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Self vs Non-self

Harmless vs DangerousPresence vs Absence

Recognition of:

hematopoiesispluripotent

Self vs Non-self


Recognition of:

What’s wrong with this fruit fly?

Missing toll or other members of the toll pathway

Is it dangerous?

Self vs Non-self


Recognition of:


Involution of the thymus


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

Ig or B cell receptor TCR or T Cell Receptor

2 Heavy chains(IgH)

2 Lightchains (IgL)

Heavychain

Lightchain

Variable domain

Constant domain

Antigen

Generation of Diversity in Antigen Receptors

T cell

2 32113

3212

Vn V3 V2 V1

DJC

Vn V3 V2 V1 JC

Germline DNA

Recombination

Transcription –Splicing -Translation

Protein: T Cell Receptor

Germline DNA

Recombination

Transcription –Splicing -Translation

V

V

D J C

CJ

313

322

Fig 8-8

Self vs Non-self


Recognition of:

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

Self vs Non-self


Recognition of:

Fig 8-8

Mice & Cattle Mice & Primates

Primates & Cattle

Fig 12-5