Antibodies and B lymphocytes Flashcards
Immunoglobulin molecular structure; Antigen binding; B lymphocyte origin; B lymphocyte activation
What is an antibody?
Immunoglobulin class glycoprotein that is produced in response to a foreign antigen Specifically binds to antigens
What is the structure of an antibody?
2 outer light chains (same) 2 inner longer heavy chains (same) Held together by disulphide bonds Y shape Hinge region - where antibody can bend
How does an antibody fragment?
Papain digestion
Fragments at hinge region
Fab fragment - light chain + heavy chain - binds to antigens, gives it specificity
Fc fragment - modulates activity, determines class of antibody
What is the function of an antibody?
Bind to antigen and then:
- Activate complement
- Opsonise to promote phagocytosis
- Activate cells via Fc receptors
What gives the antibody specificity?
Complementarity determining regions (CDRs) - 3 hypervariable regions that determine the complementary fit of an antigen and AB
No covalent bonds between antigen and AB so many other bonds required to bind them
Why is avidity more relevant than affinity in the case of antibody-antigen binding?
Avidity- takes into account OVERALL strength of TOTAL non covalent interactions between antibody and multiple epitopes of a complex antigen
You can have antibody with weak affinity but high avidity
What are the 5 different classes of immunoglobulin and their subclasses?
IgG - 1,2,3,4 IgA - 1,2 IgM IgE IgD
What are the properties of IgG?
ɣ heavy chain gamma Most abundant Monomeric Found in blood and ECF Crosses placenta and protects foetus during pregnancy Activates complement
What are the properties of IgA?
α alpha heavy chain
Second most abundant
Monomer in blood, dimer in secretions (held by j chains)
Protects mucosal surfaces in secretions
Has secretory component to protect against degradation
Found in breast milk
What are the properties of IgM?
ɥ heavy chain mu Pentameric First antibody made during 1° immune response Multiple binding sites Causes agglutination of RBCs Activates complement Mainly in blood
What are the properties of IgE?
ε heavy chain epsilon
Monomeric
Low concentration in serum
Defence against parasitic infections and allergy
Binds to mast cells and basophils
Trigger histamine release from mast cells
What are the properties of IgD?
δ heavy chain delta
Monomeric
V low serum concentration
Involved in B cell development/activation
What are the roles played by antibodies in defence?
Neutralisation Agglutination Opsonisation Complement activation Innate immunity to newborns
What are the roles played by antibodies in medicine?
Levels help diagnose diseases
Passive immunity
Monoclonal antibodies for cancer therapy
Where do B cells originate?
Derived from stem cells in bone marrow where they mature
Once developed are released into circulation as naive cells
How do B cells carry out humoral immunity?
They produce antibodies if antigens are recognised by B cell receptors
Proliferate via clonal selection
What is a B cell receptor?
Membrane bound antibody (same as produced if B cell activated)
IgAlpha and IgBeta components form disulphate heterodimers
What is the principle of immunoglobulin gene arrangement?
Each BCR receptor chain is encoded by separate multigene families on different chromosomes
Rearranged during maturation to for unique BCRs
What are the 3 possible outcomes when a B cell encounters its antigen?
1) Becomes a plasma cell and produces antibodies (requires accessory signal)
2) Becomes a memory cell
3) Enters somatic hypermutation and affinity maturation
How is a B cell activated?
1) Antigen binds to BCR and is internalised
2) Antigen degraded into peptides and is presented on B cell membrane by MHC II receptor
3) Dendritic cell with same antigen presented on its MHC II is recognised by CD4 T helper cell
4) T cell migrates to lymph nodes and encounters B cell with the same antigen
5) T cell activates B cell (via cytokines, CD28 etc)
6) B cell proliferates and divides
How does a B cell undergo somatic hypermutation and affinity maturation?
1)Once B cell bound to antigen, AID enzyme alters variable region in B cell DNA
2)Introduces point mutations in DNA, changing AB structure and helps AB-Antigen bind more strongly
3) Weaker binding ABs are selected against
(IgM changed to IgG)
