Helper-T-cell regulated B-cell differentiation. Phase I begins at the site of infection with acute inflammation that leads to the activation and
|
|
- Silvester Payne
- 5 years ago
- Views:
Transcription
1 1
2 2
3 Helper-T-cell regulated B-cell differentiation. Phase I begins at the site of infection with acute inflammation that leads to the activation and emigration of DCs to the T- cell zones of the lymph nodes that drain the area of tissue. Antigen uptake, processing and presentation within the context of MHC II allows the activated DCs to contact and trigger naı ve Th cells expressing specific T-cell receptor (TCR) and initiating immune synapse I (Synapse I). B cells have the capacity to recognize soluble protein antigen; however, they are more efficiently activated by cell-bound antigen and may also initiate an immune synapse with an activated antigen-bearing DC. Following clonal expansion, antigen-activated Th cells migrate to the T B borders of the lymph node to initiate cognate contact with activated antigen-specific B cells. Phase II begins with immune synapse II formation (Synapse II) between these antigen-specific Th and B cells. Synapse II drives a major bifurcation in B-cell differentiation to either short-lived plasma-cell production, which progresses in the T-cell areas, or movement into the follicular areas and the formation of secondary lymphoid follicles. Phase III begins with the polarization of secondary follicles into light-zone and dark-zone regions of activity that typify the GC reaction. This dynamic cycle of activity involves clonal expansion, SHM of the BCR, antigenspecific selection for high affinity variants and then export of memory B cells. These memory B cells can either differentiate into long-lived plasma cells, or remain as non-secreting precursors for antigen recall. Synapse III interactions involve antigenspecific GC Th cells and GC B cells and are proposed to play a critical regulatory role in these late-stage B-cell developmental decisions. 3
4 Memory B-cell differentiation. At least two phenotypically-distinct types of nonsecreting memory B cells clonally expand in response to antigen recall, together with a rapid and massive production of antigen-specific plasma cells (B220-/CD138- antigen-binding). B220-CD138 antigen binding cells demonstrate greater proliferative capacity but lower differentiative potential than their B220CD138 counterparts over five days after adoptive transfer and antigen re-challenge. These experiments also indicate a parent-progeny relationship between the two memory B-cell subsets,as displayed above. Antigen was required for responsiveness of both memory B-cell subsets; however, the requirement for memory Th cells for each subset was not tested, as it was provided in all cases. Memory B-cell differentiation is generally regarded to be memory-th-cell regulated, suggesting that the formation of immune synapse IV is a critical checkpoint in Phase IV of TD immune responsiveness. 4
5 5
6 6
7 Relationship between immunological memory and protective immunity following smallpox vaccination. Two independent studies [20,24] have quantitated the duration of T-cell- and B- cell/antibody-mediated immunity over the course of several decades and came to remarkably similar conclusions: T-cell memory declines slowly over time, with a half-life of 8 15 years (representative thin line), whereas serum antibody responses (and B-cell memory; [20]) are maintained essentially for life with little or no observable decline (representative bold line). Immunological memory quantitated directly ex vivo does not necessarily demonstrate protective immunity; this can only be accomplished by natural exposure or experimental challenge experiments with the virulent pathogen of interest. In this regard, the protection afforded by smallpox vaccination was determined at the indicated intervals (bar graph inset) following immunization and shows that >90% of vaccinees are protected against lethal smallpox (normally 30% mortality in unvaccinated individuals) for at least 60 years post-vaccination [47,48]. Similar results showing long-term immunity were observed during imported smallpox outbreaks throughout Europe between 1950 and 1971 [49,50], decades after endemic smallpox had been eradicated [49]. 7
8 8
9 9
10 10
11 11
12 The formation of B-cell memory in response to antigen. a After activation by antigen, mature naive B cells (which are located in B-cell follicles in secondary lymphoid organs) migrate to the edge of the follicles, where they receive help from cognate T cells. If the B cells express the appropriate molecules, such as a combination of B-cell lymphoma 6 (BCL-6), inducible T-cell co-stimulator ligand (ICOSL), CD40 and B-lymphocyteinduced maturation protein 1 (BLIMP1), the interaction of the B cells and T cells leads to the formation of short-lived plasma cells and to the establishment of germinal centres in the follicles. In the germinal centre, proliferating antigen-specific B cells (known as centroblasts) are localized at one pole (the dark zone), whereas their non-proliferating immunoglobulin-expressing counterparts (known as centrocytes) localize at the other pole (the light zone). Centrocytes and centroblasts cycle within the germinal centre in a chemokine-driven process. Centrocytes can differentiate into memory B cells or plasma cells, or undergo apoptosis if they fail to receive an antigen-mediated survival signal. Although expression of BLIMP1 is crucial for the formation of plasma cells, the factors that control memory B-cell formation are less well defined. Memory B cells recirculate in the periphery, whereas germinal-centre-derived plasma cells accumulate preferentially in the bone marrow. b B1b cells can also generate memory B cells in response to T-cell-independent antigens. Exposure to antigen leads to the formation of plasma cells and to the clonal expansion and persistence of antigenspecific memory B1b cells with a phenotype that is indistinguishable from that of naive B1b cells. Conventional B cells have also been shown to be able to give rise to memory B cells in response to T-cell-independent antigens. 12
13 Figure 2 A model for the generation of memory B cells and plasma cells in germinal centres during a primary immune response. Cells emigrate from the germinal centre throughout the immune response, as either plasma cells or memory B cells. Under the influence of B-cell receptor (BCR) stimulation, centrocytes with high affinity for antigen differentiate preferentially, but not exclusively, into plasma cells. These plasma cells migrate through the blood, and they accumulate in the bone marrow if they gain access to a survival niche. By contrast, memory B cells that emigrate from the germinal centre constitute a random sampling of centrocytes with various affinities. The size of the memory B-cell pool is finite, so the survival of memory B cells is competitive. Prolonged survival in the germinal centre, which correlates with increased affinity for antigen, improves the competitiveness also known as the fitness of the memory B-cell emigrants and, consequently, their representation in the ultimate memory B-cell population. Increasing intensity of colour corresponds to increasing affinity and fitness. 13
14 Figure 2 Model of homeostasis in the memory pool. a For each new memory cell that is generated, one must be deleted. This should be on the basis of their ability to access or respond to survival factors, such as antigen or cytokines, both of which replenish the memory pool and can balance homeostatic deletion. b A simple model of how this might work is suggested: the expression of receptors for the survival factor (for example, IL-15 receptor; IL-15R) decays over time after antigen stimulation. So, the longer the time from encounter with antigen, the more likely the cells will be lost from the system. 14
15 Possible regulation of plasma cell homeostasis by survival niches. Probably recruited by the chemokine receptors indicated in bold, plasma cells formed in secondary lymphoid tissues such as spleen and Peyer s patches migrate into lamina propria, bone marrow or inflamed tissue. Here, their survival depends on the availability of factors provided in a limited number of survival niches. The relatively high numbers of plasma cells competing for survival niches that are present in mucosa-associated tissues result in tough competition conditions and in consequence in the observed short average lifetimes of plasma cells in the lamina propria. The short half-life of plasma cells outside survival niches is probably due to the lack of specific survival signals; however, active elimination can not be excluded. 15
16 16
17 Figure 6 Long-lived plasma cells in the bone marrow. Postgerminal-centre plasma cells, which express somatically mutated, classswitched immunoglobulin, lose expression of CXC-chemokine receptor 5 (CXCR5), facilitating their exit from the germinal centre. These cells then increase their expression of CXCR4, which helps them to home to the bone marrow, where stromal cells produce high amounts of CXCchemokine ligand 12 (CXCL12). Endothelial-cell selectin (E-selectin) and vascular cell-adhesion molecule 1 (VCAM1) expressed at the surface of bone-marrow stromal cells are important for the retention of plasma cells in the bone marrow, through association with polysaccharides and integrins expressed at the surface of the plasma cells. Plasma cells induce the stromal cells to produce interleukin-6 (IL-6). B-cell-activating factor (BAFF), probably produced by macrophages or dendritic cells, activates the receptor B-cell maturation antigen (BCMA) and, together with IL-6, provides crucial survival signals to the plasma cells. BLIMP1, B-lymphocyte-induced maturation protein 1; IL-6R, IL-6 receptor; SDC1, syndecan; XBP1, X-box-binding protein 1. 17
18 18
19 Figure 1. Distinct sets of transcriptional regulators control commitment to the plasma cell differentiation pathway during the humoral immune response. Naïve B cells are activated by antigen (Ag) in the presence of CD4 T-cell help. The activated B cells then continue down one of two divergent pathways: plasma cell (PC) differentiation, or initiation of a GC reaction. MBCs and LLPCs are generated in the GC. When MBCs are re-exposed to antigen they divide rapidly and differentiate into either PCs or more MBCs. The commitment of B cells to the PC differentiation pathway is regulated by the transcription factors Blimp-1, XBP-1 and IRF-4. These factors repress the gene-expression program that defines B-cell identity (Pax5, MITF etc.) and activate a program that drives terminal differentiation and antibody secretion. 19
20 Figure 3 Transcriptional repression inforces mutually exclusive B-cell and plasma-cell gene-expression programmes. Several transcription factors BCL-6 (B-cell lymphoma 6), MTA3 (metastasisassociated 1 family, member 3), MITF (microphthalmia-associated transcription factor) and PAX5 (paired box protein 5) repress plasmacytic development by repressing BLIMP1 (B-lymphocyte-induced maturation protein 1), XBP1 (X-box-binding protein 1) and IRF4 (interferon-regulatory factor 4). In plasma cells, BLIMP1 represses B-cell gene-expression programmes. This mutual repression prevents the unelicited formation of plasma cells in the germinal centre and prevents the reversion of plasma cells to a B-cell stage. BCR, B-cell receptor; TLR, Toll-like receptor. BCL-6, MTA3, PAX5 and MITF also regulate the expression of genes that are required for B-cell and germinal-centre functions, which are outlined in the pink box. BLIMP1, XBP1 and IRF4 induce the expression of genes that are required for plasma cells, which are outlined in the blue box. 20
21 Figure 5 Gene expression in immunoglobulin-secreting plasma cells is regulated by BLIMP1 and XBP1. Induction of B-lymphocyteinduced maturation protein 1 (BLIMP1) expression in developing plasma cells leads to decreased expression of paired box protein 5 (PAX5) and increased expression of immunoglobulin. These two events are required for the expression of mrna that encodes X-box-binding protein 1 (XBP1) and for the activation of the endoribonuclease inositol-requiring 1 (IRE1 ), which processes Xbp1 mrna to yield mrna that encodes a different carboxyl terminus and a more active and stable protein. XBP1 then induces the expression of many genes that are involved in the secretory pathway, which generates a physiological unfolded-protein response. The unfolded-protein response allows the continuous production and secretion of high levels of antibody by plasma cells. ER, endoplasmic reticulum; IgH, immunoglobulin heavy chain; IgL, immunoglobulin light chain; J chain, joining chain; M, transmembrane form of the IgH; S, secretory form of the IgH; PERK, RNA-dependent protein kinase (PKR)-like ER kinase. 21
22 Proposed model of how BCR affinity controls long-lived humoral immune responses. During an oligoclonal B-cell response, antigen-specific B cells ranging in affinity are activated and undergo proliferation. (a) From this oligoclonal response, B cells with initially low affinity towards antigen will form germinal centers, undergo somatic hypermutation, and differentiate to long-lived memory B (Bmem) cells, plasma cell precursors (PCpre), and bone marrow plasma cells (PCs), each of which has improved antibody affinity. (b) Oligoclonal responding B cells that have moderate affinity for antigen will also form germinal centers yet show a skewing in terminal differentiation whereby they can become long-lived PCpre and PCs, but do not commit to Bmem. (c) When the innate BCR affinity on a naı ve B cell exceeds a certain threshold for antigen, its differentiation fate is to become a short-lived PC. Shuttling intrinsically high-affinity B cells towards an extrafollicular pathway provides rapid local antibody production with the best possible protection early during an immune response while preventing the development of B-cell memory. 22
23 The transcriptional development of plasma cells is mediated by the total signal strength on the B cell. We propose that the sum signal strength induces high IRF-4 expression in a subset of light-zone centrocytes exiting the germinal center (GC). These signals are composed of BCR signal strength and controlled by BCR affinity to antigen as well as complement receptor and CD40 engagement. Low IRF-4 expression induces AID and thus may play a role in GC B cells, although this link has not yet been made in vivo. (a) Within GC B cells, AID expression is induced by Pax5, which is also responsible for enhancing Bcl-6 expression. To maintain GC B-cell character, Pax5 suppresses XBP-1 whereas Bcl-6 represses Blimp-1, prohibiting differentiation into PCs. (b) High expression of IRF-4 in light-zone centrocytes would lead to the induction of Blimp-1, which represses Pax5 and Bcl-6 and allows for the expression of XBP-1 and terminal differentiation into a plasma cell (PC) secreting immunoglobulin (c). The second major cellular fate of GC B cells is the generation of Bmem (d). IRF-4 does not appear to be required for this fate and the transcriptional pathway driving and sustaining Bmem remains unknown. The Bmem pool supplies the body with a burst of PCs upon secondary antigen encounter and continually replenishes the PC pool through polyclonal stimulation such as TLR ligation and bystander T-cell help. During the transition from a Bmem to a PC, IRF-4 again induces the PC transcriptional pathway through Blimp-1 23
24 24
25 25
26 26
27 27
28 28
29 29
30 30
31 31
32 The classical pathway of complement activation. Antigen-antibody complexes that activate the classical pathway may be soluble, fixed on the surface of cells (as shown), or deposited on extracellular matrices. The classical pathway is initiated by the binding of C1 to antigen-complexed antibody molecules, which leads to the production of C3 and C5 convertases attached to the surfaces where the antibody was deposited. The C5 convertase cleaves C5 to begin the late steps of complement activation
33 Late steps of complement activation and formation of the MAC. A schematic view of the cell surface events leading to formation of the MAC is shown. Cell-associated C5 convertase cleaves C5 and generates C5b, which becomes bound to the convertase. C6 and C7 bind sequentially, and the C5b,6,7 complex becomes directly inserted into the lipid bilayer of the plasma membrane, followed by stable insertion of C8. Up to 15 C9 molecules may then polymerize around the complex to form the MAC, which creates pores in the membrane and induces cell lysis. C5a released on proteolysis of C5 stimulates inflammation.
34 Functions of complement. The major functions of the complement system in host defense are shown. Cell-bound C3b is an opsonin that promotes phagocytosis of coated cells (A); the proteolytic products C5a, C3a, and (to a lesser extent) C4a stimulate leukocyte recruitment and inflammation (B); and the MAC lyses cells (C).
35 35
36 36
37 37
38 38
39 39
How plasma cells develop. Deutsches Rheuma Forschungs Zentrum, Berlin Institut der Leibniz Gemeinschaft
How plasma cells develop Deutsches Rheuma Forschungs Zentrum, Berlin Institut der Leibniz Gemeinschaft 1 Plasma cells develop from activated B cells Toll Like Receptor B Cell Receptor B cell B cell microbia
More informationAdaptive immune responses: T cell-mediated immunity
MICR2209 Adaptive immune responses: T cell-mediated immunity Dr Allison Imrie allison.imrie@uwa.edu.au 1 Synopsis: In this lecture we will discuss the T-cell mediated immune response, how it is activated,
More informationIntroduction. Abbas Chapter 10: B Cell Activation and Antibody Production. General Features. General Features. General Features
Introduction Abbas Chapter 10: B Cell Activation and Antibody Production January 25, 2010 Children s Mercy Hospitals and Clinics Humoral immunity is mediated by secreted antibodies (Ab) Ab function to
More informationCELL BIOLOGY - CLUTCH CH THE IMMUNE SYSTEM.
!! www.clutchprep.com CONCEPT: OVERVIEW OF HOST DEFENSES The human body contains three lines of against infectious agents (pathogens) 1. Mechanical and chemical boundaries (part of the innate immune system)
More informationThe Development of Lymphocytes: B Cell Development in the Bone Marrow & Peripheral Lymphoid Tissue Deborah A. Lebman, Ph.D.
The Development of Lymphocytes: B Cell Development in the Bone Marrow & Peripheral Lymphoid Tissue Deborah A. Lebman, Ph.D. OBJECTIVES 1. To understand how ordered Ig gene rearrangements lead to the development
More informationB cell activation and antibody production. Abul K. Abbas UCSF
1 B cell activation and antibody production Abul K. Abbas UCSF 2 Lecture outline B cell activation; the role of helper T cells in antibody production Therapeutic targeting of B cells 3 Principles of humoral
More informationImmunobiology 7. The Humoral Immune Response
Janeway Murphy Travers Walport Immunobiology 7 Chapter 9 The Humoral Immune Response Copyright Garland Science 2008 Tim Worbs Institute of Immunology Hannover Medical School 1 The course of a typical antibody
More informationThe Adaptive Immune Response. B-cells
The Adaptive Immune Response B-cells The innate immune system provides immediate protection. The adaptive response takes time to develop and is antigen specific. Activation of B and T lymphocytes Naive
More informationAntigen-Independent B-Cell Development Bone Marrow
Antigen-Independent B-Cell Development Bone Marrow 1. DNA rearrangements establish the primary repertoire, creating diversity 2. Allelic exclusion ensures that each clone expresses a single antibody on
More informationPBS Class #2 Introduction to the Immune System part II Suggested reading: Abbas, pgs , 27-30
PBS 803 - Class #2 Introduction to the Immune System part II Suggested reading: Abbas, pgs. 15-25, 27-30 Learning Objectives Compare and contrast the maturation of B and T lymphocytes Compare and contrast
More informationGeneral Biology. A summary of innate and acquired immunity. 11. The Immune System. Repetition. The Lymphatic System. Course No: BNG2003 Credits: 3.
A summary of innate and acquired immunity General iology INNATE IMMUNITY Rapid responses to a broad range of microbes Course No: NG00 Credits:.00 External defenses Invading microbes (pathogens). The Immune
More informationAdaptive Immunity: Humoral Immune Responses
MICR2209 Adaptive Immunity: Humoral Immune Responses Dr Allison Imrie 1 Synopsis: In this lecture we will review the different mechanisms which constitute the humoral immune response, and examine the antibody
More informationEffector mechanisms of cell-mediated immunity: Properties of effector, memory and regulatory T cells
ICI Basic Immunology course Effector mechanisms of cell-mediated immunity: Properties of effector, memory and regulatory T cells Abul K. Abbas, MD UCSF Stages in the development of T cell responses: induction
More informationIg light chain rearrangement: Rescue pathway
B Cell Development Ig light chain rearrangement: Rescue pathway There is only a 1:3 chance of the join between the V and J region being in frame Vk Jk Ck Non-productive Rearrangement Light chain has a
More informationAndrea s SI Session PCB Practice Test Test 3
Practice Test Test 3 READ BEFORE STARTING PRACTICE TEST: Remember to please use this practice test as a tool to measure your knowledge, and DO NOT use it as your only tool to study for the test, since
More informationChapter 3, Part A (Pages 37-45): Leukocyte Migration into Tissues
Allergy and Immunology Review Corner: Chapter 3, Part A (pages 37-45) of Cellular and Molecular Immunology (Seventh Edition), by Abul K. Abbas, Andrew H. Lichtman and Shiv Pillai. Chapter 3, Part A (Pages
More informationAntigen Presentation and T Lymphocyte Activation. Abul K. Abbas UCSF. FOCiS
1 Antigen Presentation and T Lymphocyte Activation Abul K. Abbas UCSF FOCiS 2 Lecture outline Dendritic cells and antigen presentation The role of the MHC T cell activation Costimulation, the B7:CD28 family
More informationImmunology 2017: Lecture 12 handout. Secondary lymphoid organs. Dr H Awad
Immunology 2017: Lecture 12 handout Secondary lymphoid organs Dr H Awad INTRODUCTION So far we discussed the cells of the immune system and how they recognize their antigens and get stimulated. The number
More informationPutting it Together. Stephen Canfield Secondary Lymphoid System. Tonsil Anterior Cervical LN s
Putting it Together Stephen Canfield smc12@columbia.edu Secondary Lymphoid System Tonsil Anterior Cervical LN s Axillary LN s Mediastinal/Retroperitoneal LN s Thoracic Duct Appendix Spleen Inguinal LN
More informationTime course of immune response
Time course of immune response Route of entry Route of entry (cont.) Steps in infection Barriers to infection Mf receptors Facilitate engulfment Glucan, mannose Scavenger CD11b/CD18 Allows immediate response
More informationPLAN. Réponses B thymodépendantes et thymoindépendantes. B cell development and classification. B cell activation. Thymodependent B(2) cell response
Réponses B thymodépendantes et thymoindépendantes PLAN B cell development and classification B cell activation Thymodependent B(2) cell response BMC 423 (IF) - 2007 Antonino Nicoletti Thymo-independent
More informationchapter 17: specific/adaptable defenses of the host: the immune response
chapter 17: specific/adaptable defenses of the host: the immune response defense against infection & illness body defenses innate/ non-specific adaptable/ specific epithelium, fever, inflammation, complement,
More informationACTIVATION OF T LYMPHOCYTES AND CELL MEDIATED IMMUNITY
ACTIVATION OF T LYMPHOCYTES AND CELL MEDIATED IMMUNITY The recognition of specific antigen by naïve T cell induces its own activation and effector phases. T helper cells recognize peptide antigens through
More informationCOURSE: Medical Microbiology, MBIM 650/720 - Fall TOPIC: Antigen Processing, MHC Restriction, & Role of Thymus Lecture 12
COURSE: Medical Microbiology, MBIM 650/720 - Fall 2008 TOPIC: Antigen Processing, MHC Restriction, & Role of Thymus Lecture 12 FACULTY: Dr. Mayer Office: Bldg. #1, Rm B32 Phone: 733-3281 Email: MAYER@MED.SC.EDU
More informationAdvances in Cancer Immunotherapy
Advances in Cancer Immunotherapy Immunology 101 for the Non-Immunologist Arnold H. Zea, PhD azea@lsuhsc.edu Disclosures No relevant financial relationships to disclose This presentation does not contain
More informationEffector T Cells and
1 Effector T Cells and Cytokines Andrew Lichtman, MD PhD Brigham and Women's Hospital Harvard Medical School 2 Lecture outline Cytokines Subsets of CD4+ T cells: definitions, functions, development New
More informationThe development of T cells in the thymus
T cells rearrange their receptors in the thymus whereas B cells do so in the bone marrow. The development of T cells in the thymus The lobular/cellular organization of the thymus Immature cells are called
More informationTCR, MHC and coreceptors
Cooperation In Immune Responses Antigen processing how peptides get into MHC Antigen processing involves the intracellular proteolytic generation of MHC binding proteins Protein antigens may be processed
More informationImmunodermatology. Danielle Tartar, MD, PhD Assistant Clinical Professor Co-Director of Inpatient Dermatology University of California - Davis
Immunodermatology Danielle Tartar, MD, PhD Assistant Clinical Professor Co-Director of Inpatient Dermatology University of California - Davis Outline Adaptive Immunity: T and B cell development, activation,
More information1. Overview of Adaptive Immunity
Chapter 17A: Adaptive Immunity Part I 1. Overview of Adaptive Immunity 2. T and B Cell Production 3. Antigens & Antigen Presentation 4. Helper T cells 1. Overview of Adaptive Immunity The Nature of Adaptive
More informationFollicular Lymphoma. ced3 APOPTOSIS. *In the nematode Caenorhabditis elegans 131 of the organism's 1031 cells die during development.
Harvard-MIT Division of Health Sciences and Technology HST.176: Cellular and Molecular Immunology Course Director: Dr. Shiv Pillai Follicular Lymphoma 1. Characterized by t(14:18) translocation 2. Ig heavy
More informationLymphoid Organs and Lymphocyte Trafficking. Dr. Issa Abu-Dayyeh
Lymphoid Organs and Lymphocyte Trafficking Dr. Issa Abu-Dayyeh Invader recognition Where does invader recognition take place?? Secondary lymphoid organs: Lymph nodes Spleen Mucosal-associated lymphoid
More informationThe T cell receptor for MHC-associated peptide antigens
1 The T cell receptor for MHC-associated peptide antigens T lymphocytes have a dual specificity: they recognize polymporphic residues of self MHC molecules, and they also recognize residues of peptide
More informationLECTURE 12: MUCOSAL IMMUNITY GUT STRUCTURE
LECTURE 12: MUCOSAL IMMUNITY GUT STRUCTURE - Small intestine in humans is around 3-4 metres long - Internal surface of the small intestines are lined by villi o Villi are composed of absorptive cells (epithelial/enterocytes)
More informationWHY IS THIS IMPORTANT?
CHAPTER 16 THE ADAPTIVE IMMUNE RESPONSE WHY IS THIS IMPORTANT? The adaptive immune system protects us from many infections The adaptive immune system has memory so we are not infected by the same pathogen
More informationAdaptive Immunity. PowerPoint Lecture Presentations prepared by Mindy Miller-Kittrell, North Carolina State University C H A P T E R
PowerPoint Lecture Presentations prepared by Mindy Miller-Kittrell, North Carolina State University C H A P T E R 16 Adaptive Immunity The Body s First Line of Defense Innate Immunity The Role of Skin
More informationall of the above the ability to impart long term memory adaptive immunity all of the above bone marrow none of the above
1. (3 points) Immediately after a pathogen enters the body, it faces the cells and soluble proteins of the innate immune system. Which of the following are characteristics of innate immunity? a. inflammation
More informationImmunology for the Rheumatologist
Immunology for the Rheumatologist Rheumatologists frequently deal with the immune system gone awry, rarely studying normal immunology. This program is an overview and discussion of the function of the
More informationIntroduction to Immunology Part 2 September 30, Dan Stetson
Introduction to Immunology Part 2 September 30, 2016 Dan Stetson stetson@uw.edu 441 Lecture #2 Slide 1 of 26 CLASS ANNOUNCEMENT PLEASE NO TREE NUTS IN CLASS!!! (Peanuts, walnuts, almonds, cashews, etc)
More informationChapter 1. Chapter 1 Concepts. MCMP422 Immunology and Biologics Immunology is important personally and professionally!
MCMP422 Immunology and Biologics Immunology is important personally and professionally! Learn the language - use the glossary and index RNR - Reading, Note taking, Reviewing All materials in Chapters 1-3
More informationThe Adaptive Immune Response. T-cells
The Adaptive Immune Response T-cells T Lymphocytes T lymphocytes develop from precursors in the thymus. Mature T cells are found in the blood, where they constitute 60% to 70% of lymphocytes, and in T-cell
More informationChapter 11. B cell generation, Activation, and Differentiation. Pro-B cells. - B cells mature in the bone marrow.
Chapter B cell generation, Activation, and Differentiation - B cells mature in the bone marrow. - B cells proceed through a number of distinct maturational stages: ) Pro-B cell ) Pre-B cell ) Immature
More informationAdaptive Immunity. PowerPoint Lecture Presentations prepared by Mindy Miller-Kittrell, North Carolina State University C H A P T E R
PowerPoint Lecture Presentations prepared by Mindy Miller-Kittrell, North Carolina State University C H A P T E R 16 Adaptive Immunity The Body s Third Line of Defense Adaptive Immunity Adaptive immunity
More informationOverview B cell development T cell development
Topics Overview B cell development T cell development Lymphocyte development overview (Cont) Receptor diversity is produced by gene rearrangement and is random Includes specificities that will bind to
More informationNormal GC initiation then collapse; normal mutation and 10. Constitutive signalling leads to spontaneous GC in PP, even BCR -/- 19
S1 Genetic modifications affecting germinal-centre formation and function Gene Compartment GC Phenotype Ref LTα, LTβ, TNF, Organ Disorganized lymphoid architecture in spleens; poor 1 TNFRI, LTβR architecture
More informationDefensive mechanisms include :
Acquired Immunity Defensive mechanisms include : 1) Innate immunity (Natural or Non specific) 2) Acquired immunity (Adaptive or Specific) Cell-mediated immunity Humoral immunity Two mechanisms 1) Humoral
More informationAdaptive Immunity. PowerPoint Lecture Presentations prepared by Mindy Miller-Kittrell, North Carolina State University C H A P T E R
CSLO7. Describe functions of host defenses and the immune system in combating infectious diseases and explain how immunizations protect against specific diseases. PowerPoint Lecture Presentations prepared
More informationStructure and Function of Antigen Recognition Molecules
MICR2209 Structure and Function of Antigen Recognition Molecules Dr Allison Imrie allison.imrie@uwa.edu.au 1 Synopsis: In this lecture we will examine the major receptors used by cells of the innate and
More informationMedical Virology Immunology. Dr. Sameer Naji, MB, BCh, PhD (UK) Head of Basic Medical Sciences Dept. Faculty of Medicine The Hashemite University
Medical Virology Immunology Dr. Sameer Naji, MB, BCh, PhD (UK) Head of Basic Medical Sciences Dept. Faculty of Medicine The Hashemite University Human blood cells Phases of immune responses Microbe Naïve
More informationChapter 17B: Adaptive Immunity Part II
Chapter 17B: Adaptive Immunity Part II 1. Cell-Mediated Immune Response 2. Humoral Immune Response 3. Antibodies 1. The Cell-Mediated Immune Response Basic Steps of Cell-Mediated IR 1 2a CD4 + MHC cl.
More informationInnate immunity (rapid response) Dendritic cell. Macrophage. Natural killer cell. Complement protein. Neutrophil
1 The immune system The immune response The immune system comprises two arms functioning cooperatively to provide a comprehensive protective response: the innate and the adaptive immune system. The innate
More informationImmunology Basics Relevant to Cancer Immunotherapy: T Cell Activation, Costimulation, and Effector T Cells
Immunology Basics Relevant to Cancer Immunotherapy: T Cell Activation, Costimulation, and Effector T Cells Andrew H. Lichtman, M.D. Ph.D. Department of Pathology Brigham and Women s Hospital and Harvard
More informationThe recruitment of leukocytes and plasma proteins from the blood to sites of infection and tissue injury is called inflammation
The migration of a particular type of leukocyte into a restricted type of tissue, or a tissue with an ongoing infection or injury, is often called leukocyte homing, and the general process of leukocyte
More informationChapter 11. B cell generation, Activation, and Differentiation. Pro-B cells. - B cells mature in the bone marrow.
Chapter B cell generation, Activation, and Differentiation - B cells mature in the bone marrow. - B cells proceed through a number of distinct maturational stages: ) Pro-B cell ) Pre-B cell ) Immature
More informationExamples of questions for Cellular Immunology/Cellular Biology and Immunology
Examples of questions for Cellular Immunology/Cellular Biology and Immunology Each student gets a set of 6 questions, so that each set contains different types of questions and that the set of questions
More informationImmune Regulation and Tolerance
Immune Regulation and Tolerance Immunoregulation: A balance between activation and suppression of effector cells to achieve an efficient immune response without damaging the host. Activation (immunity)
More informationChapter 2 (pages 22 33): Cells and Tissues of the Immune System. Prepared by Kristen Dazy, MD, Scripps Clinic Medical Group
Allergy and Immunology Review Corner: Cellular and Molecular Immunology, 8th Edition By Abul K. Abbas, MBBS; Andrew H. H. Lichtman, MD, PhD; and Shiv Pillai, MBBS, PhD. Chapter 2 (pages 22 33): Cells and
More informationT-cell activation T cells migrate to secondary lymphoid tissues where they interact with antigen, antigen-presenting cells, and other lymphocytes:
Interactions between innate immunity & adaptive immunity What happens to T cells after they leave the thymus? Naïve T cells exit the thymus and enter the bloodstream. If they remain in the bloodstream,
More informationT-cell activation T cells migrate to secondary lymphoid tissues where they interact with antigen, antigen-presenting cells, and other lymphocytes:
Interactions between innate immunity & adaptive immunity What happens to T cells after they leave the thymus? Naïve T cells exit the thymus and enter the bloodstream. If they remain in the bloodstream,
More informationLESSON 2: THE ADAPTIVE IMMUNITY
Introduction to immunology. LESSON 2: THE ADAPTIVE IMMUNITY Today we will get to know: The adaptive immunity T- and B-cells Antigens and their recognition How T-cells work 1 The adaptive immunity Unlike
More informationκ λ Antigen-Independent B-Cell Development Bone Marrow Ordered Rearrangement of Ig Genes During B-Cell Development in the Bone Marrow
Antigen-Independent B-Cell Development Bone Marrow 1. DNA rearrangements establish the primary repertoire, creating diversity 2. Allelic exclusion ensures that each clone expresses a single antibody on
More informationT Cell Activation, Costimulation and Regulation
1 T Cell Activation, Costimulation and Regulation Abul K. Abbas, MD University of California San Francisco 2 Lecture outline T cell antigen recognition and activation Costimulation, the B7:CD28 family
More information2014 Pearson Education, Inc. Exposure to pathogens naturally activates the immune system. Takes days to be effective Pearson Education, Inc.
The innate immune interact with the adaptive immune system 1. Damage to skin causes bleeding = bradykinin activated, resulting in inflammation 2. Dendritic phagocytose pathogens Adaptive immunity 4. Dendritic
More informationREVIEWS. Dynamics of B cells in germinal centres
FOCUS ON 50 years of B cells REVIEWS Dynamics of B cells in germinal centres Nilushi S. De Silva and Ulf Klein Abstract Humoral immunity depends on the germinal centre (GC) reaction during which somatically
More informationAdaptive Immunity: Specific Defenses of the Host
17 Adaptive Immunity: Specific Defenses of the Host SLOs Differentiate between innate and adaptive immunity, and humoral and cellular immunity. Define antigen, epitope, and hapten. Explain the function
More informationThird line of Defense. Topic 8 Specific Immunity (adaptive) (18) 3 rd Line = Prophylaxis via Immunization!
Topic 8 Specific Immunity (adaptive) (18) Topics - 3 rd Line of Defense - B cells - T cells - Specific Immunities 1 3 rd Line = Prophylaxis via Immunization! (a) A painting of Edward Jenner depicts a cow
More informationIntroduction to Immunology Lectures 1-3 by Bellur S. Prabhakar. March 13-14, 2007
Introduction to Immunology Lectures 1-3 by Bellur S. Prabhakar. March 13-14, 2007 TheComponents Of The Immune System and Innate Immunity: Ref: Immunobiology-5 th edition. Janeway et al. Chapters-1 & 2.
More informationThe Immune System: Innate and Adaptive Body Defenses Outline PART 1: INNATE DEFENSES 21.1 Surface barriers act as the first line of defense to keep
The Immune System: Innate and Adaptive Body Defenses Outline PART 1: INNATE DEFENSES 21.1 Surface barriers act as the first line of defense to keep invaders out of the body (pp. 772 773; Fig. 21.1; Table
More informationTest Bank for Basic Immunology Functions and Disorders of the Immune System 4th Edition by Abbas
Test Bank for Basic Immunology Functions and Disorders of the Immune System 4th Edition by Abbas Chapter 04: Antigen Recognition in the Adaptive Immune System Test Bank MULTIPLE CHOICE 1. Most T lymphocytes
More informationReview Questions: Janeway s Immunobiology 8th Edition by Kenneth Murphy
Review Questions: Janeway s Immunobiology 8th Edition by Kenneth Murphy Chapter 11 (pages 429-460): Dynamics of Adaptive Immunity prepared by Kelly von Elten, Walter Reed National Military Medical Center,
More informationGeneral Overview of Immunology. Kimberly S. Schluns, Ph.D. Associate Professor Department of Immunology UT MD Anderson Cancer Center
General Overview of Immunology Kimberly S. Schluns, Ph.D. Associate Professor Department of Immunology UT MD Anderson Cancer Center Objectives Describe differences between innate and adaptive immune responses
More informationThird line of Defense
Chapter 15 Specific Immunity and Immunization Topics -3 rd of Defense - B cells - T cells - Specific Immunities Third line of Defense Specific immunity is a complex interaction of immune cells (leukocytes)
More informationLecture 9: T-cell Mediated Immunity
Lecture 9: T-cell Mediated Immunity Questions to Consider How do T cells know where to go? Questions to Consider How do T cells know where to go? How does antigen get targeted to a T cell expressing the
More informationThe Adaptive Immune Responses
The Adaptive Immune Responses The two arms of the immune responses are; 1) the cell mediated, and 2) the humoral responses. In this chapter we will discuss the two responses in detail and we will start
More informationWhite Blood Cells (WBCs)
YOUR ACTIVE IMMUNE DEFENSES 1 ADAPTIVE IMMUNE RESPONSE 2! Innate Immunity - invariant (generalized) - early, limited specificity - the first line of defense 1. Barriers - skin, tears 2. Phagocytes - neutrophils,
More informationFoundations in Microbiology
Foundations in Microbiology Fifth Edition Talaro Chapter 15 The Acquisition of Specific Immunity and Its Applications Chapter 15 2 Chapter Overview 1. Development of the Dual Lymphocyte System 2. Entrance
More informationDevelopment of B and T lymphocytes
Development of B and T lymphocytes What will we discuss today? B-cell development T-cell development B- cell development overview Stem cell In periphery Pro-B cell Pre-B cell Immature B cell Mature B cell
More informationB and T cell Memory. Bengt Lindbom Adap6ve Immunity BMC D14
B and T cell Memory Bengt Lindbom Adap6ve Immunity BMC D14 Immunity: a historical perspec6ve 430 B.C. Thucydides describes the ongoing plague of Athens:.the same man was never attacked twice 15th century:
More informationMicro 204. Cytotoxic T Lymphocytes (CTL) Lewis Lanier
Micro 204 Cytotoxic T Lymphocytes (CTL) Lewis Lanier Lewis.Lanier@ucsf.edu Lymphocyte-mediated Cytotoxicity CD8 + αβ-tcr + T cells CD4 + αβ-tcr + T cells γδ-tcr + T cells Natural Killer cells CD8 + αβ-tcr
More informationB Lymphocyte Development and Activation
Harvard-MIT Division of Health Sciences and Technology HST.176: Cellular and Molecular Immunology Course Director: Dr. Shiv Pillai 09/26/05; 9 AM Shiv Pillai B Lymphocyte Development and Activation Recommended
More informationPrinciples of Adaptive Immunity
Principles of Adaptive Immunity Chapter 3 Parham Hans de Haard 17 th of May 2010 Agenda Recognition molecules of adaptive immune system Features adaptive immune system Immunoglobulins and T-cell receptors
More informationMucosal Immunology Sophomore Dental and Optometry Microbiology Section I: Immunology. Robin Lorenz
Mucosal Immunology Sophomore Dental and Optometry Microbiology Section I: Immunology Robin Lorenz rlorenz@uab.edu Why do we Need to Understand How the Mucosal Immune System Works? The mucosa is the major
More informationI. Lines of Defense Pathogen: Table 1: Types of Immune Mechanisms. Table 2: Innate Immunity: First Lines of Defense
I. Lines of Defense Pathogen: Table 1: Types of Immune Mechanisms Table 2: Innate Immunity: First Lines of Defense Innate Immunity involves nonspecific physical & chemical barriers that are adapted for
More information5/1/13. The proportion of thymus that produces T cells decreases with age. The cellular organization of the thymus
T cell precursors migrate from the bone marrow via the blood to the thymus to mature 1 2 The cellular organization of the thymus The proportion of thymus that produces T cells decreases with age 3 4 1
More informationQuestion 1. Kupffer cells, microglial cells and osteoclasts are all examples of what type of immune system cell?
Abbas Chapter 2: Sarah Spriet February 8, 2015 Question 1. Kupffer cells, microglial cells and osteoclasts are all examples of what type of immune system cell? a. Dendritic cells b. Macrophages c. Monocytes
More informationVMC-221: Veterinary Immunology and Serology (1+1) Question Bank
VMC-221: Veterinary Immunology and Serology (1+1) Objective type Questions Question Bank Q. No. 1 - Fill up the blanks with correct words 1. The British physician, who developed the first vaccine against
More informationI. Critical Vocabulary
I. Critical Vocabulary A. Immune System: a set of glands, tissues, cells, and dissolved proteins that combine to defend against non-self entities B. Antigen: any non-self chemical that triggers an immune
More informationThe generation of antibody-secreting plasma cells
REVIEWS The generation of antibody-secreting plasma cells Stephen L. Nutt, Philip D. Hodgkin, David M. Tarlinton and Lynn M. Corcoran Abstract The regulation of antibody production is linked to the generation
More informationChapter 23 Immunity Exam Study Questions
Chapter 23 Immunity Exam Study Questions 1. Define 1) Immunity 2) Neutrophils 3) Macrophage 4) Epitopes 5) Interferon 6) Complement system 7) Histamine 8) Mast cells 9) Antigen 10) Antigens receptors 11)
More informationAntigen Presentation to Lymphocytes
Antigen Presentation to Lymphocytes Jiyang O Wang, Chiba Cancer Center Research Institute, Chiba, Japan Takeshi Watanabe, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan Antigen presentation
More informationProperties & Overview of IRs Dr. Nasser M. Kaplan JUST, Jordan. 10-Jul-16 NM Kaplan 1
Properties & Overview of IRs Dr. Nasser M. Kaplan JUST, Jordan 10-Jul-16 NM Kaplan 1 Major components of IS & their properties Definitions IS = cells & molecules responsible for: 1- Physiologic; protective
More informationThere are 2 major lines of defense: Non-specific (Innate Immunity) and. Specific. (Adaptive Immunity) Photo of macrophage cell
There are 2 major lines of defense: Non-specific (Innate Immunity) and Specific (Adaptive Immunity) Photo of macrophage cell Development of the Immune System ery pl neu mφ nk CD8 + CTL CD4 + thy TH1 mye
More informationCellular & Molecular Immunology 2009
Cellular & Molecular Immunology 2009 Complement Nicholas M. Ponzio, Ph.D. Department of Pathology & Laboratory Medicine March 4, 2009 Innate and adaptive immunity FAMOUS BELGIANS Jules Jean Baptiste Vincent
More information1. The scavenger receptor, CD36, functions as a coreceptor for which TLR? a. TLR ½ b. TLR 3 c. TLR 4 d. TLR 2/6
Allergy and Immunology Review Corner: Cellular and Molecular Immunology, 8th Edition By Abul K. Abbas, MBBS, Andrew H. H. Lichtman, MD, PhD and Shiv Pillai, MBBS, PhD. Chapter 4 (pages 62-74): Innate Immunity
More informationThe Major Histocompatibility Complex (MHC)
The Major Histocompatibility Complex (MHC) An introduction to adaptive immune system before we discuss MHC B cells The main cells of adaptive immune system are: -B cells -T cells B cells: Recognize antigens
More informationimmunity produced by an encounter with an antigen; provides immunologic memory. active immunity clumping of (foreign) cells; induced by crosslinking
active immunity agglutination allografts immunity produced by an encounter with an antigen; provides immunologic memory. clumping of (foreign) cells; induced by crosslinking of antigenantibody complexes.
More informationMolecular Pathology of Lymphoma (Part 1) Rex K.H. Au-Yeung Department of Pathology, HKU
Molecular Pathology of Lymphoma (Part 1) Rex K.H. Au-Yeung Department of Pathology, HKU Lecture outline Time 10:00 11:00 11:15 12:10 12:20 13:15 Content Introduction to lymphoma Review of lymphocyte biology
More informationAdaptive (acquired) immunity. Professor Peter Delves University College London
Adaptive (acquired) immunity Professor Peter Delves University College London p.delves@ucl.ac.uk Haematopoiesis Haematopoiesis Lymphocytes = adaptive response Recognition of pathogens by adaptive cells,
More informationScott Abrams, Ph.D. Professor of Oncology, x4375 Kuby Immunology SEVENTH EDITION
Scott Abrams, Ph.D. Professor of Oncology, x4375 scott.abrams@roswellpark.org Kuby Immunology SEVENTH EDITION CHAPTER 11 T-Cell Activation, Differentiation, and Memory Copyright 2013 by W. H. Freeman and
More informationDefense mechanism against pathogens
Defense mechanism against pathogens Immune System What is immune system? Cells and organs within an animal s body that contribute to immune defenses against pathogens ( ) Bacteria -Major entry points ;open
More information