Part One: The Context Of Educational Research Part Two: Planning Educational Research Part Three: Styles Of Educational Research Part Four: Strategies And Instruments For Data Collection And Researching Part Five: Data Analysis

Research Methods in Education

Approximately 10% of peripheral CD4+ cells and less than 1% of CD8+ cells in normal unimmunized adult mice express the IL-2 receptor alpha-chain (CD25) molecules. When CD4+ cell suspensions prepared from BALB/c nu/+ mice lymph nodes and spleens were depleted of CD25+ cells by specific mAb and C, and then inoculated into BALB/c athymic nude (nu/nu) mice, all recipients spontaneously developed histologically and serologically evident autoimmune diseases (such as thyroiditis, gastritis, insulitis, sialoadenitis, adrenalitis, oophoritis, glomerulonephritis, and polyarthritis); some mice also developed graft-vs-host-like wasting disease. Reconstitution of CD4+CD25+ cells within a limited period after transfer of CD4+CD25- cells prevented these autoimmune developments in a dose-dependent fashion, whereas the reconstitution several days later, or inoculation of an equivalent dose of CD8+ cells, was far less efficient for the prevention. When nu/nu mice were transplanted with allogeneic skins or immunized with xenogeneic proteins at the time of CD25- cell inoculation, they showed significantly heightened immune responses to the skins or proteins, and reconstitution of CD4+CD25+ cells normalized the responses. Taken together, these results indicate that CD4+CD25+ cells contribute to maintaining self-tolerance by down-regulating immune response to self and non-self Ags in an Ag-nonspecific manner, presumably at the T cell activation stage; elimination/reduction of CD4+CD25+ cells relieves this general suppression, thereby not only enhancing immune responses to non-self Ags, but also eliciting autoimmune responses to certain self-Ags. Abnormality of this T cell-mediated mechanism of peripheral tolerance can be a possible cause of various autoimmune diseases.

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Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases.

Attachment--and loss.

The limited in vitro lifetime of human diploid cell strains

For centuries knowledge meant proven knowledge — proven either by the power of the intellect or by the evidence of the senses. Wisdom and intellectual integrity demanded that one must desist from unproven utterances and minimize, even in thought, the gap between speculation and established knowledge. The proving power of the intellect or the senses was questioned by the sceptics more than two thousand years ago; but they were browbeaten into confusion by the glory of Newtonian physics. Einstein’s results again turned the tables and now very few philosophers or scientists still think that scientific knowledge is, or can be, proven knowledge. But few realize that with this the whole classical structure of intellectual values falls in ruins and has to be replaced: one cannot simply water down the ideal of proven truth - as some logical empiricists do — to the ideal of’probable truth’1 or — as some sociologists of knowledge do — to ‘truth by [changing] consensus’.2

Falsification and the Methodology of Scientific Research Programmes

The experiments to be described in this article provide a solution—at present only a ‘laboratory’ solution—of the problem of how to make tissue homografts immunologically acceptable to hosts which would normally react against them. The principle underlying the experiments may be expressed in the following terms: that mammals and birds never develop, or develop to only a limited degree, the power to react immunologically against foreign homologous tissue cells to which they have been exposed sufficiently early in foetal life. If, for example, a foetal mouse of one inbred strain (say, CBA) is inoculated in utero with a suspension of living cells from an adult mouse of another strain (say, A), then, when it grows up, the CBA mouse will be found to be partly or completely tolerant of skin grafts transplanted from any mouse belonging to the strain of the original donor. This phenomenon is the exact inverse of ‘actively acquired immunity’, and we therefore propose to describe it as ‘actively acquired tolerance’. The distinction between the two phenomena may be made evident in the following way. If a normal adult CBA mouse is inoculated with living cells or grafted with skin from an A-line donor, the grafted tissue is destroyed within twelve days (see below). The effect of this first presentation of foreign tissue in adult life is to confer ‘immunity’, that is, to increase the host’s resistance to grafts which may be transplanted on some later occasion from the same donor or from some other member of the donor’s strain. But if the first presentation of foreign cells takes place in foetal life, it has just the opposite effect: resistance to a graft transplanted on some later occasion, so far from being heightened, is abolished or at least reduced. Over some period of its early life, therefore, the pattern of the host’s response to foreign tissue cells is turned completely upside down. In mice, it will be seen, this inversion takes place in the neighbourhood of birth, for there is a certain ‘null’ period thereabouts when the inoculation of foreign tissue confers neither tolerance nor heightened resistance—when, in fact, a ‘test graft’ transplanted in adult life to ascertain the host’s degree of immunity is found to survive for the same length of time as if the host had received no treatment at all.

Actively acquired tolerance of foreign cells.

An Unsolved problem of biology

Methods are described for the execution of free skin grafts in rabbits, guinea-pigs and mice. Much of the work in which use has been made of the techniques described above has been generously supported over a period of years by the Department of Plastic Surgery, University of Oxford (Prof. T. Pomfret Kilner, F.R.C.S.).

The Technique of Free Skin Grafting in Mammals

The behaviour and fate of skin autografts and skin homografts in rabbits: A report to the War Wounds Committee of the Medical Research Council

'Actively acquired tolerance' introduces into immunology the concept of a specific inhibition of response. Tolerance of a tissue homograft comes about when an animal has been confronted in foetal l...

Peter Medawar

Papers

Actively acquired tolerance of foreign cells.

An Unsolved problem of biology

The Technique of Free Skin Grafting in Mammals

The behaviour and fate of skin autografts and skin homografts in rabbits: A report to the War Wounds Committee of the Medical Research Council

Quantitative Studies on Tissue Transplantation Immunity. III. Actively Acquired Tolerance