IMMUNOLOGY INTRODUCTION LECTURE NOTES.pptx

Understanding immunology will help the students understand how the body overcome the infection, this will also be used as a lecture tool for lecturers especially in the field of health science

1. BASIC IMMUNOLOGY BY ABURA GEOFFREY (BSM, MSC. MICROBIOLOGY)

2. Introduction The term immunology is derived from immuno-+ -logy. Immuno refers to immune or immunity; logy =science; theory; study. Immunology - the scientific study of the immune system and immune responses.

3. Definition of key terms Immunity- Body’s ability to protect itself from infectious diseases or foreign substances. Antigen – A substance that can provoke the body to produce antibodies Immunogens – Are chemical compounds that cause a specific immune response Chemotaxis – A process whereby phagocytic cells are attracted to the area of infection in response to chemokines Chemokines – A low molecular weight protein that stimulates movement of a leukocyte. Antibody – A blood protein produced in response to and counteracting a specific antigen. Immune system – B ody’s defense network that includes cells and protein that work together to protect the body from infection

4. History of immunology plaque D eadliest  pandemic  recorded in human history. The black plague pandemic that starting from 1347 hit Italy and then spread over all Europe. In less than 5 years over 20 million people died, almost one-third of the whole European population of the time. The disease is transmitted through the bite of infected fleas that usually infest central Asian rodents.

5. Small pox vaccine by Jenner S mallpox 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.

6. History of immunology – Edward jenner

7. History of immunology - Antoni van Leeuwenhoek 1632 - 26 August 1723)

8. History of immunology L ouis P asteur was a  F rench chemist and microbiologist considered the most important founders of microbiology. M icrobiology developed as a scientific discipline from the era of L ouis P asteur (1822- 1895) himself. He first coined the term “microbiology” for the study of organisms of microscopic size. for his innumerable contributions in the field, he is also known as the father of modern microbiology.

9. History of immunology H e is renowned for his discoveries of the principles of  vaccination , cholera, rabies

10. History of immunology Then in 1882, Koch was able to demonstrate that the germ theory of disease applied to human ailments as well as animals, when he isolated the microbe that caused  tuberculosis . His "Koch's postulates" are still used to identify infective organisms.

11. History of immunology

12. History of immunology - Elie Metchnikoff contribution

13. Rodney Porter

14. Transplantation Immunology - Donall thomsan

15. Paul Erlich’s side chain hypothesis for antibody formation (1900) Pluripotent blood cells with variety of receptor “side chains” Contact with foreign molecules (antigen) stimulated increased receptor production Specific receptors produced on cells prior to contact with antigen Foundation of selective theory

16. CELLS OF THE IM CELLS OF THE IMMUNE SYSTEM

17. CELLS OF THE IMMUNE SYSTEM AND FORMATION All cells of the immune system originate from a single pluripotent stem cell in the bone marrow. This differentiates into: Myeloid progenitor (stem) cell which gives rise to: Erythrocytes , Platelets , Neutrophils , Monocytes/macrophages, Dendritic cells Lymphoid progenitor (stem) cell which differentiates into: Natural Killer cells, T cells, B cells.

18. HEMATOPOIESIS Cells responsible to do function of hemopoiesis are first seen in yolk sac of embryo in third week of embryonic development and these cells are known as hematopoietic stem cells

19. Lymphoid organs

20. Con’t B one marrow and thymus are sites where these cells develop and hence referred to as central (primary) lymphoid organs. B cells mature and migrate via the blood to the peripheral (secondary) lymphoid organs—the lymph nodes, spleen, and epithelium-associated lymphoid tissues in the gastrointestinal tract, respiratory tract, and skin. For T cell development, the precursor T cells must migrate to the thymus where they undergo differentiation into two distinct types of T cells; CD4+ T helper cell and the CD8+cytotoxic T cell. Two types of T helper cells are produced in the thymus ; the TH1 cells which help the CD8+ pre-cytotoxic cells to differentiate into cytotoxic T cells, and TH2 cells which help B cells differentiate into plasma cells `that secrete antibodies.

21. Primary lymphoid organs

22. Bone marrow Gelatinous tissue found in the inner spaces of bone that contains progenitor cells and stromal cells Red marrow Hematopoietic tissue Composition 40% water 40% fat 20% protein Functions of Bone Marrow Primary function of hematopoiesis controls the inner diameter of bone Yellow marrow Fatty tissue Composition 15% water 80% fat 5% protein

23. Red bone marrow Location Most commonly found in flat bones Ribs, ilium, sternum, vertebrae, skull Epiphysis of long bone (children only) Function Contains mesenchymal stem cells and hematopoietic stem cells Red marrow slowly changes to yellow marrow with age

24. Yellow bone marrow Location Most commonly found in diaphysis or shaft of long bones, femur, tibia Function Contains mostly fat cells May revert to red bone marrow if there is an increased demand for red blood cells (e.g. Trauma)

25. Thymus Lymph Nodes

26. Spleen – structure

27. Splenectomy The effects of splenectomy on the immune response depends on the age at which the spleen is removed. In children, splenectomy often leads to an increased incidence of bacterial sepsis caused primarily by; Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. Splenectomy in adults has less adverse effects, although it leads to some increase in blood-borne bacterial infections ( bacteremia ).

28. MALT {Mucus associated lymphoid tissue}

29. Tonsils The tonsils are found in three locations: lingual at the base of the tongue; palatine at the sides of the back of the mouth; and pharyngeal (adenoids) in the roof of the nasopharynx All three tonsil groups are nodular structures consisting lymphocytes (B cells & T cells), macrophages, granulocytes, and mast cells. The tonsils defend against antigens entering through the nasal and oral epithelial routes.

30. Tonsils

31. GALT The epithelial cells of mucous membranes promote the immune response by delivering small samples of foreign antigen from the lumina of the respiratory, digestive, and urogenital tracts to the underlying mucosal-associated lymphoid tissue.

32. M cells M cells are located in so-called inductive sites Antigens transported across the mucous membrane by M cells can activate B cells within these lymphoid follicles. The activated B cells differentiate into plasma cells, which leave the follicles and secrete the IgA class of antibodies. These antibodies then are transported across the epithelial cells and released as secretory IgA into the lumen, where they can interact with antigens. Among the pathogens that use M cells in these ways are several invasive Salmonella species, Vibrio cholerae, and the polio virus.

33. Cross section of mucus membrane lining the intestine

34. CLASSIFICATION OF THE IMMUNE SYSTEM The immune system is classified into two major subdivisions; Innate or non-specific immune system . The innate immune system is our first line of defense against invading organisms Adaptive or specific immune system . The adaptive immune system also protects us against re-exposure to the same pathogen. A cts as a second line of defense

35. INNATE IMMUNE RESPONSE Properties of innate immune response First line of defence mechanism Exist before the arrival of pathogens Found in plants , insects and vertebrates Functions of innate immune response Initial response to the pathogens Eliminate damaged cells and initiate cell repair Stimulate adaptive immune response

36. INNATE (NON-SPECIFIC) IMMUNITY It deploys the immediate non-specific barriers to infection such as Anatomical barriers Secretory molecules (humoral) Cellular components for protection against invading organisms. ANATOMICAL BARRIERS TO INFECTION These are classified into;

37. Mechanical barriers E pithelial surfaces form a physical barrier, impermeable to most infectious agents. D esquamation of skin epithelium helps remove bacteria and other infectious agents that have adhered to the epithelial surfaces. Movement due to cilia or peristalsis helps to keep air passages and the gastrointestinal tract free from microorganisms. F lushing action of tears and saliva helps prevent infection of the eyes and mouth. The trapping effect of mucus that lines the respiratory and gastrointestinal tract helps protect the lungs and digestive systems from infection.

38. Chemical barriers Fatty acids in sweat inhibit the growth of bacteria. Lysozyme and phospholipase found in tears, saliva and nasal secretions can disintegrate bacterial cell walls. A cidic medium of sweat & gastric secretions inhibits growth of bacteria. Low molecular weight proteins (defensins) in the lungs and gastro intestinal tract have antimicrobial activity. Surfactants in the lungs act as opsonin.

39. Biological barriers Normal flora of the skin and GIT can prevent the colonization of pathogenic bacteria by: Secreting toxic substances Competing with pathogenic bacteria for nutrients Attachment to cell surfaces.

40. 2. HUMORAL BARRIERS TO INFECTION When anatomical barriers fail for instance in tissue damage, infection may occur. Once infectious agents have penetrated tissues, the humoral defense mechanism swings into action. Humoral factors play an important role in inflammation, which is characterized by edema (accumulation of fluid beneath the skin and other cavities of the body) and the recruitment of phagocytic cells.

41. Humoral factors are found in serum or they are formed at the site of infection. They include ; a) Complement system – The complement system is the major humoral non-specific defense mechanism. Once activated, complement can lead to increased vascular permeability, recruitment of phagocytic cells, lysis and opsonization of bacteria. b) Coagulation system – O nce activated the coagulation system can cause increase vascular permeability and also act as chemotactic agents for phagocytic cells. Others like beta-lysin are directly antimicrobial. Lactoferrin and transferrin – These bind iron which is essential for bacteria growth. Interferons – These are proteins that can limit virus replication in cells. Lysozyme –breaks down the cell wall of bacteria. Interleukin-1 (Il-1) -Induces fever and the production of acute phase proteins, some of which are antimicrobial.

42. 3. CELLULAR BARRIERS TO INFECTION During inflammatory responses, there is recruitment of polymorphonuclear cells, eosinophils and macrophages to sites of infection. These cells are the main line of defense in the non-specific immune system.

43. a. Phagocytic cells Neutrophils/Polymorphonuclear cells (PMNs): They contain cationic proteins and defensins that can kill bacteria, proteolytic enzymes-like such as elastase and cathepsin G breakdown proteins, lysozyme breaks down bacterial cell walls, while myeloperoxidase is involved in the generation of bactericidal compounds. Monocytes/Macrophages: Macrophages perform both intracellular killing of microorganisms and extracellular killing of infected and altered self-target cells. They also act as antigen-presenting cells, which are required for the induction of specific immune responses. Dendritic cells: These too kill invading organisms by phagocytosis; but are majorly involved in antigen presentation.

44. Con’t Natural killer (NK) and lymphokine activated killer (LAK) cells : These can nonspecifically kill virus infected cells and tumor cells. They are not part of the inflammatory response but they are important in nonspecific immunity to viral infections and tumor surveillance. Eosinophils -Have proteins in granules that are effective in killing certain parasites.

45. Phagocytosis

46. ADAPTIVE (SPECIFIC) IMMUNITY Like innate responses, adaptive immune responses also destroy invading pathogens and any toxic molecules they produce. However, adaptive responses are highly specific to the particular pathogen that induced them and can also provide long-lasting protection. The adaptive arm is activated by innate responses upon recognition of molecules called pathogen-associated immunostimulants .

47. Con’t Pathogen –associated immunostimulants are expressed on pathogens; they are not present in the host organism, so they are unique to the pathogen. These may include; microbial DNA, lipids, polysaccharides, and proteins that form bacterial flagella e.t.c . Some cells of the innate immune system directly present microbial antigens to T cells to initiate an adaptive immune response. The cells that do this most efficiently are called dendritic cells. They recognize and phagocytose invading microbes or their products at a site of infection and then migrate with their prey to a nearby peripheral lymphoid organ.

48. Con’t There they act as antigen-presenting cells, which directly activate T cells to respond to the microbial antigens. Once activated, some of the T cells then migrate to the site of infection, where they help other phagocytic cells, mainly macrophages, destroy the microbes. Other activated T cells remain in the lymphoid organ and help B cells respond to the microbial antigens by binding to them and secrete a signal protein called interleukin 2 which stimulates B cells to produce antibodies a process called Activation. The activated B cells secrete antibodies that circulate in the body and coat the microbes, targeting them for efficient phagocytosis. Occasionally, inappropriate adaptive responses are mounted to harmless foreign molecules resulting into allergic conditions such as hay fever and asthma.

49. Adaptive immunity can be; Natural acquired active immunity- Occurs through contact with a real disease causing agent eg measles b ut the body is able to produce antibodies against such an infection. Artificial acquired active immunity- A vaccine is introduced into the body and the body reacts by producing antibodies. Examples of vaccines are; BCG, DPT-HepB+Hib, polio, measles .

50. Both natural and artificial adaptive immunity can be : Natural acquired passive immunity Mother passing antibodies to the foetus across the placenta eg IgG The mother passing to her new born baby via breast milk eg IgA This form lasts for a short time bse there is no production of memory cells Artificial acquired passive immunity This a ttained by introducing into the body of an individual antibodies got from an animal or person has produced antibodies against such an infection

51. MECHANISMS OF ADAPTIVE PROTECTION There are two broad classes of adaptive responses a) Antibody responses (Humoral immunity) : These are carried out by the B-cells/ B-lymphocytes through antibody (immunoglobulin) production. b) Cell-mediated immune responses carried out by T- lymphocytes.

52. a) Antibody responses (Humoral immunity) : Humoral immunity-is mediated by antibodies which are produced by B- lymphocytes In antibody responses, B cells are activated to secrete antibodies, proteins called immunoglobulins The antibodies circulate in the bloodstream where they bind specifically to the foreign antigen that stimulated their production. Binding of antibody inactivates viruses and microbial toxins (such as tetanus toxin or diphtheria toxin) by blocking their ability to bind to receptors on host cells. Antibody binding also marks invading pathogens for destruction, mainly by making it easier for phagocytic cells of the innate immune system to ingest them.

53. CELL MEDIATED ADAPTIVE IMMUNITY. A ctivated T cells react directly against a foreign antigen that is presented to them on the surface of a host cell. There are two main classes of T cells—cytotoxic T cells and helper T cells. - Cytotoxic T cells kill infected cells; -whereas helper T cells help activate macrophages, B cells, and cytotoxic T cells. - Effector helper T cells secrete a variety of signal proteins called cytokines, which act as local mediators. Effector cytotoxic T cells kill infected target cells also by means of proteins that they either secrete or display on their surface

54. Mechanism of action of cell mediated adaptive immunity. When T-cell binds to an antigen, an infected cell, cancer cell etc , it secrets a protein called perforin which then perforates (forms pores in) the plasma membrane of the cell being attacked allowing critical ions to diffuse out there by killing the cell. Helper T cells activate B cells to produce immunoglobulins by producing a signal protein called interleukin 2. Interleukin 2 binds to a B cell that has encountered (bound to) the antigen causing it to proliferate thereby producing antibodies specific to that antigen. E ffector helper T cell secret a variety of signal proteins called cytokines which act as local mediators in several immune biological functions

55. Cytokine –mediated biological functions include; Leukocyte activation Recruitment of inflammatory cells Hematopoiesis (formation of blood cells) Angiogenesis (formation of blood vessels) Cell mediated immunity is involved in the following; Tissue rejection Destruction of cancer cells Facilitates major histo-compatibility complex (MHC) Non- phagocytic infected cells. Cell infected with the virus etc.

56. The three main types of antigen-presenting cells in peripheral lymphoid organs that can activate T cells are; Dendritic cells (the most effective antigen presenting cells) Macrophages B cells. Immature dendritic cells are located in tissues throughout the body, including the skin, gut, and respiratory tract. When they encounter invading microbes at these sites, they endocytose the pathogens or their products and carry them via the lymph to local lymph nodes or gut-associated lymphoid organs. The encounter with a pathogen induces the dendritic cell to mature from an antigen capturing cell to an antigen-presenting cell that can activate T cells.

57. STRUCTURE OF ANTIBODY

58. Structure of immunoglobulins

59. TYPES OF ANTIBODIES Antibodies (immunoglobulins) are divided into 5 different classes. These include: Immunoglobulin M (IgM): F irst class of antibody to be produced by a developing B cell. It is also the major class secreted into the blood in the early stages of a primary antibody response, on first exposure to an antigen. In its secreted form, IgM is a pentamer composed of five-chain units = 10 antigen-binding sites. These chains are joined by another polypeptide chain, called a J (joining) chain. The Fc region of IgM can bind complement. Activation of complement by Ig- antigen complexes can either mark the pathogen for phagocytosis ( opsonisation ) or kill it directly.

60. Immunoglobulin G (IgG): Is the major class of immunoglobulin in blood, produced in large quantities during secondary immune response. Besides activating complement, it binds to specific receptors on macrophages and neutrophils. This binding allows the phagocytic cells to bind, ingest, and destroy infecting microorganisms that have become coated with the IgG antibodies produced in response to the infection. IgG molecules are the only antibodies that can pass from mother to fetus via the placenta. Cells of the placenta that are in contact with maternal blood have Fc receptors that bind IgG molecules and direct their passage to the fetus. IgG is also secreted into the mother's milk.

61. Immunoglobulin A (IgA): Principal class of antibody in secretions including; saliva, tears, milk, and respiratory and intestinal secretions. Exists in two forms; in blood as a four-chain monomer; in secretions an eight-chain dimer. IgA help to block adherence of microorganisms to mucus surfaces

62. Immunoglobulin E ( IgE ): IgE molecules are four-chain monomers. They bind to Fc receptors expressed on the surface of mast cells in tissues and of basophils in the blood. Antigen binding to IgE molecules triggers the mast cell or basophil to secrete a variety of cytokines and biologically active amines, such as histamine.

63. Immunoglobulin D ( IgD ): Occurs in low concentrations (2%) and it is short lived. Does not cross the placenta to the foetus , and usually occurs in combination with IgM on the surface of mature B-cells where it serves as a receptor for antigen recognition

64. Antibody-Mediated Effector Functions Opsonization Is Promoted by Antibody Neutralization Antibodies Activate Complement Antibody dependent cell mediated Cytotoxicity (ADCC)

65. Opsonization Opsonization is  an immune process which uses opsonins to tag foreign pathogens for elimination by phagocytes . Without an opsonin, such as an antibody, the negatively-charged cell walls of the pathogen and phagocyte repel each other.

66. HARMFUL EFFECTS OF IMMUNITY Despite its protective mechanism, to the body against infections and other antigenic substances, immunity may at times be harmful to the body. Immunity is therefore said to be harmful when it leads to autoimmunity and hypersensitivity.

67. AUTOIMMUNITY It is a condition in which the body produces antibodies against its own tissues. It may also refer to a condition in which immune responses occur to self-antigens resulting into structural and functional damage to the host. Examples of autoimmune diseases include: Autoimmune hemolytic anaemia: - it is a condition in which an individual makes antibodies against his own erythrocytes leading to the breakdown of erythrocytes ( haemolytic anaemia) Thyrotoxicosis (graves’ disease): - the body makes antibodies against the thyroid gland. These antibodies stimulate the thyroid gland resulting into hyperthyroidism Myasthenia gravis: - an autoimmune disease characterized by extreme muscle weakness due to the presence of acetyl choline receptor antibodies. It is a systemic autoimmune disorder. The antibodies bind to and block the acetyl choline receptor of the neuromuscular junctions thereby interfering with transmission of nerve impulses to the muscle fibres .

68. Con’t Rheumatoid arthritis: - the body produces antibodies to the synovial membranes. Binding of antibodies to synovial membranes leads to chronically inflamed joints that become stiff, painful and swollen. Type 1 diabetes mellitus: - this is organ specific autoimmune disorder of the pancreas in which the pancreatic beta cells are damaged Acute rheumatic fever: - it is an organ specific autoimmune disease which affects the heart valves Addison’s disease: - antibodies are produced against the adrenal gland Systemic lupus erythematous: - the affected organs include; skin, kidneys, lungs and the brain. It is a systemic autoimmune reaction

69. HYPERSENSITIVITY This is a condition in which the immune response results in exaggerated reactions that are harmful to the body tissues. Classification of hypersensitivity reactions 4 classes/types exist basing on:- time btn exposure and reaction immune mechanism involved site of action

70. Con’t Type I hypersensitivity – it is an immediate form of hypersensitivity which occurs when IgE responds to allergens such as dust, pollen, insect stings or some drugs. It may be local swelling or systemic ie anaphylaxis Examples of IgE mediated allergic reactions include; Allergic rhinitis Acute urticaria Asthma Food allergy Type II hypersensitivity – this kind of reaction is associated with drug allergy, and binding of antibodies on self antigens found on cells. The drug binds to the surface of cells and serves as a target of anti-drug IgG antibodies that cause destruction of the cells. Type II hypersensitivity reaction occurs in mismatched blood transfusions.

71. Con’t Type III hypersensitivity – occurs with soluble antigens that combine with antibodies to form immune complexes. The antigen-antibody immune complexes are deposited in the tissues, macrophages/neutrophils are attracted to the site causing tissue damage eg in post streptococcal glomerulonephritis. Type IV hypersensitivity – it is also called delayed hypersensitivity. This type of reaction is not mediated by antibodies but results from the reaction of antigen specific T-cells. The reaction occurs 2-3 days after exposure to the antigen