Transcript miller
Recognition of: Self Presence vs Absence vs Non-self Harmless vs Dangerous hematopoiesis pluripotent Recognition of: Self Presence vs Absence vs Non-self Harmless vs Dangerous What’s wrong with this fruit fly? Missing toll or other members of the toll pathway Is it dangerous? Recognition of: Self Presence vs Absence vs Non-self Harmless vs Dangerous hematopoiesis pluripotent Involution of the thymus hematopoiesis pluripotent Another accident with chickens • 1956: Bruce Glick “accidentally” vaccinates bursectomized chickens • Finds they make poor antibody responses The lymphocyte Antigen receptors assembled by somatic recombination 2 Light chains (IgL) 2 Heavy chains (IgH) b, d a, g Heavy chain Light chain Variable domain Constant domain Ig or B cell receptor TCR or T Cell Receptor Antigen Generation of Diversity in Antigen Receptors Vn V3 V2 V1 D 3 Germline DNA Recombination 12 J C 1 2 3 3 13 Transcription –Splicing -Translation Protein: T Cell Receptor V DJ C V J C T cell Transcription –Splicing -Translation Recombination 2 Germline DNA 2 V2 Vn V3 2 3 V1 1 2 3 J C Fig 8-8 Recognition of: Self Presence vs Absence vs Non-self Harmless vs Dangerous How is self-tolerance maintained? Frank Macfarlane Burnet* Believed any correct theory must explain: • How antigen selects correct specificity • Why only a single specificity is produced • How self tolerance is maintained • Why second response to same antigen is so much larger than the first *1958 Nobel Prize Clonal Selection Theory • Each cell is a unique clone with its own specificity • If the cell encounters Ag in a premature state, it dies • The mature pool of cells represent those that did not encounter the Ag they are specific for during development • When mature cell encounters Ag it begins to divide (clonal expansion) = foreign antigen Recognition of: Self Presence vs Absence vs Non-self Harmless vs Dangerous Fig 8-8 Mice & Cattle Mice & Primates Primates & Cattle Fig 12-5