Topic 3  Antigens

Introduction

Immune responses arise as a result of exposure to foreign stimuli.  The compound that evokes the response is referred to either as “antigen” or as “immunogen.”  The distinction between these terms is functional. In the previous lessons we learned about major components of the immune system.  We have been introduced to the cells of the immune system which recognize “self” from “foreign.” We begin this lesson by looking at the properties that make a foreign substance immunogenic.    We will then examine antigens in more detail and  learn what special features are recognized by the immune system.  Antigenic determinants or epitopes are specific sites on the macromolecules which are recognized by lymphocytes.  Some of the molecular properties of antigens recognized by B or T cells are described here.  These special features tell us much about how the body  recognizes invaders as well as about the structure of biological molecules.   Finally,  we will briefly discuss haptens, small molecules that can bind to antibodies but are not able by themselves to induce an immune response, and mitogens which can nonspecifically induce proliferation of immune cells.

Objectives

On completion of this section and the required reading, you should be able to:

n  explain the factors that induce immunogenicity on molecules;

n  describe the specific and distinctive sites on antigen that are recognized by a B cell Immunoglobulin;

n  describe the specific and distinctive sites on antigen that are recognized by a T cell receptor;

n  describe the specific and distinctive sites on antigen that are recognized by the Major Histocompatability Complex;

n  discuss some important characteristics of protein antigenic determinants;

n  differentiate between and antigen’s inductive and reactive abilities.

Required Reading

Refer to the Textbook Key for the appropriate chapter of the textbook.

P Key Terms

P Key Concepts

n  Immunogenicity is the capacity to induce an immune response. It requires that the compound is foreign to the immunized individual and that it possesses a certain complexity and minimal molecular weight.

n  Antigenicity is the ability to bind with antibodies or with cells of the immune system. This binding is highly specific and it involves several weak forces operating over short distances.

n  The smallest unit of the antigen that is capable of binding with antibodies is called an antigenic determinant or epitope.  Compounds may have one or more epitopes capable of reacting with immune components

n  Haptens are small molecules that can bind to antibodies but cannot by themselves induce an immune response.

n  Mitogens nonspecifically induce proliferation of cells, especially lymphocytes.

DID YOU KNOW?

Vaccines Against Heart Disease?

Since antibodies can be raised against small organic molecules by using them as haptens, is it possible to make antibodies against cholesterol?  If so, could these antibodies then control the development of heart disease?  In experiments where cholesterol esters linked as haptens, to protein carriers are used to vaccinate rabbits, a significant reduction in atherosclerotic plaque formation was observed.  The rabbits had made antibodies against the cholesterol haptens.  It is probable that the antibodies bound to cholesterol linked to lipoprotein and enhanced their removal from the circulation.  Unfortunately this cholesterol-lowering effect could not be sustained, despite repeated immunization.  Studies have also shown that many humans possess natural antibodies to cholesterol that can be boosted by appropriate vaccination.  While these are exciting results, considerably more basic research must be undertaken before the practicality of this approach is established.

Immunology an Introduction., 4^th Ed. I.R. Tizard.  Sunders College Publishing, Harcourt Brace College Publishers.  1995

Some Commonly Used Antigens

The major considerations used in selecting antigens for immunological research are that they be cheap, pure and available in large quantity.  Recall the information given in your textbook about what makes a molecule a good antigen and suggest why the listed compounds qualify as ones. 

Bacterial Lipopolysaccharide.  Usually derived from Escherichia coli, it is also known as endotoxin.

Bovine Serum Albumin.  A soluble white protein from bovine blood with reasonable antigenicity.

Flagellin.  A protein derived from the flagella of mobile salmonellae.  Commonly polymerized to improve its antigenicity and stability.

Hemocyanin.  A very potent protein antigen in mammals.  It is the blood pigment of giant keyhole limpet Megathura crenulata.

Immunoglobulin G.  Derived from human blood, this protein is an excellent antigen in experimental animals.

Lysozyme.  This protein is derived from egg white.  Because its complete structure is well known, it is useful for careful investigations into the structure of protein epitopes.

Sheep Red Blood Cells.  Plentiful and inexpensive washed sheep red blood cells are potent antigens and used in a wide variety of immunological techniques.  Purists make certain that the sheep are of a specific blood group to insure reproducibility.

Tetanus toxoid.  Formalin-treated tetanus toxin.  A good protein antigen, also used to protect against tetanus.

TGAL .  A multi chain synthetic antigen in which tyrosine and glutamic acid residues are attached to alanine side chains on a lysine backbone.  Useful for analyzing the immune response to define epitopes.

Immunology an Introduction., 4^th Ed. I.R. Tizard.  Sunders College Publishing, Harcourt Brace College Publishers.  1995

Review Questions

1. Textbook Study Questions

Review questions at the end of the Chapter 4.  The answers with explanations are available at the end of the textbook.

2. Multiple Choice Questions

1.  Which of the following chemicals is the least antigenic?

A) Glycoproteins

B)  Sugars

C)  Proteins

D) Lipoprotein

E)  Nucleoproteins

2.  A haptens is a(n)

A) carbohydrate side chain

B)  amino acid side chain

C)  small molecule attached to a protein

D) large protein attached to a small molecule

E)  antibiotic

3.  A common feature of T-independent antigens is that they are

A) globular proteins

B)  simple repeating polymers

C)  very large molecules

D) carbohydrate

E)  bacterial in origin

4.  Glycoproteins are proteins that

A) contain lipids

B)  contain oligosaccharides

C)  contain interchain bonds

D) stimulate the immune system

5.  Which one of the following is not immunogenic?

A) keyhole limpet hemocyanin

B)  bovine serum albumin

C)  bacterial lipopolysaccharide

D) glucose

E)  DNA

6.  An antigenic determinant is about the size of

A) 1 amino acid residue

B)  5 amino acid residues

C)  20 amino acid residues

D) 50 amino acid residues

E)  100 amino acid residues

3.  Short Answer Questions

1.  Differentiate between immunogenicity and antigenicity.

2.  All immunogens are antigens but all antigens are not immunogens. Explain  with the use of specific examples.

3.  An entire microbe or molecule does not induce and immune response.  Explain.

4.  Irrespective of the number of epitopes that a molecule has, the immune response is biased and sees what it wants to see. Explain.

5.  Haptens are usually coupled to a carrier molecule before they are immunogenic.  How can you demonstrate that the selected immunoglobulins are specific for the haptens and not for the carrier? As a corollory, would you expect ALL of the antibodies to be specific for the hapten? explain.

6.  Why is the definition of an antigen considered to be an operational definition.

7.  Differentiate between epitopes and agreotopes.

8.  Differentiate between epitopes recognized by B cell receptor and epitopes recognized by T cell receptors.

Where to Go from Here

Once you have completed the review, take some time and complete the objectives. If you are having trouble with any of the concepts, contact your instructor.

It is important that you get clarification on any of the topics or concepts that you are having difficulty with as soon as they arise. Many of the concepts build on each other so it is vital that you not only keep up with the schedule, but clear up any questions or problems as they arise. Remember to regularly check your Instructor and Assignment Information provided by your instructor for assignments and due dates for completing them.

When you are confident that you can complete the objectives, proceed to the next topic.