Clonal Vs. Negative Selection in Artificial Immune Systems
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Ch. 43 the Immune System
Ch. 43 The Immune System 1 Essential Questions: How does our immunity arise? How does our immune system work? 2 Overview of immunity: Two kinds of defense: A. innate immunity present at time of birth before exposed to pathogens nonspecific responses, broad in range skin and mucous membranes internal cellular and chemical defenses that get through skin macrophages, phagocytic cells B. acquired immunity (adaptive immunity)develops after exposure to specific microbes, abnormal body cells, foreign substances or toxins highly specific lymphocytes produce antibodies or directly destroy cells 3 Overview of Immune System nonspecific Specific 4 I. Innate immunity Nonspecific defenses A. First line of defense: skin, mucous membranes skin protects against chemical, mechanical, pathogenic, UV light damage mucous membranes line digestive, respiratory, and genitourinary tracts prevent pathogens by trapping in mucus *breaks in skin or mucous membranes = entryway for pathogen 5 secretions of skin also protect against microbes sebaceous and sweat glands keep pH at 35 stomach also secretes HCl (Hepatitis A virus can get past this) produce antimicrobial proteins (lysozyme) ex. in tears http://vrc.belfastinstitute.ac.uk/resources/skin/skin.htm 6 B. Second line of defense internal cellular and chemical defenses (still nonspecific) phagocytes produce antimicrobial proteins and initiate inflammation (helps limit spread of microbes) bind to receptor sites on microbe, then engulfs microbe, which fused with lysosome nitric oxide and poisons in lysosome can poison microbe lysozyme and other enzymes degrade the microbe *some bacteria have capsule that prevents attachment *some bacteria are resistant to lysozyme macrophages 7 Cellular Innate defenses Tolllike receptor (TLR) recognize fragments of molecules characteristic of a set of pathogens [Ex. -
The RAG Recombinase Dictates Functional Heterogeneity and Cellular Fitness in Natural Killer Cells
The RAG Recombinase Dictates Functional Heterogeneity and Cellular Fitness in Natural Killer Cells Jenny M. Karo,1 David G. Schatz,2 and Joseph C. Sun1,* 1Immunology Program and Gerstner Sloan Kettering Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA 2Department of Immunobiology and the Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA *Correspondence: [email protected] http://dx.doi.org/10.1016/j.cell.2014.08.026 SUMMARY completely absent (Mombaerts et al., 1992; Shinkai et al., 1992). There is as yet no evidence that RAG plays a physiological The emergence of recombination-activating genes role in any cell type other than B and T lymphocytes or in any pro- (RAGs) in jawed vertebrates endowed adaptive cess other than V(D)J recombination. immune cells with the ability to assemble a diverse Although NK cells have long been classified as a component set of antigen receptor genes. In contrast, innate of the innate immune system, recent evidence suggests that lymphocytes, such as natural killer (NK) cells, are this cell type possesses traits attributable to adaptive immunity not believed to require RAGs. Here, we report that (Sun and Lanier, 2011). These characteristics include ‘‘educa- tion’’ mechanisms to ensure self-tolerance during NK cell devel- NK cells unable to express RAGs or RAG endonu- opment and clonal-like expansion of antigen-specific NK clease activity during ontogeny exhibit a cell-intrinsic cells during viral infection, followed by the ability to generate hyperresponsiveness but a diminished capacity long-lived ‘‘memory’’ NK cells. -
LECTURE 05 Acquired Immunity and Clonal Selection
LECTURE: 05 Title: ACQUIRED "ADAPTIVE" IMMUNITY & CLONAL SELECTION THEROY LEARNING OBJECTIVES: The student should be able to: • Recognize that, acquired or adaptive immunity is a specific immunity. • Explain the mechanism of development of the specific immunity. • Enumerate the components of the specific immunity such as A. Primary immune response. B. Secondary immune response • Explain the different phases that are included in the primary and secondary immune responses such as: A. The induction phase. B. Exponential phase. C. Steady phase. D. Decline phase. • Compare between the phases of the primary and secondary immune responses. • Determine the type of the immunoglobulins involved in each phase. • Determine which immunoglobulin is induced first and, that last longer. • Enumerate the characteristics of the specific immunity such as: A. The ability to distinguish self from non-self. B. Specificity. C. Immunological memory. • Explain naturally and artificially acquired immunity (passive, and active). • Explain the two interrelated and independent mechanisms of the specific immune response such as : A. Humoral immunity. B. Cell-mediated (cellular) immunity. • Recognize that, the specific immunity is not always protective, for example; sometimes it causes allergies (hay fever), or it may be directed against one of the body’s own constituents, resulting in autoimmunity (thyroditis). LECTURE REFRENCE: 1. TEXTBOOK: ROITT, BROSTOFF, MALE IMMUNOLOGY. 6th edition. Chapter 2. pp. 15-31 2. TEXTBOOK: ABUL K. ABBAS. ANDREW H. LICHTMAN. CELLULAR AND MOLECULAR IMMUNOLOGY. 5TH EDITION. Chapter 1. pg 3-12. 1 ACQUIRED (SPECIFIC) IMMUNITY INTRODUCTION Adaptive immunity is created after an interaction of lymphocytes with particular foreign substances which are recognized specifically by those lymphocytes. -
Med-Pathway Zoom Workshop
MCAT Immunology Dr. Phillip Carpenter medpathwaymcat Med-pathway AAMC MCAT Content Outline: Immunology Category 1A: Structure/Function of Proteins/AA Immune System Category 3B: Organ Systems Innate vs. Adaptive Immunity T and B Lymphocytes Macrophages & Phagocytes Tissue-Bone marrow, Spleen, Thymus, Lymph nodes Antigen and Antibody Antigen Presentation Clonal Selection Antigen-Antibody recognition Structure of antibody molecule Self vs. Non-self, Autoimmune Diseases Major Histocompatibility Complex Lab Techniques: ELISA & Western Blotting Hematopoiesis Creates Immune Cells Self vs. Non-self Innate vs Adaptive Innate Immunity Physical Barriers: Skin, mucous membranes, pH Inflammatory mediators: Complement, Cytokines, Prostaglandins Cellular Components: Phagocytes-Neutrophils, Eosinophils, Basophils, Mast Cells Antigen Presenting Cells-Monocytes, Macrophages, Dendritic Cells Adaptive (Acquired) Immunity Composed of B and T lymphocytes: Activated by Innate Immunity B cells: Express B cell receptor and secrete antibodies as plasma cells T cells: Mature in thymus, express TCR surface receptor; Activated by Antigen Presenting Cells (APCs) Direct Immune response (The Ringleaders of immune system) Major Lymphoid Organs TYPE SITE FUNCTION Fetal production of Liver 1° lymphoid cells Hematopoietic production of 1° Bone marrow myeloid and lymphoid cells Receives bone marrow T 1° Thymus cells; site where self is selected from non-self Lymph nodes 2° Sites of antigen activation Spleen of lymphocytes; clearance Macrophages (Sentinel Cells) Pattern Recognition -
Artificial Immune System Based Intrusion Detection: Innate Immunity
Artificial Immune System Based Intrusion Detection: Innate Immunity using an Unsupervised Learning Approach Farhoud Hosseinpour, Payam Vahdani Amoli, Fahimeh Farahnakian, Juha Plosila, Timo Hämäläinen Artificial Immune System Based Intrusion Detection: Innate Immunity using an Unsupervised Learning Approach 1Farhoud Hosseinpour, 2Payam Vahdani Amoli, 3Fahimeh Farahnakian, 4Juha Plosila and 5 Timo Hämäläinen 1 Corresponding Author, 3 and 4 Department of Information Technology, University of Turku, Finland. {farhos;fahfar;juplos}@utu.fi 2 and 5Faculty of Information Technology, University of Jyväskylä, 40100, Jyväskylä, Finland. 2 [email protected] 5 [email protected] Abstract This paper presents an intrusion detection system architecture based on the artificial immune system concept. In this architecture, an innate immune mechanism through unsupervised machine learning methods is proposed to primarily categorize network traffic to “self” and “non-self” as normal and suspicious profiles respectively. Unsupervised machine learning techniques formulate the invisible structure of unlabeled data without any prior knowledge. The novelty of this work is utilization of these methods in order to provide online and real-time training for the adaptive immune system within the artificial immune system. Different methods for unsupervised machine learning are investigated and DBSCAN (density-based spatial clustering of applications with noise) is selected to be utilized in this architecture. The adaptive immune system in our proposed architecture also takes advantage of the distributed structure, which has shown better self-improvement rate compare to centralized mode and provides primary and secondary immune response for unknown anomalies and zero-day attacks. The experimental results of proposed architecture is presented and discussed. Keywords: Distributed intrusion detection system, Artificial immune system, Innate immune system, Unsupervised learning 1. -
How Do We Evaluate Artificial Immune Systems?
How Do We Evaluate Artificial Immune Systems? Simon M. Garrett [email protected] Computational Biology Group, Department of Computer Science, University of Wales, Aberystwyth, Wales, SY23 3DB. UK Abstract The field of Artificial Immune Systems (AIS) concerns the study and development of computationally interesting abstractions of the immune system. This survey tracks the development of AIS since its inception, and then attempts to make an assessment of its usefulness, defined in terms of ‘distinctiveness’ and ‘effectiveness.’ In this paper, the standard types of AIS are examined—Negative Selection, Clonal Selection and Im- mune Networks—as well as a new breed of AIS, based on the immunological ‘danger theory.’ The paper concludes that all types of AIS largely satisfy the criteria outlined for being useful, but only two types of AIS satisfy both criteria with any certainty. Keywords Artificial immune systems, critical evaluation, negative selection, clonal selection, im- mune network models, danger theory. 1 Introduction What is an artificial immune system (AIS)? One answer is that an AIS is a model of the immune system that can be used by immunologists for explanation, experimentation and prediction activities that would be difficult or impossible in ‘wet-lab’ experiments. This is also known as ‘computational immunology.’ Another answer is that an AIS is an abstraction of one or more immunological processes. Since these processes protect us on a daily basis, from the ever-changing onslaught of biological and biochemical entities that seek to prosper at our expense, it is reasoned that they may be computa- tionally useful. It is this form of AIS—methods based on immune abstractions—that will be studied here. -
Theories of Antibodies Production
THEORIES OF ANTIBODIES PRODUCTION 1. Instructive Theories a. Direct Template Theory b. Indirect Template Theory 2. Selective Theories a. Natural Selection Theory b. Side Chain Theory c. Clonal Selection Theory d. Immune Network Theory INSTRUCTIVE THEORIES Instructive theories suggest that an immunocompetent cell is capable of synthesizing antibodies of all specificity. The antigen directs the immunocompetent cell to produce complementary antibodies. According to these theories the antigen play a central role in determining the specificity of antibody molecule. Two instructive theories are postulated as follows: Direct template theory: This theory was first postulated by Breinl and Haurowitz (1930). They suggested that a particular antigen or antigenic determinants would serve as a template against which antibodies would fold. The antibody molecule would thereby assume a configuration complementary to antigen template. This theory was further advanced as Direct Template Theory by Linus Pauling in 1940s. Indirect template theory: This theory was first postulated by Burnet and Fenner (1949). They suggested that the entry of antigenic determinants into the antibody producing cells induced a heritable change in these cells. A genocopy of the antigenic determinant was incorporated in genome of these cells and transmitted to the progeny cells. However, this theory that tried to explain specificity and secondary responses is no longer accepted. SELECTIVE THEORIES Selective theories suggest that it is not antigen, but the antibody molecule that play a central role in determining its specificity. The immune system already possess pre-formed antibodies of different specificities prior to encounter with an antigen. Three selective theories were postulated as follows: Side chain theory: This theory was proposed by Ehrlich (1898). -
A Series of Adaptive Models Inspired by the Acquired Immune System
A Series of Adaptive Models Inspired by the Acquired Immune System JASON BROWNLEE Technical Report 070227A Complex Intelligent Systems Laboratory, Centre for Information Technology Research, Faculty of Information Communication Technology, Swinburne University of Technology Melbourne, Australia [email protected] Abstract-The acquired immune system is capable of the presented series of adaptive models as a novel specialising a defence of an organism in response to the its hierarchal framework for which existing and future antigenic environment. This complex biological system possess acquired immunity inspired adaptive models may be interesting information processing features such as learning, interpreted and related. memory, and the ability to generalize. The clonal selection theory is a cornerstone of modern biology in understanding the acquired II. PRINCIPLE COMPONENTS immune system from the perspective of B-lymphocyte cells and This section lists a series of principles (operators or antibody diversity. This work presents a series of computational mechanisms) that are sufficiently low in complexity to adaptive systems inspired by features of the biological immune be analysed independently. It is expected that the system and the clonal selection theory in particular. Starting with mechanisms listed in this section may act as component basic clonal operators as principle components, models are features in larger adaptive models. Operators are presented in increasing complexity from canonical clonal assigned a notation of O# and -
Good and Bad Memory Control in Artificial Immune System
Adaptive clusters formation in an Artificial Immune System Sławomir T. Wierzchoń1,2), Urszula Kużelewska2) 1) Institute of Computer Science, Polish Academy of Sciences 01-237 Warszawa, ul. Ordona 21 2) Department of Computer Science, Białystok Technical University 15-351 Białystok, ul. Wiejska 45a e-mail: [email protected] A new version of an artificial immune system designed for automated cluster formation in training data is presented. The algorithm fully exploits self-organizing properties of the vertebrate immune system and produces stable immune network. Keywords: immune network, clonal selection, somatic mutation, cluster formation 1. Introduction From a computer science perspective the immune system is a complex, self organizing and highly distributed system which has no centralized control and which uses learning and memory when solving particular tasks. The learning process does not require negative examples and the acquired knowledge is represented in explicit form. These features attract computer scientists offering new paradigm for information processing. Particularly, Jerne’s idea of the immune network, [7], has been used to develop new tools for data analysis. The first paper devoted to this subject was that of Hunt and Cooke, [6], where the idea of the immune network with cells represented by the binary strings has been applied to the recognizing promoters in DNA sequences. Next this idea was refined by Timmis, [10], who proposed an interesting algorithm for unsupervised learning, data analysis and data visualization. Here instead of binary representation of antigens and antibodies (see Section 2 for explanation of these terms) real vectors were used. De Castro and von Zuben, [3] developed another algorithm for data analysis and data reduction that refers to the meta- dynamics typical for the so-called second generation immune networks, [11]. -
A Network Model for Clonal Differentiation and Immune Memory
ARTICLE IN PRESS Physica A 355 (2005) 408–426 www.elsevier.com/locate/physa A network model for clonal differentiation and immune memory Alexandre de Castroa,b,Ã aCentro Regional VI, Universidade Estadual do Rio Grande do Sul 90010-030, Porto Alegre, RS, Brazil bInstituto de Fı´sica, Universidade Federal do Rio Grande do Sul 91501-970, Porto Alegre, RS, Brazil Received 21 June 2004 Available online 17 May 2005 Abstract A model of bit-strings, that uses the technique of multi-spin coding, was previously used to study the time evolution of B-cell clone repertoire, in a paper by Lagreca, Almeida and Santos. In this work we extend that simplified model to include independently the role of the populations of antibodies, in the control of the immune response, producing mechanisms of differentiation and regulation in a more complete way. Although the antibodies have the same molecular shape of the B-cells receptors (BCR), they should present a different time evolution and thus should be treated separately. We have also studied a possible model for the network immune memory, suggesting a random memory regeneration, which is self-perpetuating. r 2005 Elsevier B.V. All rights reserved. Keywords: Immune memory; Antibodies evolution; Memory regenerating 1. Introduction In the last decades, due in part to the spread of the world AIDS epidemy, the scientific community started to dedicate special attention to the immunological system, responsible for the defense of the organism against microscopic invaders. ÃCorresponding author. Centro Regional VI, Universidade Estadual do Rio Grande do Sul 90010-030, Porto Alegre, RS, Brazil. -
Artificial Immune Systems
Search Methodologies: Introductory Tutorials in Optimization and Decision Support Techniques Edmund K. Burke (Editor), Graham Kendall (Editor) Chapter 13 ARTIFICIAL IMMUNE SYSTEMS U. Aickelin # and D. Dasgupta* #University of Nottingham, Nottingham NG8 1BB, UK *University of Memphis, Memphis, TN 38152, USA 1. INTRODUCTION The biological immune system is a robust, complex, adaptive system that defends the body from foreign pathogens. It is able to categorize all cells (or molecules) within the body as self-cells or non-self cells. It does this with the help of a distributed task force that has the intelligence to take action from a local and also a global perspective using its network of chemical 2 messengers for communication. There are two major branches of the immune system. The innate immune system is an unchanging mechanism that detects and destroys certain invading organisms, whilst the adaptive immune system responds to previously unknown foreign cells and builds a response to them that can remain in the body over a long period of time. This remarkable information processing biological system has caught the attention of computer science in recent years. A novel computational intelligence technique, inspired by immunology, has emerged, called Artificial Immune Systems. Several concepts from the immune have been extracted and applied for solution to real world science and engineering problems. In this tutorial, we briefly describe the immune system metaphors that are relevant to existing Artificial Immune Systems methods. We will then show illustrative real-world problems suitable for Artificial Immune Systems and give a step-by-step algorithm walkthrough for one such problem. -
Interplay of Natural Killer Cells and Their Receptors with the Adaptive Immune Response
REVIEW BRIDGING INNATE AND ADAPTIVE IMMUNITY Interplay of natural killer cells and their receptors with the adaptive immune response David H Raulet Although natural killer (NK) cells are defined as a component of the innate immune system, they exhibit certain features generally considered characteristic of the adaptive immune system. NK cells also participate directly in adaptive immune responses, mainly by interacting with dendritic cells. Such interactions can positively or negatively regulate dendritic cell activity. Reciprocally, dendritic cells regulate NK cell function. In addition, ‘NK receptors’ are frequently expressed by T cells and can directly regulate the functions of these cells. In these distinct ways, NK cells and their receptors influence the adaptive http://www.nature.com/natureimmunology immune response. Natural killer (NK) cells, a component of the innate immune system, Themes of NK cell recognition mediate cellular cytotoxicity and produce chemokines and inflamma- The recognition strategies used by NK cells are diverse. These include tory cytokines such as interferon-γ (IFN-γ) and tumor necrosis factor recognition of pathogen-encoded molecules; recognition of self pro- (TNF), among other activities1. They are important in attacking teins whose expression is upregulated in transformed or infected cells pathogen-infected cells, especially during the early phases of an infec- (‘induced-self recognition’); and inhibitory recognition of self pro- tion1,2. They are also efficient killers of tumor cells and are believed to be teins that are expressed by normal cells but downregulated by infected involved in tumor surveillance. The long-standing hypothesis that NK or transformed cells (‘missing-self recognition’). What follows are cells exert an immunoregulatory effect is supported by recent evidence examples of each.