Antigens and Receptors

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Introduction

  • The immune system protects the body from infectious agents and foreign substances.

  • When foreign molecules enter the body, the immune system recognizes them as non-self and activates immune defenses.

  • These foreign molecules are called antigens (Ag).

  • Antigens interact with immune cells and receptors to initiate an immune response.

  • The immune response mainly involves B-lymphocytes and T-lymphocytes.

  • B-cells produce antibodies (humoral immunity), while T-cells mediate cellular immunity.

  • Understanding antigens, immunogens, epitopes, and haptens is important for studying vaccines, autoimmune diseases, allergies, transplantation, and immunotherapy.

Immunogen and Antigen

When foreign substances (antigens – Ag) enter the body, they stimulate the production of antibodies (Ab) against them.

These foreign substances may include:

  • Bacteria

  • Viruses

  • Parasites

  • Foreign proteins

  • Toxins

When these substances enter the body, they stimulate the immune system and produce an immune response.

Immune Response

Immune response refers to the activation of immune cells after antigen exposure.

Antigenic stimulation leads to activation of:

  • B-lymphocytes → Humoral immune response

  • T-lymphocytes → Cellular immune response

Immunogenic and Antigenic Substances

Foreign substances may be classified as immunogenic or antigenic depending on their ability to stimulate immune responses.

Immunogens

Immunogens are substances that:

  • Produce a specific immune response

  • Stimulate immune cells

  • Activate B-cells or T-cells

  • Lead to humoral or cellular immune reactions

Example:

  • Bacterial proteins

  • Viral antigens

  • Toxins

Antigens

Antigens are substances that:

  • Can bind to antibodies or immune receptors

  • May not directly stimulate an immune response

  • Often require carrier proteins to become immunogenic

Therefore:

All immunogens are antigenic, but not all antigens are immunogenic.

In everyday usage, the term antigen is commonly used to describe both.

Antigens

Antigens may be classified into two types:

1. Complete Antigens

Complete antigens are capable of:

  • Stimulating an immune response

  • Reacting with antibodies

Example:

  • Bacterial toxins

  • Viral proteins

2. Incomplete Antigens (Haptens)

Incomplete antigens are called haptens.

These substances:

  • Cannot stimulate immune response alone

  • Become antigenic when attached to carrier proteins

Examples include:

  • Drugs

  • Antibiotics

  • Chemicals

 

Properties of Antigen

For a substance to act as an effective antigen, it must possess certain characteristics.

A. Foreignness

Foreignness is the most important property of an antigen.

The immune system must recognize a substance as non-self in order to respond.

The immune system normally develops tolerance to self-antigens, meaning it does not react against its own tissues.

However, in some diseases, antibodies react against self-antigens, producing autoimmune diseases.

Examples of Antigenic Structures

The cell membrane contains:

  • Proteins

  • Phospholipids

  • Cholesterol

  • Carbohydrates

These molecules form:

  • Glycoproteins

  • Glycolipids

Certain regions of these molecules act as antigenic determinants called epitopes.

Other examples:

  • Bacterial capsules are strongly immunogenic.

  • Non-capsulated bacteria have surface structures that act as antigens.

 

Types of Antigens Based on Origin

Autologous Antigens

  • Self antigens

  • No immune response occurs.

Allogenic Antigens

  • From the same species but genetically different individuals.

  • May cause immune reactions.

Examples:

  • Blood transfusion

  • Kidney transplantation

Heterologous Antigens

  • From different species

  • Cause strong immune reactions and rejection.

Example:

  • Animal proteins injected into humans.

B. Chemical Nature

Most antigens are proteins or large polysaccharides.

Rarely, lipids or nucleic acids act as antigens.

Antigens may exist as:

  • Cell surface molecules

  • Membrane-bound antigens

  • Soluble proteins

Types of Molecules Acting as Antigens

Proteins

  • Most powerful antigens

  • High molecular weight

  • High structural complexity

Example:

  • Enzymes

  • Bacterial toxins

Lipoproteins

  • Present on cell membranes

  • Can act as antigens

Lipopolysaccharides

  • Components of bacterial endotoxin

  • Capsular polysaccharides of bacteria such as pneumococci

Carbohydrates

Polysaccharides are generally weak antigens but may become antigenic when attached to carrier molecules.

Example:

Red blood cell antigens are glycoproteins.

Nucleic Acids

  • Generally poor antigens

  • Single stranded DNA may act as antigen in some cases

Polypeptides

Examples include:

  • Hormones

  • Insulin

These are usually weak antigens.

Nucleoproteins

These are strong antigens.

Lipids

Lipids are usually non-immunogenic.

Exception:

  • Cardiolipin

Lipids may become antigenic when combined with proteins or polysaccharides.

C. Molecular Size 

The larger the molecule, the stronger its antigenic potential.

Molecules with molecular weight:

  • >10,000 Daltons → highly immunogenic

  • <10,000 Daltons → weakly immunogenic

Small molecules such as:

  • Amino acids

  • Monosaccharides

are not immunogenic.

D. Molecular Structure

Structural stability of antigen is essential.

More complex molecules act as strong immunogens.

Example:

Protein with different amino acids:

A – B – C – D – G → strong antigen

Protein with repeating units:

A – A – A – A → weak antigen

E. Route of Entry

The route of antigen entry influences the immune response.

Natural Routes

  • Gastrointestinal tract

  • Respiratory tract

Artificial Routes

  • Subcutaneous injection

  • Intramuscular injection

  • Intravenous injection

Local exposure may produce localized immune reactions, whereas systemic entry causes generalized immune responses.

F. Dose of Immunogen

An optimal antigen dose is required for effective immune response.

  • Very small dose → no immune response

  • Very large dose → immune tolerance may occur

G. Genetic Host Factors

Immune responses vary between individuals due to genetic differences.

Genes controlling immune response are called:

Immune Response Genes (Ir genes).

These genes influence:

  • Antibody production

  • T-cell activation

  • Immune sensitivity

 

Epitope

An epitope is the specific region of an antigen recognized by antibodies or immune receptors.

Characteristics of epitopes:

  • Small molecular regions

  • Usually composed of 4–5 amino acids or monosaccharides

  • Present on antigen surfaces

Types of Epitopes

Surface (Topographical) Epitopes

  • Located on the antigen surface

  • Directly recognized by antibodies.

Internal Epitopes

  • Hidden within antigen structure

  • Exposed after antigen processing by APC.

Valency of Antigen

Antigens may contain multiple epitopes.

The number of epitopes present on an antigen is called valency.

An antigen may contain one to hundreds of epitopes.

Hapten

The word hapten is derived from Greek meaning “to fasten.”

Haptens are:

  • Small molecules

  • Not immunogenic alone

  • Become antigenic when attached to carrier proteins

Carrier proteins include:

  • Albumin

  • Globulin

  • Synthetic polypeptides

Hapten-Carrier Mechanism

Hapten + Carrier Protein → Immunogenic Complex

This complex stimulates antibody production.

The antibodies produced react specifically with the hapten.

Karl Landsteiner Experiment

Karl Landsteiner demonstrated the hapten concept.

Experiment:

  1. Hapten combined with carrier protein was injected into guinea pigs.

  2. Antibody formation occurred.

  3. Antibodies reacted with the hapten molecule.

This proved that haptens are antigenic but not immunogenic.

Examples of Haptens

Common hapten molecules include:

  • Penicillin

  • Antibiotics

  • Analgesic drugs

  • Alpha-methyldopa

These may cause drug allergies.

Adjuvants

The word adjuvant comes from Latin meaning “to aid.”

Adjuvants are substances that enhance immune responses to antigens.

They are also called immunopotentiating agents.

Types of Adjuvants

General Adjuvants

These enhance both:

  • Humoral immunity

  • Cellular immunity

Specific Adjuvants

These enhance only one immune response:

  • B-cell response

  • T-cell response

Mechanism of Adjuvant Action

Adjuvants enhance immune responses through several mechanisms.

  1. Slow release of antigen

  2. Increased exposure time

  3. Increased antigen size

  4. Enhanced antigen presenting cell activity

  5. Increased lymphokine production

Functions of Adjuvants

Adjuvants perform several important roles.

  • Increase antibody production

  • Decrease threshold dose of antigen

  • Convert weak antigens into strong immunogens

  • Enhance vaccine efficacy

Examples of General Adjuvants

Common general adjuvants include:

  • Water-in-oil emulsions

  • Aluminum hydroxide gel

  • Synthetic polynucleotides

  • Bacterial endotoxins

Freund’s Complete Adjuvant

Freund’s complete adjuvant consists of:

  • Killed Mycobacterium tuberculosis

  • Oil-in-water emulsion

Functions:

  • Increases antibody production

  • Enhances cell mediated immunity

Freund’s Incomplete Adjuvant

Freund’s incomplete adjuvant contains:

  • Water-in-oil emulsion

  • No bacterial components

Function:

  • Enhances humoral immune response

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