MLT 302: LECTURE 1

IMMUNITY AND SUSCEPTIBILITY

Introduction

The word immune literally means free from burden. Used in a general sense, immunity refers to

the ability of an individual to recognize and defend itself against foreign invaders. Susceptibility,

the opposite of immunity, is the vulnerability of the host to harm by infectious agents.

Immunology and Immune System

Immunology is the study of specific immunity and how the immune system responds to specific

infectious agents. The immune system consists of various cells, especially lymphocytes, and

organs such as thymus gland, which participate in providing the host with specific immunity to

infectious agents.

The immune system protects an individual against invasion by foreign bodies especially microbial

agents and their toxic products.

The integrity of the body is maintained by the multiple defense systems including immune

response.

Types of Immunity

a. Innate Immunity

b. Acquired immunity

Innate immunity

This is an inborn immunity that protects the body against all foreign invaders. It is also called non-

specific immunity and it involves the following:

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i. Resistance of the skin to invasion by organisms.

ii. Destruction of swallowed organisms by the acid secretions of the stomach and the digestive

enzymes.

iii. Phagocytosis of bacteria and other invaders by white blood cells and cells of the tissue

macrophage system

iv. Presence in the blood of certain chemical compounds that attach to foreign organisms or

toxins and destroy them. Some of these compounds are, lysozyme, basic polypeptides,

complement complex and natural killer cells (NK cells).

Acquired Immunity (Specific or Adaptive Immunity)

Acquired immunity, also called specific immunity, is an immunity that develops after the body is

first attacked by a bacterium, virus, or toxin, often requiring weeks or months to develop the

immunity. It can be acquired naturally or artificially.

Acquired immunity is caused by a special immune system that forms antibodies and/or activated

lymphocytes that attack and destroy the specific invading organism or toxin.

Types of acquired immunity

a) Passive immunity: In this type of immunity antibodies are introduced into the body either

by a natural or artificial means. These antibodies are globulin molecules in the blood plasma that

are capable of attacking an invading agent.

✓ Examples of natural passive immunity: Antibodies received from mother by the

developing fetus and antibodies from breast milk

✓ Examples of artificial passive immunity: Antibodies prepared from animals (antisera),

or antibodies prepared from humans (human immunoglobulins) which are then introduced

into the body of an individual.

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b) Active Immunity: Unlike in passive immunity whereby the antibodies are obtained from

another individual or animal, in active immunity, it’s the persons’ body that produces the antibodies

as well as activated T cells in response to the body invasion by a microorganism (natural) or

vaccination (artificial).

✓ Example of natural active immunity: production of antibodies and/or activated T cells in

response to the body invasion by microorganisms

✓ Example artificial active immunity: production of antibodies and/or activated T cells in

response to a vaccine (vaccination)

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 LECTURE 2

ANTIGEN AND ANTIBODY

A. ANTIGEN

The term antigen was coined from the word antibody and generator. Thus, an antigen was

originally considered to be a substance that induced production of antibody. However, with greater

insight into mechanisms of immune response following definition is considered appropriate for

antigen:

“An antigen when introduced into a host induces the formation of specific antibodies and T

lymphocytes that are reactive against the antigen.”

Immunogenicity and Antigenicity

Antigens have two very important characteristics:

immunogenicity, or the ability to stimulate the specific immune response , and antigenicity, the

ability to react specifically with antibodies.

An antigen with both these characteristics is called a complete antigen. An antigen which has

reactivity but not immunogenicity is called an incomplete antigen or hapten (haptein: to grasp).

A hapten can be made into a complete antigen by combining it with a larger carrier molecule, such

as a protein.

Determinants of Antigenicity

There are several important determinants of any antigenicity.

I. Foreignness

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 II. Chemical nature

III. Macromolecular size

IV. Molecular complexity

V. Biodegradibility

VI. Specificity.

Foreignness:

To be antigenic, the macromolecule must be foreign to the animal being immunized. Foreignness

here denotes being of different antigenicity as the host. The more foreign the antigen source the

better it will be.

Chemical nature:

Proteins or large polysaccharides are much more antigenic than lipids and nucleic acids.

Macromolecular Size:

Proteins of molecular weight exceeding 10,000 daltons are good antigens. Tetanus toxoid, egg

albumin, thyroglobulin and haemocyanin—all with molecular weight ranging between 14,000–

6,000,000 are examples of good protein antigens. Polysaccharides are poor antigens.

Molecular Complexity:

The antigenic potency of macromolecule increases with the complexity of structure and

accordingly quaternary structures are antigenically most potent. In other words, heterogeneity

increases immunogenicity, for example, quaternary proteins that are the most heterogenous are the

most immunogenic among the four types of protein structures (40 > 30 > 20 > 10 structures of

proteins).

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Biodegradibility/Susceptibility to tissue enzymes: If a substance is insoluble in body fluids and

cannot be converted to soluble forms by tissue enzymes, it may not act as an antigen. All cellular

antigens, bacteria, viruses and red blood cells are quickly engulfed by phagocytic macrophages

and digested to their soluble constituents.

Specificity:

Antigen attaches specifically to an antibody because of the "fit" between the antigenic

determinant on its surface as well as the receptor on antigen binding site on antibody. The effect

of antibody is activated only after the "fit" has taken place. The specificity can be:

Species specific: Human antigens v/s animal antigens with the exception of heterophile antigens

which are present in more than one species.

Organ specific: Every organ has its specific antigens. In exceptional instances there is sharing

which may lead to immunological problems.

Isospecific: These antigens differentiate members of same species viz HLA and blood group

antigens.

ANTIGEN NOMENCLATURE

The antigens that require T cells in order to generate an immune response are called as T cell-

dependent (TD) antigens. Antigens that stimulate B cells without the intervention of T cells are the

T cell-independent (TI) antigens. The booster or memory response is mediated through T cells and

hence can be initiated only by TD antigens.

There are certain other terms which are in common use regarding some varieties of antigens.

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Autologous Antigen

An autologous antigen is one’s own antigen, which under abnormal circumstances would induce

autoantibody formation. Thus, autologous antigen is synonymous with auto or self-antigen.

Heterologous Antigen

A heterologous antigen is an antigen that stimulates the production of an antibody which will react

with another different antigen.

Homologous Antigen

The homologous antigen is the antigen that stimulates the production of an antibody which will

specifically react with it. It is the antigen used in the production of antiserum.

Isoantigen

The isophile antigens or isoantigens are the molecules of one individual of a species that are

antigenic in another member of same species. Best example of isoantigens is blood group system.

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 LECTURE 3

B. ANTIBODY

The production of antibody is a part of the response of the immune system to antigenic stimulation.

Antibodies are blood proteins, all of which are globulins (hence the synonymous

immunoglobulins) part of gamma fraction of serum globulins. In addition to those found in blood

(humoral antibodies), some types of antibodies are fixed to body cells or tissues or exist in body

secretions (cell bound antibodies).

Structure

Immunoglobulin (Ig) molecules are symmetrical structures. In solution they become ‘Y’-shaped

after binding to an antigen. Each molecule consists of four polypeptide chains: two identical

heavy (H) chains and two identical light (L) chains. These are designated light or heavy based

upon their molecular weight which is 50,000 to 70,000 daltons for heavy chains and 20,000 to

25,000 daltons for light chains (Fig. 18.1). The L-chain is attached to H-chain by a disulphide

bond. The two H-chains are joined together by 1 to 5 S-S-bonds depending on the class of

immunoglobulins. The H-chains are structurally and antigenically distinct for each class of

immunoglobulin. The L-chains are similar in all classes of Ig. They occur in two types: Kappa (κ)

and lambda (λ). A molecule of immunoglobulins could have either kappa or lambda but never

both. L- and H-chains are subdivided into variable regions and constant regions. An L-chain

consists of one variable domain (VL) and one constant domain (CL). Most H-chains consist of one

variable domain (VH) and 3 or more constant domains (CH). Each domain is approximately

110 amino acids long. Variable regions are responsible for antigen binding while the constant

regions are responsible for biological functions. In the variable regions of both L and H-chains

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are three extremely variable (hypervariable) amino acid sequences that form the antigen-binding

site.

Fig. 2. Antibody molecule Fig. 3. Structure of Ab molecule

The antibody molecule can be split by papain to yield two identical fragments, each with a single

combining site for antigen. This is called as Fab-fragment antigen binding. The third fragment

which lacks the ability to bind to antigen is termed as Fc-fragment crystallizable (Fig. 2). In an

experimental setting, enzymes can be used to cleave the antibody into Fc and Fab fragments, which

have several uses:

Fc region: The Fc region (fragment, crystallizable), is derived from the stem of the “Y,” and is

composed of two heavy chains that contribute two or three constant domains depending on the

class of the antibody. The Fc region binds to various cell receptors and complement proteins. In

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this way, it mediates different physiological effects of antibodies such as opsonization, cell lysis,

degranulation of mast cells, basophils and eosinophils and other processes.

Fab region: Each end of the forked portion of the “Y” on the antibody is called the Fab region

(fragment, antigen binding). It is composed of one constant and one variable domain of each of

the heavy and light chain. These domains shape the paratope—the antigen binding site—at the

amino terminal end of the monomer. The two variable domains bind the epitope on their specific

antigens.

Classes (Isotype of Ig)

Based upon the structure of their heavy chain constant region, immunoglobulins are classed into

major groups called classes and also termed as isotypes. In human beings there are five classes:

i. Immunoglobulin G (IgG)
ii. Immunoglobulin G (IgA)
iii. Immunoglobulin M (IgM)
iv. Immunoglobulin D (IgD)
v. Immunoglobulin E (IgE).
The heavy chains of these immunoglobulins are designated by Greek letter as gamma (γ), alpha

(α), mu (μ), delta (δ) and epsilon (ε) respectively. Within class IgG, based upon different distinctive

heavy chains and differing functional properties, there are four subclasses: IgG1, IgG2, IgG3 and

IgG4. Similarly, there are two subclasses each of IgA and IgM.

Characteristics of Immunoglobulins

Immunoglobulin G

Immunoglobulin G (IgG) is the class of immunoglobulin which has maximum concentration in

serum and is the major immunoglobulin to be synthesized during the secondary immune response.

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It is the major line of defense in a newborn because of its capability to pass through placenta as

well as to be secreted in colostrum. IgG can be further subgrouped into four isotypic subclasses -

IgG1, IgG2, IgG3, and IgG4.

Immunoglobulin M

Because of high molecular weight (900,000) and a polymer of five four-peptide units, the IgM is

also referred to as the macroglobulin antibody.

These antibodies are extremely efficient, appear early in response to infection and are largely

confined to the bloodstream.

Figure 4. IgM Structure

Immunoglobulin A

The main function of IgA is to defend the exposed external surfaces of the body against attack by

microorganisms. It appears selectively in saliva, tears, nasal fluid, sweat, colostrum and secretions

of lungs, genitourinary and gastrointestinal tracts. IgA is synthesized locally by plasma cells. It

prevents the entry of microbes into body tissues. Aggregated IgA binds to polymorph, and also

activates the alternative pathway of complement.

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Two subclasses of IgA have also been found, IgA1 and IgA2. The human secretory IgA is

associated with two proteins, termed secretory component and J chain.

Secretory Component. Secretory IgA differs from serum IgA in having an additional protein

called secretory component (SC). The functional role of SC remains enigmatic.

J-chain. This protein has been named as J-chain (joining chain) because it is found only in

immunoglobulins composed of more than one four peptide units. The biological role of J chain is

believed to initiate polymerization of IgA and IgM molecules.

Fig. 5. Structure of IgA with J chain and secretory piece

Immunoglobulin D

IgD is present on the surface of a proportion of blood lymphocytes where it seems likely that they

may operate as mutually interacting antigen receptors for the control of lymphocyte activation and

suppression.

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Immunoglobulin E

Very few plasma cells in body synthesize this immunoglobulin and the concentration of IgE in

serum is also very low. IgE antibodies remain firmly fixed for an extended period when injected

into human skin where they are probably bound to mast cells where they play an important role

in allergy. Contact with antigen leads to release of vasoactive amines.

The main physiological role of IgE seems to be protection of external mucosal surfaces of the body

through triggering an acute inflammatory reaction.

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