T cells which produce cytokines to drive B and T cell development, cytotoxic T cells which can kill intracellularly infected cells, NK T cells which have unique TcR for the recognition of non-peptide antigens
Gamma/delta T cells which have a limited repertoire which is important for the recognition of non-peptide antigens and non-MHCs
What are the molecules involved in pathogen recognition in the innate immune system?
Toll-Like Receptor C-type lectins NOD-like receptors Invariant TcR (NKT recognition) Non-Polymorphic MHC Non-classical MHC
What are the molecules involved in pathogen recognition in the adaptive immune system?
TcR
Immunoglobulins
MHC
What are the requirements to get an effective immune response?
Requires a combination of both adaptive and innate response
Don’t get commitment without innate signals
Adjuvants promote formation of a protective immune response to antigen
What is an adjuvant?
This is an agent which modifies the effect of other agents such as drugs or vaccines, they are typically included in vaccines to enhance the recipients immune response to a supplied antigen while keeping the injected foreign material to a minimum
What are therapeutic adjuvants?
These are also termed immunomodulators and typically enhance the innate immune mechanisms which lead to the resolution of infections such as TLR and NLR agonists
What are vaccine adjuvants?
These are adjuvants administered alongside vaccines which work to skew antigen specific adaptive immune responses
What are the three basic mechanisms associated with different vaccine adjuvants?
Recruitment of innate immune cells
Appropriate presentation of the antigen in those cells
Activation of those cells
What are the features of innate immune receptors?
There a now a vast range of these discovered, and they are absolutely critical for the generation of an immune response
LPS is a potent activator of B cells as first discovered by mice which were resistant to LPS due to a mutation in the CD14 molecule
Later evidence found presence of genes similar to drosophila Toll for pattern recognition in development and it was later discovered that TLRs recognized various microbial products and they have proved extremely important to vaccine and adjuvant development though they may also be important in autoimmune disease through inappropriate activation
How does TLR expression vary among tissues?
Most tissues express at least one TLR, spleen and peripheral blood leukocytes express all of the TLRs with professional phagocytes expressing the greatest variety of TLRs
Neutrophils were found to express all TLRs except TLR3
Eosinophils constuituvely express TLR 1,2,4,6,7,9 and 10
Basophils express TLR 2 and 4 but CD14
Mast cells express TLR1,2 and 6 but not 4
Monocytes/Macrophages express all TLRs except TLR3
Myeloid DCs express all TLRs except 7 and 9
Plasmacytoid DCs express TLR 7 and 9 almost exclusively
What is the basic structure of TLRs?
Type 1 transmembrane glycoproteins with molecular weights ranging from 90 to 115 kDa containing 16-28 extracellular leucine rich repeat domains typically 20-30 amino acids long
These Leucine rich repeat domains, along with an intracellular TIR characterizes the structure of these proteins
The receptors have a typical horseshoe shape with the concave structure formed by parallel beta-strands and convex structure formed by loops and 3(10) helices
How are TLRs activated?
These form dimers in the membrane which are drawn closer together after ligand bidnign which allows signalling to occur, typically through MYD88
What are inflammasomes?
These are intracellular sensors of stress and inflammation, the NLRP3 inflammasome contains 3 proteins, ASC, caspase-1 and NLRP3- which is a member of the nucleotide binding domain LRR family of proteins
Formation of NLRP3 induces caspase 1 mediated activation of proinflammatory cytokine interleukin 1-beta
