Immunology -Lecture 3. Recognition of antigen by B cells and antibody

Understand the 2 main types of lymphocytes and the structure of antibody. Understand antigen and antigenic epitopes and binding. Affinity and avidity. Also understand antibody functions and classes of antibody.

2 types of lymphocytes and what they do

B lymphocytes and T lymphocytes (CD4 and CD8). B cells secrete antibodies and T cells attack stuff inside cells.

What is the origin of B and T cells

B cells originate and differentiate from bone marrow then migrate to lymphoid tissue and T cells originate from bone marrow.

BCR B cell receptors …

Found on membrane. BCR signalling determines the fate of antigen encountered B cells. Modulates gene expression, adhesion or survival. Differentiate into plasma B cell.

Antibodies are produced by..

B cells. Can be on surface or secreted.

Antibodies are

Immunoglobulins (Ig)

Antibody structure - describe the cleavage of antibodies

Proteolytic cleavage occurs by papain. Papain cuts at the disulphide bonds that link the heavy chains. 2 identical fragments with antigen binding activity- Fab fragment. Remaining domain doesnt bind antigen but does crystallise. Fc fragment

Antibodies are heterodimers. Explain

Two identical light chains (L) and two identical heavy chains (H). Heavy are longer. N terminal is on both at the top of the Y structure. L is on the outer side.

Where is the antigen binding site on an antibody

Top of the Y on both arms. N terminal is key for function.

What is an antigen

A molecule recognised by an antibody. usually large. Proteins/carbohydrates/lipids/DNA

The parts of antigens recognised by antibodies are called…

Antigenic epitopes.

The interaction of antibodies with a specific binding site is determined by..

The hyper variable regions of the antibody. the binding site must be complementary in shape to the antigenic epitope. Hypervariable regions form the complementary determining region CDR.

2 types of epitopes

Linear and conformational. Conformational is structural, formed by protein folding. may not be a continuous sequence of amino acids. Linear is a continuous amino acid sequence and is less common.

What type of bond keeps antigens and antibodies together

Non-covalent . Hydrogen bonds, electrostatic interaction, vdw, hydrophobic interactions.

Affinity of antibody binding =

Strength of the binding between an epitope and an antibody antigen binding site. molecules need to be close together.

avidity of antibody binding is

the overall strength of an antibody antigen complex. if an antibody is using both binding sites to bind 2 epitopes on the same particle this is increasing the total binding strength (the avidity).

Antibody production. Explain the antibody response and the innate immune response

Antibody is made after infection. Antibody response can be acquired after exposure to pathogen, specific and memory which is 2nd response bigger and faster. Innate immune response is immediate and pre existing. non specific and there is no memory.

Antibody effector functions… What drives it and what are the functions

Fc portion drives the function (the effector domain). The functions are neutralisation, opsonisation complement activation and ADCC (antibody dependent cell mediated cytotoxicity). This is the humoral immune response

What is neutralisation?

Antibodies prevent a pathogen or protein from binding to their target. Important in protection against virus as this prevents entering the cell and replicating.

What is opsonisation?

A pathogen tagged by antibodies is phagocytose by phagocytic cells such as macrophage or neutrophil. Fc domain of the antibody bind the Fc receptor on the phagocyte to trigger phagocytosis

What is complement activation?

Antibodies attached to the surface of a pathogen activate the first protein in the complement system. This can cause deposit complement proteins on the surface of the bacterium that leads to pore formation and lyse the bacterium directly. Complement receptors on phagocytes recognise these complement proteins and induce phagocytosis.

What is ADCC (TEXT)

Antibody dependent cell mediated cytotoxicity. Host cells infected by some viruses can express viral proteins in the surface. These are recognised by antibodies against that particular virus. Cells with FcR like NK cells or macrophages can bind the antibody and kill the target cell by releasing perforin (lytic enzyme) and granzymes. It mediates extracellular killing.

What is ADCC (DESCRIBE DIAGRAM)

1. Antibody binds antigens on surface of cell. 2. Fc receptors on NK cell recognise bound antibody. 3. cross linking of fc receptors signals the NK cell to kill target cell. 4. Target cell dies by apoptosis.

Agglutination:

Ability of an antibody to immunoprecipitate a soluble/non soluble antigen.

Describe blood genotypes A, B, AB and O

A - A antigen. A and O are compatible. B - B antigen. B and O are compatible. AB - A and B antigens. All are compatible. O- no antigens. O is the only compatible. O is the universal donor.

Antibody classes depend on…

The different C regions used by the heavy chain. CH3, CH2, CH1. They are designed to bind to fc receptors and complement activation as well as regulating secretion.

What are the 5 antibody classes

IgG, IgM, IgD, IgA1, IgE

IgG

Most abundant, 4 classes, most common is IgG1

IgM

Earliest antibody made after Ag contact. Pentamer. Up to 10 binding sites.

IgD.

rare, function in serum unclear

IgA1

Serum and major Ig in mucosa. 2 subclasses. Diff structure in secretions. 2 Ig molecules joined by J chain

IgE

Lowest in serum, produced by mast cells and important in allergy.

MALT

B cells and antibody are made in bone marrow then move to secondary lymphoid tissue. MALT - Mucosal associated lymphoid tissue. This is a major site for b cell activity and antibody. It produces IgA

Immunoglobulin A

Is the predominant immunoglobulin in external secretions. Saliva, tears, mucus.i Is the main entry site for pathogens. It forms a dimer as soon as it is secreted.