Antigen Recognition Notes (2023-2024) PDF

Block 1.2 (2023-2024) Antigen recognition Done by : Ali Alahmed Injoud Yasir  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...

Block 1.2 (2023-2024) Antigen recognition Done by : Ali Alahmed Injoud Yasir  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 The total number of distinct lymphocyte clones call immun reprertoire or lymphocyte repertoire 24. What are the structural and functional similarities and differences between antigen receptors on Band T lymphocytes? Lymphocyte recognise antigen by antigen receptor. We have two types of lymphocytes: 1- B-lymphocyte 2- T-lymphocyte. B- Lymphocyte antigen receptor it is a membrane bond immunoglobulin or antibody. 1. TCR and BCR recognize chemically different structure. TCR = T cell receptor BCR = B cell receptor BCR can recognize proteins, carbohydrates, lipids and nucleic acids in native forms. original It means the form TCR can recognize processed peptide antigen displayed on APCs with MHC. Antigen receptor can recognize antigen by different receptors including: peptides, polysaccharid, lipids similarities and differences between B and T cell receptors. Variable: there is an amino acid variation or different 2.AR contains 2 regions AR = antigen receptor Constant: area of antigen receptor that same in all antigen receptor no variation a.variableantigen binding region b.constantregion for structural integrity &effectorfunctions 3.AR attached to other molecules; deliver activation signals after antigen recognition.  Difference between BCR & TCR Diversity: You should know every colon have different specificity  Deleted The epitopes or antigenic determinants is a small area on the antigen that get recognized by the antibodies there are 2 types of epitopes 1- linear epitopes 2- conformation epitopes T Cell can recognize linear only But B-cell can recognize both types Linear epitope: is an amino acid sequence sequence: it is like a line and it is adjacent to each other( beside each other) Conformational epitope: is non- adjacent to each other(beside each other) because there is a folding is not a sequence. Folding result of non- adjacent polypeptide(non beside each other)  Students must know that the TCR signal transduction are CD3 and zeta (ζ) are proteins which are responsible for signal transduction Ig alpha: recognize T- lymphocyte Ig alpha and beta is a signal transduction protein. Signal transduction mean: to activate the cell.  The structure of immunoglobulin There are 4 chains looks like the letter Y 2 long chains called heavy chains 2 short chains called light chains Structure of Immunoglobulin The heavy chain consist of 3 constant domain and 1 variable domain The light chain consist of 1 constant domain and 1 variable domain The hinge: can be broken down by enzymes Fab = Fragment antigen binding Fc = fragment crystalline  Addition Explaination by doctor Immunoglobulin made of four polypeptide chain two Goblet domain is unfolding area of are long chain with the blue and red colour and two are protein. short chain with the green colour. light chain have: 2 goblet domain Short chain: light chain heavy chain have: 4 goblet domain long chain: heavy chain Heavy chain linked with each other by covalent bond. Each light chain: link with half heavy chain  Very important information Structure of Immunoglobulin  4 poloypeptidechains –2 heavy(H) and 2 light (L) chainsform a ‘Y’ shaped structure.  Attached to each other by ‘disulfide’ bonds. Some of them are explaining in previous slide  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.  Very important information 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’.  Very important information Structure of Immunoglobulin Why there are 5 classes?  2 types of L chains –‘κ’ & ‘λ’ because each type mediate a different type of responses  5 types of H chains –μ, δ, γ, ε & α  Antibody Isotype/Class –determined by H chain type.  IgM, IgD, IgG, IgE& IgA – ‘κ’= kappa The heavy chain: ‘λ’: lambda IgM= μ each distinct physical μ,:mu IgG:Y δ:delta IgD:δ &biologicalproperties. Y= gamma IgE:ε ε: epsilon  α: alpha IgA:α AR on naïve B-lymphocytes – membrane bound IgM /IgD. Heavy chain in immunoglobuli: determine the antibody class The part of antigen recognized by antibody –‘epitope/ antigenic determinant’  Very important information B –Cell Receptor (BCR) what form BCR  Membrane Ig + 2 Proteins, Igα Igβ = BCR. After membrane Ig bind to antigen – Ig α Ig β transmit the signal –B-cell activation  Very important information 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  Very important information 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.  Very important information 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. It will come in MSQ exam You should know the highest and the lowest The highest concentration in the serum is IgG IgD: membrane bond(receptor T lymphocyte) 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 specifitiesdo not change. Initial part naïve B-lymphocyte which is not encounter as an antigen still to become antigen they produce antibody. initially part that produce antibody isIgM. and then switching to other classes of immunoglobulin. It is like start from heavy chain and then switching to other chains. Sweatching means: Changing Antibody affinity and avidity Strength it means strongly bind  The strengthwith 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. Affinity: the strength with which antigen binding site  of humoglubilns is binding to it is antigen Total strength of binding to an antigen –‘Avidity’.  Example of of affinity weak and strong binding Antibody affinity maturation Antibodies in primary IR have low affinity but with reputed stimulation (Sec.IR) , affinity increases –‘Affinity Maturation’. Weak Strong The binding site of one immunoglobulin=2 Dimer= 4 binding site like IgA Pentamer: 10 binding site like IgM Monoclonal antibodies Antibodies produced by a single clone of B-cell and thus single antigenic specificity. Monoclonal antibodies widely used as therapeutic diagnostic purpose. Deleted Deleted Deleted 1- Which of the following is a function of B7 co- 2- Which of the following function as signal stimulation molecules expressed by dendritic cells? transduction in TCR? A-Activation of T cells by binding to CD28 receptors A- CD3 B-Display of antigen to T cells B- CD21 C- Migration of T cells to the site of infection C- CD4 D- Transport of antigen in the blood 3- What type of Ig acts as a receptor in Naive 4- The antigen receptors of naive B lymphocytes, after b lymphocyte? stimulation by antigen and helper T lymphocytes, the B A- IgE cells may produce antibodies of other heavy-chain B- IgA classes C- IgM A- class switching B- Clonal selection C- Clonal expression D- Affinity maturation 1-A 2-A 3-C 4-A