Lecture 3: Antigen and antibodies

Question 1

Define..
Antigen
Self vs non self
Immunogenicity
Antigenicity

Answer 1

An antigen is a substance that can be recognised by the immune system (for example, a bacterium)

The antigen may originate from within the body (“self”).. or from the external environment (“non-self”)

Immunogenicity is the ability to induce a humoral and/or cell-mediated immune response

Antigenicity is the ability to combine specifically with the final products of the immune response (i.e. antibodies and/or surface receptors on T-cells).

Question 2

Epitope: Defination

Answer 2

Any site on an antigen to which an antibody can bind. Most antigens have more than one epitope

the specific regions on an antigen recognised by specific antibodies

Question 3

Antibodies: Define and define plasmocyte and polyclonal

Answer 3

Typically, an animal’s immune system will generate a large group of antibodies that recognize several epitopes of a particular antigen.

Each antibody is secreted by a different antibody-producing plasma cell (plasmocyte).

As the antibodies found in serum are collectively produced by many plasma cells (clones), they are described as polyclonal. This is an advantage for fighting infections in nature. Recognise multiple epitopes on any one antigen. Contain a heterogeneous complex mixture of antibodies of different affinity

Question 4

Why is the human antibody response polyclonal?

Answer 4

Polyclonal antibodies, binding to many pathogen epitopes is more likely to kill the pathogen, than if we just made an antibody to one epitope

Question 5

Antibody structure
N and C terminus
importance of Fc

Answer 5

2 identical heavy chains
2 identical light chains

The N-terminus of each heavy chain associates with one of the light chains to create two Fragment Antigen Binding (Fab) domains.

The C-termini of the two heavy chains combine to form the Fc domain (fragment crystallisation); this is the tail of the “Y”.

The Fc domain is important for the antibody’s interaction with effector cells such as macrophages and also the activation of the complement cascade.

The four polypeptide chains are held together by covalent disulfide bridges and non-covalent bonds.

Question 6

Light and heavy chain structure

Answer 6

Light and heavy chain structure. Light chains are approximately 220 amino acids in length and can be divided into two equal ‘variable’ and ‘constant’ regions. Heavy chains are about 440 amino acids in length and are subdivided into four 110 amino acid segments - one variable region and three constant regions.

Question 7

Different immunoglobulin classes: the 5 types and what are they classed on?

Answer 7

They are distinguished by the type of heavy chain they contain.

Antibody classes also differ in their valency

Question 8

Describe how many LC, HC, antigen binding regions, units the IgM has

Answer 8

The complete IgM contains 5 units (pentamer)
Each unit has 2 heavy chains and 2 light chains
In total, IgM has:
* 10 heavy chains
* (in green and blue) * 10 light chains
* (in yellow)
* 10 antigen binding arms IgM has a valency of 10.

Also has J chain between units

Question 9

IgM:
How abundant?
is it made first?
role

Answer 9

IgM is the third most abundant human immunoglobulin.

IgM is also the first human immunoglobulin to be made by B cells which are challenged with antigen.

IgM is a strong complement activator and agglutinator due to its pentameric structure

Question 10

IgG:
Found where?
role?
Structure

Answer 10

Human immunoglobulin IgG is the most prevalent Ig in plasma and in extravascular spaces.

IgG1, IgG2 and IgG3 are complement activators, with IgG3 being the strongest.

IgG is also the only human immunoglobulin to pass from mother to fetus to transfer immunity.

The complete IgG contains 1 unit (monomer).
IgG has 2 heavy chains (in green), 2 light chains (in yellow), 2 antigen binding arms IgG has a valency of 2.

Question 11

IgA
Found where?
Role?
Strucure

Answer 11

Human immunoglobulin IgA is the second most common human immunoglobulin in serum.

It is secreted in milk and is also the most prevalent lg in secretions (e.g. tears, saliva and mucous).

IgA can activate complement

2 units, valency of 4, 4 HC, 4 LC,4 antigen binding arms

Question 12

IgE
Role
Structure
Location

Answer 12

Human immunoglobulin IgE is the least abundant Ig and does not activate complement.

As a result of its binding to basophils and mast cells, IgE is involved in allergic reactions.

This happens when allergen is bound to IgE on cells and releases various pharmacological mediators which cause allergies.

The complete IgE contains 1 unit
IgE has 2 heavy chains
IgE has 2 light chains
IgE has 2 antigen binding arms
IgE has a valency of 2.

Question 13

IgD
Where is it found?
Role
Structure

Answer 13

Expressed on the surface of mature B cells, human immunoglobulin IgD works with IgM in B cell development.

IgD is found in very low levels in serum and does not activate complement.

The complete IgE contains 1 unit
IgE has 2 heavy chains
IgE has 2 light chains
IgE has 2 antigen binding arms
IgE has a valency of 2.

Question 14

Compare all immunoglobulins:
Structure
HC,
antigen binding sites
MW
% of total antibody in serum
crosses placenta?
Fixes complement?
FC binds to..
Function

Answer 14

IgM
10
900,000
6%
no
yes
-
Fixing complement and B cell receptor when in monomer form

IgG
2
150,000
80%
yes 
yes
phagocytosis 
Neutralisation and oponisation

IgA
4
385,000
13%
no
no
- 
secreted in mucous, saliva and tears

IgE
2
200,000
0.002%
no
no
mast and basophils
Allergic responses

IgD
2
180,000
1%
no
no
-
B cell receptor

Question 15

ACTIONS OF ANTIBODY for destruction of pathogens: Once an antibody is bound to its specific pathogen, pathogen destruction may be by:

Answer 15

1. Neutralisation
   Recruiting other cells and molecules to help:
2. Complement activation (classical pathway)
3. Phagocytosis (using antibody as opsonin)
4. Antibody dependent cell-mediated cytotoxicity (ADCC)