Immunity

IMMUNOGLOBULIN CLASSES AND THEIR FUNCTIONS

• IgA: Called secretory immunoglobulin because it is present in all body secretions including colostrum and mother’s milk. Functions as first line of defense against inhaled and ingested pathogens by activating alternate  pathway of complement system.
• IgD: Along with IgM occurs over B-lymphocytes as antigen receptors activation of B-cells, also present in serum tissue and effective against toxins and allergens.
• IgE : Present in mucous membranes, skin and lungs. Attaches to mast cells and basophils for releasing histamine and other substances that mediate hypersensitive response to allergens.
• IgG : Constitue 75% of total Ig, present in call body parts including milk and can pass through placenta providing passive immunity to neonates, stimulates complement system and phagocytes against toxins, fungi, viruses and bacteria
• IgM : Largest Ig with 10 binding sites, activates B-cells over which it is present along with IgD, also first to reach the site of infection and activate classical pathway of complement system.

COMPONENTS OF IMMUNITY SYSTEM

• Immunity system contains antibodies, specific cells, tissues and lymphoid organs. It takes part in recognition of foreign antigens, eliminates them and keeps a memory of the same. It has also a role in allergies, autoimmunity and organ transplantation.
• The immunesystem has two components humoral and cell mediated. Humoral Immune System or antibody mediated immune response ( AMIR) –
• Antibody – mediated immunity is associated with the appearance of antibodies, secreted by cells of the B-lymphocyte series, in extra cellular fluids such as plasma, lymph and external secretions.
• The AMIR defends the body against
  a) Some viruses.
  b) Bacteria with polysaccharide capsule.
  c) Toxins that enter the body fluids ( blood and lymph).
• When antibodies on a B cell’s surface bind antigens, the B cell is activated and divides producing a clone of daughter B Cells. The daughter cell specialize into plasma B cells and memory B cells
• The plasma B cells are antibody factories. The antibodies pass into and circulate in three lymph to dispose of the antigens. For this, the antibodies selectively bind to the antigens forming antigen – antibody complexes to destroy the antigen. Each person can make 107 to 108 different kinds of antibody molecules so that there is an antibody molecules, so that there is an antibody on a B cells to fit any antigen
• The plasma cells do not migrate to the site of infection and act through a fluid (lymph). Hence they are said to form humoral immune system ( L. humor = liquid). The B – lymphocytes are short lived and are replaced every few days from the bone marrow
• The memory B cells live for a long time and serve to quickly dispose off the antigens in case re-infection of the same virus or bacterium occurs.
• The antibiotics bind to their specific antigens an inactivate the invading microorganism or foreign molecules so that these are conveniently disposed of by the pathogen.

The antibodies fight the antigene in five different ways

1. Neutralization – some antibodies neutralize the antigens termed toxins and make them ineffective. They are called antitoxins. The phagocytes dispose off the neutralized antigen – antibody complexes
2. Agglutination – Certain antibodies causes the particulate antigen to stick together in clumps, thus immobilizing then for easy disposal by the phagocytes through ingestion. They are termed agglcutinins.
3. Opsonziation – Other antibodies coat the surface of the microbes and make them more susceptible to phagocytosis. Such antibodies are known as opsonin
4. Precipitation – other antibodies combine with the antigens to form precipitates that are easily ingested by phagocytes
5. Complement activation – Antibody antigen complexes activate complement protein which may –
   a) Lyse cell walls of bacteria, causing their disintegration.
   b) Incite inflammatory response.
   c) Opsonize antigen.
   d) Attract phagocytes to area of infection.

Cell mediated immunity / Action of T cells
T cells are long – lived cells which have upto 100,000 receptors sites on their surface for binding antigens. The cells develop antigen specificity through previous contact. They are often called competent lymphocytes. The latter respond to specific antigen by forming a clone of cells. The cells then differentiate into following types

1. Cytotoxic or killer T-cells : The cells reach the site of infection or agglutination and get attached to antigen containing microorganisms. They secrete perforins that produce holes in the attached cells. The killer T cells then pass toxic chemicals into attached cell for killing the same. Afterwards they move away for attacking new antigen containing cells. Killer T cells attack virus, invaded cells, cancer cells and cells of transplanted organs. They also destroy helper T cells when the latter are invaded by HIV. AIDS is due to deficiency of helper T cells. The killed cells are removed by phagocytes
2. Helper T cells : They constitute more than 75% of total T- cells. They regulate immune functions by secreting lymphokines. Interleukin-2 has positive feedback system for helper T cells, stimulates growth and proliferation of other T cells. Interleukin-4,5 and 6 stimulate B lymphocytes macrophages are attracted to the site of infection and stimulated to phagocytosis by lymphokines.
3. Suppressor T cells : The cells act as negative feedback and keep the activity of other T-cells under check. This protects the body tissues and chemicals from attack of phagocytes and their antibodies
4. Memory T cells : They are sensitized T Cells which retain memory of antigen specificity for future. Sometimes lifelong. Other T Cells are amplifier T cells, killer, helper and suppressive T-cells are also called effectors cells.

CELLS OF IMMUNE SYSTEM

• They are lymphocytes and antigen presenting cells like macrophages. A healthy human has about a trillion lymphocytes. Lymphocytes are of two types, T-layphocytes ( T-cells) and B-lymphocytes ( B-cells). Both of them develop in bone marrow from lymphatic system cells by the process called haematopoiesis, some of the young lymphocytes migrate into thymus for preprocessing. They are called T-lymphocytes. Afterwards they pass on to all the lumphoid tissues of the body and get lodged there. The other types of lymphocytes remain in the bone marrow and get preprocessed there. They are called B lymphocytes because in birds they are preprocessed in lymphoid diverticulum of cloaca called bursa of Fabricius. After being preprocessed B lymphocytes also migrate to all the lymphoid tissue of the body where they reside near but separate from T-lymphocytes
• MHC / HLA molecules ( HLA antigen )
  Polymorphic molecules call MHC class I are present on most body cells, Another group of molecules, , MHC class II, occur over professional antigen presenting cells. They bind to peptide antigen producing MHC antigen complex. The same is present to CD4 and CD8 T-cells respectively
• Activation of adaptive / acquired immunity
  An antigen is processed by antigen presenting cells like macrophages and Blymphocytes. A type of T-cells ( T-helper cells) interacts with presented antigen and becomes activated. The activated T-cells not only form a clone of T-cells but also B-lymphocytes.

CLONAL SELECTION

• Formation of a clone of cells by each activated T-lymphocyte and antibody producing plasma cells by activated B-lymphocyte, each exhibiting the specificity for the same antigen is called clonal selection. The cells are of course of more than one type and perform different functions. One type of cloned lymphocyte do not function as effector cells but instead develop into long lived memory cells.

PRIMARY AND SECONDARY IMMUNE RESPONSES

• Primary immune response is the first immune response developed during the first encounter with the antigen. It is feeble but relatively longer
• Secondary immune response is quick heightened immune response against a subsequent encounter with some antigen. It is due to the presence of memory cells against that antigen. A person having caught chicken pox or measles only becomes immune to subsequent attack of the pathogen due to it.

LYMPHOID ORGANS

• They are those organs having lymphatic tissues where maturation and proliferation of lymphocytes occur. The sites where T-lymphocytes and Blymphocytes mature and develop antigen specific receptors are called primary lymphoid organs viz. thymus for T-lymphocytes. And bone marrow for Blymphocytes
• Secondary lymphoid organs are those organs having lymphatic tissues where B and T-cells are settled after maturation and where they undergo proliferation / differentiation on being activated by specific antigens e.g. lymph nodes, spleen and tonsils, MALT is mucosal lymphoid associated tissue. It constitutes more than 50% of the total lymphoid tissue.

VACCINATION AND IMMUNISATION
Immunization is phenomenon of increasing specific antibody production and development of memory B and T cells against the potential attack of apathogen. It is carried out through vaccination and injection of antiserum.
When an immunized person is attacked by the pathogen, the existing antibodies immediately attack the antigen while the memory T and B cells give rise to a massive crop of lymphocytes and antibodies.

• Vaccination is a process of inoculation of harmless antigenic material into healthy person for providing active acquired immunity against the disease. A single vaccination against the disease. A single vaccination may not give adequate immunity. Therefore 2-3 booster doses of vaccine are administered later on at specific intervals. Vaccine is suspension / extract of weakened attenuated dead germs or antigen containing compound of pathogens which when injected into healthy person provides active acquired immunity to the disease
• Now vaccines are also available for diphtheria, cholera, typhoid, whooping cough, tetanus, tuberculosis, plague, measles, mumps and polio. The cells infected with cancer causing viruses usually show on their surface to the virus. This has led to the first successful immunization against cancer in cats and chickens. Unfortunately, efforts to produce antibodies to cancers not caused  by virus have had very little success
• Many serious infectious diseases also have no effective vaccines. These
  include malaria, trypanosomiasis and AIDS
• In India, vaccines are generally produced at Hoffkins Institute at Mumbai and Virus Institute at Pune
• National Institute of Immunology ( NII), New Delhi is involved in the
  production of antifertility vaccine kits to detect pregnancy and infectious
  disease etc.

DISORDERS OF IMMUNE SYSTEM
AUTOIMMUNITY ( Auto immune diseases)

• Auto immunity is an abnormal immune response against self antigens. When the cell acts as antigens in the same body then they are called autoantigens
• The nature of auto immune diseases depends on the autoantigens involved. For example, if the autoantigens are RBC then the body destroys its own RBCs, resulting in chromic anemic, if the autoantigens are muscle cells then it results in the destruction of its own muscles resulting in severe weakness (myasthenia gravis); if the autoantigens are liver cells, then it results in chronic hepatitis, etc. Other autoimmune diseases are insulin dependent diabetes, Addison’s disease, ulcerative colitis and rheumatoid arthritis

ALLERGY ( Hypersensitivity)

• Allergy is the inappropriate immune response of person to harmless substances coming in contact with the body or entering the body from the environment or in food or in medicine
• The substances which causes allergic reaction are called allergens. They are generally weak antigens. The common allergens are dust, dust mites, cat, pollen, feathers, fur, venom etc.
• Allergic reaction depends on the nature of the allergen. The common allergic reactions are inflammation of mucous membrane, sneezing, gasping, running of eyes, irritation of upper respiratory tract, itching, skin rash
• Allergy involves mainly IgE antibodies and histamine. It causes marked dilation of all the peripheral blood vessels and the capillaries becomes highly permeable so that large amounts of fluid leak out from the blood into tissues.
• The blood pressure decreases drastically often resulting in the death of the
  individual within a short time
• Hay fever : In this allergic form, there is swollen, reddened, running eyes and nose. The drugs called antihistamines are of major importance in treatment.
• Asthma: The tissue surrounding the respiratory tubes in the lungs swell up and compress the tubes. Hence there is difficulty in breathing. Antihistamine drugs are also given in this disease

IMMUNODEFICIENCY
Severe combined immune deficiency ( SCID)

• Severe combined immunodeficiency ( SCID) represents a group of rare, sometimes fatal congential disorders characterized by little or no immune response
• It is a defect in the specialized white blood cells ( B and T-lymphocytes)
• Without a functional immune system, SCID patients are susceptible to recurrent infections such as pneumonia, meningitis and chicken pox. Though invasive, new treatment such as bone marrow and stem cells transplantation save as many as 80% of SCID patients.
• Sometimes new born children are without T-cells and B-cells. These children are susceptible to various infections
• SCID is caused by a defect in the gene that codes for the enzyme adenosine deaminase on chromosome number 20. Lack of the enzyme adenosine deaminase (ADA). Means that the substrate for this enzyme accumulate in the cells. Immature lymphoid cells of the immune system are particularly sensitive to the toxic effects of these unused substrates, so fail to reach maturity.
• As a result, the immune system of the afflicted individual is severely compromised or completely lacking. Lack of this enzyme makes the body defenseless against infections.
• SCID is the first genetic disorder to be combated with gene therapy.Acquired immune deficiency syndrome ( AIDS)
• AIDS is a disorder of cell mediated immune system of the body. There is a reduction in the number of helper T-cells which stimulate antibody production of B-cells. This results in loss of natural defense against viral infection
• AIDS infection were detected in India for the first time in prostitutes of Chennai in 1986.

Virus responsible for AIDS was identified and named HIV
AIDS virus – HIV

• HIV virus belong to the retrovirus family, a family of single stand RNA viruses distinguished by possession of viral reverse transcriptase that transcribes viral RNA into provirus DNA which is integrated into the host cell genome.
• HIV is 100 to 140 nm in diameter, has a cylindrical core, single-stranded linear RNA and reverse transcriptase enzyme surrounded by glycoprotein coat, double lipid membrane and two protein coats
• Virus of AIDS was isolated and identified in green monkey by Prof. Luc Montagnier in France in 1983 and almost the same time by Prof Robert Gallo in USA ( 1984 )
• HIV is subdivided into two distantly related types, HIV-1 and HIV-2. HIV-1 is  the predominant world wide isolated from individuals with AIDS or at high risks for the development of AIDS. HIV-2 is endemic among people in west Africa.

HIV -1 and HIV-2 differ in their ability to cause disease and their geographical
distribution

• Both, HIV-1 and HIV-2, cause the body to produce antibodies with three to six months, although the period between initial infection and illness may be longer in case of HIV-2
• The incubation period of HIV is 15 -57 months. Average incubation period is 28
  months Transmission
• AIDS is transmitted only by a constant of infected cells containing blood of a
  patient with the blood of a healthy person as in:
  (i) Unprotected sexual intercourse with an infected person (ii) Use of contaminated needles and syringes to inject drugs or vaccines. (iii) Use of contaminated razors for shaving (iv) Use of infected blood or blood product for transfusion (v) Organ transplant (vi) Parturition from mother to baby due to rupturing of blood vessels
• The sexual rout of transmission accounts for over 75% of infections
• AIDS can not be acquired by
  i) Insect bites
  ii) Crowded transport
  iii) Shaking hands
  iv) Sharing towels
  v) Coughing and sneezing
  vi) Kissing and embracing
  vii) Sharing utilities

Signs and symptoms of AIDS

• People infected with AIDS virus remain apparently well even after infection. They may not show any physical symptoms of illness for a long time
• When the AIDS virus enters the blood stream it begins to attack certain white blood vessels and antibodies. These antibodies can be detected by a specific blood test usually two weeks to three months after infection.
• In some people, the protective immune system may be destroyed by the virus and then other germs that ordinarily do not attack cause opportunistic disease to infect and destroy the body.
• Opportunistic infections occur during the last phase of HIV, which can occur up to 10 to 11 years after the infection. These infections are described as AIDS related complex (ARC)
• AIDS virus may attack nervous system causing damage to the brain resulting in memory loss and other neurological disorders.
• Some early signs may be persistent cough and fever associated with difficulty in breathing.
• Certain cancers
• Tuberculosis
• A typical pneumonia by fungus pneumocystis carinii
• Brain damage
• Night sweats and tiredness
• Swollen lymph nodes and fever
• Weight loss, chronic diarrhea that last for more than one week, loss of appetite and lack of resistance to infection.

Diagnostic test

• HIV is diagnosed by testing the blood for the presence of antibodies to the
  virus.
• ELISA ( Enzyme -linked immunosorbent assay) screening test is the initial one. The test works by detecting antibodies, substances, proteins which are produced in the blood, when the virus is present.
• Western blot test will confirm the result of repeated test through detection of HIV proteins.
• Viral load test measures the amount of virus in the blood which will help in determining the probable progression of the disease

Treatment

• However, no specific treatment has been found so far, and the mortality from AIDS is virtually 100%
• A combination of three and more antiretroviral agents, called triple therapy or highly active anti-retroviral theory ( HAART ), has been highly effective in reducing the number of HIV particles in blood stream though HAART is not cure for HIV.
  Prevention
• The following steps may help in controlling this dreaded disease:
  i) People should be educated about AIDS transmission, advantage of
  condoms.
  ii) Disposable needles and syringes should be used
  iii) High risk group should be refrain from donating blood
  iv) Sexual habits should be changed
  v) Before receiving blood, ensure that it has been screened for HIV
  vi) While getting dental treatment, insist on the use of thoroughly
  sterilized equipment.
• December 1 is celebrated every year as the world AIDS Day.