Immune System

 




IMMUNITY System 

Animal  body  is  always  exposed  to  various  harmful  invaders  like viruses, bacteria, fungi and parasites and toxic substances. It has been noticed that the persons who had been suffering from certain diseases like measles and mumps, are not attacked in future by the pathogens of the same disease. It is due to the fact that these people have become immune to the concerned disease. The human body has the ability  to resist almost all types of organisms or toxins that damage  the tissue and organs. This capacity is called immunity. In other words, immunity refers to the resistance of a host to pathogens and their toxic products. The system of animals  body, which protects it from various infections agents and cancer is known is known as Immune system .The study of the immune system is called immunology.


 The credit for having  observed and described bacteria goes to Antony van Leeuwenhoek.In 1683, he made accurate descriptions of various  types of bacteria and communicated them to the Royal Society of London  Edward Jenner (1796) observed that milkmaids did not get small pox infection apparently because they were exposed to a similar but milder form  of disease called cowpox. Edward Jenner infected first James Phipps, a healthy boy of 8 years with cowpox and two months later he infected the boy with small pox. The boy did not suffer from small pox. Jenner proposed that an induced mild form of a disease  would protect a person from a virulent form. Edward Jenner was the first to discover a safe and effective means of producing artificial  immunity against small pox. Edward Jenner is regarded as " Father of Immunology ". The decisive step in human immunization was made in 1885, when Louis Pasteur administered the antirabies vaccine to the young Joseph Meister, severely bitten by a rabid dog. That was for the first  time in history that the rabies treatment  was done by a cultural vaccine. Robert Koch discovered the bacteria of tuberculosis ( 1882) and the cholera ( 1883). Koch formulated Koch's postulates which are as follows: 

(i) The organism (pathogen) must be regularly found in the body of the animal that is suffering from a disease. 

(ii) The organism must be isolated that grow in pure culture on artificial media.

(iii) The  same disease must be produced when the cultured organisms are injected  into other healthy animals .

(iv) The same organism must be recovered from the injected animals. 

 The Postulates orginally were applied for animal diseases but are equally applicable for  human diseases. However, Koch's Postulates are not applicable to viral diseases because viruses cannot be cultured on artificial media. Koch's Postulates are also not applicable to bacteria of leprosy because it has not been possible to grow these bacteria * in culture media.Emil Adot von Behring  (1891) discovered the technique of passive immunisation by injecting diphtheria pathogen into sheep preparing serum from its blood after some time. He got the 1901 Nobel Prize  for serum therapy for giving acquired  passive immunity against diphtheria. 

* Shephard (1960) described that Lepra bacilli  (bacteria of leprosy) could multiply in the foot of mice kept at a low temperature 20°C. The nine banded armadillo is highly susceptible to infection with Lepra bacilli. 





● Main Functions of free antibodies 

(a) Agglutination: When a  particulate (solid) antigen is mixed with its antibody in the presence of electrolytes at a suitable temperature  and  pH, the particles are clumped or agglutinated. 

(b) Opsonisation : The name ' opsonin' was originally given by Wright (1903) to a heat liable substance present in fresh normal sera, which facilitated Phagocytosis. The coating of bacteria to facilitate their subsequent Phagocytosis by cells is called opsonisation. Opsonisation is carried out by both IgG  and IgM.

(c) Neutralisation : Specific antibodies are able to neutralise the biological effects of viruses, toxins released by bacteria, e.g., tetanus toxin. Humoral or antibody __ mediated immunity ( AMI) provides defence against most extracellular bacterial pathogens and viruses that infect through the respiratory and intestinal tract. It also participates in immediate hypersensitivity reactions and certain autoimmune diseases. 


Antigens 

Antigens are substances which, when introduced into  the  body  stimulante the production of antibodies. Most antigens are proteins but some are carbohydrates, lipids or nucleic acids. Antigenic determinants or epitopes are those sites on antigens that are recognised by antibodies and receptors present on T and B cells. In fact the smallest units of antigenicity are the antigenic determinants. Each determinant can stimulate the formation of a particular kind of antibody or effector cell. Thus a pure protein antigen may give rise to many distinct antibodies and effector cells. 

 Based upon the ability  of antigens to carry out their functions antigens are of two types : complete antigens and incomplete/ antigens ( haptens).A complete antigen is able to induce antibody formation and produce a specific and observable reaction with the antibody formation by themselves, but can be capable of inducing antibodies on combining with larger molecules ( normally  proteins) which serve as carriers. 


H.  antigen : Red blood corpuscles of all ABO blood groups possess a common antigen, the H antigen, which is a precursor for the formation of A and B antigens. Due to universal distribution, H antigen is not ordinarily  important  in grouping  or blood transfusion. However, Bhende et al ( 1952) from Bombay (now named Mumbai) reported a very rare example in which A and B antigens and H antigens were absent from the red blood corpuscles. This is known as Bombay or Oh blood group. Such individuals will have anti A, anti B   and anti  H antibodies. Therefore , they can accept the blood only from their own group. 

Antibodies 

Antibodies are immunoglobulins (Igs) which are produced in response to antigenic stimulation. Thus  all antibodies are immunoglobulins but all immunoglobulins are not antibodies. The antibodies may be bound to a cell membrane or they may remain free. Antibodies are produced by B lymphocytes and plasma cells. In fact B_ lymphocytes get transformed into plasma cells. The mature plasma cell produces antibodies at an extremely rapid rate _ 2000 molecules per second. Antibodies direct the antibody _ mediated immunity (= humoral immunity).




Types :

On the basis of physicochemical and antigenic structure human Igs are grouped into five classes or isotypes namely Ig A  Ig D, Ig E, Ig G, and Ig M. They differ from each other in size, charge, carbohydrate content and aminoacid composition. A = Alpha ( æ), D = Delta (ò,) E= Ep_ silon , G= Gamma , M = Mu (ų).

Structure: 

Ig G has been studies extensively and serves as  a model of basic structural unit of all Igs. It is made up of 4 peptide chains.Of the four chains, there are two long chains, called heavy or H Chains and two short chains, called light or L Chains, which may be either lambda or kappa type.The four peptide chains are held together by disulphide blonds to form a Y_ shaped molecule. Two identical fragments or  Y_ shaped molecule possess the antigen_ binding sites and are thus named fragment _ antigen binding  (Fab). The antigen_ binding sites bind to the specific antigens in a lock and key  pattern, forming an antigen_ antibody complex .The third fragment which lacks the ability the  bind to antigen and can be crystallized, is, therefore, known as fragments crvstallizable ( Fc) .



Functions:

Functions of five types of antibioties are given below :

(i) IgA : It is the second  most abundant class of Igs, constituting about 10 per cent serum immunoglobulins. There is an additional peptide chain called joining (J) chain. It is the major immunoglobulin in colostrum ( the first milk secreted by a nursing mother), saliva and tears. It protects from inhaled and ingested pathogens. Thus it protects the body surface. When Ig A is excreted through faeces, it is called corproantibody.

(ii) IgD : It is present on the surface of G lymphocytes which are destined to differentiate into antibody _ producing plasma cells. Thus IgD activities B cells to secrete other antibodies. 

(iii) IgE : This  immunoglobulin was discovered  in 1966 by Ishizaka. It resembles IgG structurally.It exhibits unique properties such as heat liability (inactivated at 56°C in one hour). IgE medicates the Prauinitz _ Kustner ( PK) reaction. Prausnitz and Kustner in 1921 demonstrated transmission of IgE _ mediated type I hypersensitivity by injecting serum containing IgE antibodies from allergic person into the skin of a normal or non allergic person. It is called Prausnitz_ Kustner  (PK) reaction. It has the risk of transmission of Hepatitis B Virus and HIV. Thus IgE acts as mediator in allergic response. 

(iv) IgG : This is the most abundant class of Ig in the body constituting approximately 75% of the total Igs. IgG is the only maternal immunoglobin that is normally transported across the placenta and  provides natural passive  immunity in the foetus and the new born. Because,  IgG is present in the milk. IgG protects the body fluids. IgG also stimulantes Phagocytes and complement system. 

(v) IgM: It is the largest Ig. It is so named because  it is a macroglobulin atleast five times larger than IgG. It also has J chain. IgM is the oldest immunoglobulin class. It activates the B cells. It is also the earliest ( oldest) immunoglobin to  be synthesized by the foetus, beginning  about 20 weeks of age. It cannot cross the placental barrier. Ig M is 500 _ 1000 times more effective than Ig G in bacterial agglutination. But in  neutralization of toxins and viruses, it is less active than Ig G. Thus Ig M protects the blood stream. 

Types  of Immunity:

Immunity is of two types : innate and acquired .

(A) Innate Immunity (Non_ Specific  Immunity)

Innate immunity  is the resistance to infection, which  an individual  possesses by virtue  of his/ her genetic and constitutional make up. Thus innate immunity  comprises all those defense elements  with which an individual  is born, and which are always available to protect a living body. One form of innate immunity comprises various  types of barriers  which prevent entry of foreign agents into the body. When pathogens enter into the body, they are quickly  killed by some other components of this system. This is the first line of  defence of most animals and plants. Innate immunity consists of the following four types of barriers: physical, physiological,  cellular and cytokine barriers. 

1.  Physical Barriers :  These barriers  prevent the entry of organisms  into the body. 
(a) Skin : The skin is physical barrier of body. Its outer  tough layer, the stratum corneum prevents the entry of bacteria and viruses. 

(b) Mucous Membrane: Mucus secreted by mucous membrane traps the microorganisms and immobilises them. Microorganisms and dust particles  can enter the respiratory  tract with air during breathing which are trapped in the mucus. The cilia sweep the mucus loaded with microorganisms and dust particles into the pharynx ( throat). From the pharynx it is thrown out or swallowed  for elimination with the faeces. 

2. Physiological Barriers  : Body temperature, pH of the body fluids and various  body secretions prevent growth of many disease causing microorganisms. 

(a) Acid of the stomata  kills most ingested  microorganisms.

(b) Bile does not  allow growth of  microorganisms. 

(c) Cerumen  ( ear wax) traps dust particles , kills bacteria  and repels insects. 

(d) Lysosome is present in tissue fluids and in almost all secretions except in cerebrospinal fluids, sweat and urine. Lysozyme is in tissue fluids and in almost all  eyes. Lysozyme  attacks bacteria and dissolves their cell walls.

(e)  A rise of temperature (fever ) due to infection is a natural defence mechanism  and helps  not only to accelerate physiological processes but may, in some cases, destroy the infecting pathogens.

(f) Certain  kinds of cells, when infected with a virus, release interferons (glycoproteins). Interferons ( IFNs) make the cells resistant to viral infections.  

(g) Bicarbonate ions in saliva neutralise the acids in food.


3. Cellular Barriers  : Certain types of  leucocytes ( WBC) like polymorphonuclear leucocytes  ( PMNL), neutrophils and monocytes and natural killer ( type of lymphocyte) in the blood and macrophages in tissues can engulf microbes, viruses  and cellular debris etc. The phenomenon of Phagocytosis was discovered and named by Metchnikoff ( 1883). He proposed the phagocytic response as the prime defence against   the microbial invasion of tissue.  Metchnikoff and Paul Ehrlich got the 1908 Nobel Prize for their work on body resistance. 

4. Cytokine Barriers: Virus infected cells secrete proteins known as interferons which protect non infected cells from further viral infection. 

 Fever may be brought  about by toxins produced by pathogens and a protein called endogenous pyrogen ( fever producing substance), also called interleukin released by macrophages. When enough pyrogens reach the brain, the body's  thermostat is reset to a higher temperature , allowing the temperature of the entire body to rise. Mild fever strengthens the defence mechanism by activating the phagocytes  and by inhibiting the growth of microbes. A very high temperature  may prove dangerous .It must be quickly brought down by giving  antipyretics.

 In addition  to the above mentioned barriers, natural killer cells and the complement system also provide innate immunity. 

Natural Killer Cells ( NK Cells) : Besides the phagocytes, there are natural killer cells in the body which kill virus_ infected and some tumour cells. Killer cells produce Perforins which create pores in the plasma membrane of the target cells. These pores allow entry of water into the target cells, which then swell and burst. Cellular remains are eaten by Phagocytes. 

       The Complement System: It is a defensive system consisting of plasma proteins that attack and destroy  the microbes. The term ' complement' (c) refers to a system of factors occurring in normal serum, that are activated characteristically by antigen antibody interaction, and subsequently mediate a number of biologically  significant consequences. This system participates in both innate and acquired immunities; consists of over 30 proteins that act in various ways to protect the individual from  invading  microbes. The latter burst and  die. Some components of  the  complement system form a coat over the invading microbes. This coating attracts phagocytes  ( neutrophils and macrophages) for engulfing them. The complement system also causes agglutination of microbes, neutralization of viruses, activation of mast cells and basophils and has some inflammatory effects. 

Second Line of Defence : Phagocytes, interferons, inflammatory reactions, fever, natural killer cells and complement system constitute the second line of defence. 

Third Line of Defence is provided  by specific defence mechanism which includes 

(i) antibodies and 

(ii) lymphocytes  to be discussed ahead.

            Summary of Three Lines of Defence 




(B) Acquired Immunity (= Adaptive or Specific Immunity) 

 The resistance that an individual acquires during life, is called acquired immunity. Acquired or adaptive or specific immunity has the following  properties : 

(i) Specificity: It is the ability  to differentiate between  various  foreign molecules. 

(ii) Diversity : It can recognise a vast variety  of foreign molecules. 

(iii) Discrimination between  Self and Non_ self : It can recognise and respond to foreign molecules ( non_ self) and can avoid  response to those molecules that are present within the body ( self) of the animal. 


(iv)  Memory : When the immune system encounters a specific  foreign agent, (e.g., a microbe) for the first time, it generates immune response and eliminates the invader. This is called first encounter. The immune system retains the memory of the first encounter. As a result, a second encounter occurs more quickly and abundantly than the first encounter. 






Cells involved in Acquired Immunity :Two major groups of cells are involved in acquired immunity Lymphocytes and Antigen presenting cells. 

1.Lymphocytes : A healthy person has about a trillion lymphocytes. Lymphocytes are of two types : T lymphocytes or T cells and B lymphocytes  or B cells. Both types of lymphocytes and other cells of the immune system are produced in the bone marrow. The process of production of cells of immune system in the bone marrow is called haematopoiesis 

(i) T Lymphocytes (=T cells)  : Certain stem cells in the bone marrow give rise to immature lymphocytes. These lymphocytes migrate via blood to the thymus. Once these cells enter the thymus, they are called thymocytes .In the thymus these cells mature as T lymphocytes (T cells).

Types of T_ Cells and their functions : 

(a) Helper T Cells : They are numerous. These cells stimulate the B_ cells to produce antibodies . They also stimulant the killer T cells to destroy the nonself cells. Their role is overall regulation of immunity. They  do this function by forming a series of protein mediators, called lymphokines that act on other cells of the immune system as well as on bone marrow cells. 

(b) Cytotoxic T cells (= Killer Cells or K Cells): These cells directly attack the foreign cells. The cytotoxic T cells secrete  a protein perforin which punctures the invader's cell membrane. Water and cancer cells. The cytotoxic  cells are responsible  for cell mediated  immunity. 

(c) Suppressor T Cells:  They are capable of suppressing the functions of cytotoxic and helper T cells. They also inhibit the immune system from attacking the body's own cells. 
 
(d)  Memory T Cells : These cells remain in the lymphatic tissue (e.g., spleen, lymph nodes) and recognize original invading antigens, even years after the first encounter. These cells keep ready to attack as soon as the same pathogens infect the body again. 

(ii) B Lymphocytes (= B_ Cells) : Certain cells  of the bone marrow produce B lymphocytes.  These cells mature in the bone marrow itself. The B cells produce specialised proteins called antibodies and, therefore,  generate antibody mediated or humoral  immunity. 

  The B lymphocytes  give rise to :

(a) Plasma Cells ( Effector B Cells) : Some of the activated B cells enlarge, divide and differentiate  into a clone of plasma cells. Although  plasma cells liver for only a few days, they  secrete  enormous  amounts  of antibody during this period. A few days after exposure to an antigen, a plasma cell secretes hundreds of millions of antibodies daily and secretion occurs for about 4 or 5 days until the plasma cell dies. 

(b) Memory B Cells : Some activated B cells do not differentiate into plasma cells but rather remain as memory cells. They have a longer life span. The memory cells remain  dormant until activated once again by a new quantity  of the same antigen. 


2. Antigen Presenting Cells ( APCs) : These specialized cells include macrophages (monocytes) as blood macrophages and histocytes as tissue macrophages), B_ lymphocytes and dendritic cells (e.g., Langerhans cells of epidermis of skin)  They are distinguished  by two properties: 

(i) They express class II MHC molecules on the membrane,  and 

(ii) They are able to deliver a co_ stimulatory signal that is necessary for helper T cell  activation. 


Active and Passive Immunity:

1. Active Immunity: This involves the active functioning of the person's  own immune system leading  to the synthesis of antibodies and / or the production of immunologically active cells. Active immunity  may be natural or artificial. 

(i) Natural active Immunity: It results either from a subclinical or clinical infection. The large majority of adults in the developing  countries possess natural active immunity to poliomyelitis due to repeated subclinical infections with poliovirus during childhood . A persons who has recovered from an attack  of small pox  or measles  or mumps develops natural active immunity. 

(ii) Artificial active immunity:  Artificial active immunity is the resistance induced by Vaccines. Vaccines  are preparations of live or killed microorganisms or their products  used for immunisation . Examples of vaccines are as follows: 

Bacterial  vaccines : (a) Live _ BCG vaccine for tuberculosis, (b) Killed _ TAB vaccine for enteric fever.

Viral Vaccines: (a) Live _ Sabin vaccine  for poliomyelitis, MMR vaccine for measles, mumps, rubell.

(b)  Killed _ salk vaccine for  poliomyelitis, neural and non_ neural vaccines for rabies. 

Bacterial products  : Toxoids for Diphtheria and Tetanus .

2. Passive Immunity: In passive immunity,  there is transfer of immune products, like antibodies, etc. to a recipient in a ready_ made _ form. Passive immunity is also of following two types.

(i) Natural Passive immunity: This is the resistance passively  transferred from the mother to foetus through placenta.IgG antibodies can cross placental barrier to reach the foetus. After birth, Igs are passed to the newborn through the breast  milk. Human colostrum is rich in IgA antibodies. Mother's milk contains antibodies which protect the infant properly by the age of three months. 

(ii) Artificial  passive immunity: Artifical passive immunity is the resistance passively transferred to a recipient by adminstration of antibodies. This is done by administration of hyperimmune sera of man or animals.  Serum ( pl. sera) contains antibodies. For example, anti _ tetanus serum ( ATS) is prepared in horses by active immunisation of horses with tetanus toxoid, bleeding them and separating the serum. ATS is used for passive immunisation against tetanus. Similarly antidiphtheric serum ( ADS) and anti_ gas gangrene serum ( AGS) are also prepared.

Activation of Adaptive Immunity: Every antigen is processed by antigen presenting cells like macrophages, B_ cells, etc. The processed antigen is present on the surface of these cells. Helper T cells specifically interact with the presented antigen and become activated. The activated helper T cells then activate B cells and cytotoxic T cells. The activated B cells and cytotoxic T cells divide repeatedly to produce clones. All the cells of a clone recognize the same antigen and eliminate  it. 

       Immune Response: The specific reactivity induced in a host by an antigenic stimulus  is known as  the immune response.
Immune response is of two types : the humoral  or  antibody _ mediated immunity ( AMI) and cell _ mediated immunity ( CMI).

(i) Humoral immunity  or Antibody _ mediated immunity (AMI) : In human being, B lymphocytes are known  to be preprocessed  in the liver during midfoetal life and in the bone marrow during late foetal life and after birth. After pre__  processing, the B lymphocytes migrate to the lymphoid tissue throughout the body. 
 
  As we known B _ lymphocytes produce antibodies that regulate humoral immunity or antibody_   mediated immunity. Antibody formation by B cells is stimulated by helper T cells and inhibited by suppressor T cells. Certain B __ lymphocytes are transformed into plasma cells which produce antibodies at a rapid rate. All B_ lymphocytes are not converted into plasma cells. A small portion of them developed into " memory cells" which have a long life span and serve to recognise the same antigen when introduced subsequently. Antibodies produced by a single antibody forming cell or clone and directed against a single antigenic determinant are called monoclonal antibodies. Various theories have been put forward to explain antibody production.  Clonal selection theory which was proposed by Burnet in 1957, is more widely accepted  than other  theories. According to the clonal selection theory, all the immunoglobulin molecules on a single B cell have the same antigenic specificity. The method for production of mono_clonal antibodies (MCA) was described by Kohler and Milstein in 1975 for which they were awarded Nobel Prize for medicine in 1984.

    As described in the antibody, the antigen_ binding sites of the antibody bind to the specific antigens in a lock and key pattern, forming  an antigen_ antibody complex. 

 A summary of humoral immunity  is given below : 





(ii) Cell _ mediated  immunity ( CMI): T lymphocytes, after their origin in the bone marrow, first migrate to the thymus gland. Here they divide rapidly and develop extreme diversity for reacting against different specific antigens. These different types of processed T  lymphocytes now leave the thymus and like B lymphocytes migrate to the lymphoid tissue throughout  the body.

  The cell mediated immunity is the responsibility of cytotoxic T cells ( a sub group of T cells) rather than B cells and antibodies. An activated cytotoxic  T cell is specific to a target cell that has been infected, and kill the target cell. This prevents the completion of life cycle of the pathogen because  it depends on an  intact host cell . Cytotoxic T cells also kill the cancer cells. 

 The first description of a CMI response was the observation  by Jenner ( 1798). The immune response  to  tuberculin ( protein extract of tubercle bacillus) was observed by Robert Koch in 1890. Thereafter  the tuberculin test became a general model or example  for delayed hypersensitivity ( DH).The term delayed hypersensitivity refers to the appearance of skin lesion 48_ 72 hours after administration of the antigen. The cellular basis of DH was shown by Landsteiner and Chase ( 1942).

 Biologically  active substances released  by activated T lymphocytes are called lymphokines.They are regulatory proteins whose main function appears to be regulation  of immune response and growth and functions of cells of the reticulo____ endothelial system, e.g.,  macrophages , phagocytic macrophages which are present in linings of sinuses and in reticulum of various organs and tissue  ( spleen, liver, lymph nodes, bone marrow connective tissue,  etc.)

 CMI protects against  fungi, most of the viruses  and intracellular  bacterial pathogens like M. Leprae, M. Tuberculosis and Salmonella and parasites  like Leishmania and Trypanosomas. It also participates in allograft rejection, graft versus host reaction, delayed hypersensitivity and certain autoimmune diseases. It provides immunity against cancer .

A summary of cell_ mediated immunity is given below :






Clonal Selection 

As we know, each B and T lymphocyte has a specific receptor on its surface. In B lymphocyte, this receptor is the antibody which is produced by that cell. When this  receptor interacts with the antigenic determinant specific to it, the lymphocyte is activated and divides to form a clone of cells. These cells are also converted into effector cells (antigen producing B lymphocytes and cytotoxic  T cells).This phenomenon is known as clonal selection, where all the cells in a given T lymphocyte or B lymphocyte clone are derived from a single parent cell clone and show the same specificity for antigenic determinant. But some activated lymphocytes become memory cells which are long lived but do not produce antibodies  or kill infected cells. As stated earlier  memory cells remain dormant  until activated again by the same antigen. 

Primary  and Secondary  Immune Response  

The immune response involves primary immune response  and secondary immune response. 
(a) The primary immune response is produced by the initial contact of an animal with an antigen. It takes relatively  longer time, is feeble and declines rapidly .

(b) The secondary  immune response is produced by subsequent exposure of the same host to same antigen. This is also called booster response. It is  due to the memory cells that were produced during the primary response.  This response  occurs more rapidly and lasts much more longer than primary immune response. It is due to this fact that a person who had been suffering  from diseases like measles, small pox, or chicken pox becomes immune to subsequent  attacks of these diseases. 

Vaccination and Immunisation 

Vaccine  ( L. Vacca = cow) is a preparation/ suspension  or extract of a dead / attenuated  ( weakened ) germs of a disease which on inoculation ( injection) into a healthy  person provides temporary / permanent  active/passive immunity by inducing  antibodies  formation. Thus antibodies  provoking agents are called vaccines. 

 The principle of immunisation or vaccination is based on the property of ' memory' of the immune systems. Vaccine  also generate memory _ B and T cells that recognise the pathogen quickly.In snake bites the injection which is given to the patients contains performed antibodies against the snake venom. This type of immunisation is called passive immunisation. 

  The process of introduction of vaccine into an individual to provide protection against a disease is called vaccination. In vaccination, a preparation of antigenic proteins of pathogens or inactivated/ weakened pathogens ( vaccine), is introduced into the body. These antigens generate the primary immune response, and the memory B and T cells. When the vaccinated person is attacked by the same pathogen, the existing memory T or B cells recognise the antigen quickly  and  attack the invaders with a massive  production of lymphocytes and antibodies. 

   Vaccination and immunisation are two different processes. Vaccination only refers to the administration of any vaccine, while immunisation is the process by which the body produces antibodies  against the vaccine preventable diseases through administration of specific vaccines. These are used to protect us and our domestic animals  against viral and bacter diseases. 

   Louis Pasteur found that ageing cultures of cholera bacter, when injected into chickens, did not cause the disease in them. But the chickens injected with these cultures became immune. Pasteur used this  method develop a vaccine against rabies in 1885. The term vaccine and vaccination were coined by Pasteur. He established scientific basis of vaccination. Pasteur developed vaccines against rabies, anthrax and chicken cholera. Calmette and Guerin developed BCG vaccine  for TB. Salk made inactivated Polio vaccine. Sabin prepared Oral Polio vaccine. Enders developed vaccine against measles. WHO was formed in 1948 at Geneva to take health problems at global level. In May, 1974, Global Immunisation  Programme was launched by WHO for six diseases ( Diphtheria,Pertusis, Tetanus, Measles, TB and Polio). Later on two more diseases _ Cholera and Typhoid were added by India in its programme. In India this programme was started in 1985 as Universal Immunisation Programme for providing  health to all by 2000AD.



Types  of Vaccines:

Vaccine are of following types: 

1. Live Vaccine or Attenuated Vaccines: These vaccines are prepared from live ( generally attenuated __ the pathogen is made weakened to make it nonvirulent) organisms. Examples : OPV, ( Oral Polio Vaccine), BCG, ( Bacillus Calmette Guerin) Small pox, yellow fever vaccine, Influence vaccine. These vaccines provide active life long immunity. 

2. Killed Vaccines or Inactivated Vaccines: These vaccines are prepared by killing the pathogenic organisms by heat/ ultraviolet rays/ alcohol/ formalin/ phenol. Examples : Typhoid vaccine, Salk Polio Vaccine,Typhus Vaccine,  Cholera Vaccine, Rabies Vaccine,  Plague Vaccine , TAB* vaccine. 

3. Toxoids : Certain organisms such as Diphtheria and  Tetanus bacilli produce toxins. The toxins produced by these organisms are detoxicated  and used in the preparation of Vaccines. Examples: Diphtheria toxoid and Tetanus toxoid.These Vaccine  provide immunity for short period. 

4. Cellular Fractions : Vaccines  in certain instances are prepared  from extracted cellular fraction.Examples: Meningococcal vaccine  from the polysaccharides antigen of the cell wall, the pneumococcal  vaccine from the polysaccharide contained in the capsule of the organism  and hepatitis  B polypeptide vaccines.  Although the duration of experience with these vaccines  is limited, their efficiency  and safety appear to be high. 

5. Combinations : If more than one kind of immunizing agent is included in the vaccine, it is called a mixed or combined vaccine.  The following  are some of the well known combinations: DPT ( Diphtheria + pertussis + tetanus), DT ( Diphtheria  + petanus), DP ( Diphtheria + pertussis), Tetanus + Influenza, DPT and typhoid Vaccine, MMR  ( Measles  +k mumps+ rubella), Measles + rubella. 



Vaccines  are also classified  as follows: 

1. First generation  Vaccines: These vaccines  are produced by conventional technique using whole microorganisms. These are never of uniform quality and produce side effects. 

2. Second  generation  Vaccines: These vaccines  are prepared by recombinant DNA  technique/ Genetic  Engineering. Examples: Hepatitis   B virus vaccine , Herpes virus vaccine, Pneumonia  Vaccine . The Yeast ___ derived recombinant Hepatitis B virus vaccine  is the  first commercially available  human vaccine  produced by the genetic by the genetic engineering technology. Thus hepatitis B vaccine is Produced from transgenic yeast by recombinant DNA technology. 

3. Third generation Vaccines ( = Synthetic  Vaccines): These are chemically  synthesized multivalent  vaccine.  These Vaccine have high purity. Examples:Vaccine against diphtheria toxin developed  by Audibert et at, 1981, Leukemia Virus Vaccine. 

Vaccine under study : Vaccine  against  Malaria , Leprosy, Herpes, Hepatitis C, AIDS, Dental caries etc.are under study. 

Immunisation  and Pregnancy: The question of whether immunisation of a pregnant women presents any danger for the foetus is frequently raised. Idealy, immunisation should be performed before gestation,  since some vaccines are not perfectly safe during pregnancy. Pregnancy women are however,  often vaccinated  either because they  travel to foreign  countries  or when an epidemic  occurs.

 Vaccines which are safe during pregnancy  are tetanus, influenza,  inactivated Poliomyelitis, cnolera  and hepatitis  B.

 Vaccines which are to be avoided during pregnancy  are small pox vaccine, oral Poliomyelitis vaccine and rubella vaccine. 


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