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Immunology
- 1. 1 IMMUNOLOGY & ORAL IMMUNOLOGY OF DENTAL CARIES & PERIODONTAL DISEASES Dr. Poonam Dubey MDS 1st Year
- 2. Contents Definitions History Types of Immunity Development and processing of lymphocytes Development of cell- mediated immunity Development of humoral immunity Antigens Antibodies or Immunoglobulins Complement system NK cells 2
- 3. Hypersensitivity reactions Immunizations Immune deficiency diseases Autoimmunization Oral cavity as an immunological entity Immunological aspects of dental caries Immunological aspects of periodontal disease Conclusion References 3
- 4. DefinitioNS: Immunity is defined as the capacity of the body to resist pathogenic agents. It is the ability of body to resist the entry of different types of foreign bodies like bacteria, virus, toxic substances, etc. (Sembulingam, Essentials of medical physiology) Immunity is the status or quality of being free from the possibility of acquiring a given infectious disease; or being resistant to an infectious disease. (Stedman’s Medical Dictionary 26th edition) 4
- 5. History: Edward Jenner – Father of Immunology Louis Pasteur 5
- 6. TYPES OF IMMUNITY: 6 Immunity Innate or Native Immunity Acquired or Adaptive Immunity Active Natural Artificial Passive Natural Artificial
- 7. INNATE IMMUNITY Innate immunity is the inborn capacity of the body to resist pathogens. By chance, if the organisms enter the body, innate immunity eliminates them before the development of any disease. It is otherwise called the natural or non-specific immunity. This type of immunity represents the first line of defense against any type of pathogens. Therefore, it is also called non-specific immunity. 7
- 8. Types of Innate Immunity: Species Immunity- It refers to the resistance to a pathogen, shown by all members of a particular species e.g. B. anthracis infects human beings but not chickens. Racial Immunity- Within one species, different races may exhibit differences in susceptibility or resistance to infections. This is termed as racial immunity. In human beings, it is reported that American negroes are more susceptible than the white race to tuberculosis. Individual Immunity- Resistance to infection varies with different individuals of same race and species. This is known as individual immunity. 8
- 9. Factors Influencing Innate Immunity: Age Hormones Nutrition 9
- 10. Mechanisms of Innate Immunity: 10
- 11. ACQUIRED IMMUNITY: Acquired immunity is the resistance developed in the body against any specific foreign body like bacteria, viruses, toxins, vaccines or transplanted tissues. So, this type of immunity is also known as specific immunity. It is the most powerful immune mechanism that protects the body from the invading organisms or toxic substances. Lymphocytes are responsible for acquired immunity. 11
- 12. Types of Acquired Immunity: 12
- 13. NATURALACTIVE IMMUNITY Natural active immunity results from either a clinical or an in apparent infection by a microbe. The immunity is lifelong following many viral diseases such as chicken pox or measles, but short-lived in influenza or common cold. Immunity following bacterial infection is generally less permanent than that following viral infections. 13
- 14. ARTIFICIALACTIVE IMMUNITY (a) Live vaccines -BCG for tuberculosis -Ty 21a for typhoid -MMR vaccine for measles, mumps, rubella -17D vaccine for yellow fever (b) Killed vaccines -TAB for enteric fever -Killed cholera vaccine -Neural and non-neural vaccines for rabies -Hepatitis B vaccine 14
- 15. NATURAL PASSIVE IMMUNITY It is transferred from the mother to foetus or infant. Transfer of maternal antibodies to foetus transplacentally and to infant through milk (colostrum) protects them till their own immune system matures to function. Human colostrum, which is also rich in IgA antibodies, gives protection to neonate. By active immunization of mothers during pregnancy, it is possible to improve the quality of passive immunity in the infants. 15
- 16. ARTIFICIAL PASSIVE IMMUNITY Artificial passive immunity is the resistance passively transferred to a recipient by the administration of antibodies. It is through parenteral administration of antibodies. Agents used for this purpose are hyper immune sera of animal or human origin. Eg. ATS ADS(Anti-diptheric serum) 16
- 17. Uses of Passive Immunisation: To provide immediate short term protection in a non-immune host, faced with the threat of a serious infection. For suppression of active immunity which may be injurious. Example is to use Rh immunoglobulins during delivery to prevent immune response to Rh factor in Rh negative mothers with Rh positive babies. 17
- 18. 18
- 19. DEVELOPMENT AND PROCESSING OF LYMPHOCYTES In fetus, lymphocytes develop from the bone marrow. All lymphocytes are released in the circulation and are differentiated into two categories, which are: 1. T lymphocytes or T cells, which are responsible for the development of cellular immunity. 2. B lymphocytes or B cells, which are responsible for humoral immunity. 19
- 20. T LYMPHOCYTES T lymphocytes are processed in thymus. The processing occurs mostly during the period between just before birth and few months after birth. Thymus secretes a hormone called thymosin, which plays an important role in immunity. It accelerates the proliferation and activation of lymphocytes in thymus. It also increases the activity of lymphocytes in lymphoid tissues.20
- 21. Types of T Lymphocytes: During the processing, T lymphocytes are transformed into four types: 1. Helper T cells or inducer T cells. 2. Cytotoxic T cells or killer T cells. 3. Suppressor T cells. 4. Memory T cells. 21
- 22. Storage of T Lymphocytes: After the transformation, all the types of T lymphocytes leave the thymus and are stored in lymphoid tissues of lymph nodes, spleen, bone marrow and GI tract. 22
- 23. B LYMPHOCYTES B lymphocytes were first discovered in the bursa of Fabricius in birds, hence the name B lymphocytes. Bursa of Fabricius is a lymphoid organ situated near the cloaca of birds. Bursa is absent in mammals and the processing of B lymphocytes takes place in liver (during fetal life) and bone marrow (after birth). 23
- 24. Types of B Lymphocytes: After processing, the B lymphocytes are transformed into two types: 1. Plasma cells. 2. Memory cells 24
- 25. Storage of B Lymphocytes: After transformation, the B lymphocytes are stored in the lymphoid tissues of lymph nodes, spleen, bone marrow and the GI tract. 25
- 26. DEVELOPMENT OF CELL-MEDIATED IMMUNITY It involves several types of cells such as T lymphocytes, macrophages and natural killer cells and hence the name cell mediated immunity. Cellular immunity is the major defense mechanism against infections by viruses, fungi and few bacteria like tubercle bacillus. Usually, the invading microbial or non-microbial organisms carry the antigenic materials. These antigenic materials are released from invading organisms and are presented to the helper T cells by antigen-presenting cells. 26
- 27. ANTIGEN-PRESENTING CELLS: Antigen-presenting cells are the special type of cells in the body, which induce the release of antigenic materials from invading organisms and later present these materials to the helper T cells. Antigen-presenting cells are of three types: 1. Macrophages 2. Dendritic cells 3. B lymphocytes 27
- 28. 1. Macrophages: Macrophages are the large phagocytic cells, which digest the invading organisms to release the antigen. The macrophages are present along with lymphocytes in almost all the lymphoid tissues. 2. Dendritic Cells: Dendritic cells are nonphagocytic in nature. Based on the location, dendritic cells are classified into three categories: i. Dendritic cells of spleen, which trap the antigen in blood. ii. Follicular dendritic cells in lymph nodes, which trap the antigen in the lymph. 28
- 29. iii. Langerhans dendritic cells in skin, which trap the organisms coming in contact with body surface. 3. B Lymphocytes: Recently, it is found that B lymphocytes also act as antigen-presenting cells. - Thus, the B cells function as both antigen-presenting cells and antigen receiving cells. However, B cells are the least efficient antigen presenting cells and need to be activated by helper T cells. 29
- 30. ROLE OF ANTIGEN-PRESENTING CELLS: Invading foreign organisms are either engulfed by macrophages through phagocytosis or trapped by dendritic cells. Later, the antigen from these organisms is digested into small peptide products. These antigenic peptide products move towards the surface of the antigen-presenting cells and bind with human leukocyte antigen (HLA). HLA is a genetic matter present in the molecule of class II major histocompatiblility complex (MHC), which is situated on the surface of the antigen presenting cells. 30
- 31. MHC and HLA: Major histocompatibility complex (MHC): is a large molecule present in the short arm of chromosome 6. It is made up of a group of genes which are involved in immune system. It has more than 200 genes including HLA genes. MHC molecules in human beings are divided into two types: 1. Class I MHC molecule: It is found on every cell in human body. It is specifically responsible for presentation of endogenous antigens (antigens produced intracellularly such as viral proteins and tumor antigens) to cytotoxic T cells. 31
- 32. 2. Class II MHC molecule: It is found on B cells, macrophages and other antigen-presenting cells. It is responsible for presenting the exogenous antigens (antigens of bacteria or viruses which are engulfed by antigen-presenting cells) to helper T cells. 32
- 33. PRESENTATION OF ANTIGEN: Antigen-presenting cells present their class II MHC molecules together with antigen-bound HLA to the helper T cells. This activates the helper T cells through series of events. 33
- 34. ROLE OF HELPER T CELLS: Helper T cells (CD4 cells) which enter the circulation activate all the other T cells and B cells. Normal, CD4 count in healthy adults varies between 500 and 1500 per cubic millimeter of blood. Helper T cells are of two types: 1. Helper-1 (TH1) cells -Interleukin-2 -Gamma interferon 2. Helper-2 (TH2) cells. -Interleukin-4 -Interleukin-5 34
- 35. ROLE OF CYTOTOXIC T CELLS: Cytotoxic T cells that are activated by helper T cells, circulate through blood, lymph and lymphatic tissues and destroy the invading organisms by attacking them directly. Mechanism of Action of Cytotoxic T Cells: 1. Receptors situated on the outer membrane of cytotoxic T cells bind the antigens or organisms tightly with cytotoxic T cells. 2. Then, the cytotoxic T cells enlarge and release cytotoxic substances like the lysosomal enzymes. 3. These substances destroy the invading organisms. 4. Like this, each cytotoxic T cell can destroy a large number of microorganisms one after another. 35
- 36. ROLE OF SUPPRESSOR T CELLS: Suppressor T cells are also called regulatory T cells. These T cells suppress the activities of the killer T cells. Thus, the suppressor T cells play an important role in preventing the killer T cells from destroying the body’s own tissues along with invaded organisms. Suppressor cells suppress the activities of helper T cells also. 36
- 37. ROLE OF MEMORY T CELLS: Some of the T cells activated by an antigen do not enter the circulation but remain in lymphoid tissue. These T cells are called memory T cells. In later periods, the memory cells migrate to various lymphoid tissues throughout the body. When the body is exposed to the same organism for the second time, the memory cells identify the organism and immediately activate the other T cells. So, the invading organism is destroyed very quickly. The response of the T cells is also more powerful this time. 37
- 38. SPECIFICITY OF T CELLS: Each T cell is designed to be activated only by one type of antigen. It is capable of developing immunity against that antigen only. This property is called the specificity of T cells. 38
- 39. DEVELOPMENT OF HUMORAL IMMUNITY The B lymphocytes provide immunity through humors (humours or humors in Latin meaning body fluids), this type of immunity is called humoral immunity or B cell immunity. Antibodies are the gamma globulins produced by B lymphocytes. These antibodies fight against the invading organisms. The humoral immunity is the major defense mechanism against the bacterial infection. 39
- 40. As in the case of cell-mediated immunity, the macrophages and other antigen-presenting cells play an important role in the development of humoral immunity also. 40
- 41. Transformation B Cells: Proliferated B cells are transformed into two types of cells: 1. Plasma cells 2. Memory cells 41
- 42. ROLE OF PLASMA CELLS: Plasma cells destroy the foreign organisms by producing the antibodies. The rate of the antibody production is very high, i.e. each plasma cell produces about 2000 molecules of antibodies per second. Antibodies are released into lymph and then transported into the circulation. The antibodies are produced until the end of lifespan of each plasma cell, which may be from several days to several weeks. 42
- 43. ROLE OF MEMORY B CELLS: Memory B cells occupy the lymphoid tissues throughout the body. The memory cells are in inactive condition until the body is exposed to the same organism for the second time. During the second exposure, the memory cells are stimulated by the antigen and produce more quantity of antibodies at a faster rate, than in the first exposure. The antibodies produced during the second exposure to the foreign antigen are also more potent than those produced during first exposure. 43
- 44. ANTIGENS: Antigens are the substances which induce specific immune reactions in the body. Antigens are of two types: 1. Autoantigens or self antigens present on the body’s own cells such as ‘A’ antigen and ‘B’ antigen in RBCs. 2. Foreign antigens or non-self antigens that enter the body from outside. 45
- 45. NON-SELF ANTIGENS: Receptors on the cell membrane of microbial organisms such as bacteria, viruses and fungi. Toxins from microbial organisms. Materials from transplanted organs or incompatible blood cells. Allergens or allergic substances like pollen grains. 46
- 46. DETERMINANTS OF ANTIGENICITY: Size Chemical nature Susceptibility to tissue enzymes Foreignness Species specificity ISO specificity Auto specificity Organ specificity 47
- 47. ANTIBODIES OR IMMUNOGLOBULINS An antibody is defined as a protein that is produced by B lymphocytes in response to the presence of an antigen. Antibody is gamma globulin in nature and it is also called immunoglobulin (Ig). Immunoglobulins form 20% of the total plasma proteins. Antibodies enter almost all the tissues of the body. 48
- 49. TYPES IgA (Ig alpha) IgD (Ig delta) IgE (Ig epsilon) IgG (Ig gamma) IgM (Ig mu) 50
- 50. IgG lgG is the major serum immunoglobulin (about 80% of the total amount). The normal serum concentration is about 8- 16 mg/ml. Molecular weight is 150,000 (7S). Half life is about 23 days (longest amongst all the immunoglobulins). It is the only immunoglobulin that is transported through placenta and provides natural passive immunity to newborn. 51
- 51. IgG appears late but persists for longer period. It appears after the initial immune response which is IgM in nature. It participates in precipitation, complement fixation and neutralisation of toxin and viruses. IgG binds to microorganisms and enhances the process of phagocytosis (opsonization). It is protective against those microorganisms which are active in the blood and tissues. 52
- 52. IgA IgA is the second major serum immunoglobulin (about 10-13% of serum immunoglobulins). The normal serum concentration is 0.6 - 4.2 mg/ml. Half life is about 6 - 8 days. IgA occurs in two forms, serum IgA and secretory IgA. 53
- 53. IgA is the principal immunoglobulin present in secretions. It protects the mucous membranes against microorganisms. IgA covers the microorganisms to inhibit their adherence to mucosal surfaces. It does not fix complement but can activate alternative complement pathway. IgA is mainly synthesised locally by plasma cells and little is derived from serum. 54
- 54. IgM IgM is a pentamer consisting of 5 immunoglobulin subunits and one molecule of J chain, which joins the basic subunits. It constitutes about 5- 8 percent of total serum immunoglobulins. The normal level in serum is 0.5- 2 mg/ml. Half life is about five days. It is heavy molecule (19S) with a molecular weight 900,000 to 1,000,000 hence also called the 'millionaire molecule'. 55
- 55. It is the earliest synthesised immunoglobulin by foetus in about 20 weeks of age. It appears early in response to infection before IgG. IgM antibodies are short lived, and disappear earlier than IgG. Hence, its presence in serum indicates recent infection. It can not cross the placenta, presence of IgM antibody in serum of newborn indicates congenital infection. 56
- 56. IgD IgD is present in a concentration of 3 mg per 100 ml in serum. Molecular weight is 1,80,000 (7 S monomer). Half life is about three days. Like IgM, it is also present on the surface of unstimulated B lymphocytes in blood and acts as recognition receptors for antigens. 57
- 57. IgE IgE is mainly produced in the linings of respiratory and intestinal tracts. Serum contains only traces (a few nanograms per ml) It is also referred to as reagins. Molecular weight is 1,90,000 (8S molecule). Half life is 2-3 days. IgE mediates type I hypersensitivity (atopic) reaction. High level of IgE in serum is also seen in children with a high load of intestinal parasitism. 58
- 58. Mechanism of Actions of Antibodies Antibodies protect the body from invading organisms in two ways: 1. By direct actions 2. Through complement system. 59
- 59. 60
- 61. Two ways: a. Classical pathway b. Alternate pathway 62
- 62. 63
- 63. 64
- 64. Specificity of B Lymphocytes: Each B lymphocyte is designed to be activated only by one type of antigen. It is also capable of producing antibodies against that antigen only. This property of B lymphocyte is called specificity. In lymphoid tissues, the lymphocytes, which produce a specific antibody, are together called the clone of lymphocytes. 65
- 65. NATURAL KILLER CELL: Natural killer (NK) cell is a large granular cell that plays an important role in defense mechanism of the body. It is derived from bone marrow. NK cell is said to be the first line of defense in specific immunity, particularly against viruses. It is not a phagocytic cell but its granules contain hydrolytic enzymes such as perforins and granzymes. 66
- 66. Functions of Natural Killer (NK) Cell: 1. Destroys the viruses. 2. Destroys the viral infected or damaged cells, which might form tumors. 3. Destroys the malignant cells and prevents development of cancerous tumors. 4. Secretes cytokines such as interleukin-2, interferons, colony stimulating factor (GM-CSF) and tumor necrosis factor-α. 67
- 68. 69
- 69. 70
- 70. 71
- 71. 72
Editor's Notes
- Edward Anthony Jenner, is known as the Father of Immunology. It is because of his achievement of producing the First Successful Vaccine that he got this title. His vaccine was made to prevent smallpox. Louis Pasteur is traditionally considered as the progenitor of modern immunology because of his studies in the late nineteenth century that popularized the germ theory of disease, and that introduced the hope that all infectious diseases could be prevented by prophylactic vaccination, as well as also treated by therapeutic vaccination, if applied soon enough after infection
- The mechanism of such type of immunity is not clearly understood. The physiological and biochemical differences between tissues of different host species may be responsible for species specific resistance. 3. Homozygous twins exhibit similar degrees of resistance or susceptibility to lepromatous leprosy and tuberculosis Such correlation is not seen in heterozygous twins
- The two extremes of life (foetus and old persons) carry higher susceptibility to various infections. In foetus, the immune system is immature whereas in old age there is gradual waning of immune responses. The foetus in-utero is generally protected from maternal infections through the placental barrier. However, some pathogens (rubella, cytomegalovirus and Toxoplasma gondii) cross this barrier and lead to congenital malformations. Certain hormonal disorders such as diabetes mellitus, adrenal dysfunction and hypothyroidism enhance susceptibility to infections. Staphylococcal sepsis is more common in diabetes which may be associated with increased level of carbohydrates in tissues. Malnutrition predisposes to bacterial infections. Both humoral and cell mediated immune responses are reduced in malnutrition.
- Artificial active immunity is the resistance induced by vaccines. The vaccines are prepared from live, attenuated or killed microorganisms, or their antigens or toxoids. Live vaccines contain live attenuated microorganisms which are still capable of replicating within the host. The microorganisms are weekend and they have lost most of their disease causing capacity. In killed vaccines the organisms are killed by heat, formalin, phenol and alcohol. These are preserved in phenol, N-merthiolate and alcohol. Toxoids are prepared from bacterial exotoxins inactivated by formalin (formol toxoid) or by alum (alum precipitated toxoid-APT). Toxoids are immunogenic but not toxigenic.
- Convalescent sera (sera of patients recovering from infectious diseases) contain high levels of specific antibody and therefore is employed for passive immunisation against common infectious diseases .
- 1. because of the presence of molecules called CD4 on their surface These cells are also called CD4 cells . 2. These cells are also called CD8 cells because of the presence of molecules called CD8 on their surface. 3. immune cell that blocks the actions of some other types of lymphocytes, to keep the immune system from becoming over-active. Also called regulatory T cell, 4. Memory T cells are antigen-specific T cells that remain long-term after an infection has been eliminated
- 1. Plasma cells, also called plasma B cells, are white blood cells that originate in the bone marrow and secrete large quantities of proteins called antibodies in response to being presented specific substances called antigens. 2. a long-lived lymphocyte capable of responding to a particular antigen on its reintroduction, long after the exposure that prompted its production.
- Cell-mediated immunity does not involve antibodies. 5.It is also responsible for delayed allergic reactions and the rejection of transplanted tissues.
- . Among these cells, macrophages are the major antigen-presenting cells.
- B-cells ingest the foreign bodies by means of pinocytosis. Role of B cells as antigen-presenting cells in the body is not fully understood.
- HLA is made up of genes with small molecules. It encodes antigen-presenting proteins on the cell surface. Though MHC molecules and HLA genes are distinct terms, both are used interchangeably. Particularly in human, the MHC molecules are often referred as HLA molecules.
- Sequence of Events during Activation of Helper T cells Helper T cell recognizes the antigen displayed on the surface of the antigen-presenting cell with the help of its own surface receptor protein called T cell receptor. 2. Recognition of the antigen by the helper T cell initiates a complex interaction between the helper T cell receptor and the antigen. This reaction activates helper T cells. 3. At the same time, macrophages (the antigen-presenting cells) release interleukin-1, which facilitates the activation and proliferation of helper T cells. 4. Activated helper T cells proliferate and the proliferated cells enter the circulation for further actions. 5. Simultaneously, the antigen which is bound to class II MHC molecules activates the B cells also, resulting in the development of cell mediatedl immunity
- Role of TH1 Cells: TH1 cells are concerned with cellular immunity and secrete two substances: i. Interleukin-2, which activates the other T cells. ii. Gamma interferon, which stimulates the phagocytic activity of cytotoxic cells, macrophages and natural killer (NK) cells. Role of TH2 Cells: TH2 cells are concerned with humoral immunity and secrete interleukin-4 and interleukin-5, which are concerned with: i. Activation of B cells. ii. Proliferation of plasma cells. iii. Production of antibodies by plasma cell
- Other Actions of Cytotoxic T Cells 1. Cytotoxic T cells also destroy cancer cells, transplanted cells, such as those of transplanted heart or kidney or any other cells, which are foreign bodies. 2. Cytotoxic T cells destroy even body’s own tissues which are affected by the foreign bodies, particularly the viruses. Many viruses are entrapped in the membrane of affected cells. The antigen of the viruses attracts the T cells. And the cytotoxic T cells kill the affected cells also along with viruses. Because of this, the cytotoxic T cell is called killer cell.
- Humoral immunity is defined as the immunity mediated by antibodies, which are secreted by B lymphocytes. B lymphocytes secrete the antibodies into the blood and lymph, which are the body fluids .Since ,
- The presentation of antigen and sequence of events for activation of B cells are similar to that of T cells.
- This phenomenon forms the basic principle of vaccination against the infections.
- Non-self antigens are classified into two types, depending upon the response developed against them in the body: 1. Antigens, which induce the development of immunity or production of antibodies (immunogenicity). 2. Antigens, which react with specific antibodies and produce allergic reactions (allergic reactivity).
- Size : Larger molecules are highly antigenic Chemical nature : Mostly naturally occurring antigens are either proteins or polysaccharides Susceptibility to tissue enzymes : Substances that can be metabolized & are susceptible to the action of tissue enzymes behave as antigens & that can not be metabolized in body are non antigenic Foreignness: an antigen must be foreign to the individual to induce an immune response Species specificity : Tissues of all individuals in a species possess species specific antigens. ISO specificity : depends on isoantigens.. That are specific for each individual of a species; imp in HLA(Human Leucocyte antigen), blood gp Auto specificity : Self antigens are gen. non antigenic Organ specificity : confined to a particular organ
- Antibodies are gamma globulins with a molecular weight of 1,50,000 to 9,00,000. The antibodies are formed by two pairs of chains, namely one pair of heavy or long chains and one pair of light or short chains. Each heavy chain consists of about 400 amino acids and each light chain consists of about 200 amino acids. Actually, each antibody has two halves, which are identical. The two halves are held together by disulfide bonds (S–S). Each half of the antibody consists of one heavy chain (H) and one light chain (L). The two chains in each half are also joined by disulfide bonds (S – S). The disulfide bonds allow the movement of amino acid chains. In each antibody, the light chain is parallel to one end of the heavy chain. The light chain and the part of heavy chain parallel to it form one arm. The remaining part of the heavy chain forms another arm. A hinge joins both the arms (Fig. 17.3). Each chain of the antibody includes two regions: 1. Constant region 2. Variable region. Constant Region Amino acids present in this region are similar in number and placement (sequence) in all the antibodies of each type. So, this region is called constant region or Fc (Fragment crystallizable) region. Thus, the identification and the functions of different types of immunoglobulins depend upon the constant region. This region binds to the antibody receptor situated on the surface of the cell membrane. It also causes complement fixation. So, this region is also called the complement binding region. 2. Variable Region Variable region is smaller compared to constant region. Amino acids occupying this region are different in number and placement (sequence) in each antibody. So, it is called the variable region. This region enables the antibody to recognize the specific antigen and to bind itself with the antigen. So, this region of the chain is called antigen-binding region or Fab (Fragment antigen binding) region.
- Among these antibodies, IgG forms 75% of the antibodies in the body. IgA plays a role in localized defense mechanism in external secretions like tear IgD is involved in recognition of the antigen by B lymphocytes IgE is involved in allergic reactions IgG is responsible for complement fixation IgM is also responsible for complement fixation
- Serum IgA is a monomeric 7S molecule (MW 160,000), while IgA found on mucosa! surfaces and in secretions (secretory IgA, MW 400,000) is a dimer formed by two monomer units joined together by a glycoprotein named the J chain (J for joining). The J chain joins the two monomer units at their carboxyterminals. Secretory IgA and J chain are produced by the plasma cells situated near the mucosa! or glandular epithelium. J chains are also present in other polymeric immunoglobulins such as IgM. (v) Secretory IgA contains another glycine rich polypeptide called the secretory piece or secretory component. The S piece is not synthesised by lymphoid cells but by mucosal or glandular epithelial cells. It attaches two IgA molecules at their Fe portion during transport across the cells. The S piece is believed to protect IgA from denaturation by bacterial proteases in sites such as the intestinal mucosa which is rich in bacterial flora.
- IgA is the principal immunoglobulin present in secretions such as milk, saliva, tears, sweat, nasal fluids, colostrum and in secretions of respiratory, intestinal and genital systems. Two subclasses of IgA (IgAl and IgA2) are known. IgA2 is predominant (60%) in the secretions but constitutes a minor part of serum IgA. IgA2 is devoid of interchain disulphide bonds between H and L chains.
- It can not cross the placenta, presence of IgM antibody in serum of newborn indicates congenital infection. Its detection is, therefore, useful for the diagnosis of congenital syphilis, HIV infection, toxoplasmosis and rubella.
- IgE mediates type I hypersensitivity (atopic) reaction. This is responsible for asthma, hay fever, eczema and Prausnitz-Kustner (PK) reaction. (x) It cannot cross the placental barrier or fix the complement. Its deficiency is associated with impaired immune response and undue susceptibility to infection It is heat labile (inactivated at 56°C in one hour) whereas other immunoglobulins are heat stable.
- Direct Actions of Antibodies Antibodies directly inactivate the invading organism by any one of the following methods: i. Agglutination: In this, the foreign bodies like RBCs or bacteria with antigens on their surfaces are held together in a clump by the antibodies. ii. Precipitation: In this, the soluble antigens like tetanus toxin are converted into insoluble forms and then precipitated. Neutralization: During this, the antibodies cover the toxic sites of antigenic products. Lysis: It is done by the most potent antibodies. These antibodies rupture the cell membrane of the organisms and then destroy them. The indirect actions of antibodies are stronger than the direct actions and play more important role in defense mechanism of the body than the direct actions. Complement system is the one that enhances or accelerates various activities during the fight against the invading organisms In classical pathway Events produce the following activities: i. Opsonization: Activation of neutrophils and macrophages to engulf the bacteria, which are bound with a protein in the plasma called opsonin. ii. Lysis: Destruction of bacteria by rupturing the cell membrane. iii. Chemotaxis: Attraction of leukocytes to the site of antigen-antibody reaction. iv. Agglutination: Clumping of foreign bodies like RBCs or bacteria. v. Neutralization: Covering the toxic sites of antigenic products. vi. Activation of mast cells and basophils, which liberate histamine: Histamine dilates the blood vessels and increases capillary permeability. So, plasma proteins from blood enter the tissues and inactivate the antigenic products.
- The 'complement' (C) refers to a system of some nonspecific proteins present in normal human and animal serum, which are activated characteristically by antigen antibody reaction and subsequently lead to a number of biologically significant consequences. The term complement was coined by Paul Ehrlich, because it augmented (complemented) the action of antibody. C ordinarily does not combine with either free antigen or antibody, but only with antigen-antibody complex. The complement system consists of about 20 proteins which include the complement components, the properdin system and the control proteins.
- There are nine components of complement called Cl to C9. The component Cl is made up of three protein subunits named Clq, Clr and Cls. In normal serum C3 is present in the highest concentration (1.2 mg/ml) whereas C2 in the lowest concentration (0.015 mg/ml). Complement is normally present in circulation in inactive form, but when its activity is induced by antigen-antibody reaction or other stimuli, complement components react in a specific sequence as a cascade either through the classical or alternative pathway. Both the pathways have same result i.e. lysis or damage of target cell. Classical pathway is triggered by specific antigen-antibody complex; the alternative pathway can be initiated by endotoxin, lipopolysaccharides or zymosan (yeast cell wall).
- Complement components react in a specific sequence, following activation by antigen-antibody complex, and results in immune cytolysis. This is known as the classical pathway of complement The erythrocyte (E)-antibody (A) complex is named EA and later on, when C components are attached to EA, it is called EAC. Immune cytolysis is initiated by the binding of component Cl to EA. Clq is the recognition unit of Cl, hence, Clq reacts with the Fe piece of bound antibody molecule (IgM or IgG) in EA. The binding of Clq in the presence of calcium ions leads to activation of Clr and Cls. The activated Cls is an esterase which splits C4 into C4a and C4b, of which C4b joins the cascade. C14b in presence of magnesium ions act on C2 and forms C2a and C2b. The larger fragment C2a attaches to C4 to form C42 which has enzymatic activity and is called CJ convertase. The other C2 fragments possess kinin like activity and increase vascular permeability. C42 splits C3 into C3a and C3b, of which, C3b joins the cascade. C3a has chemotactic and anaphylatoxic properties. C14b2a3b has enzymatic activity and is referred to as C5 convertase. It acts on CS, to split it into C5a (anaphylatoxic and chemotactic) and C5b which joins the cascade. C6 and C7 join to form C567, some of which binds to cell membrane and prepares the cell for lysis by C8 and C9. Most of C567 absorb to unsensitised 'bystander' cells making them susceptible to lysis by C8 and C9. In this way, C567 serves to amplify the reaction. The unbound C567 complex has chemotactic and leucocyte activating properties. The lysis is done by producing 'holes' approximately 100° A in diameter on cell membrane. This disrupts the osmotic integrity of the cell membrane which results into release of the contents of the cell.
- The activation of C3 has the major role in the complement cascade. In the classical pathway, C3 activation occurs by classical C3 convertase (C142). This activation of C3 without help of Cl42, is known as the 'alternative pathway'. The alternative pathway contributes to antimicrobial defence without requiring specific antibodies. A wide range of substances (activators) are known to activate alternative pathway. These include bacterial endotoxins, yeast cell walls, IgA and D, the cobra venom factor and the nephritic factor (a protein present in the serum of glomerulonephritis patient). The binding of C3b to an activator is the first step in the alternative pathway. Although C3b is present in the circulation but in the free state it is rapidly inactivated by the serum protein factors H and I. However, bound C3b is protected from such inactivation. The bound C3b, in the presence of Mg++, interacts with plasma protein factor B forming C3bB. The factor B portion of C3bB complex is split by factor D into Ba and Bb. Bb fragment binds to C3b forming C3bBb. This C3bBb is C3 convertase of alternative pathway (Fig. 15.2). This enzyme is extremely labile. The properdin or factor P helps to stabilise the enzyme C3 convertase. C3 convertase splits more C3 to C3a and C3b. The newly formed C3b binds more factor B. The alternative pathway then proceeds from C3 to C9 in the similar way as that occurs in the classical pathway.
- 2.Considered as the third type of lymphocyte, it is often called the non-T, non-B cell. 5.NK cell kills the invading organisms or the cells of the body without prior sensitization. 7. These hydrolytic enzymes play an important role in the lysis of cells of invading organisms.
- Cytokines are the hormone-like small proteins acting as intercellular messengers (cell signaling molecules) by binding to specific receptors of target cells. These non-antibody proteins are secreted by WBCs and some other types of cells. Their major function is the activation and regulation of general immune system of the body.