ANTIGENS AND IMMUNOGENS

• Immune responses arise as a result of exposure to foreign stimuli.

• A substance/ compound capable of eliciting an immune response is referred to either as

antigen or as immunogen. The distinction between these terms is functional.

• An antigen is any agent capable of binding specifically to components of the immune system
such as B cell receptor (BCR) on B – lymphocytes and soluble antibodie

• Immunogen is any agent capable of inducing an immune response and is therefore

immunogenic.

NB: ‘All antigens are immunogens, but not all immunogens are antigens’

• Low molecular weight compounds such as drugs and antibiotics are not (by themselves)
capable of inducing an immune response. When coupled with other substances such as
proteins, the resultant conjugate induces an immune response that is directed against
various parts of the conjugate, including the low molecular weight compounds.

• The low molecular weight compound is referred to as Hapten (from the Greek – “to
grasp”);

• High molecular weight compound to which the hapten is conjugated is called the
“Carrier”

• Immune responses have been demonstrated against biochemical compounds including

carbohydrates, lipids, proteins and Nucleic acids.

• Similarly, immune responses to drugs, antibiotics, food additives (spices), cosmetics and
small synthetic peptides can also be induced but only when coupled with a carrier.

NB: It is estimated that 1 million different antigens exist to which the immune system can
react directly.

Adjuvants:

• Adjuvants are chemical compounds that within themselves are not antigenic but increase the
potency of antigens.

• Alum and aluminium hydroxide used in the preparation of toxoids are classical examples of
adjuvants.

• These chemicals also concentrate the antigen in addition to increasing its potency.

REQUIREMENTS FOR ANTIGENICITY

• For any substance to be immunogenic, it must possess the following characteristics:

 foreignness
  high molecular weight,

 chemical complexity,

 degradability

 interaction with MHC).

Foreignness:

• Under normal circumstance, animals do not respond to self.

• Thus for example if a rabbit serum is injected with its own serum albumin, it will not mount
an immune response because it recognizes the albumin as self.

• On the other hand, if rabbit serum is injected into guinea pig, the guinea pig recognizes the
rabbit serum as foreign and therefore mounts an immune reaction against it.

• Generally, compounds that are part of self are not immunogenic to the individual.

• However, there are exceptional cases where an individual reacts to its own tissues. This is
called auto immunity.

2.Molecular weight:

• For a substance / compound to be immunogenic, it must have a certain molecular weight.

• In general, small compounds with molecular weight < 10,000 Daltons (e.g. penicillin,
progesterone, and aspirin) are not immunogenic.

• Those with molecular weight between 1000 – 6000 Da (e.g. Insulin, adrenocorticotrophic
hormone) may or may not be immunogenic; and those with molecular weight > 6,000 Da (e.g.
albumin, tetanus toxin) are generally immunogenic.

3. Chemical complexity:

Immunogenicity of a compound is determined by it’s structural complexity.

Antigenicity decrease in the order of - Proteins Polysaccharides Lipids

Nucleic Acids

4. Degradability:

• For antigens that activate T – cells to stimulate immune responses, interaction with MHC
molecules expressed on antigen presenting cells (APCs) must occur.

The APCs must first degrade the antigen through a process called antigen processing
( involving enzymatic degradation of antigen) before they can express antigenic epitopes
(small fragments) of the immunogen on their surface.
 There are basically 2 types of antigens (exogenous and endogenous antigens).

Exogenous antigens are antigens presented to the host from the exterior in the form of
microorganisms, pollen grains, drugs and pollutants.

These antigens are capable of causing a number of diseases (infections, allergies, etc.).

Endogenous antigens are those when some body components change as a result of exposure
to heat, U/V radiation or chemicals.

These changes make them to become immunogenic (auto immunity) e.g. eye lens.

STRUCTURE OF IMMUNOGLOBULIN/ANTIBODY MOLECULE

An immunoglobulin molecule is a 4-polypeptide chain structure with two heavy and two light chains
linked covalently by disulphide bonds.

Light chains – Molecular weight of approximately 23000. – Two types: kappa (κ) and lambda (λ). Each
immunoglobulin molecule has either two κ or two λ chains.

• Heavy chains – Molecular weight of about twice that of light chains (i.e. 50000–75000) and twice
the number of amino acids.

– Five classes of immunoglobulin are recognized on the basis of the Fc fragment of the heavy chain,
i.e. heavy chain isotypes IgG, IgA, IgM, IgD and IgE. Heavy chain classes are also divided into
subclasses of molecules, e.g. IgG1, IgG2, etc.

Both heavy and light chains consist of two regions:

1. A constant region (CH and CL), in which the amino acid sequence of immunoglobulins of the same
class is more or less identical.

2. A variable region (VH and VL) where the amino acid sequence varies considerably from molecule
to molecule and contributes to the antigen-binding site.

Immunoglobulin G

• Most dominant antibody in most antisera

• Represent 75 – 85%

• Half-life of 25 – 35days

• MWt. Of 150,000 Daltons

• 2.5% is carbohydrate

• Antibody, most significant to neonates through trans placental/ vertical transfer.

Immunoglobulin M

 Made of 5 – IgG molecules held by disulphide bonds

 MWt of 950,000 Daltons

 Half – life of 10days

 Secreted in the breast milk (clostrum)

 It forms approximately 9% of the gamma globulins

Immunoglobulin A (2 types)

Serum IgA

 Basic Mwt. Of 160,000 Daltons

 Half-life of 6 – 8 days

 Low serum level of 225 ± 55g/dl

Secretory IgA

 In the serum, the ratio of IgG – IgA is 6: 1

 In milk, nasal mucosa, saliva, intestinal and respiratory mucosa, IgA concentration is much
higher than IgG or IgM.

 Structurally, 2 tetrapeptide molecules are held together by a J – chain and secretory

component

 Secretory component protects the IgA from enzymatic digestion

Immunoglobulin D

 First discovered in patients with IgD myeloma

 Mwt. Of 180,000 Daltons

 Half-life of 2 – 3 days

 Accounts for only 3mg/dl of the serum immunoglobulins

 It has no known protective role

 It’s contribution towards immunity is not yet clear

Immunoglobulin E

 Absolutely found in the serum of all allergic persons/ patients

 It’s concentration in normal individual is 1mg/dl

 10 times (tenfold) is found in allergic persons

• Plays a significant role in allergy/ hypersensitivity

READING ASSIGNMENT

1. Immunological tolerance and suppression

2. Hypersensitivity