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Recognition of:. Self vs Non-self. Presence vs Absence. Harmless vs Dangerous. hematopoiesis. pluripotent. Recognition of:. Self vs Non-self. Presence vs Absence. Harmless vs Dangerous. What’s wrong with this fruit fly?.
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Recognition of: Self vs Non-self Presence vs Absence Harmless vs Dangerous
hematopoiesis pluripotent
Recognition of: Self vs Non-self Presence vs Absence Harmless vs Dangerous
What’s wrong with this fruit fly? Missing toll or other members of the toll pathway
Recognition of: Self vs Non-self Presence vs Absence Harmless vs Dangerous
hematopoiesis pluripotent
hematopoiesis pluripotent
Another accident with chickens • 1956: Bruce Glick “accidentally” vaccinates bursectomized chickens • Finds they make poor antibody responses
Antigen receptors assembled by somatic recombination 2 Light chains (IgL) b, d a, g Heavy chain Light chain 2 Heavy chains (IgH) Variable domain Constant domain TCR or T Cell Receptor Ig or B cell receptor
Germline DNA Recombination 3 1 2 1 2 3 3 1 3 Transcription –Splicing -Translation Transcription –Splicing -Translation Recombination 2 2 3 2 1 2 3 Protein: T Cell Receptor Germline DNA Generation of Diversity in Antigen Receptors Vn V3 V2 V1 D JC T cell V D J C V J C Vn V3 V2 V1 JC
Recognition of: Self vs Non-self Presence vs Absence 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 vs Non-self Presence vs Absence Harmless vs Dangerous
Mice & Cattle Mice & Primates Primates & Cattle