Antibody Structure and Function

Size: px
Start display at page:

Download "Antibody Structure and Function"

Transcription

1 Antibody Structure and Function Keri C. Smith, Ph.D. January 22, 2008 (or)

2 Anatomy and Physiology of Antibodies

3 Overview Physical properties of antibodies Structural and molecular features Differences between types of antibodies Functional properties of antibodies

4 Just a review

5 Antibodies are gamma-globulins globulins

6 Multiple Myeloma Case Study #19 γ κ

7 Anatomy of Ig Light and Heavy Chains Porter and Nisonoff used enzymes to cleave Ig, studied function of isolated fragments Edelman treated Ig with reducing agents to cleave S-S S S bonds, studied the resulting polypeptide chains

8 Ig Fragmentation and Domain Structures Fab portion can bind antigen Fc portion can be crystallized

9 Ig Light Chains Two types of Light chains are found in Ig of all animals, aa sequence differs Kappa chains-human 60%, mice 95% Lambda chains-human 40%, mice 5%

10 Ig Heavy Chains 5 classes of H chains in humans Similarities in aa sequence, but each class has a unique sequence H chains named with Greek letters corresponding with the class name, IgG, IgA, IgM, IgE, IgD (γ, α, μ, ε, δ) IgG has 4 subclasses, IgA has 2 subclasses

11 Domains Early studies showed regularity of structure of all the Ig classes Each aa has a 60 aa S-S S loop V domains code the paratope, binds Ag C domains code regions important for mediating secondary biological functions, ie binding Complement, crossing the placenta.

12 Human Ig Domain Functions

13 Ig Hinge Regions Hinge regions on IgG, IgA and IgD are coded by distinct exons Short span of aa between 1 st and 2 nd C domains Rich in Cys and Pro Provides for flexibility of the molecule Is readily accessible to solvent and enzymes

14 Ig Variable and Hypervariable Regions Amino terminal aa sequence was shown to vary from one L chain to another Kabat and Wu developed the Variability Plot to measure degree of variation Found 3 Hypervariable regions in both L and H chain V regions. These are epitope contact aa regions, CDR (complementarity determining regions)

15 Definition of Variability The ratio of the number of different amino acids at a given position to the frequency of the most common amino acid at that position is defined as VARIABILITY. Example: 63 L chains were sequenced and four amino acids were found at position 7. Serine occurred 41 times, ie frequency 41/63=0.65. Thus 4/0.65=6.15 Variability

16 Variability Plot

17 CDR in 3D

18 Ig Classes or Isotypes Result from structural variation in the heavy chains Are 5 major classes or isotypes of Ig in Humans IgG, IgA, IgM, IgE, IgD Subclasses: IgG (4) and IgA (2)

19 Features of Ig Isotypes

20 Ig Allotypes Allelic variants of Ig Constant regions Co-dominant autosomal Mendelian genes Are allotypic variants of γ, α,, and κ chains Allotypes used forensically Allotype may confer some biological advantage for some infectious agents

21 Human Kappa Light Chain Allotypes ALLOTYPE AMINO ACID DIFFERENCES Km(1) 153, 191 Km(1,2) 153, 191 Km(3) 153, 191

22 Allotype effects in infection Children with G2m(23) allotype had higher levels of immunity to H. influenzae type B than G2m(23)-negative children and the Km(1) allotype was found more effective than the other kappa chain allotypes. Ambrosino,, et al. 1985, J. Clin.. Invest. 75:1935; Granoff,, et al. 1986, J. Inf. Dis. 154:257.

23 Ig Idiotypes Idios: : Greek, unique for Ab of one specificity. Are epitopes in Ig V regions Provide a natural autoimmune mechanism for regulating Ab levels Anti-id id antibodies are routinely found and down-regulate production of Ab.

24 Two Examples of Idiotypes

25 Clinical Relevance of Idiotypes Active immunotherapy with 1E10 anti- idiotype vaccine in patients with small cell lung cancer: report of a phase I trial. Neninger et al. Cancer Biol. Ther :145

26 Iso, Allo,, or Idio???

27 Ig Structural Features

28 IgG Structural Features

29 IgG Structural Features II

30 IgG Subclasses IgG1, IgG2, IgG3, IgG4 Have about 90% homology in their amino acid sequences Differ in the numbers and arrangement of the interchain disulfide bonds This results in differences in their functional properties

31 IgG Subclasses (2)

32 IgG Subclasses (3) Important Differences Between Human IgG Subclasses IgG1 IgG2 IgG3 IgG4 Occurrence (% of total IgG) Half-life Complement binding Placental passage ++ ± Binding of monocytes ±

33 IgG Biological Properties (1) Most common Ig in serum Distributed approximately equally between intravascular and extravascular spaces Long half-life life

34 IgG Recylcing

35 IgG Biological Properties (2) Agglutination and Precipitation Placental passage (G1, G3, G4) Opsonization Antibody dependent cell mediated cytotoxicity (G1, G3) Complement Activation (G1, G2, G3+) Toxin/Viral Neutralization-- --Passive Ab infusion Bacterial immobilization

36 Three Roles for IgG

37 Clinical Correlation Hemolytic disease of the fetus/newborn. Maternal IgG antibodies specific for RhD are actively transported across the placenta, opsonize fetal RhD+ RBC for phagocytosis by liver cells, fetal hematocrit drops to dangerous or fatal levels. Case 45.

38 Antibody Dependent Cell- Mediated Cytotoxicity

39 IgG Review Gamma Globulin, Enzymatic Fragmentation L & H Chains, V & C Domains, Hinge Regions, Variability and Hypervariable regions 4 Isotypes (Classes) Allotypes, Idiotypes IgG Anatomy: γ H Chains, κ/λ L Chains IgG Physiology: Agglutination, Placental Passage, Opsonization, ADCC, Complement Binding, Toxin/Viral Neutralization, Bacterial Immobilization, Recycling

40 IgM Structural Features

41 IgM Biological Properties Efficient bacterial/viral agglutinator, potentially 10 paratopes/molecule Isohemagglutinin-naturally naturally present Ab reactive with A/B blood groups, barrier to random transfusion & transplantation Most efficient Ig for mediating Complement fixation Primary antibody response to challenge

42 Affinity and Avidity Due to it s s structure, IgM has can have the same affinity,, but a higher avidity for antigen

43 Blood Groups and Isohemagglutinins

44 Jessica Santillan Heart transplant patient Duke University Hospital, Feb. 03 Patient was type O, Donor was type A

45 Kinetics of a Normal Antibody Response

46 IgA Structural Features

47 IgA Subclasses

48 IgA Secretion Mechanism

49 Biological Properties of IgA Antibodies IgA is abundant on mucosal surfaces as a First Line Defense. IgA is bactericidal for Gram negative organisms in the presence of Lysozyme. IgA is an efficient viral agglutinator, preventing viral attachment to epithelial cell viral receptors. Plays a role in passive immunotherapy can be transferred from mother to child in breast milk.

50 IgD Structural Features

51 Biological Properties of IgD Antibodies IgD is not found in significant amounts in serum. Principal function involves initial Ag triggering of B cells while bound to the membrane on the surface of B cells.

52 IgE Structural Features

53 Biological Properties of IgE Antibodies IgE mediates Type I hypersensitivity reactions. IgE antibodies bind to Fcε receptors on Mast cells. Ag binding with the IgE antibody induces degranulation,, secretion of histamine, heparin, and other pharmacologic agents. Are high IgE levels in parasitic infections.

54 IgE-Fc Fcε Structure

55 IgE Cross-linking Leads to Mast Cell Triggering

56 Clinical Vignettes-Allergies Case #32 Acute Systemic Anaphylaxis: 22 month- old, ate a cookie with peanut butter in it, describes the symptoms (BP 40/0, norm is 80/60, pulse 185, norm 80-90, respiration 76, norm 20. Gave epinephrine, saline, anti-histamine, corticosteroids. Case #33 Allergic Asthma: 14 year old with persistent wheezing, reduced peak flow rate in lungs of 180 liter min -1 (normal> liter min -1 ) and reduced expiratory volume. Elevated serum IgE and eosinophils.. Treated with inhaled steriods,, oral antihistamine, and immunotherpeutic antigen injections

57 KISS OF DEATH

58 Kinetics of a Normal Antibody Response

59 Features of Ig Isotypes

60 Ig Superfamily There are structural similarities to Ig of the molecules of numerous membrane bound glycoprotein molecules such as the MHC molecules and the T cell receptor molecules. T cell receptors and triggering will be covered in another lecture.

61 Ig Superfamily Some Some Members

62 Antibody Engineering Single Chain Fv (ScFv( ScFv) Humanized antibodies Immunotoxins

63 Coda The function of antibodies, like the rest of the body, is only understood with a firm foundation in (molecular) anatomy. The 5 Ig isotypes each mediate specific biological effects, due to different C region amino acid sequences in their respective H chain.

Basic Antibody Structure. Multiple myeloma = cancerous plasma cells Monomer = 150,000. Chapter 4. Immunoglobulin Structure and Function

Basic Antibody Structure. Multiple myeloma = cancerous plasma cells Monomer = 150,000. Chapter 4. Immunoglobulin Structure and Function Chapter 4. Immunoglobulin Structure and Function. Functional Regions. Types of chains. Constant & Variable regions 4. Glycoprotein * * * Heavy chain= 446 aa Light chain= 4aa Each heavy and light chain

More information

Chapter 4. Antigen Recognition by B-cell and T-cell Receptors

Chapter 4. Antigen Recognition by B-cell and T-cell Receptors Chapter 4 Antigen Recognition by B-cell and T-cell Receptors Antigen recognition by BCR and TCR B cells 2 separate functions of immunoglobulin (Ig) bind pathogen & induce immune responses recruit cells

More information

Immunoglobulins: Structure and Function

Immunoglobulins: Structure and Function Immunoglobulins: Structure and Function Immunoglobulins:Structure and Function Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function as antibodies

More information

Immunoglobulins. Light chain ~22-23 KDa whereas the heavy chain ~55-60 KDa

Immunoglobulins. Light chain ~22-23 KDa whereas the heavy chain ~55-60 KDa Immunoglobulins Immunoglobulin (Ig) has a common name which is "Antibody (Ab)", but actually we should say Ig, why? Because the proteins, which are involved, are actually globular proteins "known as globulins"

More information

Protein homology. Antigens & Antibodies I. Administrative issues:

Protein homology. Antigens & Antibodies I. Administrative issues: Administrative issues: Recommended text: Goldsby/Kuby Immunology, 6th edition (Note that Innate Immunity is not adequately covered in the 5th edition.) Text book reading assignments are to supplement the

More information

Antibodies and Antigens in the Blood Bank 9/7/2015 NAHLA BAKHAMIS 1

Antibodies and Antigens in the Blood Bank 9/7/2015 NAHLA BAKHAMIS 1 Antibodies and Antigens in the Blood Bank NAHLA BAKHAMIS 9/7/2015 NAHLA BAKHAMIS 1 Outline Antibodies structure, classes and functions Most important Abs in the blood bank effective roles of Abs Zeta potential

More information

Immunoglobulins. Biological Properties

Immunoglobulins. Biological Properties Immunoglobulins Biological Properties Introduction Many important biological properties are attributed to antibodies that differ depending on isotype These include; - Neutralization of toxins - Immobilization

More information

Immunology: Antibody Basics

Immunology: Antibody Basics e-learning JABSOM Immunology: Antibody Basics One :: General Structure Identify the Parts of an Antibody Two :: Isotypes Identify Antibody Isotypes Three :: Function Match Antibody Functions With Isotypes

More information

Antibodies and Antigens In the blood bank

Antibodies and Antigens In the blood bank Antibodies and Antigens In the blood bank 1 Nice game!! http://nobelprize.org/ 2 Karl Landsteiner discovered blood groups in 1901. Awarded Nobel Prize for Physiology or Medicine in 1930 3 Why we study

More information

Immunoglobulins have protective functions which enable the living organism to fight multiple different infections.

Immunoglobulins have protective functions which enable the living organism to fight multiple different infections. Immunology 8 Immunoglobulins properties 20-6-2013 **Those are just extra notes for Immunoglobulins properties slides Introduction: Immunoglobulins have protective functions which enable the living organism

More information

Immunoglobulins. Harper s biochemistry Chapter 49

Immunoglobulins. Harper s biochemistry Chapter 49 Immunoglobulins Harper s biochemistry Chapter 49 Immune system Detects and inactivates foreign molecules, viruses, bacteria and microorganisms Two components with 2 strategies B Lymphocytes (humoral immune

More information

Chapter 2. Antibodies

Chapter 2. Antibodies Chapter 2. Antibodies An iddy-biddy antibody Just nanometers long Saved the butt of a sumo man Hundreds of kilos strong Anonymous The main elements of the immune system are firstly antibodies, secondly

More information

Antibody Structure. Antibodies

Antibody Structure. Antibodies Antibodies Secreted by B lymphocytes Great diversity and specificity: >10 9 different antibodies; can distinguish between very similar molecules Tag particles for clearance/destruction Protect against

More information

Antibody Structure supports Function

Antibody Structure supports Function Antibodies Secreted by B lymphocytes Great diversity and specificity: >10 9 different antibodies; can distinguish between very similar molecules Tag particles for clearance/destruction Protect against

More information

Immunoglobulins Harry W Schroeder Jr MD PhD

Immunoglobulins Harry W Schroeder Jr MD PhD Immunoglobulins Harry W Schroeder Jr MD PhD Division of Developmental and Clinical Immunology Departments of Medicine, Microbiology, and Genetics University of Alabama at Birmingham Immunoglobulin Has

More information

1 Name. 1. (3 pts) What is apoptosis and how does it differ from necrosis? Which is more likely to trigger inflammation?

1 Name. 1. (3 pts) What is apoptosis and how does it differ from necrosis? Which is more likely to trigger inflammation? 1 Name MCB 150 Midterm Eam #1 (100 points total) Please write your full name on each page of the eam!! The eam consists of 17 questions (6 pages). Each has a different point count as indicated. Please

More information

ANTIBODIES. Agents of Immunity

ANTIBODIES. Agents of Immunity ANTIBODIES Agents of Immunity - Antibodies are: The Organization What are they? Protective agents of the immune system Neutralize foreign agents called antigens Essential part of the Adaptive Immune System

More information

GENETIC BASIS OF ANTIBODY STRUCTURE AND DIVERSITY. Steven J. Norris, Ph.D

GENETIC BASIS OF ANTIBODY STRUCTURE AND DIVERSITY. Steven J. Norris, Ph.D GENETIC BASIS OF ANTIBODY STRUCTURE AND DIVERSITY Steven J. Norris, Ph.D Topics I. General principles II. The heavy chain Ig locus and VDJ rearrangement III. Light chain rearrangement. IV. Mechanisms of

More information

LECTURE: 22 IMMUNOGLOBULIN DIVERSITIES LEARNING OBJECTIVES: The student should be able to:

LECTURE: 22 IMMUNOGLOBULIN DIVERSITIES LEARNING OBJECTIVES: The student should be able to: LECTURE: 22 Title IMMUNOGLOBULIN DIVERSITIES LEARNING OBJECTIVES: The student should be able to: Identify the chromosome that contains the gene segments that encode the surface immunoglobulin heavy chain

More information

Understanding secondary antibodies

Understanding secondary antibodies Understanding secondary antibodies IgG Fragment antigen binding antibodies and isotypes D2 D2 F(ab ) 2 after pepsin cleavage www.abcam.com/secondary_antibody Antibody structure and F(ab) antibodies The

More information

Chapter 5. Genetic Models. Organization and Expression of Immunoglobulin Genes 3. The two-gene model: Models to Explain Antibody Diversity

Chapter 5. Genetic Models. Organization and Expression of Immunoglobulin Genes 3. The two-gene model: Models to Explain Antibody Diversity Chapter 5 Organization and Expression of Immunoglobulin Genes 3 4 5 6 Genetic Models How to account for: ) Vast diversity of antibody specificities ) Presence of Variable regions at the amino end of Heavy

More information

MOLECULAR RECOGNITION

MOLECULAR RECOGNITION MOLECULAR RECOGNITION Bioanalytical Methods Classification 1. Biassay: molecular recognition, signal generation and detection in solution or on inert solid phase 2. Biosensor: molecular recognition system

More information

Blood is 55% Plasma (Liquid)

Blood is 55% Plasma (Liquid) Blood is 55% Plasma (Liquid) The plasma portion of blood is: 91% Water Maintains blood volume Transports molecules 7% Proteins (ie: clotting proteins, albumin, immunoglobulins ) 2 % Salts, gases (O 2,

More information

CHAPTER 3 ANTIBODY STRUCTURE I

CHAPTER 3 ANTIBODY STRUCTURE I CHAPTER 3 ANTIBODY STRUCTURE I See APPENDIX: (3) OUCHTERLONY ANALYSIS; (6), EQUILIBRIUM DIALYSIS; (7) CROSS-REACTIVITY Electrophoretic separation of serum proteins identifies the GAMMA-GLOBULIN fraction

More information

Serology as a Diagnostic Technique

Serology as a Diagnostic Technique Serology as a Diagnostic Technique Characteristics of Any Diagnostic Techniques Any useful detection strategy must be: Specific: yield a positive response for only the target organism or molecule. Sensitive:

More information

MEDICAL IMMUNOLOGY 544. Dr. George A. Gutman

MEDICAL IMMUNOLOGY 544. Dr. George A. Gutman I M M U N O L O G Y CORE NOTES MEDICAL IMMUNOLOGY 544 FALL 2011 Dr. George A. Gutman SCHOOL OF MEDICINE UNIVERSITY OF CALIFORNIA, IRVINE (Copyright) 2011 Regents of the University of California TABLE OF

More information

Platelet Refractoriness: The Basics. Martin H. Bluth, MD, PhD

Platelet Refractoriness: The Basics. Martin H. Bluth, MD, PhD Platelet Refractoriness: The Basics Martin H. Bluth, MD, PhD Complete Toxicology Laboratories, LLC Objectives Define platelet refractoriness and associated conditions that may cause platelet refractoriness.

More information

Jaundiced Baby. Introduction to the Patient-Oriented Problem-Solving (POPS) System

Jaundiced Baby. Introduction to the Patient-Oriented Problem-Solving (POPS) System Jaundiced Baby Developed by Larry J. McCumber, PhD Parker A. Small, Jr, MD Department of Immunology and Medical Microbiology College of Medicine University of Florida Gainesville, Florida Modified by G.

More information

Practical Applications of Immunology (Chapter 18) Lecture Materials for Amy Warenda Czura, Ph.D. Suffolk County Community College Eastern Campus

Practical Applications of Immunology (Chapter 18) Lecture Materials for Amy Warenda Czura, Ph.D. Suffolk County Community College Eastern Campus Practical Applications of Immunology (Chapter 18) Lecture Materials for Amy Warenda Czura, Ph.D. Suffolk County Community College Eastern Campus Primary Source for figures and content: Tortora, G.J. Microbiology

More information

CHAPTER 7 CELLULAR BASIS OF ANTIBODY DIVERSITY: CLONAL SELECTION

CHAPTER 7 CELLULAR BASIS OF ANTIBODY DIVERSITY: CLONAL SELECTION CHAPTER 7 CELLULAR BASIS OF ANTIBODY DIVERSITY: CLONAL SELECTION The specificity of humoral immune responses relies on the huge DIVERSITY of antigen combining sites present in antibodies, diversity which

More information

B-cell Epitope Prediction and Cloning monoclonal ADAs

B-cell Epitope Prediction and Cloning monoclonal ADAs B-cell Epitope Prediction and Cloning monoclonal ADAs Stefan Ryser, CEO, Trellis Bioscience 3 rd International Symposium on Higher Order Structure of Protein Therapeutics Arlington, Virginia, February

More information

Assays for Immunogenicity: Are We There Yet?

Assays for Immunogenicity: Are We There Yet? Assays for Immunogenicity: Are We There Yet? Mark Wener, MD Department of Laboratory Medicine & Rheumatology Division Department of Medicine University of Washington Seattle, WA 98195 wener@uw.edu Goals:

More information

See more signal with less noise

See more signal with less noise See more signal with less noise SeraCare KPL Antibodies & Conjugates See more signal with less noise In nature many animals use camouflage to escape detection. An animal s survival often depends upon its

More information

Mechanisms of extravascular destruction of red cells coated with IgG1 or IgG3 (± C3b).

Mechanisms of extravascular destruction of red cells coated with IgG1 or IgG3 (± C3b). Introduction - Antibodies involved in transfusion reactions are of two types, namely the complete and the incomplete. - whereas the complete antibodies agglutinate red cells in saline medium, the incomplete

More information

COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP)

COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP) The European Agency for the Evaluation of Medicinal Products Evaluation of Medicines for Human Use London, 25 July 2002 EMEA/ COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP) NOTE FOR GUIDANCE ON THE

More information

Chapter 17: Immunization & Immune Testing. 1. Immunization 2. Diagnostic Immunology

Chapter 17: Immunization & Immune Testing. 1. Immunization 2. Diagnostic Immunology Chapter 17: Immunization & Immune Testing 1. Immunization 2. Diagnostic Immunology 1. Immunization Chapter Reading pp. 505-511 What is Immunization? A method of inducing artificial immunity by exposing

More information

Biomolecular chemistry. 7. Antibodies: structure and function

Biomolecular chemistry. 7. Antibodies: structure and function 154 Biomolecular chemistry 7. Antibodies: structure and function Suggested reading: Sections 5.1 to 5.3 of Mikkelsen and Cortón, Bioanalytical Chemistry Primary Source Material Biochemistry Chapter 33:

More information

Make High Quality Affordable

Make High Quality Affordable Protein Antibody Gene Kit Cell Lysate Fc receptor Antibody Cancer antigen ed NK-Cell le as Cancer-Cell Perfo r i n a n d G r a n zy r me e Make Quality Affordable Fc receptor Function and s Function:,

More information

DTT Treated Reagent Red Cells for use in Resolving DARA Interference. More Than Just Kell?? Marilyn Stewart MT(ASCP)SBB

DTT Treated Reagent Red Cells for use in Resolving DARA Interference. More Than Just Kell?? Marilyn Stewart MT(ASCP)SBB DTT Treated Reagent Red Cells for use in Resolving DARA Interference More Than Just Kell?? Marilyn Stewart MT(ASCP)SBB Daratumumab Anti-myeloma and anti-lymphoma agent known to interfere with routine Blood

More information

Basic Immunology Lecture 1 st and 2 nd

Basic Immunology Lecture 1 st and 2 nd Basic Immunology Lecture 1 st and 2 nd Introduction Requirements of the Department. Historical overview. Composition of the immune system. Molecular components of the immune systemes Immunological recognition

More information

CHAPTER 5 COMPLEMENT

CHAPTER 5 COMPLEMENT CHAPTER 5 COMPLEMENT See APPENDIX (8) COMPLEMENT FIXATION ASSAY The complex of serum proteins known as COMPLEMENT plays key roles in the lytic and inflammatory properties of antibodies. The CLASSICAL pathway

More information

LECTURE: 26 SIMPLE SEROLOGICAL LABORATORY TECHNIQUES LEARNING OBJECTIVES:

LECTURE: 26 SIMPLE SEROLOGICAL LABORATORY TECHNIQUES LEARNING OBJECTIVES: LECTURE: 26 Title SIMPLE SEROLOGICAL LABORATORY TECHNIQUES LEARNING OBJECTIVES: The student should be able to: Define the term "simple serological techniques". Describe the benefit of the use of serological

More information

Immunological Techniques in Research and Clinical Medicine. Philip L. Cohen, M.D. Chief of Rheumatology, LKSOM 10 March 2016

Immunological Techniques in Research and Clinical Medicine. Philip L. Cohen, M.D. Chief of Rheumatology, LKSOM 10 March 2016 Immunological Techniques in Research and Clinical Medicine Philip L. Cohen, M.D. Chief of Rheumatology, LKSOM 10 March 2016 Antibodies Remarkable Tools for Research and Diagnosis You can make an antibody

More information

Application of Biacore Technology

Application of Biacore Technology Principles and typical results Application of Biacore Technology Common types of Biacore analyses Specificity analysis Is my molecule of interest specific for its target? Multiple binding analysis In which

More information

Antigen-Antibody Interaction

Antigen-Antibody Interaction - Interaction JASON BROWNLEE Technical Report 070427A Complex Intelligent Systems Laboratory, Centre for Information Technology Research, Faculty of Information and Communication Technologies, Swinburne

More information

بسم هللا الرحمن الرحيم. Today we're going to talk about the generation of diversity of the receptors of the lymphocytes

بسم هللا الرحمن الرحيم. Today we're going to talk about the generation of diversity of the receptors of the lymphocytes بسم هللا الرحمن الرحيم Today we're going to talk about the generation of diversity of the receptors of the lymphocytes The receptors of lymphocytes are : 1. B cells : immunoglobulins ; which are cell bound

More information

There was a reduction in number of new individuals being vaccinated / vaccine uptake was lower / higher number of babies; 1 [7]

There was a reduction in number of new individuals being vaccinated / vaccine uptake was lower / higher number of babies; 1 [7] 1. (a) Antibody binds/eq/recognises only to cancer cells; because of antibody-antigen binding/eg; enzyme activates the drug; at cancer cells only; max 3 B lymphocytes produce antibodies/involved in humoral

More information

SPECIFICITY, DIVERSITY, AND IMMUNOGLOBULIN GENES

SPECIFICITY, DIVERSITY, AND IMMUNOGLOBULIN GENES SPECIFICITY, DIVERSITY, AND IMMUNOGLOBULIN GENES ANTIBODY SPECIFICITY. This can be thought of in terms of the goodness of fit (affinity) between an antigenic determinant and a lymphocyte receptor or antibody.

More information

T and B cell gene rearrangement October 17, Ram Savan

T and B cell gene rearrangement October 17, Ram Savan T and B cell gene rearrangement October 17, 2016 Ram Savan savanram@uw.edu 441 Lecture #9 Slide 1 of 28 Three lectures on antigen receptors Part 1 (Last Friday): Structural features of the BCR and TCR

More information

Guideline on immunogenicity assessment of monoclonal antibodies intended for in vivo clinical use.

Guideline on immunogenicity assessment of monoclonal antibodies intended for in vivo clinical use. 1 2 3 18 November 2010 EMA/CHMP/BMWP/86289/2010 Committee for Medicinal Products for Human Use (CHMP) 4 5 6 Guideline on immunogenicity assessment of monoclonal antibodies intended for in vivo clinical

More information

Application of Antibody

Application of Antibody Application of Antibody -Antibody -Western blot -Immunoprecipitation -Immunohistochemical staining -Elisa -Elispot -Flow cytometry -Fluorescenct microscope -EMSA -Affinity purification -Immunotoxin -Mimickry

More information

Generation of Recombinant Antibodies and Means for Increasing Their Affinity

Generation of Recombinant Antibodies and Means for Increasing Their Affinity ISSN 0006-2979, Biochemistry (Moscow), 2010, Vol. 75, No. 13, pp. 1584-1605. Pleiades Publishing, Ltd., 2010. Original Russian Text E. P. Altshuler, D. V. Serebryanaya, A. G. Katrukha, 2010, published

More information

Identification of Critical Product Quality Attributes: Impact of Product Variants on Safety and Efficacy

Identification of Critical Product Quality Attributes: Impact of Product Variants on Safety and Efficacy Identification of Critical Product Quality Attributes: Impact of Product Variants on Safety and Efficacy Ziping Wei, Ph.D. Analytical Biochemistry MedImmune January 25, 2010 Outline Why do we need to identify

More information

Assays and Strategies for Immunogenicity Assessment. Steven J Swanson, Ph.D. Executive Director, Medical Sciences Clinical Immunology, Amgen

Assays and Strategies for Immunogenicity Assessment. Steven J Swanson, Ph.D. Executive Director, Medical Sciences Clinical Immunology, Amgen Assays and Strategies for Immunogenicity Assessment Steven J Swanson, Ph.D. Executive Director, Medical Sciences Clinical Immunology, Amgen General Antibody Assay Strategy Correlation of clinical findings

More information

Peptide libraries: applications, design options and considerations. Laura Geuss, PhD May 5, 2015, 2:00-3:00 pm EST

Peptide libraries: applications, design options and considerations. Laura Geuss, PhD May 5, 2015, 2:00-3:00 pm EST Peptide libraries: applications, design options and considerations Laura Geuss, PhD May 5, 2015, 2:00-3:00 pm EST Overview 1 2 3 4 5 Introduction Peptide library basics Peptide library design considerations

More information

Immunology- Mic : First observed by Gruber and Durham when serum antibody was found to react with bacterial cells.

Immunology- Mic : First observed by Gruber and Durham when serum antibody was found to react with bacterial cells. Immunology- Mic 451 Lab -Notes 1. Agglutination is the aggregation of particulate matter caused by the combination with specific antibody 1896: First observed by Gruber and Durham when serum antibody was

More information

Immunotherapy in myeloma

Immunotherapy in myeloma Immunotherapy in myeloma This Horizons Infosheet contains information on immunotherapy, a type of treatment being investigated in myeloma. The Horizons Infosheet series provides information relating to

More information

IMMUNOGLOBULIN GENES UNDERGO TWO DNA REARRANGEMENTS

IMMUNOGLOBULIN GENES UNDERGO TWO DNA REARRANGEMENTS A Prototype Ig Gene: Murine Kappa About 10 0 V κ gene segments 4 J Gene Segment s 1 C κ Gene Segmen t Multiple V gene segments, distant from J and C A few J gene segments One C gene segment GERMLINE Ig

More information

IMMUNOBIOLOGY : AN INTRODUCTION

IMMUNOBIOLOGY : AN INTRODUCTION Immunobiology : An Introduction MODULE - 5 30 IMMUNO : AN INTRODUCTION We all get infections, but some of us fall sick more frequently than others. This is related to the immune system. Proper functioning

More information

BLOOD TYPING REAGENTS. Product Profile

BLOOD TYPING REAGENTS. Product Profile BLOOD TYPING REAGENTS Product Profile 2 BLOOD TYPING REAGENTS Its all about Human Blood Human blood is classified based on presence or absence of inherited antigens on the surface of red blood cells (RBCs).

More information

Veins Valves prevent engorgement and backflow. Baroreceptor reflex. Veins returning blood

Veins Valves prevent engorgement and backflow. Baroreceptor reflex. Veins returning blood Veins have large radii and low resistance. Walls are thin, not elastic Most blood volume is in veins Veins returning blood Veins Valves prevent engorgement and backflow Sympathetic NS constricts veins

More information

Skills: 20 points. Objectives:

Skills: 20 points. Objectives: Exercise 5 Type and Screen Skills: 20 points Objectives: 1. List three situations in which screening for unexpected antibodies should be performed. 2. List two patient populations who are candidates for

More information

Strategies for Assessment of Immunotoxicology in Preclinical Drug Development

Strategies for Assessment of Immunotoxicology in Preclinical Drug Development Strategies for Assessment of Immunotoxicology in Preclinical Drug Development Rebecca Brunette, PhD Scientist, Analytical Biology SNBL USA Preclinical Immunotoxicology The study of evaluating adverse effects

More information

SPHERO TM Coated Particles

SPHERO TM Coated Particles SPHERO TM Coated Particles Manufactured by either passive adsorption or covalent coupling depending upon the intended application Stable for several years under proper storage condition Available in a

More information

Laboratory Procedure Handout. IMMUNOGLOBULIN M IgM

Laboratory Procedure Handout. IMMUNOGLOBULIN M IgM KING ABDUL AZIZ UNIVERSITY FACULTY OF APPLEID MEDICAL SCIENCES DEPARTMENT OF MEDICAL LABORATORY TECHNOLOGY Laboratory Procedure Handout IMMUNOGLOBULIN M IgM Immunodiffusion single diffusion precipitation

More information

Immunohematology Practicum Objectives - CLS 645

Immunohematology Practicum Objectives - CLS 645 Clinical Laboratory Sciences Department University of Kansas Medical Center Immunohematology Practicum Objectives - CLS 645 The following objectives are to be completed by the student for successful completion

More information

A Level. A Level Biology. Cells, Microscopes, Cell Cycle and Immunity Questions. AQA, OCR, Edexcel. Name: Total Marks: Page 1

A Level. A Level Biology. Cells, Microscopes, Cell Cycle and Immunity Questions. AQA, OCR, Edexcel. Name: Total Marks: Page 1 AQA, OCR, Edexcel A Level A Level Biology Cells, Microscopes, Cell Cycle and Immunity Questions Name: Total Marks: Page 1 Q1.The diagram shows a eukaryotic cell. (a) Complete the table by giving the letter

More information

Adrenal Gland. MEDULLA Epinephrine CORTEX. Zona reticularis --adrenal androgen. Zona fasciculata --glucocorticoids

Adrenal Gland. MEDULLA Epinephrine CORTEX. Zona reticularis --adrenal androgen. Zona fasciculata --glucocorticoids STRESS AND IMMUNITY STRESS Defined as life under tension Homeostatic range: normal physiological balance Stressors: physical and emotional stimuli that disrupt homeostasis Eustress vs Distress Stress response:

More information

Case Report: Atypical Presentation of Anti-Rg a

Case Report: Atypical Presentation of Anti-Rg a 100 Case Report: Atypical Presentation of Anti-Rg a Eiad Kahwash, Sameer S.Talwalkar, Jill Leonard, and William Lockwood Department of Pathology and Laboratory Medicine, University of Louisville, Louisville,

More information

Strategies to Improve Drug Tolerance in Nab Assays

Strategies to Improve Drug Tolerance in Nab Assays Strategies to Improve Drug Tolerance in Nab Assays Steven J Swanson, PhD Senior Vice President, Research ImmunoCellular Therapeutics Ltd steven.swanson@imuc.com AAPS National Biotech Conference June 2015

More information

Emerging Antibody Approaches

Emerging Antibody Approaches Emerging Antibody Approaches Sudhir Paul University of Texas Houston Medical School With collaborations from Stephanie Planque, Yukie Mitsuda, Sari Sonoda, Sarah Murphy, Eric Brown, Yasuhiro Nishiyama

More information

The Science of Monoclonal Antibody Therapy: Introducing Canine Atopic Dermatitis Immunotherapeutic*

The Science of Monoclonal Antibody Therapy: Introducing Canine Atopic Dermatitis Immunotherapeutic* The Science of Monoclonal Antibody Therapy: Introducing Canine Atopic Dermatitis Immunotherapeutic* *This product license is conditional. Efficacy and potency test studies are in progress. Michele Rosenbaum,

More information

THE UNIVERSITY OF TEXAS AT EL PASO COLLEGE OF SCIENCE DEPARTMENT OF BIOLOGICAL SCIENCES SYLLABUS

THE UNIVERSITY OF TEXAS AT EL PASO COLLEGE OF SCIENCE DEPARTMENT OF BIOLOGICAL SCIENCES SYLLABUS THE UNIVERSITY OF TEXAS AT EL PASO COLLEGE OF SCIENCE DEPARTMENT OF BIOLOGICAL SCIENCES SYLLABUS Course #: MICR 4453 Course Title: Immunology CRNs: 12950, 12952, 12953, 15016, 17668 Credit Hrs: 4.0 Term:

More information

7/6/2017. Learning Objectives

7/6/2017. Learning Objectives Learning Objectives Monoclonal Antibody Therapeutics Potential Interferents on Protein Electrophoresis and Related Tests Maria Alice V. Willrich, Ph.D., DABCC At the end of the presentation, participants

More information

Passive vaccination as a global strategy for preventing RSV disease in infants. Filip Dubovsky MD MPH FAAP MedImmune March 2016

Passive vaccination as a global strategy for preventing RSV disease in infants. Filip Dubovsky MD MPH FAAP MedImmune March 2016 Passive vaccination as a global strategy for preventing RSV disease in infants Filip Dubovsky MD MPH FAAP MedImmune March 2016 Outline for Presentation Rationale for passive immunization for RSV prophylaxis

More information

American Association of Immunology Heidi Anderson: Lesson Plan for Cell Signaling and Immune System

American Association of Immunology Heidi Anderson: Lesson Plan for Cell Signaling and Immune System B cell Modeling of Cell Communication and Signal Transduction Pathways: How can students visualize cellular discussions? Heidi M. Anderson 1 and Dr. Subbarao Bondada 2 1 Paul Laurence Dunbar High School,

More information

Discovery and Humanization of Novel High Affinity Neutralizing Monoclonal Antibodies to Human IL-17A

Discovery and Humanization of Novel High Affinity Neutralizing Monoclonal Antibodies to Human IL-17A Discovery and Humanization of Novel High Affinity Neutralizing Monoclonal Antibodies to Human IL-17A Contacts: Marty Simonetti martysimonetti@gmail.com Kirby Alton kirby.alton@abeomecorp.com Rick Shimkets

More information

Bi 8 Lecture 7. Ellen Rothenberg 26 January Reading: Ch. 3, pp ; panel 3-1

Bi 8 Lecture 7. Ellen Rothenberg 26 January Reading: Ch. 3, pp ; panel 3-1 Bi 8 Lecture 7 PROTEIN STRUCTURE, Functional analysis, and evolution Ellen Rothenberg 26 January 2016 Reading: Ch. 3, pp. 109-134; panel 3-1 (end with free amine) aromatic, hydrophobic small, hydrophilic

More information

7.06 Cell Biology QUIZ #3

7.06 Cell Biology QUIZ #3 Recitation Section: 7.06 Cell Biology QUIZ #3 This is an open book exam, and you are allowed access to books and notes, but not computers or any other types of electronic devices. Please write your answers

More information

A Level. A Level Biology. DNA Technology Questions. AQA, OCR, Edexcel. Name: Total Marks: Page 1

A Level. A Level Biology. DNA Technology Questions. AQA, OCR, Edexcel. Name: Total Marks: Page 1 AQA, OCR, Edexcel A Level A Level Biology DNA Technology Questions Name: Total Marks: Page 1 Q1.(a) (i) A mutation of a tumour suppressor gene can result in the formation of a tumour. Explain how.........(2)

More information

PRETRANSFUSION OR COMPATIBILITY TESTING

PRETRANSFUSION OR COMPATIBILITY TESTING 13 PRETRANSFUSION OR COMPATIBILITY TESTING 13.1 INTRODUCTION Pretransfusion compatibility testing serves to select a compatible unit of blood for the recipient which when transfused does not cause any

More information

Therapeutic monoclonal antibodies & blood transfusion Essential information for hospital transfusion laboratories, transfusion practitioners &

Therapeutic monoclonal antibodies & blood transfusion Essential information for hospital transfusion laboratories, transfusion practitioners & Therapeutic monoclonal antibodies & blood transfusion Essential information for hospital transfusion laboratories, transfusion practitioners & haematology clinical teams March 2018 Background Targeted

More information

Use and Abuse of Reagents and Techniques. Joann Moulds PhD, MT(ASCP)SBB Director, Scientific Support Services LifeShare Blood Centers Shreveport, LA.

Use and Abuse of Reagents and Techniques. Joann Moulds PhD, MT(ASCP)SBB Director, Scientific Support Services LifeShare Blood Centers Shreveport, LA. Use and Abuse of Reagents and Techniques Joann Moulds PhD, MT(ASCP)SBB Director, Scientific Support Services LifeShare Blood Centers Shreveport, LA. Antibody Screening & Identification Blood Grouping Reference

More information

Higher National Unit specification General information Unit title: Unit code: Superclass: Publication date: Source: Version: Unit purpose Outcomes

Higher National Unit specification General information Unit title: Unit code: Superclass: Publication date: Source: Version: Unit purpose Outcomes Higher National Unit specification General information Unit code: H92E 35 Superclass: RH Publication date: May 2015 Source: Scottish Qualifications Authority Version: 02 Unit purpose This Unit is designed

More information

Ig Isotype (Human) Quantitative Antibody Array

Ig Isotype (Human) Quantitative Antibody Array Ig Isotype (Human) Quantitative Antibody Array Catalog Number AA0113 8 Samples/Slide Version: 02 Intended for research use only www.abnova.com Introduction and Background A. Overview The human immune system

More information

Quantitative And Spatial Optimization Of Therapeutic Fusion Proteins

Quantitative And Spatial Optimization Of Therapeutic Fusion Proteins Quantitative And Spatial Optimization Of Therapeutic Fusion Proteins Jeffrey Way, Ph.D. Senior Staff Scientist, Wyss Institute, HMS CEO, General Biologics, Inc. 1 Chimeric Activators Drug design and targeted

More information

VII. Rh Blood Group System

VII. Rh Blood Group System VII. Rh Blood Group System A. The Rh system is one of the most complex genetic systems, and certain aspects of its genetics, nomenclature and antigenic interactions are unsettled. The aim of this lecture

More information

Comparison of three cytokine release assays (CRA) for hazard. syndrome potential of monoclonal

Comparison of three cytokine release assays (CRA) for hazard. syndrome potential of monoclonal Comparison of three cytokine release assays (CRA) for hazard identification of cytokine release syndrome potential of monoclonal antibody (mab) therapeutics ti Madeline Fort HESI ITC Cytokine Release Assay

More information

Red cell immunology and compatibility testing

Red cell immunology and compatibility testing CHAPTER 16 Red cell immunology and compatibility testing Connie M. Westhoff Laboratory of Immunohematology and Genomics, New York Blood Center, New York, NY, USA Introduction Immunohematology is the study

More information

ProteoGenix. Life Sciences Services and Products. From gene to biotherapeutics Target Validation to Lead optimisation

ProteoGenix. Life Sciences Services and Products. From gene to biotherapeutics Target Validation to Lead optimisation ProteoGenix Life Sciences Services and Products From gene to biotherapeutics Target Validation to Lead optimisation ProteoGenix Philippe FUNFROCK, founder and CEO French company located in Strasbourg,

More information

BCH 462. Single Radial Immunodiffusion and Immuno-electrophoresis

BCH 462. Single Radial Immunodiffusion and Immuno-electrophoresis BCH 462 Single Radial Immunodiffusion and Immuno-electrophoresis Immunoassays tests include: 1. Precipitation. 2. Agglutination. 3. Immunofluorescence. 4. Radioimmunoassay (RIA). 5. Enzyme-Linked Immuno

More information

Carol A Starks MS, MLS(ASCP), CLS. castarks

Carol A Starks MS, MLS(ASCP), CLS. castarks Carol A Starks MS, MLS(ASCP), CLS Brief review of the common blood groups ABO Rh Kell Duffy Kidd P Lutheran MNS Lewis Basic Blood Bank workups ABO discrepancies Single antibody not demonstrating Single

More information

Biopharmaceuticals - Current FDA & EMAs Regulations on glycan analysis

Biopharmaceuticals - Current FDA & EMAs Regulations on glycan analysis Biopharmaceuticals - Current FDA & EMAs Regulations on glycan analysis Jayesh Kattla, PhD March 2015 Gothenburg & Copenhagen 2013 Waters Corporation 1 Hope and Risk 2013 Waters Corporation 2 The total

More information

Do Donors With Non-Deletional Blood Group O Allels Boost Anti-A and Anti-B Titers in Blood Group O Recipients?

Do Donors With Non-Deletional Blood Group O Allels Boost Anti-A and Anti-B Titers in Blood Group O Recipients? Do Donors With Non-Deletional Blood Group O Allels Boost Anti-A and Anti-B Titers in Blood Group O Recipients? E. A. Scharberg, S. Seyboth, K. Panter, A. Ernst, J. Hagel, E. Richter, G. Rink, K. Janetzko,

More information

FORENSIC SEROLOGY. Chapter PRENTICE HALL 2008 Pearson Education, Inc. Upper Saddle River, NJ 07458

FORENSIC SEROLOGY. Chapter PRENTICE HALL 2008 Pearson Education, Inc. Upper Saddle River, NJ 07458 Chapter 8 FORENSIC SEROLOGY 8-1 Nature of Blood The word blood refers to a highly complex mixture of cells, enzymes, proteins, and inorganic substances. Plasma, which is the fluid portion of blood, is

More information

Immunogenicity Assessment - Challenges and Strategies

Immunogenicity Assessment - Challenges and Strategies Immunogenicity Assessment - Challenges and Strategies 17Nov2015 Manju Saxena, Ph.D. Scientific Director Intertek Pharmaceutical Services 1 Presentation Outline Introduction Immunogenicity Testing (ADA

More information

Atlas of Genetics and Cytogenetics in Oncology and Haematology. IMMUNOGLOBULIN GENES: CONCEPT OF DNA REARRANGEMENT * Introduction

Atlas of Genetics and Cytogenetics in Oncology and Haematology. IMMUNOGLOBULIN GENES: CONCEPT OF DNA REARRANGEMENT * Introduction Atlas of Genetics and Cytogenetics in Oncology and Haematology IMMUNOGLOBULIN GENES: CONCEPT OF DNA REARRANGEMENT * Introduction I Historical questions II Answers II.1 Light chains (kappa or lambda) II.1.1

More information