Imunology - Blog Posts
Complement Pathways
Components of complement pathways of the immune system.
Classical Pathway: binds to the pathogen surface
C1 binds to phosphocholine on bacteria, which activates C1r to cleave C1s.
Activated C1s cleaves C4 to C4a and C4b.
C4b binds to the microbial surface and also binds C2.
C2 is cleaved to C2a and C2b by C1s, forming the C4bC2a complex.
The C4bC2a complex cleaves C3 to C3a and C3b.
C3b binds to the surface and causes opsonization.
MB-Lectin Pathway: uses mannin-binding lectin to bind to mannose-containing carbohydrates on the pathogen surface
Mannin-binding lectin (MBL) binds to the pathogen surface and activates MASP-2.
MASP-2 cleaves C4 to C4a and C4b.
C4b binds to the microbial surface and also binds C2.
C2 is cleaved to C2a and C2b by MASP-2, forming the C4bC2a complex.
The C4bC2a complex cleaves C3 to C3a and C3b.
C3b binds to the surface and causes opsonization.
Alternative Pathway: binds to the pathogen surface with spontaneously activated complement, amplifies C3b
C3b deposited by the C3 convertase binds to factor B.
Factor B is cleaved by factor D into Ba and Bb, forming the C3bBb complex.
The C3bBb complex cleaves C3 into C3a and C3b.
C3 spontaneously hydrolyzes to C3(H2O).
C3(H2O) binds to factor B, and factor D cleaves factor B.
Upon factor B cleavage, the C3(H2O)Bb complex is formed.
The C3(H2O)Bb complex cleaves C3 into C3a and C3b.
Factor B binds to C3b on the surface and is cleaved to Bb.
history meme (french edition) → 7 inventions/achievements (2/7) the first vaccine for rabies by Louis Pasteur & Émile Roux
“Pasteur had, in the early 1880s, a vaccine for rabies, but he was a chemist and not a licensed physician, and potentially liable if he injured or killed a human being. In early july 1885, Joseph Meister, a nine year-old-boy, had been badly mauled and bitten by a rabid dog (…). Pasteur injected young Meister with his rabies vaccine: the boy did not develop rabies and recovered fully from his injuries. Pasteur became a hero, and the Parisian Institue which came to be named in his honour, and of which he was the first director, became the global prototype bacteriological and immunological research institute. By demonstrating beyond doubt that many diseases were transmitted by bacteria and could be prevented from becoming active by pasteurization techniques, Pasteur indeed changed the course of history.” – G. L. Geison, The Private Science of Louis Pasteur.
Antibody Therapy Creates New Opportunities For Treating Brain Diseases
Immunotherapy has proven to be effective against many serious diseases. But to treat diseases in the brain, the antibodies must first get past the obstacle of the blood-brain barrier. In a new study, a research group at Uppsala University describes their development of a new antibody design that increases brain uptake of antibodies almost 100-fold.
Immunotherapy entails treatment with antibodies; it is the fastest growing field in pharmaceutical development. In recent years, immunotherapy has successfully been used to treat cancer and rheumatoid arthritis, and the results of clinical studies look very promising for several other diseases. Antibodies are unique in that they can be modified to strongly bind to almost any disease-causing protein. In other words, major potential exists for new antibody-based medicines.
The problem with immunotherapy for diseases affecting the brain is that the brain is protected by a very tight layer of cells, called the blood-brain barrier. The blood-brain barrier effectively prevents large molecules, such as antibodies, from passing from the bloodstream into the brain. It has therefore been difficult to use immunotherapy to treat Alzheimer’s and Parkinson’s disease, which affect the brain, as well as cancerous tumours in the brain.
It has been known for a long time that some large proteins are actively transported across the blood-brain barrier. These include a protein called transferrin, whose primary task is to bind to iron in the blood and then transport it to the brain. The research group behind this new study has taken advantage of this process and modified the antibodies they want to transport into the brain using components that bind to the transferrin receptor. Then, like a Trojan horse, the receptor transports antibodies into the brain. The number of modifications to and placement of the antibodies have proven to be important factors for making this process as effective as possible.
“Bivalent Brain Shuttle Increases Antibody Uptake by Monovalent Binding to the Transferrin Receptor” by Greta Hultqvist, Stina Syvänen, Xiaotian T Fang, Lars Lannfelt, and Dag Sehlin in Theranostics. Published online January 2017 doi:10.7150/thno.17155
The green antibody is modified using two components that bind to the transferrin receptor and enable the antibody to pass through the blood-brain barrier. The components are placed in such a way that prevents them from being able to bind simultaneously. The placement is important, because otherwise the antibody would not detach on the far side of the blood-brain barrier. NeuroscienceNews.com image is credited to Greta Hultqvist.