2021-22 Antigen Recognition (PDF)

 PRACTICAL INFECTIOUS DISEASES WEEK 1 DIVISION OF MICROBIOLOGY COLLEGE OF MEDICINE KFU Title: Antigen Recognition CRN No: 15569(Male), 15581 (Female) Block: 1.2 Subject/Discipline: Immunology Expert: Dr.Sayed A.Quadri Block Coordinator: Dr.Sayed A.Quadri  Learning...

 PRACTICAL INFECTIOUS DISEASES WEEK 1 DIVISION OF MICROBIOLOGY COLLEGE OF MEDICINE KFU Title: Antigen Recognition CRN No: 15569(Male), 15581 (Female) Block: 1.2 Subject/Discipline: Immunology Expert: Dr.Sayed A.Quadri Block Coordinator: Dr.Sayed A.Quadri  Learning questions 24. What are the structural and functional similarities and differences between antigen receptors on B and T lymphocytes? 25. Describe the molecular and functional structure of membrane immunoglobulin and T cell receptors and explain why and how these are expressed as receptor as complexes on lymphocytes. 26. Explain ‘class’ and ‘subclass’ in the context of antibodies, and also heavy chain class switching and affinity maturation. 27. Explain the differences between affinity and avidity. 28. What are monoclonal antibodies?  Immune repertoire Each lymphocyte has distinct antigen specificity Total number of distinct lymphocyte clones is called Immune repertoire 24. What are the structural and functional similarities and differences between antigen receptors on Band T lymphocytes? 1. TCR and BCR recognize chemically different structure. BCR can recognize proteins, carbohydrates, lipids and nucleic acids in native forms. TCR can recognize processed peptide antigen displayed on APCs with MHC. similarities and differences between B and T cell receptors. 2. AR contains 2 regions a. variable antigen binding region b. constant region for structural integrity & effector functions 3. AR attached to other molecules; deliver activation signals after antigen recognition. Structure of Immunoglobulin Structure of Immunoglobulin  4 poloypeptide chains – 2 heavy(H) and 2 light (L) chains form a ‘Y’ shaped structure.  Attached to each other by ‘disulfide’ bonds.  H chain – 3 domains – 1 varaible (VH) & 3 constant (CH1,CH2 & CH3).  L chain – 2 domains – VL & CL.  VH & VL – 3 hypervariable regions (CDRs).  CDR3 has highest variations. Structure of Immunoglobulin L chain (VL & CL) + part of H chain (VH & CH1) – ‘Fab’ region – 2 Fab/ Ig. CH2 & CH3 – ‘Fc’ region – 1 Fc/Ig. Between Fab & Fc regions ‘Hinge region’ ‘C’ terminal anchored to plasma membrane in ‘membrane Ig’. Structure of Immunoglobulin 2 types of L chains – ‘κ’ & ‘λ’ 5 types of H chains – μ, δ, γ, ε & α Antibody Isotype/Class – determined by H chain type. IgM, IgD, IgG, IgE & IgA – each distinct physical &biologicalproperties. AR on naïve B-lymphocytes – membrane bound IgM /IgD. The part of antigen recognized by antibody – ‘epitope/ antigenic determinant’ B –Cell Receptor (BCR) Membrane Ig + 2 Proteins, Ig α Ig β = BCR. After membrane Ig bind to antigen – Ig α Ig β transmit the signal – B-cell activation T- Cell Receptors (TCR) α & β chain Each chain – ‘C’ & ‘V’ domain. Each V domain – 3 CDRs. CDR3 most variable. Both chains anchored in membrane. 5-10% T cells have TCR with - γ, δ chains TCR complex TCR complex = TCR+ CD3 + ζ protein CD3 & ζ – transmit signals TCR complex CD4 or CD8 are Co-receptors. CD4 & CD8 bind with non-Polymorphic region of either MHCII / MHCI. Antibody Class and subclass Type of heavy chain (μ, δ, γ, ε & α )of an Ig determines the class/ isotype of an antibody. 5 classes - IgM, IgD, IgG, IgE & IgA. Each has distinct physical & biological properties. Brain teaser Which of the following 2 classes of immunoglobulin are found as antigen receptors on naïve B- Lymphocytes? A. IgA & IgD B. IgE & IgD C. IgG & IgD D. IgM & IgD SWITCHING Heavy chain class switching Initially B-lymphocytes secrete IgM – later other classes – ‘heavy chain class or isotype switching’. Even after class switching antigenic specifities do not change. Antibody affinity and avidity The strength with which an antibody binds to an epitope is ‘Affinity’. Expressed as dissociation constant (Kd) –molar conc. of an antigen required to occupy half the antibody in a solution. Total strength of binding to an antigen – ‘Avidity’. Antibody affinity maturation Antibodies in primary IR have low affinity but with reputed stimulation (Sec.IR) , affinity increases – ‘Affinity Maturation’. Monoclonal antibodies Antibodies produced by a single clone of B-cell and thus single antigenic specificity. Monoclonal antibodies widely used as therapeutic diagnostic purpose.