Lymphocyte receptors, B cells and antibodies Flashcards
T cell structure
-T cell receptor is heterodimer
-Alpha and Beta chain
-One binding site for antigen
B cell structure
-B cell receptor is an antibody
-2 identical heavy chains and 2 identical light chains
-2 antigen binding sites for antigen
Memory in adaptive immunity
-Same principle for B cells and T cells
-Higher frequency of specific cells
-Respond more rapidly
-Memory only in adaptive immunity
Timeframe of Innate vs Adaptive immunity
Innate: Minutes to hours
Adaptive:
-First exposure (primary response) 12 days
-Booster (secondary response) 5-7 days
Constant vs Variable region in T cells and B cells
What 3 parts make up the variable region of the heavy chain
-Variable
-Diversity
-Joining
How many combinations of the antibody heavy chain?
What 2 parts make up the variable region of the light chain
-Variable
-Joining
What is junctional diversity
-Joining of the 3 regions in heavy chains and 2 regions in light chains is not precise
-Nucleotides are added and removed from junctions during rearrangement
-This adds further diversity
Where does B cell and T cell development and gene rearrangement occur?
-B cell development with gene rearrangement - bone marrow
-T cell development with gene rearrangement - thymus
What are the 2 main types of T cells
Cytotoxic T cell
-Differentiate to secrete cytotoxic granules
Helper T cell
-Differentiate to produce different sets of cytokines
-None of these pathways involve the T cell receptor beyond recognition of antigen
What happens when B cells recognises antigen
-It differentiates to become antibody producing plasma cell
-Plasma cell secretes antibody that has same specificity expressed by B cell
-B cell receptor ultimately becomes effector molecule
Antibody (immunoglobulin) structure
-2 identical light chains (Kappa or Lambda)
-2 identical heavy chains
-Variable regions determine specificity
-Constant regions of the heavy chain determine if antibody is IgA, IgD, IgE… and therefore determines function
Antibody terminology
-IgA, IgD, IgE are
referred to as classes/isotypes
-The classes are defined by the constant regions of
their heavy chains
-IgG1, IgG2, IgG3 and IgA1, IgA2 are subclasses
-The subclasses are coded by
different constant region gene
Fc receptors
-Some cells such as macrophages have Fc receptors that can bind antibodies
-Fc = the paired constant region
segments
How do antibodies bind antigens
-Through the tip of variable regions
-Lock and key, electrostatic, hydrostatic
-Antibody must stick to antigen on the surface of the pathogen
General functions of antibodies
-Neutralise toxins and viruses by binding to them and blocking their interaction with other cells
-Opsonise pathogens by binding to them to promote phagocytosis and killing activity by other cells by recognition of Fc receptors
-Activate the complement cascade which helps kill pathogens
-Agglutinates particles (pathogen debris, viruses etc)
What is the main serum antibody?
IgG
-Measurement of antibody titre in
serum in response to vaccine is often a measurement of specific
IgG
Features of IgG antibody
-Good at opsonisation - coating pathogens so
that phagocytic cells can recognise them
-Pathogens coated in IgG also become targets for
killing by NK cells - antibodydependent cellular cytotoxicity
-4 subclasses of IgG (IgG1,IgG2,IgG3,IgG4 - descending concentration in serum)
IgA structure
2 IgA monomers join by a joining J chain to form a dimer
How does dimeric IgA regulate bacteria in the gut?
-IgA has 4 binding sites so can agglutinate and neutralise bacteria
-Secretory component part of secreted IgA binds well to mucus, retaining antigens on mucus surface, preventing damage
What is the first antibody made in immune response?
IgM
-pentameric structure
-10 possible binding sites gives it high avidity - ability of whole molecule to bind rather than 1 binding site
-Can agglutinate pathogens effectively
Which antibody is responsible for allergies
-Individuals with allergies have higher concentrations of IgE in serum
-Mast cell has receptors for IgE
Features of IgD
-IgD isn’t considered to be a secreted antibody
-Very little IgD in serum
-However, IgM and IgD with the same specificity are expressed on the surface of newly formed B cells
What is affinity maturation
-Affinity maturation is the process of improving a cell’s specificity for
an antigen
-Only B cells can undergo affinity maturation
Refinement of antibody specificity after meeting antigen
-Lymphocytes constantly recirculate through blood and lymphoid tissues
-Secondary lymphoid tissues contain zones of dividing B cells called germinal centres
-If B cells encounter specific antigen and they have help from T cells they can enter germinal centres of dividing B cells
-B cells in the germinal centre start to divide very rapidly and MUTATE their immunoglobulin variable region genes by somatic hypermutation
-High affinity variants are SELECTED in the germinal centre
-Somatic hypermutation then selection = AFFINITY MATURATION
-B cells can also class switch in germinal centres, so they express
isotypes other than IgM and IgD
What 2 types of B cell leave the germinal centre?
-Quiescent circulating memory B cells
=> Affinity matured and possibly class switched
-Plasma cells local to bone marrow or intestine
=>Bone marrow plasma cells can secrete protective antibodies for a lifetime
Primary (initial) vs Secondary (booster) antibody responses
What are monoclonal antibodies?
-Powerful laboratory reagents and biological therapeutics
-Used to treat autoimmune diseases (rheumatoid arthritis) and inflammatory diseases (Crohn’s, cancer)
How were monoclonal antibodies first made and why did this change?
-Monoclonal antibodies were first made using mouse B cells
-Mouse monoclonal antibodies are powerful reagents for research
and diagnosis
-However, mouse monoclonal antibodies don’t make good therapeutics because the mouse
protein is seen as a foreign antigen
-An immune response is generated against it
Chimeric antibodies
-A chimeric antibody is one where the mouse monoclonal is engineered so that the mouse variable region of heavy and light chains are
associated with human constant regions
-Chimeric antibodies have the ending –ximab
-E.g. Rituximab - an antibody to
CD20. CD20 is expressed by B cells
-Rituximab targets B cells for killing and removes them from
circulation and lymphoid tissues
-Rituximab is effective against B cell lymphomas and some autoimmune diseases (rheumatoid arthritis)
Humanised monoclonal antibodies
-A monoclonal antibody can be ‘humanised’ so that only the parts of the variable region that
contact antigen are from the mouse
-Humanised antibodies have the ending –zumab
-E.g. Omalizumab
-Omalizumab is specific for IgE and can be used to treat moderate to severe allergic asthma
Human monoclonal antibodies
-Monoclonal antibodies can be fully human
-Human monoclonal antibodies have the ending -umab
-E.g.g Adalimumab is specific for TNFa and is used to treat inflammatory diseases
ABO system - antigens and antibodies
-Group O - can only receive O, universal donor
-Group A - can donate A, AB
-Group B - can donate B, AB
-Group AB - universal recipient, can only donate to AB
Rhesus
-Mother who is Rh- has IgG antibodies to Rh following exposure to Rh antigen from a first pregnancy
-Cross placental transfer of IgG targeting rhesus antigen from mother to foetus causes red blood cell lysis in the foetus and haemolytic disease of the newborn
