I&I - Harland - B cell life PDF

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I&I REVISION – HARLAND THE LIFE OF A B LYMPHOCYTE Learning outcomes:  Illustrate main steps in the life of a B cell  Outline the processes contributing to the range of antigenic specificities of an antibody  Discuss the main features of the MHC and antigen presentation  Discuss the process of clonal expression B CELL DEVELOPMENT BONE MARROW: Stem cell

proB cell

preB cell

Immature B cell

ACTIVATION BY ANTIGEN CLONAL EXPRESSION

Move to membrane – Mature B cell PLASMA CELL & MEMORY B CELL

GENERATION OF DIVERSITY HOW IS SPECIFICITY GENERATED? How to get both variable and constant regions in one molecule and to create so many different antigen-binding sites? Not enough DNA VARIABLE REGION – Multiple gene segments  DNA for variable sequence of protein is composed of segments which are brought together during cell development Somatic recombination  The gene segments do not meet up exactly  The joins between segments are ragged to enable DNA to be added to increase diversity Somatic mutation  At every cell division, mutations within the variable regions of the gene occur CLONAL EXPANSION B CELL + ANTIGEN   

Antigen with repetitive structure so it can bind to several surfaces of antibody Cross link surface antibody T independent activation – Gives limited response

RESPONSE IS:  Weak (low conc of Ab)  Mainly IgM  Short lived  Lacks memory FOR A GOOD IMMUNE RESPONSE YOU NEED:

  

B cell specific for antigen Helper T cell – stimulates antigen response Accessory cell – an antigen presenting cell

ANTIGEN PRESENTING CELLS  Dendritic cells (spleen, lymph nodes)  Macrophage ROLE OF ANTIGEN PRESENTING CELLS  Processes antigen  Presents peptides of it’s surface (chopped up bits present on surface of the cell)  Secretes cytokines to stimulate T, B cells THE MHC – Major histocompatibility complex HLA (human leukocyte antigens) are made from MHC genes    

How we distinguish ‘self’ from ‘non-self’ Involved in rejection of foreign bodies Series of genes located on chromosome 6 Within each locus there are several genes, each gene is polymorphic (several alleles in population)

MCH CLASS I AND CLASS II CLASS 1 – IMMUNOSUPRESSIVE CLASS 2 – IMMUNOSTIMULATORY  

All nucleated cells possess class I MHC (all except RBCs) Class II MHCs usually found on antigen presenting cells e.g. macrophages

FUNCTION OF MHC    

HLA molecules contain antigen fragments and are essential for antigen presenting HELPER T CELLS (CD4) respond to class II molecules SUPRESSOR T CELLS (CD8) respond to class I molecules CD4 and CD8 react directly with the MHC molecule

ANTIGENIC PEPTIDES  

CLASS I – Associated with peptides derived from proteins normally digested within the cytoplasm CLASS II – Associated with peptides produces from endocytosed molecules in the lysosome...