Antibodies and B lymphocytes

Question 1

What is an antibody?

Answer 1

Immunoglobulin class glycoprotein that is produced in response to a foreign antigen 
Specifically binds to antigens

Question 2

What is the structure of an antibody?

Answer 2

2 outer light chains (same)
2 inner longer heavy chains (same)
Held together by disulphide bonds 
Y shape
Hinge region - where antibody can bend

Question 3

How does an antibody fragment?

Answer 3

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

Question 4

What is the function of an antibody?

Answer 4

Bind to antigen and then:

• Activate complement
• Opsonise to promote phagocytosis
• Activate cells via Fc receptors

Question 5

What gives the antibody specificity?

Answer 5

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

Question 6

Why is avidity more relevant than affinity in the case of antibody-antigen binding?

Answer 6

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

Question 7

What are the 5 different classes of immunoglobulin and their subclasses?

Answer 7

IgG - 1,2,3,4
IgA - 1,2
IgM
IgE
IgD

Question 8

What are the properties of IgG?

Answer 8

ɣ heavy chain gamma
Most abundant
Monomeric
Found in blood and ECF
Crosses placenta and protects foetus during pregnancy
Activates complement

Question 9

What are the properties of IgA?

Answer 9

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

Question 10

What are the properties of IgM?

Answer 10

ɥ heavy chain mu
Pentameric
First antibody made during 1° immune response
Multiple binding sites
Causes agglutination of RBCs
Activates complement
Mainly in blood

Question 11

What are the properties of IgE?

Answer 11

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

Question 12

What are the properties of IgD?

Answer 12

δ heavy chain delta
Monomeric
V low serum concentration
Involved in B cell development/activation

Question 13

What are the roles played by antibodies in defence?

Answer 13

Neutralisation
Agglutination
Opsonisation
Complement activation
Innate immunity to newborns

Question 14

What are the roles played by antibodies in medicine?

Answer 14

Levels help diagnose diseases
Passive immunity
Monoclonal antibodies for cancer therapy

Question 15

Where do B cells originate?

Answer 15

Derived from stem cells in bone marrow where they mature

Once developed are released into circulation as naive cells

Question 16

How do B cells carry out humoral immunity?

Answer 16

They produce antibodies if antigens are recognised by B cell receptors
Proliferate via clonal selection

Question 17

What is a B cell receptor?

Answer 17

Membrane bound antibody (same as produced if B cell activated)
IgAlpha and IgBeta components form disulphate heterodimers

Question 18

What is the principle of immunoglobulin gene arrangement?

Answer 18

Each BCR receptor chain is encoded by separate multigene families on different chromosomes
Rearranged during maturation to for unique BCRs

Question 19

What are the 3 possible outcomes when a B cell encounters its antigen?

Answer 19

1) Becomes a plasma cell and produces antibodies (requires accessory signal)
2) Becomes a memory cell
3) Enters somatic hypermutation and affinity maturation

Question 20

How is a B cell activated?

Answer 20

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

Question 21

How does a B cell undergo somatic hypermutation and affinity maturation?

Answer 21

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)