Publisher Summary This chapter discusses the cytotoxic effects of lymphoid cells in vitro. The chapter discusses the complex problem of different types of cytotoxic effects of lymphoid cells. These outstanding workers in the field have managed to present a cohesive picture of the various effects on the target cells. The role of “nonspecific” factors is particularly well clarified. The interrelationships among contact lysis, release of pharmacologically active substances, and the terminal components of the complement system are given in the chapter for special consideration. In an in vitro model, it is shown that lymphoid cells from sensitized donors destroy tissue culture cells carrying the antigen to which the cell donor is sensitized. This type of cytolytic reactions is encountered in a great variety of immune situations, comprising all those mentioned in the chapter. The cell that initiates in vitro cytotoxic reaction is assumed to be the sensitized lymphocyte, equipped with its own recognition sites for antigen on the cells that are destroyed. Although this may be true in many situations, it now seems clear that “normal” lymphoid cells can become cytotoxic to other cells by a variety of pathways. The study of the various pathways by which lymphoid cells can become cytotoxic has been helpful for the understanding of effector role of these cells in cell-destructive reactions in general.

Cytotoxic effects of lymphoid cells in vitro.

Rabbit lymphocytes may be stimulated in vitro with specific antiallotype sera to transform into "blast" cells and to synthesize DNA. This transformation only occurs when the donor cells are obtained from a rabbit having a given gamma-globulin allotype (As4) and these cells are cultured in the presence of an antiserum prepared against the given allotype (As4). Heterologous (sheep, goat, and guinea pig) anti-rabbit gamma-globulin sera also induce significant blast transformation and DNA synthesis in rabbit lymphocytes. Allotypic transformation and DNA synthesis are due to 7S antiallotype antibodies and do not require complement. The degree of transformation and rate of DNA synthesis is related to the concentration of antibody. Incubation of the appropriate cells with the antiallotype antibody for as short a time as 15 minutes results in a significant degree of "blast" transformation, indicating that the recognition of the antiallotype specificity in the cells and stimulation of the cellular changes leading to eventual transformation is rapid. The activity of the antiallotype sera as measured by transforming or haemagglutinating capacity, may be absorbed by lymphocytes of the appropriate allotype, but is not absorbed by lymphocytes from a donor rabbit not having the allotype to which the antiserum is directed. Transformation does not occur with mixtures of lymphocytes from different rabbits even if 1 donor is immunized against an allotype present in the other donor. Peripheral rabbit lymphocytes can also be induced to undergo "blast transformation" in vitro by phytohaemagglutinin and staphylococcal filtrate. The lack of demonstrable leucoagglutinins in staphylococcal filtrate and antiallotype serum indicates that agglutination is not a necessary prerequisite to the induction of blast transformation.

/pdf/studies-on-rabbit-lymphocytes-in-vitro-i-stimulation-of-32nz7a83ue.pdf

Studies on rabbit lymphocytes in vitro. i. stimulation of blast transformation with an antiallotype serum

The large pyroninophilic cells that arise from small lymphocytes in graft-versus host reactions were observed to resemble morphologically the cells that appear in regional lymphoid tissue during the reaction against homo, grafts of skin and during antibody formation. This resemblance, together with the demonstration that the small lymphocyte is immunoiogically competent, suggest that primary immune responses in general may be initiated by the interaction of antigens with small lymphocytes. This possibility was investigated in two groups of experiments. The identity of the cell-type formed by the dividing large pyroninophilic cells was determined by studying the fate of rat small lymphocytes in the spleen of lethally irradiated mice. The significance of these experiments for the homograft reaction was then examined. Rats were rendered immunologicaliy unresponsive to skin homografts, sheep erythrocytes, and tetanus toxoid. Suspensions of small lymphocytes from other rats were then injected intravenously to test their ability to abolish the unresponsive states. In each experiment the proportion of small lymphocytes in the inocuium was estimated in smears from a count on 2,000 cells. The proportion ranged from 99.4 to more than 99.95%. Results indicate that small lymphocytes are involved in the inductive phase of antibody formation. It is postulated thatmore » small lymphocytes interact with antigen, become fixed in lymphoid tissue, and give rise to a dividing cell line that generates the cells that eventually synthesize antibody. It is emphasized that this has not yet been unequivocally demonstrated. (C.H.)« less

Initiation of Immune Responses by Small Lymphocytes

Publisher Summary This chapter discusses the immunobiology of mammalian reproduction. Mechanisms of the type that characterize immunological phenomena have been postulated by several authorities as indispensible components of two key events in the reproductive process: (1) a highly selective antigen–antibody–like stereochemical interaction between highly specific components of the plasma membranes of eggs and sperms which provides a plausible basis for the tissue specificity and species specificity of fertilization and (2) a local inflammatory response with which mononuclear leukocytic cells appear to be intimately associated, if not causally related, in the endometrium, having some features in common with a local delayed hypersensitivity reaction, at the site of implantation and which may be essential for nidation. The fact that spermatozoa have long been shown to possess cytospecific antigens, in addition to their recently established expression of transplantation antigens, suggests one kind of maternal sensitization that might under natural and/ or experimental conditions interfere with the early stage of the reproductive process. Sensitization to various components of seminal plasma has also long been entertained as another possible immunological complication of fertility.

Immunobiology of Mammalian Reproduction

Embryo chicks (Simonsen, 1957), newborn mice (Billingham and Brent, 1959) and newborn rats (Billingham et al., 1960) may become the victims of a lethal wasting disease if they are injected with a suspension of cells prepared from adult homologous lymphoid tissue. A similar disease may be produced in an adult F1 hybrid mouse by an injection of lymphoid cells from one of its inbred parents, particularly if the host is lightly X-irradiated before the injection (Cole and Ellis, 1958; Kaplan and Rosston, 1959). I t is generally held that these diseases are the result of an immunological attack by the lymphoid cells of the graft against the tissues of the host. The host submits to the attack because for reasons of immunological immaturity or genetic constitution it is unable to destroy the graft. The immunogenetic situations in which graftagainst-host reactions occur suggest that it is the transplantation antigens of the host which stimulate the lymphoid cells of the graft but it is possible that other antigens may also be involved. If it is accepted that a graft-against-host reaction results from the interaction of certain cells in a lymphoid graft with the tissue antigens of the host, then the exact identity and fate of these cells is of considerable interest. They must be able, by themselves, to initiate an immunological response following their first contact with antigen, and a study of their fate might help to define the cellular changes which accompany this event. The ability of leukocytes from the blood and cells from lymph nodes to cause graft-against-host reactions suggests that a blood lymphocyte may be the effective cell (Billingham and Brent, 1959). This suggestion is confirmed by the demonstration that homologous thoracic duct cells can cause runt disease in rats (Anderson et al., 1960; Billingham et al., 1960). It. now remains to be determined whether it is the small lymphocytes, the large lymphocytes, or both types of cell in combination which are responsible for inducing the disease; thoracic duct lymph from normal rats contains no other cell type (Gowans, 1957). This paper contains an account of a lethal graft-against-host reaction which occurs when parental strain thoracic duct cells are injected into normal F1 hybrid rats. There were two aims in this investigation: (1) to determine which cells in the lymph were responsible for initiating the reaction; (2) to determine the fate of the initiating cells during the earliest stages of the reaction. The first aim was realized by examining the effect on F1 recipients of inocula which contained varying proportions of large to small lymphocytes; the second, by an autoradiographic study of the fate of parental large and small lymphocytes which had been labeled radioactively and then injected into the F1 hosts. A preliminary account of some of this work has already appeared (Gowans et al., 1961). * Member of External Staff, Medical Research Council.

The fate of parental strain small lymphocytes in F1 hybrid rats.

Quantitative studies on the induction of tolerance of skin homografts and on runt disease in neonatal rats.

The conflicting interpretations of the mechanism of tissue homograft rejection are based principally on the results of passive transfer experiments. For example, in the case of skin and other solid tissue homografts, repeated failures of attempts to transfer immunity with i s o a n t i s e r ~ r n ~ ~ ~ * on the one hand, and the relative ease with which it can be transferred adoptively with “sensitized” lymphoid cells’. 2 * 6a* on the other, provide strong evidence that the rejection of homografts of these types is a cell-mediated immunological phenomenon analogous to delayed-type hypersensitivity reactions! Nevertheless it cannot be denied that there are experimental conditions in which skin homograft immunity appears to be transferable by humoral agents:-” and these findings favor plasma-borne antibodies as mediators of homograft destruction. The present paper reports a situation in which immunity to orthotopic skin homografts is readily transferable with isoimmune serum. The extent to which the conditions of the experiments parallel the homograft reaction in actively responding hosts has been considered, however, and it remains difficult to decide if the humoral factors responsible for the transfer are really involved in normal graft rejection, or if their evocation is merely an ancillary phenomenon. Moreover it will be shown that the methods used to obtain the serum transfer with one particular donor-recipient strain combination are unsuccessful when applied to others.

Passive transfer of immunity to skin homografts in rats.

The principle that rats may be rendered tolerant of homologous tissue grafts following preor early postnatal exposure to living homologous cells is now well established (Woodruff and Simpson, 1955; Billingham et al., 1956; Lengerovh, 1957; Egdahl et al., 1958). It is also known that “runt” disease (Billingham, 1958; Billingham and Brent, 1959) not infrequently occurs in this animal, as in the mouse, if the inoculum employed to induce tolerance contains a high proportion of immunologically competent cells (Woodruff and Sparrow, 1957; Egdahl et al., 1958; Billingham and Silvers, 1959~). Their size renders rats much more convenient subjects than mice for detailed analyses of quantitative aspects of the induction of tolerance and the pathogenesis of runt disease: for example, large amounts of bone marrow can be obtained from a single animal, thoracic ducts of rats can be cannulated to obtain almost pure lymphocytes in considerable quantities, and daily samples of blood may be taken from very young animals for exact hematological analyses without prejudicing their well-being. Unfortunately, however, these advantages hitherto have been more than counterbalanced by the lack of the necessary isogenic strains, so that present knowledge derives largely from work conducted on mice. The recent availability of 2 highly inbred strains of rat, the Lewis (albino phenotype) and the B.N. (chocolate), differing so widely with respect to their origins that the degree of genetic disparity between them is likely to be very great (Billingham and Silvers, 19593), has terminated this unsatisfactory state of affairs and thus facilitated the investigations that form the subject matter of this paper. Destruction of skin homografts exchanged between adult members of the B.N. and Lewis strains is invariably complete within 13 days, and the median survival time (MST) of Lewis

Quantitative studies on the induction of tolerance of homologous tissues and on runt disease in the rat.

Transplantation immunity in the newborn rat. I. The response at birth and maturation of response capacity.

Transplantation immunity in the newborn rat II. The transfer of immunity to newborn recipients

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

David Steinmuller

Author Tools

Chat about Author