Concepts of immunology
- 1. CONCEPTS OF IMMUNOLOGY DAVID NDIRANGU SNR LECTURER MLS
- 2. DEFINATION Immunology is the study of the ways in which the body defends itself from infectious agents and other foreign substances in its environment. The immune system protect us from pathogens. • It has the ability to discriminate (differentiate)between the individual`s own cells and harmful invading organisms. • The study of structure and function of the immune system • The branch of medicine and biology concerned with immunity.
- 3. Definition of terms ANTIGEN-foreign substance when introduced into the body • Will provoke or stimulate immune response • React with antibodies they stimulate Characteristics of immunogens • They are proteins or carbohydrates in nature e.g. micro-organisms, toxins and cellular cells • They are usually large in size or macro-molecules of 10,000daltons • Haptens-small molecules less than 10,000daltons (low molecular weight) with only one characteristic of antigen this is they react with antibodies i.e. specificity • Haptens are important in the purification and production of monoclonal antibodies.
- 4. Definition of terms • Antibodies molecules produced by the body in response to a foreign substance and antagonistic. Also called immunoglobulins when not referring to their specificity • Inflammation is the overall reaction of the body to injury or invasion. Involves cellular and Humoral responses e.g. loss of function, pain, swelling, heat, redness • Immune system: Cells tissues and molecules that mediate resistance to infection • Immunity: Resistance of host to pathogens and their toxic effects/ability of the body to stimulate antibodies against foreign substances • Immune response; the collective and co-ordinated response to the introduction of foreign substances in an individual mediated by the cells and molecules of the immune system
- 5. HISTORY OF IMMUNOLOGY • 1798-Edward Jenner discovered the cowpox vaccine after discovering the cowpox virus where he discovered infection with milder form of virus provided protection against the disease. • The small pox vaccine, introduced by Edward Jenner in 1796 was the first successful vaccine to be developed. • He observed that milkmaids who previously had caught cowpox did not catch smallpox and showed that inoculated vaccinia protected against inoculated Variola virus • Neil Key Verne discovered natural selection theory of form in 1955
- 6. HISTORY OF IMMUNOLOGY • Louis Pasteur in 1885 developed the rabies vaccine making an impact on human disease. • Then antitoxins and vaccines against diphtheria, tetanus, anthrax, cholera, plague, typhoid, tuberculosis, and more were developed through the 1930s • Cesar Milstein and Georges Kohler in 1975 discovered monoclonal antibody and together with Niels Kaj Jerne won the Nobel prize in physiology in 1984 for work on the immune system and production of monoclonal antibodies. • Milstein and Kohler’s technique for producing monoclonal antibodies laid the foundation for the exploitation of antibodies for diagnostics, therapeutics and many other scientific applications
- 7. HISTORY OF IMMUNOLOGY • Emil von Behring was a German physiologist who received the 1901 Nobel prize in physiology or medicine for discovery of a diphtheria antitoxin. • He was widely known as a “saviour of children” as diphtheria used to be a major cause child death. • In 1897 Edmond Nocard demonstrated the protective effect of passively transferred antitoxin and passive immunization in humans was used for treatment and prophylaxis during World War I. • A method for inactivating tetanus toxin with formaldehyde was developed in the early 1920s
- 8. HISTORY OF IMMUNOLOGY • 1900-1901 Landsteiner discovered blood group antigens and their corresponding antibodies which led to transfusing blood without provoking reactions • Late 18th Century Robert Koch made important discoveries in identifying many bacteria such as anthrax, tuberculosis, and cholera and establishing their relation to diseases. • Together with Friedrich Loeffler they developed landmark set of rules for linking a disease to the pathogen that causes it.
- 9. HISTORY OF IMMUNOLOGY • The presence of foreign particles within cells was first described by Kranid Slavjansky a pathologist, and in the 1880s Russian born zoologist and microbiologist Elie Metchnikoff introduced the term phagocyte reference to immune cells that engulf and destroy foreign bodies such as bacteria • 1903- Ainswoth Wright proposed the theory of opsonisation which suggested that antibody and phagocytes are important to immunity against disease • 1940-Linces Pulling proposed the structure theory for the synthesis of antibody molecules • 1957- Burnette proposed clonal section theory for the immunoglobulin formation • 1916-First Immunology journal publication was published. Since then the progress of immunology has been rapid in various fields such as transplantation, vaccine development etc • 1908-Mechnikoff established the concept of “cell-mediated-immunity” and won the Nobel prize in 1908
- 10. MILESTONES IN THE HISTORY OF IMMUNOLOGY • 1798-Edward Jenner initiates small pox vaccination • 1877-Paul Erlich recognises mast cells • 1879-Louis Pasteur develops an attenuated chicken cholera vaccine • 1883-Elie Metchnikoff develops cellular theory of immunisation • 1885-Louis Pasteur develops rabies vaccine • 1891-Robert Koch explored delayed type hypersensitivity
- 11. MILESTONES IN THE HISTORY OF IMMUNOLOGY • 1900-Paul Erlich theorizes specific antibody formation • 1906-Clemens von Pirquet coined the word allergy • 1938-John Marrack formulates antigen-antibody binding hypothesis • 1942-Jules Freud and Katherine McDermott research adjuvants • 1949-Macfarlane Burnet and Frank Fenner formulate immunological tolerance hypothesis • 1959-Niels Jerne, David Talmage, Macfarlane Burnet develop clonal selection theory • 1957-Alick Isaacs and Jean Lindermann discover interferon (Cytokine) • 1962-Rodney Porter and team discover structure of antibodies • 1962-Jaques Miller and team discover thymus involvement in cellular immunity
- 12. MILESTONES IN THE HISTORY OF IMMUNOLOGY • 1962-Noel Warner and team distinguish between cellular and humoral immune responses • 1968-Anthony Davis and team discover T-cell and B-cell cooperation in immune response • 1974-Rolf Zinkerand Peter Doherty explore Major Histocompatibility Complex restriction • 1985-Susumu Tonegawa, Leroy Hood and team identify genes for the T cell receptor • 1987-Leroy Hood and team identify genes for the T cell receptor • 1985-Scientists begin the rapid identification of genes for immune cells that continues to the present time
- 13. IMPORTANCE OF IMMUNOLOGY • Plays a role in combating disease • Vaccination of immunizable diseases • Cancer immunotherapy-immunotherapy combating cancer and infections (cytokines, monoclonal antibody gene therapy) • During treatment of emerging diseases like influenza, ebola, covid • Immunology of type I diabetes and variety of cancer • Application in discipline of medicine-organ transplants • Helps understand pathogenesis allergens and treatment of hypersensitivity state • Diagnosis of immune status Diabetes type I • Diseases association with MHC • Study of immunodeficiency diseases • Provides immune diagnostic technique • Understanding of graft rejection
- 14. Applications of immunology in human medicine • Organ transplant • Immunotherapy/ oncology • Virology • Bacteriology • Parasitology • Microscopy • Electrophoresis • Immunoelectrofluorescence
- 15. Property of antigens/ Factors Influencing Immunogenicity Immunogenicity is determined by: 1. Foreignness • An antigen must be a foreign substance to the animal to elicit an immune response. 2. Molecular Size • The most active immunogens tend to have a molecular mass of 14,000 to 600,000 Da. • Examples: tetanus toxoid, egg albumin, thyroglobulin are highly antigenic. • Insulin (5700 ) are either non-antigenic or weakly antigenic.
- 16. Immunogenicity is determined by: 3. Chemical Nature and Composition • In general, the more complex the substance is chemically the more immunogenic it will be. • Antigens are mainly proteins and some are polysaccharides. • It is presumed that presence of an aromatic radical is essential for rigidity and antigenicity of a substance. 4. Physical Form • In general particulate antigens are more immunogenic than soluble ones. • Denatured antigens are more immunogenic than the native form.
- 17. Immunogenicity is determined by: 5. Antigen Specificity • Antigen Specificity depends on the specific actives sites on the antigenic molecules (Antigenic determinants). • Antigenic determinants or epitopes are the regions of antigen which specifically binds with the antibody molecule. 6. Species Specificity • Tissues of all individuals in a particular species possess, species specific antigen. • Human Blood proteins can be differentiated from animal protein by specific antigen-antibody reaction.
- 18. Immunogenicity is determined by: 7. Organ Specificity • Organ specific antigens are confined to particular organ or tissue. • Certain proteins of brain, kidney, thyroglobulin and lens protein of one species share specificity with that of another species. 8. Auto-specificity • The autologous or self-antigens are ordinarily not immunogenic, but under certain circumstances lens protein, thyroglobulin and others may act as autoantigens.
- 19. Immunogenicity is determined by: 9. Genetic Factors • Some substances are immunogenic in one species but not in another. Similarly, some substances are immunogenic in one individual but not in others (i.e. responders and non-responders). • The species or individuals may lack or have altered genes that code for the receptors for antigen on B cells and T cells. • They may not have the appropriate genes needed for the APC to present antigen to the helper T cells.
- 20. Immunogenicity is determined by: 10. Age • Age can also influence immunogenicity. • Usually the very young and the very old have a diminished ability to elicit and immune response in response to an immunogen.
- 21. Immunogenicity is determined by: 11. Degradability • Antigens that are easily phagocytosed are generally more immunogenic. • This is because for most antigens (T-dependant antigens) the development of an immune response requires that the antigen be phagocytosed, processed and presented to helper T cells by an antigen presenting cell (APC). 12. Dose of the antigen • The dose of administration of an immunogen can influence its immunogenicity. • There is a dose of antigen above or below which the immune response will not be optimal.
- 22. Immunogenicity is determined by: 13. Route of Administration • Generally the subcutaneous route is better than the intravenous or intragastric routes. • The route of antigen administration can also alter the nature of the response. • Antigen administered intravenously is carried first to the spleen, whereas antigen administered subcutaneously moves first to local lymph nodes.
- 23. Immunogenicity is determined by: 14. Adjuvants • Substances that can enhance the immune response to an immunogen are called adjuvants. • The use of adjuvants, however, is often hampered by undesirable side effects such as fever and inflammation. • Example: aluminum hydroxide.
- 24. QUIZ • Who was the first person to discover response to foreign substance • Describe the contribution of Landsteiner to the field of immunology • Describe the Properties of antigens/ Factors influencing Immunogenicity