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Self vs Non-self

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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Self vs Non-self

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  1. Recognition of: Self vs Non-self Presence vs Absence Harmless vs Dangerous

  2. hematopoiesis pluripotent

  3. Recognition of: Self vs Non-self Presence vs Absence Harmless vs Dangerous

  4. What’s wrong with this fruit fly? Missing toll or other members of the toll pathway

  5. Is it dangerous?

  6. Recognition of: Self vs Non-self Presence vs Absence Harmless vs Dangerous

  7. hematopoiesis pluripotent

  8. Involution of the thymus

  9. hematopoiesis pluripotent

  10. Another accident with chickens • 1956: Bruce Glick “accidentally” vaccinates bursectomized chickens • Finds they make poor antibody responses

  11. The lymphocyte

  12. 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

  13. Antigen

  14. 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

  15. Fig 8-8

  16. Recognition of: Self vs Non-self Presence vs Absence Harmless vs Dangerous How is self-tolerance maintained?

  17. 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

  18. 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

  19. Recognition of: Self vs Non-self Presence vs Absence Harmless vs Dangerous

  20. Fig 8-8

  21. Mice & Cattle Mice & Primates Primates & Cattle

  22. Fig 12-5

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