DOCSLIB.ORG

The Ancestral Complement System in Sea Urchins Nition of Foreign Peptide Fragments Presented to Lymphocytes Ed in (3))

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Ancestral Complement System in Sea Urchins Nition of Foreign Peptide Fragments Presented to Lymphocytes Ed in (3)) L. Courtney Smith The ancestral complement system Lori A. Clow David P. Terwilliger in sea urchins Authors’ addresses Summary: The origin of adaptive immunity in the vertebrates can be traced L. Courtney Smith1,2, Lori A. Clow3, to the appearance of the ancestral RAG genes in the ancestral jawed ver- David P. Terwilliger1, tebrate; however, the innate immune system is more ancient. A central sub- 1The Department of Biological Sciences, system within innate immunity is the complement system, which has been Institute of Biomedical Sciences, George identified throughout and seems to be restricted to the deuterostomes. The Washington University, Washington DC, USA. evolutionary history of complement can be traced from the sea urchins 2The Graduate Programs in Genetics and (members of the echinoderm phylum), which have a simplified system Immunology, Institute of Biomedical Sciences, homologous to the alternative pathway,through the agnathans (hagfish and George Washington University, Washington lamprey) and the elasmobranchs (sharks and rays) to the teleosts (bony DC, USA. fish) and tetrapods, with increases in the numbers of complement compo- 3The Department of Microbiology and nents and duplications in complement pathways. Increasing complexity in Immunology, School of Medicine, University of the complement system parallels increasing complexity in the deuterosto- Maryland at Baltimore, Maryland, USA. me animals. This review focuses on the simplest of the complement sys- tems that is present in the sea urchin. Two components have been identified Correspondence to: that show significant homology to vertebrate C3 and factor B (Bf), called L. Courtney Smith SpC3 and SpBf, respectively. Sequence analysis from both molecules reveals The Department of Biological Sciences their ancestral characteristics. Immune challenge of sea urchins indicates 334 Lisner Hall that SpC3 is inducible and is present in coelomic fluid (the body fluids) in George Washington University relatively high concentrations, while SpBf expression is constitutive and is Washington DC 20052 present in much lower concentrations. Opsonization of foreign cells and USA particles followed by augmented uptake by phagocytic coelomocytes ap- Fax: 1 202 994 6100 pears to be a central function for this simpler complement system and im- e-mail: [email protected] portant for host defense in the sea urchin. These activities are similar to some of the functions of the homologous proteins in the vertebrate com- Acknowledgements plement system. The selective advantage for the ancestral deuterostome The authors are grateful to Drs Sham Nair and may have been the amplification feedback loop that is still of central im- Paul Gross for their critique of the manuscript portance in the alternative pathway of complement in higher vertebrates. and helpful suggestions. This work was Feedback loop functions would quickly coat pathogens with complement supported by the National Science Foundation leading to phagocytosis and removal of foreign cells, a system that would (MCB 9603086). be significantly more effective than an opsonin that binds upon contact as a result of simple diffusion. An understanding of the immune response of the sea urchin, an animal that is a good estimator of what the ancestral deut- erostome immune system was like, will aid us in understanding how adap- tive immunity might have been selected for during the early evolution of the vertebrates and how it might have been integrated into the pre-existing innate immune system that was already in place in those animals. Immunological Reviews 2001 Introduction Vol. 180: 16–34 Printed in Denmark. All rights reserved The mammalian immune system The mammalian immune system is composed of two major Copyright C Munksgaard 2001 Immunological Reviews subsystems: the adaptive system and the innate system. The ISSN 0105-2896 adaptive system functions through specific non-self recog- 16 Smith et al Á The ancestral complement system in sea urchins nition of foreign peptide fragments presented to lymphocytes ed in (3)). The classical pathway is activated by antigen–anti- by phagocytic antigen-presenting cells. Non-self recognition body interactions that bind and activate C1q/C1r/C1s com- is mediated by the immunoglobulin gene family and the abil- plexes. These, in turn, activate C4, which binds C2, forming ity of these genes to undergo rearrangements and generate a a C3-convertase complex that can activate C3. The alternative finely tuned and specific mechanism for recognizing all poss- pathway is initiated by C3, which undergoes a constant, low- ible foreign antigens. This system is very flexible and can level spontaneous auto-activation reaction, enabling it to bind adapt to molecular changes in pathogens or to changes in to appropriate groups on proteins and sugars (reviewed in pathogen populations in the environment. Yet, reactions to (9, 10)). Both C3 and C4 have thioester sites that are con- new non-self contacts are slow because the development of structed of intrachain bonds between the side groups of cys- antigen-specific reactions take time. The innate system, on teine and a nearby glutamic acid to form a thioester bond. the other hand, is a non-adaptive system that is mediated by The bond is unstable and reactive, and the carbonyl group non-lymphoid, phagocytic cells. It is always available, re- easily forms covalent bonds with nearby hydroxyl or amino sponds quickly, and has been established from evolutionary groups (11, 12). The alternative pathway has an effective associations between host and pathogen. The molecular inter- feedback loop in which C3 is cleaved to form C3b and C3a actions that initiate the innate response are based on molecu- by a C3 convertase, and the larger fragment, C3b, binds to lar structures or ‘‘patterns’’ on or within pathogens that are any local surface. The smaller fragment, C3a, diffuses away essential either for their survival or their virulence and are and functions as a chemoattractant for phagocytes and other conserved within major groups of microorganisms (1, 2). cells (13). The C3-convertase complex that functions in the Examples of molecular patterns include lipopolysaccharide alternative pathway is formed between factor B (Bf) and acti- (LPS) on gram-negative bacteria, mannans on fungi, and vated C3b in circulation or surface-bound C3b. Upon bind- double-stranded RNA in some viruses. The host response to ing, Bf alters its conformation and is then cleaved by factor these patterns is mediated by pattern recognition receptors D, which activates the serine protease domain. The serine that are essential for pathogen recognition in primary re- protease activity is the basis for the feedback loop to activate sponses where lymphocyte populations have not been ex- additional C3, which quickly coats foreign cells with C3b. panded in response to specific antigens. This recognition sys- The lectin pathway is initiated by mannose-binding lectin tem is not flexible, it does not change its genetic arrange- (MBL), which interacts with polysaccharides on foreign cell ments to recognize pathogens, and it is not designed to surfaces (14–17) that have a specific spatial orientation typical recognize detailed differences between similar antigens. of prokaryotes that is absent from eukaryotes (18). The three initiation pathways converge with the formation The mammalian complement system of C3 convertases, which lead to several possible results, none The two subsystems of the immune system in higher ver- of which are exclusive of the others. First, bound C3b func- tebrates are tightly linked and their inter-regulation is com- tions as an opsonin to augment phagocytosis which results in plex and impressive. The association involves the initial inter- the destruction of the opsonized particle by phagocytic cells action between molecular patterns and pattern recognition bearing C3 receptors. Pathogen-bound C3b is also recognized receptors of the innate system, followed by uptake and pro- by some lymphocytes, which results in the activation of the cessing by the cells mediating the innate system, and finally adaptive immune system (4). Second, C3 convertases are presentation of pathogen fragments to the cells mediating the readily remodulated to form C5 convertases. These activate adaptive system. The complement system, which is a major C5 and the terminal pathway, leading to the formation of subsystem of innate immunity in vertebrates and is composed membrane attack complexes, which destabilize the mem- of about 30 distinct humoral and cell surface proteins (3), has branes of foreign cells, leading to lysis. The above description emerged as an essential link between the innate and adaptive is the commonly understood way in which the complement immune systems in higher vertebrates (4) (reviewed in pathways function. However, there are a significant number (5–8)). The deposition of fragments of the central compo- of variations in how this system can recognize foreignness, nent of complement, C3, onto surfaces of pathogens essenti- plus mechanisms through which the ‘‘non-self-binding mol- ally acts as an effective adjuvant for activating the adaptive ecule’’ can activate the system (reviewed in (19)). In general, immune response. The complement system is organized into the complement system is always available, acts quickly, and three initiating pathways, termed classical, alternative, and is lethal to foreign cells. lectin, that converge to activate the terminal pathway (review- Because of the lack of discrimination between surfaces
Load more

Recommended publications
  • Objectives Complement (C') Complement Proteins Functions Of
    Complement Objectives Foundations of Public Health Identify functions of complement Immunology Recognize the similarities and differences of the three complement pathways Complement Identify important complement components & their functions Identify deleterious effects of complement activation and deficiency 1 2 Complement (C’) Complement Proteins Synthesized in the liver and by several Series of approximately 30 heat-labile proteins cells types (splenic macrophages) Normally inactive in the serum Plays an essential role in Inactive complement proteins known as zymogens inflammation and in facilitating Can be sequentially activated in a antibody effectiveness controlled sequence Amplification of the reaction occurs at each step Severe infections or autoimmune Production of biologically active fragments diseases can result from complement for lysis or killing of the target deficiencies (rare in the population) 3 4 Functions of Complement Functions of Complement Essential role in inflammation Assists antibodies in effector functions (Antibody Dependent Cell- mediated Cytotoxicity- ADCC) Assist in clearing immune complexes Opsonization and facilitation of phagocytosis No antigen specificity 5 6 1 Complement 3 Pathways of Activation Complement Activators Classical Triggered when IgM or certain IgG subclasses bind antigens Alternative (Properdin) Triggered by the deposition of complement protein, C3b, onto microbial surfaces No antibodies required for activation Lectin Triggered by the attachment of plasma mannose-binding lectin (MBL) to microbes No antibodies required for Activators start the domino effect… activation 7 8 Early Steps Late Steps The initial steps vary between pathways Dependent on activating substance C3 convertase quickly forms in all paths to cleave C3 Watch this well-done animation on the activation of complement, the Late steps (after C5 convertase) are same in all pathways steps in the complement pathways, Lead to formation of MAC & the functions of complement.
    [Show full text]
  • Understanding the Complement System
    Understanding the Complement System WHAT IS THE IMMUNE SYSTEM? The immune system is a complex network of organs, cells and proteins which work together to protect the body against infection and disease. WHAT IS THE COMPLEMENT SYSTEM? The complement system is a part of the immune system and is essential to the body’s defense against infection. Classical Pathway Lectin Pathway Alternative Pathway Made up of 3 UNIQUE PATHWAYS (Classical, Lectin and Alternative) Each pathway can become activated to trigger a cascade of protein reactions that initiate an immune response Inflammation Marks pathogen/damaged to detect and eliminate: cells for elimination Bacteria Viruses Inflammation Targeted destruction of damaged cells Dead cells When the complement system is working properly, it is a strong and powerful tool that protects the body against harmful invaders. • brain But when the system is thrown out of • nervous system balance, or dysregulated, the proteins can trigger a dangerous, uncontrolled cascade • blood stream of reactions that attack cells and tissues. • kidneys UNLOCKING THE POTENTIAL OF THE COMPLEMENT SYSTEM Alexion’s pioneering legacy in rare diseases is rooted in being the first to translate the complex biology of the complement system into transformative medicines. 3 DECADES 20 YEARS of complement of real-world evidence demonstrating the safety inhibition research and power of targeted complement inhibitors Dysregulation of the complement system is a key driver of many devastating diseases. Alexion has paved the way for a new class of medicines that inhibit the complement system, prevent further damage and reduce disease symptoms. Alexion is committed to continue unlocking the potential of the complement system and accelerating the discovery and development of new life-changing therapies for even more patients.
    [Show full text]
  • Complement Herbert L
    Host Defense 2011 Complement Herbert L. Mathews, Ph.D. COMPLEMENT Date: 4/11/11 Reading Assignment: Janeway’s Immunobiology, 7th Edition, pp. 54-55, 61-82, 406- 409, 514-515. Figures: (Unless otherwise noted) Janeway’s Immunobiology, 7th Edition, Murphy et al., Garland Publishing. KEY CONCEPTS AND LEARNING OBJECTIVES You will be able to describe the mechanism and consequences of the activation of the complement system. To attain the goals for these lectures you will be able to: a. List the components of the complement system. b. Describe the three activation pathways for complement. c. Explain the consequences of complement activation. d. Describe the consequence of complement deficiency. Page 1 Host Defense 2011 Complement Herbert L. Mathews, Ph.D. CONTENT SUMMARY Introduction Nomenclature Activation of Complement The classical pathway The mannan-binding lectin pathway The alternative pathway Biological Consequence of Complement Activation Cell lysis and viral neutralization Opsonization Clearance of Immune Complexes Inflammation Regulation of Complement Activation Human Complement Component Deficiencies Page 2 Host Defense 2011 Complement Herbert L. Mathews, Ph.D. Introduction The complement system is a group of more than 30 plasma and membrane proteins that play a critical role in host defense. When activated, complement components interact in a highly regulated fashion to generate products that: Recruit inflammatory cells (promoting inflammation). Opsonize microbial pathogens and immune complexes (facilitating antigen clearance). Kill microbial pathogens (via a lytic mechanism known as the membrane attack complex). Generate an inflammatory response. Complement activation takes place on antigenic surfaces. However, the activation of complement generates several soluble fragments that have important biologic activity.
    [Show full text]
  • Understanding the Immune System: How It Works
    Understanding the Immune System How It Works U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES NATIONAL INSTITUTES OF HEALTH National Institute of Allergy and Infectious Diseases National Cancer Institute Understanding the Immune System How It Works U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES NATIONAL INSTITUTES OF HEALTH National Institute of Allergy and Infectious Diseases National Cancer Institute NIH Publication No. 03-5423 September 2003 www.niaid.nih.gov www.nci.nih.gov Contents 1 Introduction 2 Self and Nonself 3 The Structure of the Immune System 7 Immune Cells and Their Products 19 Mounting an Immune Response 24 Immunity: Natural and Acquired 28 Disorders of the Immune System 34 Immunology and Transplants 36 Immunity and Cancer 39 The Immune System and the Nervous System 40 Frontiers in Immunology 45 Summary 47 Glossary Introduction he immune system is a network of Tcells, tissues*, and organs that work together to defend the body against attacks by “foreign” invaders. These are primarily microbes (germs)—tiny, infection-causing Bacteria: organisms such as bacteria, viruses, streptococci parasites, and fungi. Because the human body provides an ideal environment for many microbes, they try to break in. It is the immune system’s job to keep them out or, failing that, to seek out and destroy them. Virus: When the immune system hits the wrong herpes virus target or is crippled, however, it can unleash a torrent of diseases, including allergy, arthritis, or AIDS. The immune system is amazingly complex. It can recognize and remember millions of Parasite: different enemies, and it can produce schistosome secretions and cells to match up with and wipe out each one of them.
    [Show full text]
  • Activation of the Complement System on Human Endothelial Cells by Urban Particulate Matter Triggers Inflammation-Related Protein Production
    International Journal of Molecular Sciences Article Activation of the Complement System on Human Endothelial Cells by Urban Particulate Matter Triggers Inflammation-Related Protein Production Myoung Su Choi 1,† , Hyungtaek Jeon 2,†, Seung-Min Yoo 2 and Myung-Shin Lee 2,* 1 Department of Otorhinolaryngology, Eulji University Medical Center, Eulji University School of Medicine, Daejeon 35233, Korea; [email protected] 2 Department of Microbiology and Immunology, Eulji University School of Medicine, Daejeon 34824, Korea; [email protected] (H.J.); [email protected] (S.-M.Y.) * Correspondence: [email protected]; Tel.: +82-42-259-1662 † These authors have contributed equally to this work. Abstract: Exposure to particulate matter (PM) is becoming a major global health issue. The amount and time of exposure to PM are known to be closely associated with cardiovascular diseases. However, the mechanism through which PM affects the vascular system is still not clear. Endothelial cells line the interior surface of blood vessels and actively interact with plasma proteins, including the complement system. Unregulated complement activation caused by invaders, such as pollutants, may promote endothelial inflammation. In the present study, we sought to investigate whether urban PM (UPM) acts on the endothelial environment via the complement system. UPM-treated human endothelial cells with normal human serum showed the deposition of membrane attack complexes Citation: Choi, M.S.; Jeon, H.; Yoo, (MACs) on the cell surface via the alternative pathway of the complement system. Despite the forma- S.-M.; Lee, M.-S. Activation of the tion of MACs, cell death was not observed, and cell proliferation was increased in UPM-mediated Complement System on Human complement activation.
    [Show full text]
  • Complement System: Immune Effector Mechanism Subhadipa 2020 What Is Complement System??? • Humoral Branch of the Immune System
    Subhadipa 2020 Complement system: Immune effector mechanism Subhadipa 2020 What is complement system??? • Humoral branch of the immune system. • Complement includes more than 30 soluble and cell-bound proteins. • After initial activation, the various complement components interact, in a highly regulated cascade, to carry out a number of basic functions including: Lysis of cells, bacteria, and viruses Opsonization, which promotes phagocytosis of particulate antigens Binding to specific complement receptors on cells of the immune system, triggering specific cell functions, inflammation, and secretion of immunoregulatory molecules. Immune clearance, which removes immune complexes from the circulation and deposits them in the spleen and liver Subhadipa 2020 Basic Functions The complement components Subhadipa 2020 • The proteins and glycoproteins that compose the complement system are synthesized mainly by liver hepatocytes, although significant amounts are also produced by blood monocytes, tissue macrophages, and epithelial cells of the gastrointestinal and genitourinary tracts. • These components constitute 5% (by weight) of the serum globulin fraction. Most circulate in the serum in functionally inactive forms as proenzymes, or zymogens, which are inactive until proteolytic cleavage, which removes an inhibitory fragment and exposes the active site. The complement-reaction sequence starts with an enzyme cascade. • Complement components are designated by numerals (C1–C9), by letter symbols (e.g., factor D), or by trivial names (e.g., homologous restriction factor). • Peptide fragments formed by activation of a component are denoted by small letters . In most cases, the smaller fragment resulting from cleavage of a component is designated “a” and the larger fragment designated “b” (e.g., C3a, C3b; note that C2 is an exception: C2a is the larger cleavage fragment).
    [Show full text]
  • I M M U N O L O G Y Core Notes
    II MM MM UU NN OO LL OO GG YY CCOORREE NNOOTTEESS MEDICAL IMMUNOLOGY 544 FALL 2011 Dr. George A. Gutman SCHOOL OF MEDICINE UNIVERSITY OF CALIFORNIA, IRVINE (Copyright) 2011 Regents of the University of California TABLE OF CONTENTS CHAPTER 1 INTRODUCTION...................................................................................... 3 CHAPTER 2 ANTIGEN/ANTIBODY INTERACTIONS ..............................................9 CHAPTER 3 ANTIBODY STRUCTURE I..................................................................17 CHAPTER 4 ANTIBODY STRUCTURE II.................................................................23 CHAPTER 5 COMPLEMENT...................................................................................... 33 CHAPTER 6 ANTIBODY GENETICS, ISOTYPES, ALLOTYPES, IDIOTYPES.....45 CHAPTER 7 CELLULAR BASIS OF ANTIBODY DIVERSITY: CLONAL SELECTION..................................................................53 CHAPTER 8 GENETIC BASIS OF ANTIBODY DIVERSITY...................................61 CHAPTER 9 IMMUNOGLOBULIN BIOSYNTHESIS ...............................................69 CHAPTER 10 BLOOD GROUPS: ABO AND Rh .........................................................77 CHAPTER 11 CELL-MEDIATED IMMUNITY AND MHC ........................................83 CHAPTER 12 CELL INTERACTIONS IN CELL MEDIATED IMMUNITY ..............91 CHAPTER 13 T-CELL/B-CELL COOPERATION IN HUMORAL IMMUNITY......105 CHAPTER 14 CELL SURFACE MARKERS OF T-CELLS, B-CELLS AND MACROPHAGES...............................................................111
    [Show full text]
  • The Complement System1
    The complement system1 Piet Gros Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Dept. Chemistry, Faculty of Science, Utrecht University, Utrecht, The Netherlands [email protected] Abstract The mammalian complement system plays an important role in the immune defense in blood and interstitial fluids. This set of ~30, mostly multi-domain, plasma proteins and cell-surface receptors enables the host to recognize and clear invading pathogens and altered host cells, while protecting healthy host cells and tissues. In addition to humoral immune defense, complement proteins are produced in the brain, where these proteins contribute to clearance processes such as synaptic pruning. Overall, the complement system may be considered as a broad surveillance mechanism to maintain healthy tissue in mammals. These lecture notes present structural data that provided insights into the underlying molecular mechanism that regulate complement activity. Examples of experimental results are taken primarily from the Gros lab. For an overview of the field the reader is referred to reviews published elsewhere. Introduction The complement system can be activated through three main routes: 1) the classical pathway, 2) the lectin-mediated pathway and 3) the alternative pathway of complement activation; see figure 1 (for reviews see e.g. Ricklin et al., 2010; Dunkelberger & Song, 2010). The alternative pathway may be considered as the evolutionary core of the complement system. It is activated non-specifically by a low level of hydrolysis of complement component C3, yielding C3(H2O), which serves as a starting point for activation, a process referred to as “tick-over mechanism”. The other two pathways provide specificity to complement.
    [Show full text]
  • Complement System and Potential Therapeutics in Age-Related Macular Degeneration
    International Journal of Molecular Sciences Review Complement System and Potential Therapeutics in Age-Related Macular Degeneration Young Gun Park 1, Yong Soo Park 2 and In-Beom Kim 2,3,4,* 1 Department of Ophthalmology and Visual Science, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; [email protected] 2 Department of Anatomy, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; [email protected] 3 Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea 4 Catholic Institute for Applied Anatomy, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea * Correspondence: [email protected]; Tel.: +82-2-2258-7263 Abstract: Age-related macular degeneration (AMD) is a complex multifactorial disease characterized in its late form by neovascularization (wet type) or geographic atrophy of the retinal pigment epithelium cell layer (dry type). The complement system is an intrinsic component of innate immunity. There has been growing evidence that the complement system plays an integral role in maintaining immune surveillance and homeostasis in AMD. Based on the association between the genotypes of complement variants and AMD occurrence and the presence of complement in drusen from AMD patients, the complement system has become a therapeutic target for AMD. However, the mechanism of complement disease propagation in AMD has not been fully understood. This concise review focuses on an overall understanding of the role of the complement system in AMD and its ongoing clinical trials. It provides further insights into a strategy for the treatment of AMD targeting the complement system.
    [Show full text]
  • Immunology & the Lymphoid System Objectives
    Introduction to Immunology & The Lymphoid system Objectives: • To know the historical perspective of immunology • To be familiar with the basic terminology and definitions of immunology • Cells of immune response Immunology - introduction • To understand types of immune responses Immune System: "Body Defenses Against Disease" 2nd Ed 1978 Encyclopaedia • To know about the lymphoid system Britannica Films • To understand T and B cell functions Your Immune System: Natural Born Killer - Crash Course Biology #32 Videos to get you warmed up (^^) Edward jenner • In 1798 Edward Jenner began the science of Immunology. After he noticed that Milkmaids who contracted cowpox (a mild disease) were subsequently immune to small pox. • Louis Pasteur Introduced Weakened Virulence (attenuated: weakened, non-virulent strain whose exposure can confer resistance to disease.) Louis Pasteur Bacterial culture > Normal healthy chicken > No disease or death > produce IMMUNE chicken . Fresh Bacterial ‘No culture ‘> IN IMMUNE chicken > Live chicken. Or > IN NORMAL chicken > Dead chicken. Edward How we conquered the Louis Pasteur - deadly smallpox virus - Jenner Story Simona Zompi Mini Biography Basic terminology & Definitions of immunology Immunoglobulin (Ig) or Allergen Antibodies Antigen (Ag) Noninfectious antigens that Any substance that binds • Secreted from plasma cell. induce hypersensitivity reactions, specifically to a component of • Consist of a heavy or light most commonly IgE-mediated adaptive immunity. polypeptide chain. type 1 reactions. Immunology Immune Immunity Immune system Immune The study of mechanisms Refers to People survived Is the collection of cells, response that humans and other protection tissues and molecules ravages of epidemic animals use to defend The reaction of the against that function to defend diseases when faced their bodies from immune system infection.
    [Show full text]
  • The Humoral Immune System Structure and Diversity Discussion
    The Humoral Immune system Structure and Diversity Discussion: Introduction Our immune system protects our bodies from the harmful affects of a dizzying array of disease causing pathogens. Although our skin and mucous membranes serve as primary defense systems, many antigens are find their way into our bodies. Our immune system has developed an extensive array of cells, and sophisticated processes that help identify, and eliminate foreign invaders. Given that there are essentially billions of possible antigens it is indeed amazing that we can respond to so many in an efficient and timely manner. What is most impressive of our immune system is it’s specificity, memory, and flexibility. This lesson plan will seek to explore part of our immune system: the humoral system. We will seek to understand how gene expression within the immunoglobulin variable regions is able to produce the billions of antibodies that defend us. A. Two modes of response (See Figure 1 & 1a.) ( *Teacher note 1) The Immunity of the body is achieved by two distinct methods of immune response: the cellular immune system and the humoral immune system. The two systems work through different methods and types of lymphocytes to protect the body from invading pathogens. 1. Cellular Immunity System: (see Figure 1 &1a for overview of Cytotoxic T cells, Helper T cells and B-lymphocytes. Note the use of Helper T cells in both cases. Refer to role of the AIDS virus in the obstruction of the work of these Helper cells.)The Cellular immune system possesses three very effective sets of killing cells. They are termed T lymphocytes because they are formed in the Thymus gland.
    [Show full text]
  • The Role of Igm and Complement in Antibody Responses
    Trassla inte till saken genom att komma dragande med fakta Groucho Marx List of Papers This thesis is based on the following papers, which are referred to in the text by their Roman numerals. Ia Rutemark C, Alicot E, Bergman A, Ma M, Getahun A, Ellmerich S, Carroll M, Heyman B. Requirement for complement in antibody responses is not explained by the classic pathway activator IgM. Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):E934-42. Epub 2011 Oct 10. Ib Rutemark C, Alicot E, Bergman A, Ma M, Getahun A, Ellmerich S, Carroll M, Heyman B. Requirement for complement in antibody responses is not explained by the classic pathway activator IgM. Author summary. Proc Natl Acad Sci U S A 2011 108(43): 17589-90 II Carlsson F, Getahun A, Rutemark C, Heyman B. Impaired antibody responses but normal proliferation of specific CD4+ T cells in mice lacking complement receptors 1 and 2. Scand J Immunol. 2009 Aug;70(2):77-84. III Rutemark C, Bergman A, Getahun A, Henningson-Johnson F, Hallgren J, Heyman B. B cells lacking complement receptors 1 and 2 are equally efficient producers of IgG in vivo as wildtype B cells. Manuscript. Reprints were made with permission from the respective publishers. Contents Introduction ................................................................................................... 11 Background ................................................................................................... 12 B cells ....................................................................................................... 12 Antibodies
    [Show full text]