Microbiology-II UNIT 3 Structure

3.0 Objectives 3.1 Introduction 3.2 Definitions 3.3 What is Immunity? 3.4 The Three Lines of Defense in the Body 3.5 3.6 Types of Immunity 3.6.1 Innate Immunity 3.6.2 Factors Influencing Innate Immunity in an Individual 3.6.3 Acquired Immunity 3.6.4 Active Acquired Immunity 3.6.5 Passive Acquired Immunity 3.6.6 Differences between Active and Passive Immunity 3.7 The 3.8 and 3.9 //Anaphylaxis 3.10 Practical Application of Immunology 3.10.1 Immunizing Agents 3.10.2 Vaccines and Vaccinations 3.10.3 Immunoglobulins 3.10.4 The Immune Responses 3.11 Let Us Sum Up 3.12 Key Words 3.13 Answers to Check Your Progress

3.0 OBJECTIVES

After going through this unit, you should be able to: l define Immunity; l differentiate between the older and modern concept of immunity; l determine the three lines of defense in the body; l enumerate the different types of immunity; l differentiate between active and passive immunity; l explain the innate and ; l distinguish between antigens and antibodies; l state the phenomenon of allergy; l describe the various - reactions; l discuss the various immunizing agents; and l define primary and secondary response.

3.1 INTRODUCTION

The word ‘Immunity’ comes from a Latin term ‘immunis’ meaning free or exempt. It has been recognised from very early times that those who suffer from infectious diseases such 38 as diphtheria, whooping cough, mumps, measles, small pox etc. do not get the disease a second time. Also it had long been known that when a disease occurs in epidemic form, Immunity some persons do not get the infection and in some the infection is very mild. The answer to all these questions is that they have developed some kind of immunity in the body to resist infection. Immunity is a very broad scientific discipline and in recent years many new technologies have developed and with one recent technique ‘hybridoma’ it is now possible to obtain unlimited amounts of specific antibodies which could be used for treating the patients.

In this unit, you are going to learn the older and modern concepts of immunity, the three lines of defense in the body, types of immunity and differences between innate and acquired immunity. You will also study the practical applications of immunology including different types of antigens and antibodies. You will also become familiar with different types of antigen-antibody reactions. An account of concept of allergy is also included in this unit and various immunizing agents are discussed in the end.

3.2 DEFINITIONS

Older Concept of Immunity: The resistance of the individual to an infected organism is called immunity. Modern Concept of Immunity: It is defined as the ability of the body to recognise, destroy and eliminate antigenic material foreign to its own. Antigens: Antigens are specific substances which when introduced into the body give rise to the production of antibodies. Antibodies: Antibodies are specific substances in response to antigenic material. They are produced in the body to help fight disease germs. Immunizing Agents (Biologicals): Substances used in practical immunology are called immunizing agents (Biologicals). They may be antigenic immunizing agents or anitbody immunizing agents. Immunology: The branch of science which deals with immunity is called immunology.

3.3 WHAT IS IMMUNITY?

We often experience that one person may have one cold after another while the other person never catches cold although both have the same chances for exposure. This is because of his resistance towards some infected organisms. In earlier days, immunity was defined as the resistance of the individual to an infected organism. Expanding knowledge about blood groups, tissue grafts and drug reactions has shown that this older concept of immunity is inadequate. In the modern sense, immunity is the ability of the body to recognise, destroy and eliminate antigenic material foreign to its own.

Immunity may also be regarded as the result of the fight of two opposite forces—the infected organism on one hand and the host on the other hand. The result may be complete immunity, partial immunity or total absence of immunity. In fact no one ever enjoyed complete immunity or ever had total absence of immunity. Most of us fall in the category of partial immunity. If an individual possess complete immunity it means he is proof against any infection and would not contract any disease. On the other hand if a person possess no immunity he would die of any infection. We do not encounter such situations in life. So most of us are partially immune and the science of immunity is concerned with making the partially immune individual completely immune as far as possible.

3.4 THE THREE LINES OF DEFENSE IN THE BODY

There are three lines of defense (barriers) in the body that must be overcome by a pathogen before it can establish an infection or disease.

Mechanical Barriers (First Line of Defense) They form a part of innate (natural) immune system. Our body is surrounded by both pathogenic and non-pathogenic organisms which through various portals (water, milk, food, 39 Microbiology-II air, vectors etc.) try to enter the body but are stopped by many efficient mechanical barriers, which would restrict the entry of such microbes. These mechanical barriers are: a) Unbroken skin: Although unbroken skin is a good mechanical barrier and does not permit the organisms to enter the tissues, sometimes the organisms gain their entry through the hair follicle or opening of sweat gland or through the skin if it is torn or there is any cut or wound. b) The conjunctivae: The conjunctivae are protected by the motion of the eyelids and the constant washing of the tears, still the organisms may enter through the conjunctivae. c) Mucous membranes and mucous secretions: The mucous secretions of respiratory, digestive and urinogenital organs form a protective covering to mucous membranes. Secretions from the sweat glands, gastric juice and vagina hold many microorganisms and make them lose their infectivity. Peristalsis, that is rhythmic contractions of the intestine, also help in trapping the microbes into mucous and other such secretions. These secretions whether they are acidic (sweat, gastric, juice, vaginal) or alkaline (bile) keep the bacterial flora of the alimentary canal in check. Although the mucous membranes of the genitalia are protected from most , yet several organisms can invade the body through sexual intercourse (organisms of gonorrhoea, syphilis, AIDS, etc.). d) Mechanical arrangement of the structures: Turbinate bone in the nose also forms a line of defense. The bacteria when they enter through nose, they either stick to the mucous surface of the nose or they take a lot of time to reach the alveoli because of its structure. By the time they reach the alveoli, most of the organisms die and very few succeed in entering the organ. e) Other barriers: Coughing, sneezing, shedding tears, perspiring, salivating etc. also help mechanically to remove the organisms. It may be mentioned here that Lysozyme, an enzyme present in most secretions of the body, acts as a chemical barrier.

Phagocytes (Second Line of Defense) These also form a part of innate immune system. If the microorganisms succeed in passing the first line of defense and enter the deeper tissues, they are attacked by the specific cells of the body called phagocytes or natural killer cells (NK), which include the cells of the reticuloendothelial system (RES). These phagocytes ingest the microbes and destroy them within an hour or two.

Antibodies (Third Line of Defense) These form a part of adaptive immune system. If the organisms succeed in passing through the second line of defence also, then the body tissues produce special substances known as antibodies which act against the germs and kill them. The antibodies apart from destroying the infective microbes, also neutralize any poisonous substance, which may have been formed.

3.5 INFLAMMATION

If the antibody production in the body is slow and quantity produced is insufficient to destroy the organisms or neutralize their toxins, the organisms overcome the specific resistance of the host, invade the tissues, start multiplying very rapidly, injure the tissue cells, cause irritation, pain, swelling, redness and finally lead to inflammatioin. The swelling and redness are due to dilation of the blood vessel of the affected part. However, if the antibodies are produced in large quantities, the organisms may be killed. Let us now study one by one the different types of immunity as shown in Fig. 3.1.

3.6 TYPES OF IMMUNITY

Fig. 3.1 summarises the various types of immunity. 3.6.1 Natural Immunity (Innate Immunity)

It is also known as native or inherited immunity. It means an inherited resistance to 40 infection. It is present from birth and is generally passed on from one generation to the Immunity IMMUNITY

Natural (Innate) Acquired Immunity acquired during lifetime

a) Species b) Racial c) Individual Immunity among Immunity among Immunity among the members of a the races of the the individuals of particular species same species the same species and race

Active Passive Patient actively participates Patient does not participate in making antibodies, in making antibodies ready-made antibodies are injected.

a) Natural b) Artificial a) Natural b) Artificial Immunity acquired Mother to By injection artificially by vaccines/ offspring of antibodies toxoids

a) Immunity acquired as a b) Immunity acquired result of an attack of a unconsciously on account of disease. subclinical infections (Immunity acquired by carriers)

Fig. 3.1: Types of immunity other. A child may possess resistance to certain diseases to which mother is immune. That is why breast-feeding is very important because child obtains immunity from the mother. Natural immunity is divided into the following three subtypes: a) Species Immunity: It means immunity among the members of a particular species. Many diseases which occur in human beings do not occur in animals and vice-versa. For example, diseases such as measles, mumps, polio, syphilis, leprosy, cholera etc., are found only in human beings. Species other than human beings are immune to such diseases. Fish has a form of tuberculosis but the tubercle bacillus which causes this disease in fish will not infect human beings. Similarly, the human tubercle germs will not infect fish. This type of immunity is largely due to differences in body temperatures, although metabolic, chemical, physiological and anatomical differences between the different species also play an important part. b) Racial Immunity: It means immunity present among the races of the same species. Some races are immune to certain diseases while other races are susceptible. For example, in human beings Jews are immune to tuberculosis but Negroes are more susceptible to it. On the other hand, Negroes have high degree of immunity to malaria, dysentery, yellow fever than whites. Complete racial immunity is very rare. Races differ from one another primarily in degree of immunity. This type of immunity partly depends on the same physiological differences that exist between different species and partly depends upon the nutrition, cleanliness, differences in mode of life, economic and genetics of the race. c) Individual Immunity: It means immunity present among the individuals of the same species and race. It varies with the different individuals of the same species and race. The resistance of the same individual may also vary from day to day and time to time. An individual may be very susceptible to one disease organisms and very resistant to another. An individual in good health may never catch cold but if he is weak and exhausted he could catch one cold after another. Individual resistance also depends upon the physical state of the individual and varies with such factors as diet, fatigue and exposure etc. 41 Microbiology-II 3.6.2 Factors Influencing Innate Immunity in an Individual

There are four main factors which influence the level of innate immunity in an individual viz. age, hormonal influence, drugs and nutrition. i) Age: The very young in whom the immune system is not fully developed and the very old people in whom the immune system is on the decline, are more susceptible to infectious diseases compared to adults. The foetus is normally protected from the maternal infection by the placental barrier. ii) Hormonal Influence: Endocrine disorders such as diabetes mellitus, hypothyroidism etc. due to metabolic changes also influence susceptibility to infection. iii) Drugs: Constant use of drugs is also responsible for lowering the level of immunity and making the body more susceptible to infection by opportunistic pathogens. iv) Nutrition: Defective nutrition is also one of the factors that depresses the level of immunity. If a person is already having some infection, malnutrition depresses all types of immune response and leads to secondary infection such as pneumonia etc. 3.6.3 Acquired Immunity

The immunity acquired during lifetime of an individual is known as acquired immunity. It is associated with the presence of specific circulating antibodies. Acquired immunity differs from innate immunity in two respects: i) It is not inherent in the body, it is acquired during lifetime. ii) It is specific for a single type of microorganism. Acquired immunity is of two types— Active and Passive. 3.6.4 Active Acquired Immunity

If the patient actively participates in making his antibodies, the immunity is called active acquired immunity. There are two methods of acquiring active immunity—Natural and Artificial. a) Natural Active Immunity: It may be acquired in two ways: i) Immunity acquired as a result of an attack of disease: An individual may become immune to certain infectious diseases by actually contracting them and recovering. It is entirely specific which means if a person recovers from small pox; he is immune only to small pox but this does not prevent him from contracting typhoid or mumps. This immunity of the body is due to the presence of antibodies which the body develops as a part of the reaction or response to the presence of invading bacteria or other poisons (toxins). In some diseases, the antibody production is so great that the immunity may persist for the life time of the individual. The diseases of this type are typhoid, diphtheria, measles, mumps, small pox, whooping cough. On the other hand, there are some diseases such as pneumonia, influenza, gonorrhoea, dengue fever, staphylococci and streptococci infections, where antibody formation is not prolonged and thus there is only temporary resistance. Second and third attacks are also possible. ii) Immunity acquired unconsciously on account of subclinical infections (Immunity acquired by carriers): This kind of immunity develops gradually unconsciously after repeated exposure to small doses of the infecting organisms. The doses of such germs or toxins although are not sufficient to give rise to the disease, yet they are enough to stimulate the production of antibodies. Such persons are not suffering from the disease but they are carriers of the disease. Infectious diseases such as diphtheria, yellow fever and typhoid affect children more frequently and more seriously than adults. The adults develop immunity to such diseases. b) Artificial Active Immunity (Immunity acquired by immunizing agents i.e. antigens such as vaccines or toxoids): If the immunity is acquired artificially by the introduction of an antigen or toxoid into the body in the form of vaccine and the antigen stimulates the individual to develop specific antibodies, the immunity is called as artificial active immunity. It is a method to protect persons against infections to which they may be exposed in future. The antibodies formed are similar to those formed by a natural infection. In this method the vaccines are given by injections into the superficial layer of skin or into the subcutaneous tissue. A single injection of antigen results in the 42 formation of small quantity of the antibody. It has been found that for an effective immunity against many diseases, two or more injections are required which are given at Immunity intervals of one to several weeks. 3.6.5 Passive Acquired Immunity

If the patient does not participate in making his antibodies, the immunity is called passive acquired immunity. Here the patient is immunized by prepared antibodies and the body cells do not take any part in the production of antibodies. There are two methods of acquiring passive immunity. a) Natural Passive Immunity (Mother to Offspring): It is temporary immunity passed on from mother to the baby before birth. The antibodies from the maternal blood through the placenta or mother’s milk enter the foetus. Mothers immune to diphtheria may transfer diphtheria antitoxins to infants. It is sometimes also spoken of as congenital immunity. This immunity lasts for few months and protects infants from diphtheria, tetanus, measles, mumps, small pox etc. b) Artificial Passive Immunity: It is the immunity produced in an individual by intra-muscular injection of readymade antibodies (sera). In this case some other animal or person is vaccinated or inoculated with the disease germs or toxins and made immune. Then some of the serum from the blood of this immune animal is injected in the person to be immunized. The greatest disadvantage of the artificial passive immunity is that antibodies are rapidly excreted and gradually disappear from the blood. Thus the immunity lasts for a short time. The greatest advantage is that protection is possible immediately when the person is very ill.

Readymade antibodies or sera are of three varieties: a) Antitoxic Sera: They are produced by injection of toxoid into horse in increasing doses till the blood is rich in circulating antibodies. Then the anterior vena cava is cut, the animal bleeds and serum is collected. They are used in infections due to bacteria such as diphtheria, tetanus, gas gangrene. b) Anti bacterial Sera: In this case antibodies are produced by injections of bacteria into the animal and serum is collected. Example: pneumococceal and meningococcal infections, Anthrax, dysentery. c) Artificial Sera: They are used against viral infections. 3.6.6 Differences Between Active and Passive Acquired Immunity

Active Immunity Passive Immunity 1) Produced actively by immune system The host’s immune system does not participate. of host. 2) Body cells take part in the production Cells of the body do not take part in the production of antibodies, i.e. active immunity is of antibodies. Readymade antibodies are injected. acquired after infection or inoculation. 3) Immunity lasts long. Immunity lasts for short period, i.e. 10 to 14 days. 4) Immunity not effective immediately. Immunity is effective immediately. 5) It takes some time to develop the No time is lapsed to get the antibodies. antibodies in the system. 6) Immunological memory present. No immunological memory. 7) Serves no purpose in immunodeficient Applicable in immunodeficient host. host. 8) No inheritance of immunity. May be acquired from mother. 9) After antigenic stimulus negative No negative phase. phase may occur.

Check Your Progress 1 1) Define Immunity......

...... 43 Microbiology-II 2) List the three lines of defense in the body...... 3) List the different types of immunity...... 4) Differentiate between naturally acquired and artificially acquired active immunity...... 5) Distinguish between naturally acquired and artificially acquired passive immunity......

3.7 THE IMMUNE SYSTEM

The environment in which we live contains a large variety of infectious organisms such as Bacteria, Viruses, Fungi, Protozoa or Helminth parasites. These organisms enter in our body and cause infections which may be sometimes fatal but fortunately our body has an immune system which protects us from these infections. The immune system is of two types viz. innate and adaptive and both function side by side and protect the host. Let us now discuss the innate and adaptive immune system separately.

The Innate Immune System The innate immune system consists of mechanical barriers and phagocytes, the natural killer cells (NK) which protect the body from entry of germs. The germs while trying to enter the body are first stopped by mechanical barriers which form the first line of defense (see section 3.4). If the microorganisms succeed in passing the first line of defense and enter the tissues, they are attacked by the phagocytes the natural killer cells (NK) which form the second line of defense (see section 3.4). These phagocytes ingest the microbes and destroy them within an hour or two. The innate immune system is not antigen specific and it does not have memory. It does not even have the ability to improve resistance on repeated exposure to the same antigen.

Adaptive Immune System If the germs have breached the innate immune system and enter the deeper tissues, adaptive immune system becomes active and protects the host from invading organisms. The adaptive immune system is antigen specific and it has memory. It has the ability to remember the chemical nature of the infecting organism. It becomes more and more vigorous on repeated exposure to the same antigen. The adaptive immune system consists of lymphoid cells and lymphoid organs.

The Lymphoid cells: These are B cells and T cells which circulate in the blood. B cells are named after primary lymphoid organ the bone marrow and T cells derive their name from another primary lymphoid organ Thymus. B cells and T cells are produced in bone marrow and Thymus respectively. The T cells include T helper cells and cytotoxic T cells. T helper cells help B cells to make antibodies while cytotoxic T cells secrete the glycoproteins lymphokines. The T cells while developing in the Thymus are able to discriminate self from nonself. Besides B and T cells, the stem cells of the bone marrow can give rise to many other cell types which are also involved in immune response.

The Lymphoid Organs: These are of two types viz. primary and secondary. Bone marrow and thymus form the primary lymphoid organs while lymph nodes and spleen constitute the secondary lymphoid organs. The secondary lymphoid organs create the environment in which B and T cells can interact with the antigens and produce immune response which is so vital for the survival of man.

44 Immunity Primary Lymphoid Organs Secondary Lymphoid Organs

Waldeyer's ring (lymph nodes tonsils and adeniods)

Thymus

Lymph nodes

Bone marrow Spleen

Mesenteric lymph nodes

Peyer's patch

Lymph nodes

Fig. 3.2: Lymphoid organs in man

Differences Between Innate and Adaptive Immune System

Innate Adaptive 1) It forms the first and second line of It forms the third line of defense in the body. defense in the body. 2) Cells involved are phagocytes the The cells involved are B and T cells. natural killer cells (NK). 3) It is not antigenic specific. It is antigenic specific. 4) It does not have memory. It has memory. It has the ability to remember the chemical nature of the infecting organism. 5) Resistance not improved on repeated Resistance improved and becomes more and more exposure to the same antigen. vigorous on repeated exposure to the same antigen.

Check Your Progress 2 Differentiate between Innate and Adaptive Immune System......

3.8 ANTIGENS AND ANTIBODIES

Antigens Antigens are specific substances which when introduced into the body of the host give rise to the production of antibodies. These antibodies are poured into the plasma to neutralise the effect of antigens and appear in the patient’s serum 8 to 10 days after the start of an infection. The antibodies produced in response to the infection are specific. For example, an attack of diphtheria causes the production of antibodies which will only neutralise the diphtheria toxin or poison and will be of no use in fighting a streptococcal infection. Many substances act as antigens, such as bacteria, viruses, other microbes, pollens, egg white etc. 45 Microbiology-II Types of Antigens Complete Antigen: If antigen when introduced into the body of the host is capable of stimulating antibody production, it is called complete antigen, e.g. Proteins, polysaccharides.

Partial Antigen (): If antigen when introduced into the body of the host is not capable of stimulating antibody production in the host but produces specific reactions with the antibody, it is called as partial antigen.

Antibodies Antibodies are specific substances produced in the body in response to antigenic material to fight disease germs. They serve as protective agents against organisms and kill them. These antibodies may be found in the fluid part of the circulating blood (plasma and serum) as well as in certain tissues and are mostly produced in the body in reticuloendothelial cells located in bone marrow, liver, spleen, nodes etc. Antibody may be univalent or multivalent. Univalent antibody is one in which each molecule of antibody combines with one molecule of antigen. A multivalent antibody is one in which each molecule of antibody combines with two or more molecules of antigen.

Types of Antibodies

i) Antitoxins: The antibodies which neutralise the toxins of bactria are known as antitoxins. ii) Precipitins: The antibodies which cause the precipitation of bacteria/antigen are called precipitins. iii) Agglutinins: The antibodies which cause bacteria to form clumps are called agglutinins. iv) : The antibodies which dissolve or have a lytic action on foreign cells are called cytolysins. v) Bacteriolysins: The antibodies which dissolve or have a lytic action on bacteria cells are called bacteriolysins. vi) : The antibodies which render microorganisms more susceptible to ingestion are known as opsonins.

Antigen-Antibody Reactions When molecules of an antigen and an antibody are brought together in a solution, they cause specific reactions known as antigen-antibody reactions. A number of different antigen-antibody reactions have been observed in test tube experiments in humans as well as in animals. These reactions depend on numerous factors such as nature of antigen, environmental conditions and the origin of antibody etc. These reactions are very useful in the laboratory diagnosis of various diseases. They are stated below: i) Toxin-Antitoxin Reaction (Neutralization): A toxin is an antigenic poison such as diphtheria and tetanus toxins. When such a toxin is mixed with the corresponding antibody called antitoxin in the presence of electrolytes (Sodium Chloride) at a suitable temperature and pH, the antibody (antitoxin) becomes fixed to the antigen (toxin) resulting in a loss of poisonous properties of the toxin. This loss of toxicity is known as neutralisation of the toxin. ii) Precipitation Reaction (Precipitation) : When the antigen precipitinogen is mixed with the corresponding antibody preciptin in the presence of electrolytes at a suibtale temperature and pH, the antibody precipitin becomes fixed to the antigen precipitinogen resulting in precipitation. Precipitation reactions are most striking of all the reactions and are used in the laboratory for many purposes where the identity of a protein antigen or antibody is in question. iii) Agglutination Reaction: When red blood corpuscles or bacterial cells are mixed with the corresponding antibodies in the presence of electrolytes at a suitable temperature and pH, the cells (RBC or bacterial cells) clump together as seen in typhus and typhoid fevers. This phenomenon of clumping is called agglutination. The antigen involved is called agglutinogen, and the antibody is known as agglutinin. This reaction is used for the identification of Salmonella, Shigella and Brucella. iv) Compliment Fixation Text (CFT) (/Hemolysin/Bacteriolysin): When animal cells, blood cells or bacteria are mixed with the corresponding antibody- 46 cytolysin, hemolysin, or bacteriolysin respectively, the cells may be dissolved Immunity provided a third factor known as complement is present. The antigen involved is called lysin and the antibody is known as cytolysin, hemolysin and bacteriolysin. This test is used for bacterial diseases (gonorrhoea, brucellosis), spirochaetal disease (syphilis), rickettsial disease (typhus fever) and for several viral and parasitic diseases. v) Immobilisation (Opsonisation): When the animal cells phagocytes are mixed with the corresponding antibody , the latter immobilises the cells followed by ingestion and destruction. The phenomenon is called phagocytosis. This immobilisation test is used for spirochaete Treponema pallidum which causes syphilis and the test is known as Treponema pallidum immobilisation test (TPI) to detect syphilis. vi) Allergy Reaction: Sometimes under certain conditions antigens while reacting with the corresponding antibodies within certain organs of human body may cause allergic/hypersensitive reaction.

Check Your Progress 3 1) Define antigen...... 2) Define antibody...... 3) Name some diseases where complement fixation test (CFT) is used......

Activity 1 From the report of the patients name some diseases for which CFT has been used.

3.9 ALLERGY/HYPERSENSITIVITY/ANAPHYLAXIS

Allergy or hypersensitivity is a disease caused by a body’s reaction to a foreign substance (antigen), which may be harmless to others. Such an antigen is called . Whenever such an allergic or hypersensitive person comes in contact with such an allergen, he becomes allergic and develops the symptoms of the disease. For example, if a person allergic to pollens of a plant inhales a large quantity of pollen, he develops Hay Fever with the symptoms as inflammation in eyes and nasal cavities, sneezing, excessive secretions from the nose etc. This disease may even result in allergic asthma. A person may become allergic to house dust, eggs, curd or to any antigen (allergen) which is induced in the body. A person may be allergic to certain drugs or injection of high concentration of foreign serum which if not treated in time may be even fatal. The allergy or hypersensitivity develops in many infections with bacteria, fungi, viruses and parasites.

The words allergy and anaphylaxis are used to describe hypersensitive reactions or abnormal reactions which may be of the mild or serious type. If the reactions are mild they are described as allergy but if the reactions are of serious type they are described as anaphylaxis. Allergic state occurs in the course of some bacterial disease. Anaphylaxis is seen most commonly after a second injection of serum.

Types of Allergy Allergy may be immediate or delayed. Both are related to immunity and antibody formation. In both types, the reaction has occurred between antigen and its specific antibody. These reactions are determined by: a) the kind of antigen, b) the kind of antibody (precipitin or reagin), c) the concentration of antigen and antibody, 47 Microbiology-II d) the location and the kind of tissue cells involved, and e) the kind of animal involved.

Immediate Allergy: It occurs within a few seconds in persons, who are by nature specially sensitive to the foreign protein. In immediate allergy the antibody precipitin is involved. This precipitin occurs in or on certain tissue cells and also circulates freely in the blood. In this case precipitin or an antibody like precipitin is essential. This kind of allergy appears but recedes rapidly and is short lived.

Delayed Allergy: It occurs often at interval of a few days. In this case the antibody allergin reagin is involved. These antibodies occur in or on certain tissues but rarely or never circulate freely in the blood. This kind of allergy is induced by injection of antigen and it appears slowly, but lasts longer.

Types of Allergic Reactions Allergic reactions in human being are varied, only some of the commonest types are described below:- i) Respiratory : Asthma and hay fever are very common respiratory allergies. They are mostly due to the inhalation of dusts of animal origin or wind borne pollens, which may be absorbed by nasal sinus and lung membranes. Some respiratory allergies are also due to food or drugs. ii) Gastrointestinal Allergies: There is a long list of food causing gastrointestinal allergies. It includes eggs, milk, wheat, fish, white potato, fruits etc. Food sensitivity may be evidenced by itching, rash, eczema, respiratory and intestinal disorders. The severe type of headache known as migraine is often due to ingestion of foods to which a person is hypersensitive. iii) Drug Allergies: Some persons are hypersensitive to certain drugs such as iodine, aspirin, quinine, morphine, mercury, formaldehyde etc. There may be skin eruptions, fever, local , asthmatic attacks. iv) Cutaneous Allergies: Allergic dermatitis, urticaria, popularly called hives, eczema are usually due to food allergies but may also be because of sera or inhaled antigens.

Check Your Progress 4 Differentiate between allergy and allergen......

Activity 2 List some types of allergic reactions from which you or anyone in your family have suffered in the last two years.

3.10 PRACTICAL APPLICATION OF IMMUNOLOGY

3.10.1 Immunizing Agents

The Immunizing Agents may be classified as Vaccines (antigenic material) and Immunoglobulins (antibody material). 3.10.2 Vaccines and Vaccinations Vaccines Vaccine is a preparation of an antigen which when administered stimulates specific antibody formation in the body. Vaccines may be prepared from live organisms generally attenuated, killed organisms or toxoids or from combination of these. If more than one 48 immunizing agent is included in the vaccine, it is called a mixed or combined vaccine. Vaccination Immunity Vaccination is the transference of the organisms from the skin of an animal into the skin of human being for preventing the disease. The principle of vaccination was discovered more or less by accident in 1776 by an English physician Jenner. He noticed that the dairy maids who had become infected with cow pox were immune to the dangerous disease small pox. Jenner applied this principle on human beings to protect them from small pox. Jenner found that the organisms causing small pox in human beings also produce similar but mild cow pox disease in the cows which appeared as eruptions on the udder. Then the material from eruptions of the cow pox was taken and transferred into human beings with the result that the human beings never developed small pox even during an epidemic. This principle of vaccination has now been extended to many diseases. Rabies vaccination discovered by Pasteur depends on a principle very similar to that of vaccination against small pox. Typhoid, diphtheria, tetanus, whooping cough etc. are the diseases that are controlled by vaccination.

Activity 3

1) List the different types of vaccines used in your hospital. 2) From the report of patients name some diseases where vaccinations could have been used. 3.10.3 Immunoglobulins (Gamma Globulins)

The term immunoglobulin was introduced in 1959 for serum proteins formerly known as gamma globulins. Immunoglobulins are very important in the study of immunity and are formed by the reticuloendothelial system in the body. The human immunoglobulin system (human serum) consists of five classes namely IgG, IgA, IgM, IgD and IgE which are distinguished from each other on the basis of antigenicity and on the basis of physical and chemical properties.

IgG: IgG is the most abundant immunoglobulin of serum and it comprises 80% of the serum antibodies of the normal human being. It contains four subclasses IgG1, IgG2, IgG3 and IgG4 and all the four subclasses diffuse in the interstitial fluid. IgG is the only class of immunoglobulin which is transported across the placenta and is responsible for all the immunity which the foetus acquires by the placental route. The normal human infant is born with IgG equal to or higher than that of the mother.

IgA: It constitutes 10% of the antibodies in the human serum. It contains two subclasses

IgA1, and IgA2. It is present in many body fluids such as milk, saliva, tears, mucous secretions of respiratory, genitourinary and intestinal tracts and prevents the passage of organisms into circulation through minute leakage in the mucous surfaces of these tracts. IgA synthesis begins about 2 weeks after birth and in one year reaches a level of 4 to 5% of the adult.

IgM: It constitutes 5 to 10% of the antibodies in the human serum. It is a large antibody molecule often called macroglobulin. Because of its large molecular weight, IgM antibodies remain largely intravascular and cannot pass through placenta. IgM antibody molecules are capable of killing bacteria more effectively and thus cause lysis of cells. IgM antibodies are short lived.

IgD: It comprises less than 1% of the total immunoglobulin. It has not been shown to have antibody activity although it is found in greater amounts in some sera obtained from individuals with chronic infections.

IgE: It comprises the smallest fraction of immunoglobulin in the body. Normally, it is found in traces in serum. It has a distinctive biological activity which identifies it easily. It is concentrated in submucous tissues and is the major antibody responsible for symptoms of immediate allergy and anaphylaxis.

Activity 4 List the different immunoglobulins used in your hospital. 3.10.4 The Immune Responses

The response of the body to the immunizing agent (antigen) is called an immune response. It is of two types—Primary and Secondary. 49 Microbiology-II Primary Response The response of the body to initial contact with most immunizing agents (antigens) is called as primary response. In other words it is a response of the body to an immunizing agent administered for the first time to an animal or human who has never been exposed to it. After the first injection there is a period of 3 to 10 days before antibodies are formed in the blood. Thus, primary response is very slow. The nature and extent of primary response to an antigen is determined by a number of factors such as dose of antigen, nature of antigen, route of administration, nutritional status of the host etc.

Secondary Response It has been found that for an effective immunity against many diseases two or more injections are required for establishing high degree of immunity. This second dose of an antigen is called booster dose and the reimmunization is called secondary response. In reimmunization the body cells respond more rapidly as compared to the primary one. Persons having once received an initial course of injection need only take an annual booster dose.

Check Your Progress 5 1) What is a vaccine? ...... 2) Name the five classes of human immunoglobulin system...... 3) Define immune response, primary response and secondary response......

3.11 LET US SUM UP

l Immunity is defined as the power of an individual to resist infection (older concept). l Immunity is also defined as the ability of the body to recognise, destroy and eliminate antigenic material foreign to its own (modern Concept). l There are three lines of defense in the body (mechanical barriers, phagocytes and antibodies) which do not permit the organisms to enter the tissue. l If the pathogenic organisms manage to escape the three lines of defense and enter the body, they cause inflammation. l Immunity may be of different types. It may vary from species to species and individual to individual. l Immunity may be naturally acquired as a result of an attack of disease or artificially acquired by the introduction of an antigen in the form of vaccine or readymade antibodies. l Antibodies on the basis of their reactions with the antigen may be antitoxins, bacteriolysins, agglutinins, opsonins and precipitinis. l Antigens under certain conditions react with the antibodies and may cause allergy/ hypersensitivity which may be even fatal. l The immunizing agents may be classified as vaccines (antigenic material) and immunoglobulins (antibody material). l The human immunoglobulin system consists of five classes namely IgG, IgA, IgM, IgD and IgE of which IgG constitutes 80% of the serum antibodies of the normal human being. l The response of the body to initial contact with most immunizing agents (antigens) is called as primary response. l For an effective immunity against many diseases two or more injections are required. The second dose of an antigen is called booster dose and the reimmunization is called 50 secondary response. 3.12 KEY WORDS Immunity

Allergen : Any foreign substance (antigen) which causes allergy is called allergen. Antiserum : Blood serum which contains antibodies is called antiserum. Attenuated : Weakened. Bacteriolysin : An agent or substance which causes disintegration of bacteria. CFT : Complement Fixation Test. Complement : A protein constituent of blood serum which precipitates in antigen antibody reaction. Dark Field : A type of microscopic examination in which microscopic field is dark Microscopy and object is brightly illuminated. Epidemic : A sudden increase in the incidence rate of a disease affecting a large number of people over a wider area. Immunology : The science which deals with immunity is called immunology. Opportunistic : If a commensal or a saprophyte produces disease when the Pathogen resistance is low, it is called opportunistic pathogen. Peristalsis : Progressive and rhythmic contraction of the intestine. RES : Reticuloendothelial system. Serology : Serology is the study of the blood serum with particular reference to the antibodies which it contains. Species : It is a subdivision of a genus, the second word in the scientific name of plant or animal. Toxoid : It is a toxin that has been treated to destroy its toxic property without affecting its antigenic properties. TPI : Treponema pallidum Immunization. Vaccines : Killed cultures of microorganisms are called vaccines.

3.13 ANSWERS TO CHECK YOUR PROGRESS

Check Your Progress 1 1) Older Concept: The resistance of the individual to an infected organism is called immunity.

Modern Concept: It is defined as the ability of the body to recognise, destroy and eliminate antigenic material foreign to its own. 2) The three lines of defense are a) Unbroken skin, mucous membranes and secretions, (b) Phagocytes, and (c) Antibodies. 3) Different types of immunity are: Natural or acquired. Natural may be at birth/inherent and it is further divided into species, racial and individual. Acquired may be active and passive. Active and passive may be natural and artificial. 4) Naturally acquired active immunity may be acquired as a result of an attack of disease or unconsciously on account of subclinical infection. Artificially acquired active immunity may be acquired artificially by the introduction of an antigen or toxoid into the body in the form of vaccine of bacteria or toxoid (chemical) and the antigen stimulates the individual to develop specific antibodies. 5) Naturally acquired passive immunity is temporary immunity passed on from mother to the baby before birth. The antibodies from the maternal blood through the placenta or mother’s milk pass on to the foetus. Artificially acquired passive immunity is the immunity produced in an individual by intramuscular injection of readymade antibodies.

51 Microbiology-II Check Your Progress 2

Innate Adaptive a) Non-antigenic specific Antigenic specific b) Does not have memory It has memory. It has the ability to remember the clinical nature of infecting organism. c) Resistance not improved on repeated Resistance improved and becomes more and more exposure to the same antigen. vigorous on repeated exposure to the same antigen. d) Cells involved are phagocytes the The cells involved are B and T cells. natural killer cells (NK).

Check Your Progress 3 1) Antigen is a specific substance which when introduced into the body gives rise to the production of antibodies. 2) Antibody is a specific substance produced in response to antigenic material. 3) CFT is used for bacterial diseases (gonorrhoea, brucellosis); spirochaetal disease (syphilis); rickettsial disease (typhus fever) and it is also used for several viral and parasitic diseases.

Check Your Progress 4 Allergy is a disease caused by a body’s reaction to a foreign substance (antigen) which may be harmless to other bodies. Any antigen which causes allergy is called allergen.

Check Your Progress 5

1) Vaccine is a preparation of antigen. It is prepared from live organisms, killed organisms or toxoids or combination of these. 2) The five classes of human immunoglobulin system are IgG, IgA, IgM, IgD and IgE. 3) The response of the body to an immunizing agent is called an immune response. The response of the body to an immunizing agent for the first time is called primary response. The response of the body to an immunizing agent for the second time is called as secondary response.

52