T Cell Receptor & T Cell Development

Save this PDF as:
 WORD  PNG  TXT  JPG

Size: px
Start display at page:

Download "T Cell Receptor & T Cell Development"

Transcription

1 T Cell Receptor & T Cell Development

2 Questions for the next 2 lectures: How do you generate a diverse T cell population with functional TCR rearrangements? How do you generate a T cell population that is self-mhc restricted? How do you ensure that those diverse T cell receptors are not-self reactive? How do you coordinate lineage specification with MHC specificity and coreceptor expression? - vs. T cell - CD4 vs. CD8 2

3 T lymphocyte: a key regulator of the immune system

4 T Lymphocytes Arise from stem cells resident in the bone marrow and migrate to the thymus which serves as an indoctrination center where thymocytes must learn to distinguish self from nonself Thymocytes that cannot make this induction are eliminated, those that can may further differentiate, mature, and graduate as T lymphocytes and enter the circulation

5 Origin, generation and differentiation of T cells

6 T Cell Development T cell progenitors migrate from bone marrow and seed thymus. T cell progenitors undergo differentiation to CD4, CD8 and NKT cells in thymus. Mature CD4 and CD8 T cells circulate between blood and lymphoid tissues until they meet antigens presented on dendritic cells in lymphoid tissues. T cells further undergo maturation to become functional memory or effector T cells in LT

7 Figure 5-2 Thymic involution: Human thymus is fully developed before birth and increases in size until puberty. It then progressively shrinks during adult life. Most thymectomized adults have no problem in T cell immunity because they have enough memory T cells in the periphery, and these T cells are longlived.

8 T Cell Functions Collectively, T cells display a number of diverse functions: - They often function to initiate, regulate, and fine-tune humoral immune response - They are effector cells responsible for various types of cell mediated immune responses like; DTH, contact sensitivity, transplantation immunity, and cytotoxicity

9 T Cell Surface Molecules TCR: A very diverse heterodimer that lacks a cytoplasmic tail that would allow direct cytoplasmic signaling once TCR binds an epitope CD3 Complex: It is composed of a group of six invariant accessory molecules; one CD3, one CD3, two CD3ε, and an intracytoplasmic homodimer of ξ or CD247 chains Cytoplasmic signaling occurs through CD3 that noncovalently associate with TCR

10 TCR Complex Figure 3-6

11 The CD3 complex is essential for both cell surface expression of the TCR and for signal transduction once the TCR recognizes an antigen Unlike antibodies that can readily bind free antigen, a TCR cannot bind soluble antigens, but only enzymatically cleaved fragments of larger peptides presented as peptide MHC (pmhc) complexes

12 CD4 or CD8: Most mature T cells express CD4 or CD8 molecules, they function as important co-receptors in association with the TCR By binding to invariant portions of the MHC I (CD8) or MHC II (CD4), they serve to increase the interaction of the MHC-bound antigenic fragment and the TCR

13 The structures of CD4 and CD8 Figure 3-10

14 CD8 binds MHC class I CD4 binds MHC class II Most mature T cells are either CD4+ or CD8+. CD8 T cells kill cells infected with intracellular pathogens or tumor cells while CD4 T cells regulate (activate or suppress) other immune cells function.

15 Both: TCR Vs Immunoglobulin Bind antigen Have Variable region and Constant region Have a binding site that is a heterodimer (composed of 2 different chains) TCRs act only as receptors Igs act as receptors and effector molecules (soluble antigen-binding molecules)

16 Similarity between TCR and Ig

17 TCR Structure The TCR is a member of the immunoglobulin supergene family and is composed of two polypeptide chains; a light α or chain and a heavy β or chain Each polypeptide chain of the heterodimer pair contains a variable and a constant region domain The Vα and V regions are encoded by V and J gene clusters The Vβ and V regions are encoded by V, D, and J gene clusters The D gene cluster provides an additional source of variation

18 Figure 3-7

19 and TCR gene loci (germline configuration)

20 The gene clusters undergo DNA rearrangement, similar to that already described for immunoglobulin genes, to synthesize αβ dimers or dimers As with immunoglobulins, the constant domain of the α and β or and chains are encode by constant region genes (Cα and Cβ or C or C ) T cell receptors do not undergo any subsequent changes equivalent to isotype switch, and somatic hypermutation, important to generating diversity of immunoglobulins.

21 As might be imagined, in the random process of generating diversity, a variety of TCR specificities would be generated for peptides that one may never encounter during his lifetime Three distinct categories of TCR specificities can be identified: - Those that recognize peptides that will never be encountered - Those that recognize peptides produced by potential pathogens or peptides of foreign origin - Those that recognize peptides that are produced by cells of self

22 TcR gene rearrangement by SOMATIC RECOMBINATION Germline TcR V n V 2 V 1 J C Rearranged TcR 1 transcript Spliced TcR mrna Rearrangement very similar to the IgL chains

23 TcR gene rearrangement RESCUE PATHWAY There is only a 1:3 chance of the join between the V and J region being in frame V n+1 V n V 2 V 1 J C chain tries for a second time to make a productive join using new V and J elements Productively rearranged TcR 1 transcript

24 TcR gene rearrangement SOMATIC RECOMBINATION L & V x52 D 1 J C 1 D 2 J C 2 Germline TcR D-J Joining V-DJ joining Rearranged TcR 1 transcript C-VDJ joining Spliced TcR mrna

25 TcR gene rearrangement RESCUE PATHWAY There is a 1:3 chance of productive D-J rearrangement and a 1:3 chance of productive V D-J rearrangement (i.e only a 1:9 chance of a productive chain rearrangement) V D 1 J C 1 D 2 J C 2 D-J Joining Germline TcR V-DJ joining 2 nd chance at V-DJ joining Need to remove non productive rearrangement Use (DJC) 2 elements

26 TCR gene rearrangements occur in the thymus n=70-80 n=52 The same RSS and the same enzymes are used to rearrange both the TCR genes and the Ig genes. P and N nucleotides are added at the junctions between rearranged segments

27 V TCR Chain D region can be read in all frames D GTACTGCAGATT J J starts with ATT No additions: J is in frame V V V D J GTACCTGCAGATT D J GTACCTGCAGGATT D J GTACCTGCAGGCATT One addition and J is out of frame; the ATT start for J is lost (as are all appropriate downstream codons) Two addition and J is out of frame; the ATT start for J is lost (as are all appropriate downstream codons) Three addition and J is in frame; the ATT start for J is is present (as are all appropriate downstream codons)

28 -chain locus is first to be rearranged

29 Two chances for productive (=correct reading frame) rearrangement: chain

30 -chain rearrangement

31 Multiple rounds of -chain rearrangement can rescue nonproductive TCR

32 TCR gene rearrangement generates the TCR repertoire Pre-TCR complex stops further gene rearrangement at locus, and induces thymocyte proliferation Finally TCR+ DP cells are made

33 Germline configuration of and loci TCR D, J and C exons are encoded in the intron between the the Vs and the Js of the TCR locus. The V segments for TCR (4 known) are mixed in with the V segments of the TCR

34

35 Figure 3-8 part 2 of 2 Most T cells do not express CD4 or CD8. They are thought to be: First line of defense? Bridge between innate and adaptive responses?

36 Signals through the TCR and the pre-tcr compete to determine thymocyte lineage

37 Generation of diversity in the TcR COMBINATORIAL DIVERSITY Multiple germline segments In the human TcR Variable (V) segments: ~70, 52 Diversity (D) segments: 0, 2 Joining (J) segments: 61, 13 The need to pair and chains to form a binding site doubles the potential for diversity JUNCTIONAL DIVERSITY Addition of non-template encoded (N) and palindromic (P) nucleotides at imprecise joints made between V-D-J elements SOMATIC MUTATION IS NOT USED TO GENERATE DIVERSITY IN TcR

38 The Generation of Diversity (GOD)

39 T Cell Development T cell precursors migrate from the bone marrow to enter the thymus as thymocytes, they express neither αβtcr nor CD4 or CD8 and are called double negative (DN) cells DN cells proliferate in the subcapsular region of the thymus and differentiate to express low levels of newly generated αβtcr, both CD4 and CD8, and are called double positive (DP) cells

40 DP cells move inward to the deeper portion of the thymus, where they are fated to die within 3-4 days, unless their TCRs recognize an MHC class I or class II molecules on thymic dendritic cells. This process is called positive selection Although the mechanism of positive selection is yet unclear, partial recognition of class II by CD4 or class I by CD8 molecules must occur T cells that recognize self MHC molecules survive

41 A DP thymocyte with a TCR that engage MHC class I may become a CD8 + T cell and a DP thymocyte that recognizes MHC class II may become a CD4 + T cell Class I and class II molecules are not displayed on cell surface unless they are loaded with a peptide Only molecules of self origin are available on thymic APCs, and these are presented to the DP thymocyte in the deep or medullary area of the thymus

42 CD4+CD8+ DP cells: To be CD4 or CD8?

43 Thymocytes that show strong interaction with MHC molecules or pmhc complexes undergo apoptosis, a process known as negative selection Thymocytes that survive both positive and negative selection migrate from the thymus to populate lymphoid tissues and organs as T cells

44 Figure 5-3 part 2 of 2

45 Each thymocyte maturation stage occurs at a distinct location of the thymus Young adult:~5x10 7 thymocytes produced/day ~1.5x10 6 mature cells leave/day

46 Differentiation Figure 5-3 part 1 of 2 DN (CD4-CD8-) and DP (CD4+CD8+) Immature thymocytes are here More mature SP (CD4+CD8-or CD8+CD4-) thymocytes are here

47 Positive Selection Positive selection selects T cells that recognize peptides on self MHC This is to assure that mature T cells can respond to antigen-presented on self MHC. Self MHC I and II harboring self peptides on thymic epithelial cells recognize and activate TCRs on some DP thymocytes. DP thymocytes should receive this signal within 3-4 days to survive, otherwise they undergo apoptosis.

48 Negative Selection Negative selection eliminates T cells with TCRs that bind too strongly to self antigen/mhc complex (autoreactive cells are removed by this process) Dendritic cells and macrophages in corticomedullary junction mediate it. Negative selection cannot eliminate T cells whose receptors are specific for self peptides that are present outside of the thymus These cells enter circulation, but soon to be rendered anergic or unresponsive by other mechanims.

49

50 Does receptor occupancy explain positive and negative selection? Low occupancy Survival High occupancy Negative selection

51 Does the TIME of receptor occupancy explain positive and negative selection? Short occupancy Survival Long occupancy Negative selection Short signaling Long signaling

52 Stage of maturation can be distinguished by the expression of specific surface molecules DN DP SP

53 Types of T cells Conventional: Uses TCR Helper (CD4+) and cytotoxic (CD8+) T cells More abundant and highly specific Restricted by classical MHC (I and II) molecules Non-conventional: Uses TCR Primitive with broad specificity Restricted by non-classical molecules

54 CD4+ T cells T cells with CD4 marker (glycoprotein) represent 70% of T cells in the periphery Named T helper cells Play central role in modulating cellular immunity via secretion of cytokines that mediate: B cell activation Immunoglobulin secretion (quality) Macrophage and dendritic cell activation Cellular chemotaxis and inflammation Two subsets; Th1 and Th2 cells

55 Th1 and Th2 cells CD4+ T helper cells can be classified into two types based on their cytokine profiles: T helper cell type 1 (Th1) and T helper cell type 2 (Th2). Cytokine profile is influenced by several factors: Nature and dose of antigen Route of administration Type of antigen presenting cell/ costimulation Genetic background The cytokine profile determines the effector function of the helper cell

56 Differentiation of naive CD4 T cells into different subclasses

57 The nature and amount of ligand determine CD4 T cell functional phenotype

58 T Helper (CD4 + ) Subsets Antigen APC FasL Suicide Fas Th1 DR4 Pro-Inflammatory Cytokines Th1 response Cellular Immunity DTH IL-12 IFN- IL-2 LT Th0 IL-4 Th2 IL-4 IL-10 IL-13 IL-5 IL-6 Anti- Inflammatory Cytokines Th2 response, Humoral Immunity and Acute Hypersensitivity

59 Differences between Th1 and Th2 cells Th1 cell Produces type 1 cytokines IL-2, IFN-, TNF-α, TNF-β Activates macrophages and DCs for intracellular killing of pathogens Mediates CMI Th2 cell Produces type 2 cytokines IL-4, IL-5, IL-10, IL-13 Provides help to B cells in antibody response Mediates allergy and immunity to extracellular pathogens, including parasites

60 Cytotoxic T cells T cells that express CD8 molecule on their surface and they represent 30% of T cells in the periphery Destroy cells infected by intracellular pathogens and cancer cells Class I MHC molecules (nucleated body cells) expose foreign proteins TC cell releases perforin and granzymes, proteins that form pores in the target cell membrane; causing cell lysis and/or apoptosis

61

62 Effector molecules of T cell subsets

63 Regulation of the Immune Response How does the immune system prevent self reactivity while maintaining reactivity to invaders/non-self? Clonal deletion/inactivation of autoreactive cells Regulatory T cells keep potentially pathogenic self reactive T cells in check through suppressive mechanisms

64 New T cell phenotypes Regulatory T cells Naturally occurring (CD25 positive) Induced (IL-10 and TGF-β) Some NK T cells Suppressor T cells Th17 cells: produce IL-17, role in acute inflammation, suppress Th2.

65 Bettelli et al., Nature 2008

66 Th17 and Treg

67 Regulatory T Cells (Treg) CD3 +, TcR +, CD4 +, CD25 + Function Suppress the activity of effector Th and Tc cells Inhibition is antigen specific and MHC restricted Inhibition depends on cell:cell contact Appear to function in autoimmunity Development Develop in the bone marrow from DP cells Arise as a result of strong binding to self MHC and self Ag during negative selection. Alternative to cell death or anergy Development and maintenance are dependent upon B7

68 What are the requirements for Treg development? TCR engagement in the thymus (high affinity but not so high as negative selection) Higher percentage of thymocytes with high affinity TCR in context of auto antigen develop into regs T cells of appropriate affinity are instructed to become Tregs Selective sparing of pre-committed cells from negative selection or promotion of Treg lineage development? higher percentage, but not higher absolute number Preferential elimination of non-regulatory T cells rather than increased production of Tregs TCR engagement serves as survival or expansion signal of Tregs pre-committed to that lineage.

69 GITR CD4 Foxp3 T reg CD25 The T reg cell phenotype CTLA-4 CD4 Co-receptor for TCR recognition of MHC II/Ag CD25 IL-2R IL-2R component, confers high affinity binding to IL-2R Key T R growth factor CTLA-4 cytotoxic T lymphocyte Ag-4 Binds to B7s (CD80/86) on APC, acts as co-stimulatory molecule for T R (blocking CTLA-4 inhibits T R ) GITR glucocorticoid induced TNF related protein Ligation inhibits TR function (agonist inhibit T R, blocking augments T R ) FoxP3 Forkhead /winged-helix TF critical for T R activity and development Unlike surface markers / receptors, T E do not express FoxP3

70 Modulation of immune responses by T reg cells T reg cells are crucial for the induction and maintenance of peripheral tolerance to self-antigens T reg cells can also suppress immune responses to 1. Tumor antigens 2. Alloantigen 3. Allergens 4. Microbial antigens Tumor Clearance T reg Microbial Immunity Self-tolerance Transplantation Autoimmunity tolerance Transplant rejection Graft-versus Tumor Self-tolerance Progression host disease Microbial Immunocompetence Allergy Persistence T eff Sheng Cai

Defensive mechanisms include :

Defensive 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 information

T cell development October 28, Dan Stetson

T cell development October 28, Dan Stetson T cell development October 28, 2016 Dan Stetson stetson@uw.edu 441 Lecture #13 Slide 1 of 29 Three lectures on T cells (Chapters 8, 9) Part 1 (Today): T cell development in the thymus Chapter 8, pages

More information

ACTIVATION OF T LYMPHOCYTES AND CELL MEDIATED IMMUNITY

ACTIVATION 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 information

Introduction. Introduction. Lymphocyte development (maturation)

Introduction. Introduction. Lymphocyte development (maturation) Introduction Abbas Chapter 8: Lymphocyte Development and the Rearrangement and Expression of Antigen Receptor Genes Christina Ciaccio, MD Children s Mercy Hospital January 5, 2009 Lymphocyte development

More information

The Adaptive Immune Response. T-cells

The 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 information

The Adaptive Immune Responses

The 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 information

Introduction to Immunology Part 2 September 30, Dan Stetson

Introduction 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 information

T Cell Effector Mechanisms I: B cell Help & DTH

T Cell Effector Mechanisms I: B cell Help & DTH T Cell Effector Mechanisms I: B cell Help & DTH Ned Braunstein, MD The Major T Cell Subsets p56 lck + T cells γ δ ε ζ ζ p56 lck CD8+ T cells γ δ ε ζ ζ Cα Cβ Vα Vβ CD3 CD8 Cα Cβ Vα Vβ CD3 MHC II peptide

More information

General 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 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 information

Antibodies and T Cell Receptor Genetics Generation of Antigen Receptor Diversity

Antibodies and T Cell Receptor Genetics Generation of Antigen Receptor Diversity Antibodies and T Cell Receptor Genetics 2008 Peter Burrows 4-6529 peterb@uab.edu Generation of Antigen Receptor Diversity Survival requires B and T cell receptor diversity to respond to the diversity of

More information

Effector T Cells and

Effector 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 information

White Blood Cells (WBCs)

White 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 information

Immunology 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 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 information

Innate immunity (rapid response) Dendritic cell. Macrophage. Natural killer cell. Complement protein. Neutrophil

Innate 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 information

The Major Histocompatibility Complex (MHC)

The 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 information

SEVENTH EDITION CHAPTER

SEVENTH EDITION CHAPTER Judy Owen Jenni Punt Sharon Stranford Kuby Immunology SEVENTH EDITION CHAPTER 16 Tolerance, Autoimmunity, and Transplantation Copyright 2013 by W. H. Freeman and Company Immune tolerance: history * Some

More information

Chapter 23 Immunity Exam Study Questions

Chapter 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 information

Cell-mediated Immunity

Cell-mediated Immunity Cellular & Molecular Immunology Cell-mediated Immunity Nicholas M. Ponzio, Ph.D. Department of Pathology & Laboratory Medicine April 6, 2009 Today s Presentation: Overview Cellular Interactions In Humoral

More information

T-cell activation T cells migrate to secondary lymphoid tissues where they interact with antigen, antigen-presenting cells, and other lymphocytes:

T-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 information

Adaptive Immunity. Jeffrey K. Actor, Ph.D. MSB 2.214,

Adaptive Immunity. Jeffrey K. Actor, Ph.D. MSB 2.214, Adaptive Immunity Jeffrey K. Actor, Ph.D. MSB 2.214, 500-5344 Lecture Objectives: Understand role of various molecules including cytokines, chemokines, costimulatory and adhesion molecules in the development

More information

Adaptive Immunity: Specific Defenses of the Host

Adaptive 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 information

Antigen Receptor Structures October 14, Ram Savan

Antigen Receptor Structures October 14, Ram Savan Antigen Receptor Structures October 14, 2016 Ram Savan savanram@uw.edu 441 Lecture #8 Slide 1 of 28 Three lectures on antigen receptors Part 1 (Today): Structural features of the BCR and TCR Janeway Chapter

More information

T Cell Differentiation

T Cell Differentiation T Cell Differentiation Ned Braunstein, MD MHC control of Immune Responsiveness: Concept Whether or not an individual makes an immune response to a particular antigen depends on what MHC alleles an individual

More information

Examples of questions for Cellular Immunology/Cellular Biology and Immunology

Examples 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 information

WHY IS THIS IMPORTANT?

WHY 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 information

There 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 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 information

Allergy and Immunology Review Corner: Chapter 1 of Immunology IV: Clinical Applications in Health and Disease, by Joseph A. Bellanti.

Allergy and Immunology Review Corner: Chapter 1 of Immunology IV: Clinical Applications in Health and Disease, by Joseph A. Bellanti. Allergy and Immunology Review Corner: Chapter 1 of Immunology IV: Clinical Applications in Health and Disease, by Joseph A. Bellanti. Chapter 1: Overview of Immunology Prepared by David Scott, MD, Scripps

More information

Chapter 11. B cell generation, Activation, and Differentiation. Pro-B cells. - B cells mature in the bone marrow.

Chapter 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 information

Page 4: Antigens: Self-Antigens The body has a vast number of its own antigens called self-antigens. These normally do not trigger immune responses.

Page 4: Antigens: Self-Antigens The body has a vast number of its own antigens called self-antigens. These normally do not trigger immune responses. Common Characteristics of B and T Lymphocytes Graphics are used with permission of Pearson Education Inc., publishing as Benjamin Cummings (http://www.aw-bc.com). Page 1: Introduction While B and T lymphocytes

More information

Antigen-Independent B-Cell Development Bone Marrow

Antigen-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 information

Two categories of immune response. immune response. infection. (adaptive) Later immune response. immune response

Two categories of immune response. immune response. infection. (adaptive) Later immune response. immune response Ivana FELLNEROVÁ E-mail: fellneri@hotmail.com, mob. 732154801 Basic immunogenetic terminology innate and adaptive immunity specificity and polymorphism immunoglobuline gene superfamily immunogenetics MHC

More information

Chapter 11. B cell generation, Activation, and Differentiation. Pro-B cells. - B cells mature in the bone marrow.

Chapter 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 information

Cell Mediated Immunity CELL MEDIATED IMMUNITY. Basic Elements of Cell Mediated Immunity (CMI) Antibody-dependent cell-mediated cytotoxicity (ADCC)

Cell Mediated Immunity CELL MEDIATED IMMUNITY. Basic Elements of Cell Mediated Immunity (CMI) Antibody-dependent cell-mediated cytotoxicity (ADCC) Chapter 16 CELL MEDIATED IMMUNITY Cell Mediated Immunity Also known as Cellular Immunity or CMI The effector phase T cells Specificity for immune recognition reactions TH provide cytokines CTLs do the

More information

The 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. 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 information

IMMUNE CELL SURFACE RECEPTORS AND THEIR FUNCTIONS

IMMUNE CELL SURFACE RECEPTORS AND THEIR FUNCTIONS LECTURE: 07 Title: IMMUNE CELL SURFACE RECEPTORS AND THEIR FUNCTIONS LEARNING OBJECTIVES: The student should be able to: The chemical nature of the cellular surface receptors. Define the location of the

More information

Introduction. 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. 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 information

Basic Immunology. Lecture 5 th and 6 th Recognition by MHC. Antigen presentation and MHC restriction

Basic Immunology. Lecture 5 th and 6 th Recognition by MHC. Antigen presentation and MHC restriction Basic Immunology Lecture 5 th and 6 th Recognition by MHC. Antigen presentation and MHC restriction Molecular structure of MHC, subclasses, genetics, functions. Antigen presentation and MHC restriction.

More information

Chapter 21: Innate and Adaptive Body Defenses

Chapter 21: Innate and Adaptive Body Defenses Chapter 21: Innate and Adaptive Body Defenses I. 2 main types of body defenses A. Innate (nonspecific) defense: not to a specific microorganism or substance B. Adaptive (specific) defense: immunity to

More information

Allergy and Immunology Review Corner: Chapter 19 of Immunology IV: Clinical Applications in Health and Disease, by Joseph A. Bellanti, MD.

Allergy and Immunology Review Corner: Chapter 19 of Immunology IV: Clinical Applications in Health and Disease, by Joseph A. Bellanti, MD. Allergy and Immunology Review Corner: Chapter 19 of Immunology IV: Clinical Applications in Health and Disease, by Joseph A. Bellanti, MD. Chapter 19: Tolerance, Autoimmunity, and Autoinflammation Prepared

More information

Properties & 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 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 information

Introduction to the Immune System

Introduction to the Immune System MICR2209 Introduction to the Immune System Dr Allison Imrie allison.imrie@uwa.edu.au 1 Synopsis: In this lecture we will review basic concepts in immunology, including the cells of the immune system, the

More information

Biochemistry. Immunology. Principal Investigator. Dr. Sunil Kumar Khare,Professor Dept. of Chemistry, I.I.T. Delhi

Biochemistry. Immunology. Principal Investigator. Dr. Sunil Kumar Khare,Professor Dept. of Chemistry, I.I.T. Delhi Paper : 16 Module : 19 Principal Investigator Paper Coordinator and Content Writer Dr. Sunil Kumar Khare,Professor Dept. of Chemistry, I.I.T. Delhi Dr. M.N.Gupta, Emeritus Professor Dept. of Biochemical

More information

Chapter 21 The Immune System: Innate and Adaptive Body Defenses

Chapter 21 The Immune System: Innate and Adaptive Body Defenses Chapter 21 The Immune System: Innate and Adaptive Body Defenses 1/25/2016 1 Annie Leibovitz/Contact Press Images The Immune System Immune system provides resistance to disease Made up of two intrinsic

More information

JPEMS Nantes, Basic Immunology Introduction to the immune system Definitions Structure and General Organization

JPEMS Nantes, Basic Immunology Introduction to the immune system Definitions Structure and General Organization JPEMS Nantes, 2014- Basic Immunology Introduction to the immune system Definitions Structure and General Organization Teacher: Pr. Régis Josien, Laboratoire Immunologie and INSERM U1064, CHU Nantes Regis.Josien@univ-nantes.fr

More information

Significance of the MHC

Significance of the MHC CHAPTER 8 Major Histocompatibility Complex (MHC) What is is MHC? HLA H-2 Minor histocompatibility antigens Peter Gorer & George Sneell (1940) Significance of the MHC role in immune response role in organ

More information

Question 1. Kupffer cells, microglial cells and osteoclasts are all examples of what type of immune system cell?

Question 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 information

Significance of the MHC

Significance of the MHC CHAPTER 7 Major Histocompatibility Complex (MHC) What is is MHC? HLA H-2 Minor histocompatibility antigens Peter Gorer & George Sneell (1940) Significance of the MHC role in immune response role in organ

More information

A second type of TCR TCR: An αβ heterodimer

A second type of TCR TCR: An αβ heterodimer How s recognize antigen: The T Cell Receptor (TCR) Identifying the TCR: Why was it so hard to do By the early 1980s, much about function was known, but the receptor genes had not been identified Recall

More information

Clinical Basis of the Immune Response and the Complement Cascade

Clinical Basis of the Immune Response and the Complement Cascade Clinical Basis of the Immune Response and the Complement Cascade Bryan L. Martin, DO, MMAS, FACAAI, FAAAAI, FACOI, FACP Emeritus Professor of Medicine and Pediatrics President, American College of Allergy,

More information

Antigen presenting cells

Antigen presenting cells Antigen recognition by T and B cells - T and B cells exhibit fundamental differences in antigen recognition - B cells recognize antigen free in solution (native antigen). - T cells recognize antigen after

More information

Autoimmunity. Autoimmunity arises because of defects in central or peripheral tolerance of lymphocytes to selfantigens

Autoimmunity. Autoimmunity arises because of defects in central or peripheral tolerance of lymphocytes to selfantigens Autoimmunity Autoimmunity arises because of defects in central or peripheral tolerance of lymphocytes to selfantigens Autoimmune disease can be caused to primary defects in B cells, T cells and possibly

More information

Regulatory T Cells and Maintenance of Tolerance

Regulatory T Cells and Maintenance of Tolerance Regulatory Cells and Maintenance of olerance Stephen Canfield, MD, PhD Asst. Prof. Medicine smc12@columbia.edu What constitutes immune tolerance? Discrimination between: non-self and self e.g., virally

More information

IMMUNITY AND DISEASE II

IMMUNITY AND DISEASE II IMMUNITY AND DISEASE II A. Evolution of the immune system. 1. Figure 1--57.25, p. 1167 from Raven and Johnson Biology 6 th ed. shows how the immune system evolved. Figure 1. How the immune system evolved.

More information

Antigen Presentation to T lymphocytes

Antigen Presentation to T lymphocytes Antigen Presentation to T lymphocytes Immunology 441 Lectures 6 & 7 Chapter 6 October 10 & 12, 2016 Jessica Hamerman jhamerman@benaroyaresearch.org Office hours by arrangement Antibodies and T cell receptors

More information

Microbiology 204: Cellular and Molecular Immunology

Microbiology 204: Cellular and Molecular Immunology Microbiology 204: Cellular and Molecular Immunology Class meets MWF 1:00-2:30PM (*exceptions: no class Fri Sept 23, Fri Oct 14, Nov 11, or Wed Nov 23) Lectures are open to auditors and will be live-streamed

More information

Lymphatic System. Where s your immunity idol?

Lymphatic System. Where s your immunity idol? Lymphatic System Where s your immunity idol? Functions of the Lymphatic System Fluid Balance Drains excess fluid from tissues Lymph contains solutes from plasma Fat Absorption Lymphatic system absorbs

More information

1. The scavenger receptor, CD36, functions as a coreceptor for which TLR? a. TLR ½ b. TLR 3 c. TLR 4 d. TLR 2/6

1. 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 information

Significance of the MHC

Significance of the MHC CHAPTER 8 Major Histocompatibility Complex (MHC) What is MHC? HLA H-2 Minor histocompatibility antigens Peter Gorer & George Sneell (1940) - MHC molecules were initially discovered during studies aimed

More information

The Immune System is the Third Line of Defense Against Infection. Components of Human Immune System

The Immune System is the Third Line of Defense Against Infection. Components of Human Immune System Chapter 17: Specific Host Defenses: The Immune Response The Immune Response Immunity: Free from burden. Ability of an organism to recognize and defend itself against specific pathogens or antigens. Immune

More information

Stage I Stage II Stage III Stage IV

Stage I Stage II Stage III Stage IV Harvard-MIT Division of Health Sciences and Technology HST.176: Cellular and Molecular Immunology Course Director: Dr. Shiv Pillai Stage I Stage II Stage III Stage IV Receptor gene Rearrangement Elimination

More information

Unit 6: Adaptive Immunity. Adaptive Immunity (Humoral Immunity; Cell-Mediated Immunity; Immunodeficiency; Hypersensitivity)

Unit 6: Adaptive Immunity. Adaptive Immunity (Humoral Immunity; Cell-Mediated Immunity; Immunodeficiency; Hypersensitivity) Unit 6: Adaptive Immunity Adaptive Immunity (Humoral Immunity; Cell-Mediated Immunity; Immunodeficiency; Hypersensitivity) : ADAPTIVE IMMUNITY: AN OVERVIEW OF INNATE AND ADAPTIVE IMMUNITY Adaptive Immunity

More information

Lymphoid tissue. 1. Central Lymphoid tissue. - The central lymphoid tissue (also known as primary) is composed of bone morrow and thymus.

Lymphoid tissue. 1. Central Lymphoid tissue. - The central lymphoid tissue (also known as primary) is composed of bone morrow and thymus. 1. Central Lymphoid tissue Lymphoid tissue - The central lymphoid tissue (also known as primary) is composed of bone morrow and thymus. Bone Morrow - The major site of hematopoiesis in humans. - Hematopoiesis

More information

Topics in Parasitology BLY Vertebrate Immune System

Topics in Parasitology BLY Vertebrate Immune System Topics in Parasitology BLY 533-2008 Vertebrate Immune System V. Vertebrate Immune System A. Non-specific defenses against pathogens 1. Skin - physical barrier a. Tough armor protein KERATIN b. Surface

More information

Chapter 22: The Lymphatic System and Immunity

Chapter 22: The Lymphatic System and Immunity Immunity or Resistance Chapter 22: The Lymphatic System and Immunity Ability to ward off damage or disease through our defenses 2 types of immunity Innate or nonspecific immunity present at birth No specific

More information

Chapter 15. The Lymphatic System and Immunity

Chapter 15. The Lymphatic System and Immunity Chapter 15 The Lymphatic System and Immunity Objectives Describe general functions of the lymphatic system and list the main lymphatic structures Compare nonspecific and specific immunity Name the major

More information

CTLA-4 regulates pathogenicity of antigen-specific autoreactive T cells by cell-intrinsic and -extrinsic mechanisms

CTLA-4 regulates pathogenicity of antigen-specific autoreactive T cells by cell-intrinsic and -extrinsic mechanisms Class 15, BBS821: Control of pathogenic self-reactive T cells by co-inhibitory molecules, J. Kang Oct 29, 2015 CTLA-4 regulates pathogenicity of antigen-specific autoreactive T cells by cell-intrinsic

More information

Class I Ag processing. TAP= transporters associated with antigen processing Transport peptides into ER

Class I Ag processing. TAP= transporters associated with antigen processing Transport peptides into ER Antigen processing Class I Ag processing TAP= transporters associated with antigen processing Transport peptides into ER Proteosome degrades cytosolic proteins Large, multi-subunit complex Degrades foreign

More information

Lines of Defense. Immunology, Immune Response, and Immunological Testing. Immunology Terminology

Lines of Defense. Immunology, Immune Response, and Immunological Testing. Immunology Terminology Immunology, Immune Response, and Immunological Testing Lines of Defense If the First and Second lines of defense fail, then the Third line of defense is activated. B and T lymphocytes undergo a selective

More information

Autoimmune diseases. Autoimmune diseases. Autoantibodies. Autoimmune diseases relatively common

Autoimmune diseases. Autoimmune diseases. Autoantibodies. Autoimmune diseases relatively common Autoimmune diseases Fundamental abnormality: the adaptive immune system is triggered by self antigens to initiate a sustained immune response against self molecules that results in tissue injury Specificity

More information

Sustained adaptive immune response to self antigens may or may not result in tissue injury according to particular host genetics

Sustained adaptive immune response to self antigens may or may not result in tissue injury according to particular host genetics Autoimmune diseases Fundamental abnormality: the adaptive immune system is triggered by self antigens to initiate a sustained immune response against self molecules that results in tissue injury Specificity

More information

CANCER IMMUNOPATHOLOGY. Eryati Darwin Faculty of Medicine Andalas University

CANCER IMMUNOPATHOLOGY. Eryati Darwin Faculty of Medicine Andalas University CANCER IMMUNOPATHOLOGY Eryati Darwin Faculty of Medicine Andalas University Padang 18 Mei 2013 INTRODUCTION Tumor: cells that continue to replicate, fail to differentiate into specialized cells, and become

More information

Generation of post-germinal centre myeloma plasma B cell.

Generation of post-germinal centre myeloma plasma B cell. Generation of post-germinal centre myeloma. DNA DAMAGE CXCR4 Homing to Lytic lesion activation CD38 CD138 CD56 Phenotypic markers Naive Secondary lymphoid organ Multiple myeloma is a malignancy of s caused

More information

MHC class I MHC class II Structure of MHC antigens:

MHC class I MHC class II Structure of MHC antigens: MHC class I MHC class II Structure of MHC antigens: MHC class I antigens consist of a transmembrane heavy chain (α chain) that is non-covalently associated with β2- microglobulin. Membrane proximal domain

More information

The Major Histocompatibility Complex

The Major Histocompatibility Complex The Major Histocompatibility Complex Today we will discuss the MHC The study of MHC is necessary to understand how an immune response is generated. And these are the extra notes with respect to slides

More information

Adaptive Immune Response

Adaptive Immune Response OpenStax-CNX module: m44821 1 Adaptive Immune Response OpenStax College This work is produced by OpenStax-CNX and licensed under the Creative Commons Attribution License 3.0 By the end of this section,

More information

Microbiology 204: Cellular and Molecular Immunology

Microbiology 204: Cellular and Molecular Immunology Microbiology 204: Cellular and Molecular Immunology Class meets MWF 1:00-2:30PM (*exceptions: no class Fri Oct 11; Wed Nov 27 will be moved to 11/25) Lectures are open to auditors Discussions are restricted

More information

chapter 10 T-Cell Maturation, Activation, and Differentiation T-Cell Maturation and the Thymus

chapter 10 T-Cell Maturation, Activation, and Differentiation T-Cell Maturation and the Thymus 8536d_ch10_221 8/29/02 2:03 M age 221 mac83 Mac 83:379_kyw: T-Cell Maturation, Activation, and Differentiation chapter 10 THE ATTRIBUTE THAT DISTINGUISHES ANTIGEN recognition by most T cells from recognition

More information

IMMUNOBIOLOGY OF TRANSPLANTATION. Wasim Dar

IMMUNOBIOLOGY OF TRANSPLANTATION. Wasim Dar IMMUNOBIOLOGY OF TRANSPLANTATION Wasim Dar Immunobiology of Transplantation Overview Transplantation: A complex immunologic process Contributions Innate Immunity Adaptive immunity T Cells B Cells HLA Consequences

More information

AP Biology Campbell - Chapter 43 - The Immune System

AP Biology Campbell - Chapter 43 - The Immune System AP Biology Campbell - Chapter 43 - The Immune System Name What?...Read?...The Overview? Name the three general categories of pathogens: 1. 2. 3. Our immune system is designed to protect us against p Dedicated

More information

T cells III: Cytotoxic T lymphocytes and natural killer cells

T cells III: Cytotoxic T lymphocytes and natural killer cells T cells III: Cytotoxic T lymphocytes and natural killer cells Margrit Wiesendanger Division of Rheumatology, CUMC September 17, 2008 Killer cells: CD8 + T cells (adaptive) vs. natural killer (innate) Shared

More information

Immunity to Viruses. Patricia Fitzgerald-Bocarsly September 25, 2008

Immunity to Viruses. Patricia Fitzgerald-Bocarsly September 25, 2008 Immunity to Viruses Patricia Fitzgerald-Bocarsly September 25, 2008 The Immune System Deals with a Huge Range of Pathogens Roitt, 2003 Immune Responses to Viruses Viruses are dependent on the host cell

More information

Immune surveillance hypothesis (Macfarlane Burnet, 1950s)

Immune surveillance hypothesis (Macfarlane Burnet, 1950s) TUMOR-IMMUNITÄT A.K. Abbas, A.H. Lichtman, S. Pillai (6th edition, 2007) Cellular and Molecular Immunology Saunders Elsevier Chapter 17, immunity to tumors Immune surveillance hypothesis (Macfarlane Burnet,

More information

Bacterial Diseases IMMUNITY TO BACTERIAL INFECTIONS. Gram Positive Bacteria. Gram Negative Bacteria. Many Infectious agents and many diseases

Bacterial Diseases IMMUNITY TO BACTERIAL INFECTIONS. Gram Positive Bacteria. Gram Negative Bacteria. Many Infectious agents and many diseases IMMUNITY TO BACTERIAL INFECTIONS Chapter 18 Bacterial Diseases Many Infectious agents and many diseases Bacteria can Infect any part of the body Cause disease due to Growth of the microbe in a tissue Produce

More information

Following T-cell activation and differentiation with HTRF reagents: IL-2, IFN-γ and IL-17

Following T-cell activation and differentiation with HTRF reagents: IL-2, IFN-γ and IL-17 Following T-cell activation and differentiation with HTRF reagents: IL-2, IFN-γ and IL-17 4 th HTRF Symposium for Drug Discovery Avignon, Sept. 24-26, 28 Introduction: T-cells have effector and helper

More information

Chapter 24 The Immune System

Chapter 24 The Immune System Chapter 24 The Immune System The Immune System Layered defense system The skin and chemical barriers The innate and adaptive immune systems Immunity The body s ability to recognize and destroy specific

More information

I. 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 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 information

Principles of Anatomy and Physiology

Principles of Anatomy and Physiology Principles of Anatomy and Physiology 14 th Edition CHAPTER 22 The Lymphatic System and Immunity Introduction The purpose of this chapter is to: 1. Understand the lymphatic system structure and function

More information

Optimizing Intracellular Flow Cytometry:

Optimizing Intracellular Flow Cytometry: Optimizing Intracellular Flow Cytometry: Simultaneous Detection of Cytokines and Transcription Factors Presented by Jurg Rohrer, PhD, BD Biosciences 23-10780-00 Outline Introduction Cytokines Transcription

More information

Acquired Immunity 2. - Vaccines & Immunological Memory - Wataru Ise. WPI Immunology Frontier Research Center (IFReC) Osaka University.

Acquired Immunity 2. - Vaccines & Immunological Memory - Wataru Ise. WPI Immunology Frontier Research Center (IFReC) Osaka University. Acquired Immunity 2 - Vaccines & Immunological Memory - Wataru Ise WPI Immunology Frontier Research Center (IFReC) Osaka University Outline 1. What is vaccine (vaccination)? 2. What is immunological memory?

More information

Innate Immunity. Hathairat Thananchai, DPhil Department of Microbiology Faculty of Medicine Chiang Mai University 2 August 2016

Innate Immunity. Hathairat Thananchai, DPhil Department of Microbiology Faculty of Medicine Chiang Mai University 2 August 2016 Innate Immunity Hathairat Thananchai, DPhil Department of Microbiology Faculty of Medicine Chiang Mai University 2 August 2016 Objectives: Explain how innate immune system recognizes foreign substances

More information

Chapter 17. Immunity. Copyright 2015 Wolters Kluwer Health Lippincott Williams & Wilkins

Chapter 17. Immunity. Copyright 2015 Wolters Kluwer Health Lippincott Williams & Wilkins Chapter 17 Immunity Copyright 2015 Wolters Kluwer Health Lippincott Williams & Wilkins Overview Key Terms allergy dendritic cells mast cell anaphylaxis gamma globulin natural killer (NK) cell antibody

More information

VISTA, a novel immune checkpoint protein ligand that suppresses anti-tumor tumor T cell responses. Li Wang. Dartmouth Medical School

VISTA, a novel immune checkpoint protein ligand that suppresses anti-tumor tumor T cell responses. Li Wang. Dartmouth Medical School VISTA, a novel immune checkpoint protein ligand that suppresses anti-tumor tumor T cell responses Li Wang Dartmouth Medical School The B7 Immunoglobulin Super-Family immune regulators APC T cell Co-stimulatory:

More information