However the phenomena of  G.V.H.  M.L.C . & Linkage of H.2 to Ig etc can all be equally well explained by 1) pathogens being evolved to be near-self  2) possible constant neoplastic transform being reacted against. Both → high conc of 'near-self' AB and their cells. A [?]variable system tending to generate quicker certain AB specif. against near anti H.2. AB should be selected in evol. & linked to its H.2.

Reads:

G v H  Inject P → F. 1.  In theory F1 should have foreign AG in excess → P † [death]

Explain G v H by low specificity cells just strong enough to react but not enough to get 2 sites occupied at once.  

Problem. For any AG there must be spectrum of low affinity cells just stim but not tol. There will be stim → buff AB → stim ↓  

Near 'self' cells unbuffered when emerge from thymus - but low specificity would be stim → AB → buffer ↑ so that not stim again  Therefore should have enhanced near-self cells along with near-self nat AB .  

[Circle with T in middle indicating thymus, has arrow pointing right to following 3 options of cells released from thymus]  

1). Strong self specific →  †  [picture of lymphocyte with arrow to fragments thereof]

2). V Weak self specific → stim [picture of lymphocyte multiplying, producing natural antibody that decreases stimulation]  

3). non-self specific → [picture of lymphocyte remaining unchanged]  

Propose near-self more likely to X-react with - mutated self cells → neoplasia

        - antigens of same species → MLC & GvH demonstrate mainly in same species

[Figure at bottom of page showing plots of cell number (ordinate) against specificity for self antigen (abscissa), with high on left, through low in middle and zero on right. Segments of text related to the figure, from left to right, read:]  

Nat AB secreted buffering & making tol more diff. so that cells continually produced are now buffered.

No Nat AB init  

Antigens of ext pathogens adapted to fool immune system by being near self.  

- internal "pathogens" moving from effete cell to new host cell 

Init no nat AB 

Integrated area under curve regulated by some population homeostatic mechanism. So that while nearself cells constantly maintained - zero self will be limited

If [?]fact bact unless they are identical with self are confronted with this barrier of near-self AB - & so would be more likely to reach a posⁿ of inducing tol if they were separate from near self. 

Note Smithies in Cinnader's "Regⁿ of the AB Resp" 1968  p. 367 says curve not predicted a priori - gives similar to a Bolzmann distribution.  

Smithies [Top of 3 figures on this page]

[Ordinate reads] Fraction of AB (Me - cells making AB)

[Abscissa reads] energy of interaction 

[Middle of 3 figures on this page]

[Ordinate reads] Cell No

[Abscissa reads]  Specificity for self  AG [From high on left to zero on right]

[Words on figure read] late   early 

[Bottom of 3 figures on this page]

[Ordinate reads] Cell No

[Abscissa reads] Specificity for non - self AG [From high on left to zero on right]

[Text associated with figure read from left to right]

sec resp popⁿ after a supra-opt - sl. Tolerogenic dose of AG 

sec. resp popⁿ after an 'opt' imm dose of AG. 

Prim - responding popⁿ  

[Bottom of page reads] Why need near  histocompat for grafting → better survival than far histocompatability? Perhaps graft → slow release so that no tolerance only imm response → expected to be particularly active if graft near-self (from above premises)  ?more easily triggered to IgG → enhancement during establishment period