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  1. Article ; Online: Rationalizing the path to a universal graft recipient.

    Cohn, Melvin

    Immunologic research

    2018  Volume 66, Issue 3, Page(s) 332–335

    Abstract: The goal of this essay is to take the reader through the logic that would predict universal graft acceptance. The story begins with what we learned from an experiment performed 65 years ago and develops that information in greater depth. The pathway of ... ...

    Abstract The goal of this essay is to take the reader through the logic that would predict universal graft acceptance. The story begins with what we learned from an experiment performed 65 years ago and develops that information in greater depth. The pathway of the analysis leads to the conclusion that controlling the immune system at the level of the T-helper would be the best way to approach a general solution to the problem of graft acceptance.
    MeSH term(s) Animals ; Graft Rejection/immunology ; Graft Survival/immunology ; Graft vs Host Disease/immunology ; Humans ; Immune System/cytology ; Immune System/immunology ; Signal Transduction/immunology ; T-Lymphocytes, Helper-Inducer/immunology ; Transplantation Immunology/immunology
    Language English
    Publishing date 2018-05-22
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 632857-x
    ISSN 1559-0755 ; 0257-277X
    ISSN (online) 1559-0755
    ISSN 0257-277X
    DOI 10.1007/s12026-018-9001-z
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  2. Article ; Online: Exploring the elements for a successful immune offense against cancer.

    Cohn, Melvin

    Experimental and molecular pathology

    2018  Volume 105, Issue 2, Page(s) 213–215

    Abstract: A successful immune attack on a tumor requires two elements. First, a nonself (NS) epitope that can act as an effective target must be expressed uniquely and uniformly on the tumor. Second, the immune system must be induced to produce an appropriate ... ...

    Abstract A successful immune attack on a tumor requires two elements. First, a nonself (NS) epitope that can act as an effective target must be expressed uniquely and uniformly on the tumor. Second, the immune system must be induced to produce an appropriate ridding effector activity specific for the cell expressing that de novo displayed NS-epitope. Today, the major effort is directed toward nonspecifically increasing the horsepower of the immune system by relieving suppressive and resistance factors using checkpoint blockade. This is coupled to the hope that the cancer will display a unique nonself determinant and that tolerance to Self (S) will not be abrogated. Here, these two elements will be explored in order to see what a more defined approach to the immune system treatment of cancer entails. While a Hail Mary approach may, in the end, be our only alternative, defining the elements of a solution, attainable or not, based on basic immunology, can only be salutary.
    MeSH term(s) Animals ; Epitopes/immunology ; Humans ; Immune Tolerance/physiology ; Immunity/genetics ; Immunity/physiology ; Neoplasms/immunology ; T-Lymphocytes, Helper-Inducer/immunology
    Chemical Substances Epitopes
    Language English
    Publishing date 2018-08-18
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 207655-x
    ISSN 1096-0945 ; 0014-4800
    ISSN (online) 1096-0945
    ISSN 0014-4800
    DOI 10.1016/j.yexmp.2018.08.006
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  3. Article ; Online: The real "danger" lies in the failure to confront fundamentals.

    Cohn, Melvin

    Scandinavian journal of immunology

    2018  Volume 88, Issue 6, Page(s) e12726

    Abstract: Can we formulate a framework that would provide an agreed upon basis for discussions of immune behaviour? An attempt to do this is, in the end, the main goal of this essay. If you tell a physicist that you have invented a perpetual motion machine, he ... ...

    Abstract Can we formulate a framework that would provide an agreed upon basis for discussions of immune behaviour? An attempt to do this is, in the end, the main goal of this essay. If you tell a physicist that you have invented a perpetual motion machine, he would not spend any time trying to reveal the flaw. Rather, he would shrug you off because in his framework, such a machine is an impossibility. However, immunologists lacking an agreed upon, preferably default, framework spend their time chasing into dead-end alleys or take refuge in descriptive empiricism. This will be illustrated using Danger theory, which ignores fundamentals to generate a framework believed to obviate the need for a Self (S)-Nonself (NS) discrimination and which is claimed to be bolstered with monogamous data (observation married to a single explanation). The arguments presented here apply to all NS-marker theories (pathogenicity, discontinuity, localization, danger, etc.).
    MeSH term(s) Alarmins/immunology ; Allergy and Immunology ; Animals ; Autoantigens/immunology ; Epitopes/immunology ; Humans ; Immunity ; Models, Immunological ; Receptors, Pattern Recognition/immunology ; Self Tolerance
    Chemical Substances Alarmins ; Autoantigens ; Epitopes ; Receptors, Pattern Recognition
    Language English
    Publishing date 2018-11-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 120476-2
    ISSN 1365-3083 ; 0300-9475
    ISSN (online) 1365-3083
    ISSN 0300-9475
    DOI 10.1111/sji.12726
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  4. Article ; Online: Core principles characterizing immune function.

    Cohn, Melvin

    European journal of immunology

    2017  Volume 47, Issue 1, Page(s) 35–40

    Abstract: The immune system is an anticipatory mechanism designed by evolution to protect the individual against noxious agents and harmful cellular debris. In order to recognize substances that it has never encountered, the immune system somatically generates an ... ...

    Abstract The immune system is an anticipatory mechanism designed by evolution to protect the individual against noxious agents and harmful cellular debris. In order to recognize substances that it has never encountered, the immune system somatically generates an appropriately sized random (with respect to self and nonself [NS]) recognitive repertoire that is coupled to a biodestructive and ridding output. Consequently, a Self-NS discrimination is required in order to avoid autoimmunity. This essay is an attempt to highlight the core principles upon which this anticipatory mechanism depends in order to function.
    MeSH term(s) Animals ; Humans ; Immune System/physiology
    Language English
    Publishing date 2017-01
    Publishing country Germany
    Document type Letter
    ZDB-ID 120108-6
    ISSN 1521-4141 ; 0014-2980
    ISSN (online) 1521-4141
    ISSN 0014-2980
    DOI 10.1002/eji.201646706
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  5. Article ; Online: History of the antibody workshops.

    Cohn, Melvin

    Immunologic research

    2017  Volume 66, Issue 1, Page(s) 1–5

    Abstract: At a critical period in the history of contemporary immunology, a handful of biochemists and fringe immunologists formed a group known as the Antibody Workshop. They had a major impact on the field by attracting molecular biologists who worked to reduce ... ...

    Abstract At a critical period in the history of contemporary immunology, a handful of biochemists and fringe immunologists formed a group known as the Antibody Workshop. They had a major impact on the field by attracting molecular biologists who worked to reduce the study of cellular and organ level immunology to the molecular level. This had a dramatic effect on the field both conceptually and practically by providing the targets for clinical manipulation. The story of the origin and development of this group over time is recounted here.
    MeSH term(s) Allergy and Immunology/education ; Allergy and Immunology/history ; Animals ; Antibodies/immunology ; Autoimmunity ; Biochemistry ; Consensus Development Conferences as Topic ; History, 20th Century ; Humans ; Lymphocytes/immunology ; Molecular Biology ; Self Tolerance ; United States
    Chemical Substances Antibodies
    Language English
    Publishing date 2017-10-20
    Publishing country United States
    Document type Historical Article ; Journal Article
    ZDB-ID 632857-x
    ISSN 1559-0755 ; 0257-277X
    ISSN (online) 1559-0755
    ISSN 0257-277X
    DOI 10.1007/s12026-017-8964-5
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  6. Article ; Online: Signaling interactions predicted by the Tritope model of the TCR.

    Cohn, Melvin

    Immunologic research

    2017  Volume 65, Issue 5, Page(s) 977–981

    Abstract: As the data accumulates, it becomes obvious that the Standard Model of TCR structure-function relationships is in jeopardy. The proposed Tritope model has become more meaningful and, in any case, is richer in prediction and explanation. This is ... ...

    Abstract As the data accumulates, it becomes obvious that the Standard Model of TCR structure-function relationships is in jeopardy. The proposed Tritope model has become more meaningful and, in any case, is richer in prediction and explanation. This is illustrated here by using the signaling interactions of the TCR as examples. An unsuspected signaling pathway for positive selection, and for alloreactivity, is predicted. Further, crucial data needed to elucidate the structural elements that distinguish signaling for restrictive- versus allo-reactivity are identified.
    MeSH term(s) Animals ; Antigen Presentation ; Clonal Selection, Antigen-Mediated ; Histocompatibility Antigens/immunology ; Histocompatibility Antigens/metabolism ; Humans ; Isoantigens/immunology ; Models, Immunological ; Receptors, Antigen, T-Cell/metabolism ; Signal Transduction ; T-Lymphocytes/immunology
    Chemical Substances Histocompatibility Antigens ; Isoantigens ; Receptors, Antigen, T-Cell
    Language English
    Publishing date 2017
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 632857-x
    ISSN 1559-0755 ; 0257-277X
    ISSN (online) 1559-0755
    ISSN 0257-277X
    DOI 10.1007/s12026-017-8941-z
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  7. Article ; Online: Learning from a contemporary history of immunology.

    Cohn, Melvin

    Immunologic research

    2017  Volume 65, Issue 3, Page(s) 573–591

    Abstract: This essay is a selected aspect of the history of contemporary immunology seen from a "what can we learn" point of view. It is limited to the ideas and experiments from which we might draw a take-home message. The emphasis is on the convoluted pathway ... ...

    Abstract This essay is a selected aspect of the history of contemporary immunology seen from a "what can we learn" point of view. It is limited to the ideas and experiments from which we might draw a take-home message. The emphasis is on the convoluted pathway that was actually used by immunologists to arrive at understanding compared to the direct pathway that could have been used given the knowledge at that time. It takes the reader through the instructionist era of the 1940s to the present by stressing the elements of thinking most conducive to the arrival at a default understanding of the intact immune system. It is a personalized account because the author participated directly in the debates that led eventually to agreed-upon or default conceptualizations. Given this, a peek at the future is attempted as a test of the validity of a Cartesian or reductionist approach to arriving at simplification of complexity and at the maximizing of generalization. A reasoned guess (i.e., a theory) is the only way we have to understand the world around us.
    Language English
    Publishing date 2017-06
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 632857-x
    ISSN 1559-0755 ; 0257-277X
    ISSN (online) 1559-0755
    ISSN 0257-277X
    DOI 10.1007/s12026-017-8908-0
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  8. Article ; Online: An observation that illustrates most T cell receptor structure-function relationships.

    Cohn, Melvin

    Immunologic research

    2017  Volume 65, Issue 6, Page(s) 1095–1098

    Abstract: The Standard model of the T cell receptor (TCR) structure-function relationships is based on an analogy with the B cell receptor. Here a single observation is analyzed to show why this appears to be untenable. The Standard model cannot account for allele- ...

    Abstract The Standard model of the T cell receptor (TCR) structure-function relationships is based on an analogy with the B cell receptor. Here a single observation is analyzed to show why this appears to be untenable. The Standard model cannot account for allele-specific recognition of theMHC-encoded presenter of peptide (R) by the TCR nor can it adequately explain alloreactivity. The competing framework is based on the assumptions that (1) single V-domains recognize the alleles of R, (2) restrictive reactivity is peptide specific, whereas alloreactivity is peptide unspecific, and (3) the TCR is born in two conformations, which display reciprocal behaviors (see text). In any case, whatever position one takes regarding these two models, competing conceptualizations are of crucial value in guiding experimentation, not to mention creative thinking.
    MeSH term(s) Alleles ; Allosteric Regulation ; Animals ; Antigen Presentation ; Histocompatibility Antigens/genetics ; Histocompatibility Antigens/metabolism ; Humans ; Isoantigens/immunology ; Lymphocyte Activation ; Models, Immunological ; Peptides/immunology ; Peptides/metabolism ; Protein Conformation ; Receptors, Antigen, B-Cell/metabolism ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/metabolism ; Structure-Activity Relationship ; T-Lymphocytes/immunology
    Chemical Substances Histocompatibility Antigens ; Isoantigens ; Peptides ; Receptors, Antigen, B-Cell ; Receptors, Antigen, T-Cell
    Language English
    Publishing date 2017
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 632857-x
    ISSN 1559-0755 ; 0257-277X
    ISSN (online) 1559-0755
    ISSN 0257-277X
    DOI 10.1007/s12026-017-8958-3
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  9. Article ; Online: Dissecting the two models of TCR structure-function relationships.

    Cohn, Melvin

    Immunologic research

    2016  Volume 64, Issue 4, Page(s) 795–803

    Abstract: There are only two comprehensive models attempting to account for the TCR structure-function relationships, referred to as the Standard or Centric model (Model I) and the Tritope model (Model II). This essay is written to analyze comparatively the two ... ...

    Abstract There are only two comprehensive models attempting to account for the TCR structure-function relationships, referred to as the Standard or Centric model (Model I) and the Tritope model (Model II). This essay is written to analyze comparatively the two formulations of restrictive reactivity, stressing in particular the logic of each. Model I is essentially built on an analogy between the TCR and the BCR. Given a TCR with only one combining site (paratope), restrictive recognition requires that its ligand be viewed as a composite structure between the peptide and restricting element. It is this relationship that entrains a set of correlates that makes Model I untenable. Model II is predicated on the postulate that the recognition of the allele-specific determinants expressed by MHC-encoded restricting elements (R) is germline encoded and selected, whereas the recognition of peptide (P) is somatically encoded and selected. These selective pressures must operate on definable structures and this, in turn, necessitates a multiply recognitive T cell antigen receptor (TCR) with independent anti-R and anti-P paratopes that function coherently to signal restrictive reactivity. The consequences of this "two repertoire" postulate give us a concept of TCR structure quite distinct from that at present generally accepted, as well as a surprising relationship between numbers of functional TCR V gene segments and allele-specific determinants in the species. In the end, both models must deal with the relationship between the epitope-paratope interaction(s) and the signals to the T cell necessary for its differentiation and function.
    Language English
    Publishing date 2016-08
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 632857-x
    ISSN 1559-0755 ; 0257-277X
    ISSN (online) 1559-0755
    ISSN 0257-277X
    DOI 10.1007/s12026-016-8796-8
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  10. Article ; Online: Two unresolved problems facing models of the Self-Nonself discrimination.

    Cohn, Melvin

    Journal of theoretical biology

    2015  Volume 387, Page(s) 31–38

    Abstract: Although the Associative (linked) Recognition of Antigen (ARA) model for a Self (S)-Nonself (NS) discrimination, now over 50 years old, is built on a solid conceptual and experimental base, two unsettled questions remain. In examining these questions, ... ...

    Abstract Although the Associative (linked) Recognition of Antigen (ARA) model for a Self (S)-Nonself (NS) discrimination, now over 50 years old, is built on a solid conceptual and experimental base, two unsettled questions remain. In examining these questions, unanticipated aspects of the ARA Model itself had to be reconsidered. This essay spells out these problems and suggests possible solutions.
    MeSH term(s) Antigen-Presenting Cells/immunology ; Autoantigens/immunology ; Models, Immunological ; Receptors, Antigen, T-Cell/metabolism
    Chemical Substances Autoantigens ; Receptors, Antigen, T-Cell
    Language English
    Publishing date 2015-12-21
    Publishing country England
    Document type Journal Article
    ZDB-ID 2972-5
    ISSN 1095-8541 ; 0022-5193
    ISSN (online) 1095-8541
    ISSN 0022-5193
    DOI 10.1016/j.jtbi.2015.09.021
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