IMMUNOLOGY

BY- SREELAKSHMI (MSIWM012)

Immunology is the branch of science dealing with the study of immunity. Louis Pasteur is considered as the Father of Immunology.

HISTORY OF IMMUNOLGY

 Immunology started from the observation of people who recovered from certain infectious diseases and who never got infected with the same.

• The earliest written evidence on immunology is by Thucydides during 430 BC .He was describing about a plague in Athens where he mentioned that people who recovered from plague could only nurse the sick because they won’t get the disease again.
• The first recorded attempt was by Chinese and turks in the 15 century. Dried crusts of from smallpox pustules was inhaled through nostrils or inserted into cuts in the skin. They used in this technique called variolation  to prevent the deadly and fatal smallpox.
• Variolation technique was later improved by Edward Jenner in 1718.
• Next major advancement was that success of Louis Pasteur in growing bacterium responsible for fowl cholera in chicken. After completing, he concluded that ageing weekend the virulence of pathogen. He called the attenuated strain as vaccine .he named it so in honor of Jenner’s technique of cowpox inoculation.
• Next decade various researchers demonstrated that an active component from the serum of immune animals are capable neutralizing toxins, precipitating toxins and occlude rich bacteria. They were termed as angio toxin precipitating and agglutinating respectively. Gamma –globulin present in serum is responsible for this activities. This active molecule is called as antibody.

DIFFERENT TYPES OF IMMUNE RESPONSE

1. Inherent Immunity

It’s a first line of defense mechanism and non-specific. Inherent immunity include physical barriers (e.g., skin, saliva etc.)and cells (e.g. Macrophages, neutrophils, basophils, mast cells etc.).It is active for first few days during infection period.

• Adaptive Immunity

It is the second line of defense. It responds to anything that is foreign and also remembers it.It involves antibodies and lymphocytes. Active and passive immunity comes under Acquired immunity

ANTIGEN

It can be any substance that can be recognized by immunoglobulin receptor of B-cells or by the T-cell receptor when complexes with MHC. Antigens include toxins, bacteria, foreign blood and the cells of transplanted organs.

   TYPES OF ANTIGENS

• Exogenous Antigen: Antigens that have entered the body from outside either by inhalation, ingestion or injection .Immune response to these antigens is often sub-clinical. Some Exogenous Antigen later become endogenous Antigens.
• Endogenous Antigens: They are generated within an individual normal cells as a result of cell metabolism. Endogenous antigens include xenogenic, autologous and idiotypic antigens.
• Tumour Antigens: They are present on the surface of tumor cells. They can sometimes be presented only by tumour cells and never by the normal ones due to some tumour specific mutations, such antigens are called Tumour specific Antigens (TSAs).Commonly these antigens are presented by both tumour cells and normal cells, and they are called Tumour Associated Antigens.

       ANTIBODIES (IMMUNOGLOBULINS)

         

They are group of glycoproteins which are present in the serum and tissue fluids of all mammals. They are produced by the immunocompetent B-cells called as plasma cells .Some of these antigen-binding proteins are carried on the surface of B-cells, where they act as receptors for specific antigens and thus, confers antigenic specificity on B-cells.

Structure of Antibodies: It is Y-shaped in appearance whose arms can swing at an angle of 180 degree. It consist of two identical light chains and heavy chains which are linked by disulphide bonds and non-covalent interactions such as hydrogen bonds, salt bridges and hydrophobic bonds in the form of heterodimer.

TYPES OF ANTIBODIES

• Immunoglobulin G (IgG): It is a major immunoglobulin present in serum. It is the major Ig produced during the secondary response. It is the only Ig which can cross placenta. It also helps in the activation of classical compliment pathway.

• Immunoglobulin A (IgM): It accounts for approximately 5%-10% of the total serum immunoglobulin with an average serum concentration of 1.5 mg/mL is the first immunoglobulin to be synthesized by the newborn. It is confined to the intravascular pool only. IgM are capable of agglutinating the antigen as well as it can neutralize the viral particles.IgM is also more efficient activator of the classical complement pathway.

• Immunoglobulin a (IgA): It constitutes only 10%-15% of the total immunoglobulin in serum. It served as a first line of defense against the microbial invasion at the mucosal surfaces. Secretory IgA present in breast milk protect the newborn against infection during the first month of life.

• Immunoglobulin E (IgE): It’s present in extremely low in serum. It mediate the immediate hypersensitivity reactions or allergic reactions. On the exposure of allergen, IgE will be produced which binds to Fc receptors present on the membranes of blood basophils and tissue mast cells. It also plays a major role in parasitic infections

• Immunoglobulin D (IgD): It constitutes only 0.2% of the total immunoglobulin in serum. It is expressed by mature B-cells on its surface together with IgM.

SCOPE OF IMMUNOLOGY

Immunology is a diverse and growing discipline. It plays an important role in the development vaccines. Immunology is associated with the treatment of allergy and asthma. It plays a major role in the disciplines of medicine especially for organ transplantation, oncology, virology, bacteriology. Immunoinformatics is special stream which link immunology and bioinformatics.Majorily for vaccine design.

VACCINE: Characteristics and Types.

vaccine

About:

• Vaccine is an artificial biological preparation that contains antigens or mixture of antigens to acquired active immunity to the particular infectious disease.
• Vaccine is prepared by the various different substances like disease causing microorganism or weakened or killed form of microbe, can be from one of the surface protein or its toxins.
• Agent used in vaccine stimulates body’s immune system which recognise the antigen and destroy it and also encounter the agent if in future that antigen enters in the body.
• Vaccine is prophylactic (prevent future infection by the pathogens) or therapeutic (fight against the disease already occurred).
• The process of administration of vaccine is called vaccination; it is the most effective method to prevent infectious diseases.
• The term vaccine and vaccination are coined by Edward Jenner. He described that how cowpox is to produce immunity against smallpox.
• Vaccine stimulates T-cells and B- cells which further produces antibodies against the antigen.

First vaccine:

• The first vaccine was introduced by Edward Jenner, used the cowpox virus to protect against smallpox in humans
• Prior to this Asian physician used to give dried lesions from the diseased person to children. But by this process some individuals developed immunity while some develop disease.
• Jenner introduced a safer way to counter this disease. He uses similar cowpox virus to confer immunity against smallpox (rare condition in which immunity of one virus protect against another virus).
• Louis Pasteur in 1881 shows immunization against anthrax disease and four years later he develops vaccine of rabies.

Characteristics of vaccine:

• Safe
• Long term protection
• Induced b and t cells
• No or very few side effect
• Low cost and biologically stable
• Easy to use

Types of vaccine:

Live attenuated:

• Is containing live organism which is weakened in the lab so that it cannot cause disease and activate the immune system against the antigen.
• It is relatively easy to produce live attenuated vaccine for viruses then bacteria because bacteria have thousands of genes which is much harder to control.
• Uses whole organism as vaccine which loses their pathogenicity but can induce immune response, they continuously multiply in human and provide immunity over the period of time.
• Examples of live attenuated vaccine are mumps vaccine, measles vaccine, chickenpox, BCG, Sabin’s polio vaccine.

Killed or inactivated vaccine:

• Microorganism causing diseases are killed by the means of chemicals, heat or radiation. These are more stable and safer than live vaccines reason is that the dead microorganism cannot mutate back to cause diseases.
• They are the easiest preparations to use
• Chemical which are used to kill microorganism are formaldehyde or beta-propiolactone, traditionally used chemical for virus is formalin.
• The process should be observed carefully because excessive treatment can destroy immunogenicity and insufficient treatment leave infectious microbes to cause disease.
• Example: anthrax vaccine, cholera vaccine, purtusis vaccine, hepatitis vaccine, salk polio vaccine.

Subunit vaccines:

• Like above it doesn’t uses whole organism, only the part which server as antigen and stimulate the immune system is used to prepare vaccine.
• Composed of purified macromolecule derived form the pathogen known as subunit vaccine.
• General forms of such vaccine are

Purified capsular polysaccharide vaccine: pathogenicity of some bacteria depend on their capsule and this capsule protect bacteria from binding to the antibody. In this way infants and younger children’s immune system cannot recognise and respond against them.Example: Hib vaccine, vaccine for Streptococcus pneumoniae

Recombinant microbial vaccine: various genes encoding surface antigen of viral, bacterial and protozoan pathogens were successfully cloned into the cells of a vector. This genetic material is in bacteria cause to represent other microbial gene on its surface i.e. harmless bacterium mimics the harmful microbe and provide immunity against it. Hepatitis B is the only recombinant vaccine at present.

Synthetic peptide: development of synthetic peptide vaccine depends on the immunogenic sites. They have many advantages like low cost production and relatively stable.it is not applicable for all viruses like polio virus.

Inactivated exotoxin: this vaccine is made for some bacteria that produce toxins or harmful chemical substances. This toxins or inactivated(toxoid) by formalin and serve as vaccine which produces the anti-toxoid antibodies and neutralizes the toxin. Example of such vaccine is diphtheria and tetanus vaccine.

DNA vaccine:

• The DNA vaccine is the DNA sequence used as vaccine.
• The sequence is responsible for the antigenic activity of the pathogen.
• The gene of the microbe’s antigen is introduced in the body the host cell take up the DNA, DNA instruct to produce the antigen molecule which is represented by the cell on its surface, now the body’s own cells become the vaccine producing factory and stimulates the immune system.
• Immune response is raised against the protein produces by the cell
• Example: DNA vaccine against west nile virus, herpes and influenza virus.

History of Microbiology

Louis Pasteur

• He was a French microbiologist.
• He Known for his work in the field of Microbial fermentation, vaccination, and pasteurization

 Born– 27 December 1822

Died– 28 December 1895

Award’s

• Legion of Honor Grand Cross (1881)
• Rumford Medal (1856)
• Foreign members of the Royal society (1869)
• Copley Medal (1874)
• Albert Medal (1882)
• Leeuwenhoek Medal (1895)

Contribution:

• He was one of the leading microbiologist during the golden age of microbiology(1860-1910) .
•  He is considered as the father of modern microbiology.

• Pasteur was a French microbiologist gave the theory of Bio-genesis is most powerful of spontaneous generation, using swan neck flask experiment his work on the subject was published in 1861 as  memory of the organised bodies which exist in the atmosphere.
• He gave  Microbial theory of fermentation in 1857.
• He observed the fermentation of lactic acid from sugar by several different kind of yeast, bacteria and noticed microscopic globules in the very deposit of fermentation vessels, when these globules was transferred to a fresh nutrient consisting sugar yeast extract, the globule greatly lactic acid was formed.
•  In 1867 Pasteur, was suggested that mild heating at 62.8°C  for 30 minutes rather that boiling was enough to destroy or kills the undesirable microorganisms without ruining the  taste of product, this process was referred as Pasteurization.
• Pasteur developed Anthrax vaccine in 1881 5 years later, he was successful in preparing vaccine against Rabies.
• Pasteur work seems to be demonstrate that microbes may  be cause of diseases or if they  may spoil the wine, perhaps they may also makes the body sick. This developed the germ theory of disease.

ROBERT KOCH   

Full name: Robert Heinrich Hermann Koch.

Born: 11 December 1843.

Died: 27 May 1910.

Discoveries:

• Koch’s postulates.
• Mycobacterium tuberculosis.
• Asiatic cholera.
• Anthrax bacterium.

Awards:

• For MemRS [1897].
• Nobel Prize in medicine [1905].
• The first direct demonstration of the role of bacteria is causing disease was provided by Robert Koch.
• A German physician who first of all isolated Anthrax bacillus [i.e. Bacillus anthracic] the cause of anthrax in 1876.
• In 1882 he discovered Mycobacterium tuberculosis.
• The most notable contribution of was the establishment of the casual relationship between the microorganism and a specific disease by applying a set of criteria referred to as Koch’s postulates.
• Koch’s postulates published in 1884 and are the cornerstone of germ theory of disease and are still in use today to prove the Etiology [specific cause] of an infection disease.5
• The postulates are : –

• The suspected microorganisms must always be found in diseased but never in healthy individuals.
•  The microorganism must be isolated in a pure or nutrient medium.
•  The same disease must result when the isolated microorganisms is inoculated into a healthy host.
•  The same organism must be re-inoculated from the experimentally infected host.
•  Also demonstrated Vibrio Cholera that is the causing agent of the disease Cholera in 1883.

ANTONIE VAN LEEUWENHOEK   

Full name: Antoine Philips Van Leeuwenhoek.

Born: 24 October 1632.

Died: 26 August 1723.

Subject of study:

• Bacteria
•  Protozoa,
• Microscope,
•  red blood cell,
• weevil.

• He  was the first to observe bacteria and protozoa.
• Van Leeuwenhoek was the first to experiment by using single lens microscope of his own design with microbes, which he originally referred to as ANIMALCULES.

• He is commonly known as the father of Microbiology [Ancient].
• He assembled simple microscope in 1674 and made more than 500 optical lenses. He also made at least 25- single lens microscope of different types out of which only nine survived.
• He was also examined the blood and other tissues of human including his own tooth scrapping, minerals and plant materials.
• Leeuwenhoek was the first person to give precise and accurate description of bacteria and protozoa using microscope ,he made himself because of this extraordinary contribution to microbiology. He is referred as the Father of Bacteriology and Protozoology.

Main Discoveries:

• Infusoria in 1674
• Bacteria [e.g. large Selenomonas from the human mouth] in 1683.
• The vacuole of the cell.
• Spermatozoa in 1677.
• The banded of Muscle of fibers in 1682.