Basic Immunology nures.pptx immuoloy of

immunology material

1. Basic Immunology By: Dessalew W.

2. Why you get some infections only once? How does the body defend itself from a microbes?

3. Learning Objectives for Immunology Overview Upon completion of this lecture and exercises the student will be able to: Define the terms immunity, immunology Differentiate innate and adaptive immunity in terms of components and type of immune response. Explain the major defenses of innate immunity Describe the mechanisms used by the body to defend itself in an innate response . Immunization Auto immune response and hyper sensitivity reaction

4. Outline 1.1. Terminologies in immunology 1.2. The immune system 1.3. Natural immune system 1.4. Adaptive immune system Immunization Auto immune response and hyper sensitivity reaction

5. 1.1. Definition of terms Individuals who recover from certain infectious diseases achieve a state of protection (exemption/immunity). Origin: Latin immūnis : exempt Immunity: exemption from obligation Immunology is The study of immune system or immunity the study of all aspects of host defense against infection and of adverse consequences of immune responses.

6. Immunity State of protection from infectious diseases Immune system: System of biological structures and processes with in an organism that protects against disease It is able to generate an enormous variety of cells and molecules capable of specifically recognizing and eliminating an apparently limitless variety of foreign invaders. Immune response: The collective and coordinated response to the introduction of foreign substances Variolation: dried crusts derived from smallpox pustules were either inhaled into the nostrils or inserted into small cuts in the skin cont…

7. 1.3. The immune system

8. Innate and Adaptive immunity: Overview Innate Adaptive Provide the 1st line of defense Consists of cellular and chemicals that are in place even before infection Respond in the same way to repeated infection Include phagocytes, NK cells , cytokines, complements , normal flora , etc Stimulated upon exposure to pathogens. Increase in efficiency with each exposure to microbes. Come into action late in immune response Comprises lymphocytes (T&B cells)

9. Overview of the Immune System 1.3. The immune system Acquisition of Immunity Natural (active and passive) Artificial (active and passive)

10. Naturally acquired immunity Active Antigens enter body naturally with response of Innate and adaptive immune systems Provides long term protection Passive Antibodies pass from mother to Fetus across placenta Infant in breast milk Provides immediate short term protection

11. Artificially acquired immunity Active Antigens enter body through vaccination with response of Innate and adaptive immune systems Provides long term protection Passive Antibodies from immune individuals injected into body Referred to as Immune serum globulins (ISG) Immune globulins (IG) Gamma globulins Provides immediate short term protection

12. Principal function of the immune system To protect humans from pathogenic microorganisms Pathogenic microorganisms (Pathogens) Microorganisms capable of causing infection and/or disease Like Bacteria, Viruses, Fungi, Parasites Infection Ability of pathogen to enter host, multiply and stimulate an immune response Disease Clinical manifestations associated with infection

13. Defense mechanisms of the human host Innate Mechanisms (Innate immunity) First line of defense Non-specific Adaptive Mechanisms (Adaptive immunity) Second line of defense Highly specific with memory Cooperation between mechanisms

14. Origin of cells of the immune system Derived from common progenitor cell in bone marrow Pluripotent hematopoietic stem cell Progenitor Stem Cells Erythroid lineage Erythrocytes and Megakaryocytes Myeloid lineage Monocyte /macrophage, dendritic cells, PMN’s, mast cells Lymphoid lineage Small and large lymphocytes

15. Cells of innate and adaptive immunity Cells of innate immune system From myeloid Lineage Neutrophil Principal phagocytic cell of innate immunity Eosinophil Principal defender against parasites Basophil Functions similar to eosinophils and mast cells (participat e in allergic reaction) Referred to as Polymorphonuclear leukocytes (PMN’s) Nuclei are multilobed (2 to 5) Granulocytes (neutrophil, basophil and eosinophil) Cytoplasmic granules

16. Cells of innate and adaptive immunity Cells of innate immune system Myeloid lineage Monocytes Leukocytes with bean shaped or brain-like convoluted nuclei Circulate in blood with half life of 8 hours Precursors of tissue macrophages Macrophages Mononuclear phagocytic cells in tissue and present antigens Derive from blood monocytes Participate in innate and adaptive immunity

17. Cells of innate and adaptive immunity Cells of innate immune system Myeloid lineage Dendritic cells Cells with dendriform (star shaped) morphology Interdigitating reticular cells (synonym) Capture and present antigens to T lymphocytes Mast cells Located in mucous membrane and connective tissue throughout body Major effector cell in allergy Modulation of initial immune response

18. Cells of innate and adaptive immunity Lymphoid Lineage Large lymphocytes (large granular lymphocytes) Natural killer (NK) cells (CD16, CD56) Innate immunity to viruses and other intracellular pathogens Participate in antibody-dependent cell-mediated cytotoxicity (ADCC) Small lymphocytes B cells (CD19) T cells (CD3, CD4 or CD8) Adaptive immunity NB. B-cells and T-cells are the adaptive immune cells ;

19. The Cluster of differentiation (CD) A protocol for identification and investigation of cell surface molecules CD number assigned on basis of 1 cell surface molecule recognized by 2 specific monoclonal antibodies CD nomenclature established in 1982 1 st International Workshop and Conference on Human Leukocyte Differentiation Antigens (HLDA)

20. The cluster of differentiation ( CD) A protocol for identification and investigation of cell surface molecules CD number assigned on basis of 1 cell surface molecule recognized by 2 specific monoclonal antibodies CD markers on leukocytes Granulocyte CD45+, CD15+ Monocyte CD45+, CD14+ T lymphocyte CD45+, CD3+ T helper lymphocyte CD45+, CD3+, CD4+ T cytotoxic lymphocyte CD45+, CD3+, CD8+ B lymphocyte CD45+, CD19+ Natural killer cell CD45+, CD16+, CD56+, CD3-

21. The lymphatic system Lymph Fluid and cells in lymphatic vessels Lymphatic vessels Collect and return interstitial fluid to blood Transport immune cells throughout body Transport lipid from intestine to blood Lymph nodes Kidney shaped organs at intervals along lymphatic vessels Other secondary lymphatic tissues and organs

22. Lymphocytes and the lymph nodes Naïve lymphocytes circulate between blood, lymph and secondary lymph nodes Pathogens from infected tissue sites are picked up by lymphatic vessels and arrive at closest lymph node T and B cells congregate at specific regions of nodes Architecture and size of nodes change in response to activation of lymphocytes

23. Lymphocytes and the spleen Spleen Lymphoid organ in upper left abdomen Functions Remove damaged or old erythrocytes Activation of lymphocytes from blood borne pathogens Architecture of Spleen Red pulp Erythrocytes removed White pulp Lymphocytes stimulated

24. 1.4 The Innate immunity Natural immune system (Innate Immunity) Non – specific First line of defense Repeated exposure - no augmentation Components Biochemical Physical Cells

25. Components Biochemical enzymes, C’, etc. secretions pH Physical skin cilia Cells Phagocytes, NK Example Burn response This results in multiple complications including high risk for infections. Lysozymes Mucus Sebaceous glands Skin Cilia: trachea Acid in stomach Commensal organisms in gut & vagina Spermine in semen cont…

26. cont…

27. Overall non-specific reaction of body to injury or invasion – starts immediately with infection or trauma Reactants may initiate, expand, or sustain the response Can be acute (short duration) or become chronic (prolonged duration) Has 4 cardinal signs: heat, pain, redness, loss of function resulting from: cont…

28. Increased blood and plasma flow to the area Increased capillary permeability by retraction of endothelial cells mediated by vaso active agents such as histamine and prostaglandins. derived from injured cells and later from cells that infiltrate the area. Migration of leucocytes, particularly Neutrophils and macrophages, from the capillaries to the site of injury is due to a process called chemotaxis . cont…

29. Migration of white cells, especially early migration of neutrophils then macrophages to the area Increased release of mediators such as histamine from damaged mast cells – furthering capillary dilation Increased concentration of acute phase reactants that can amplify and/or control the response Complement – a series of enzymes (proteins) normally circulating in an inactive form may be activated resulting in lysis or enhanced phagocytosis of cells cont…

30. 1.4.1 External Innate Defense Systems Prevent entrance: Structural barriers – effective with most microorganisms Skin - epidermis = layers of tightly packed epithelial cells. Outer layer is dead cells and keratin, waterproofing protein Inner layer skin - dermis = blood vessels, hair follicles, sweat glands, and sebaceous glands that produce an oily secretion called sebum Cilia and cough reflex – helps expel microbe containing mucous Sneeze cont…

31. 1.4.1 External Innate Defense Systems Mucus - conjunctivae, alimentary, respiratory, and urogenital tracts . Saliva, tears, and mucous secretions wash away invaders and contain antibacterial or antiviral substances. Acidity (pH 5.6) of sweat, sebaceous glands, vagina (pH 5) and stomach (pH 1) – unfriendly to many microorganisms Enzymes present in the skin and stomach, tears Normal flora - out compete pathogens for attachment sites on the epithelial cell surface and for necessary nutrients . cont…

32. 1.4.2 Internal Innate Defense System To prevent expansion of penetration Recognize carbohydrates not normally present on cells such as mannose May cause nonspecific activation of white cells Phagocytosis – by neutraphils , eosinophils , basophils, or macrophages, mast cells, and dendritic cells Clotting mechanism which entraps organisms in fibrin clots Complement System can lyse cells or enhance phagocytosis cont…

33. Physiologic Barriers Soluble factors contribute to innate immunity, they are collectively known as acute phase reactants . Normal serum components, non-specific responders to inflammation Increase because of infection, injury, trauma Produced mostly by liver in response to inflammation and cytokine stimulation Cytokines: IL-1, IL-6 and TNF alpha which are produced by macrophages and monocytes at inflammatory site are activators cont…

34. Acute phase reactants are chemically varied and include: C-reactive protein, Serum amyloid A, Mannose binding protein, Alpha-1 anti-trypsin, Hapto globulin, Fibrinogen, Cerulo plasmin, Alpha-1 acid glycoprotein Complement cont…

35. Complement – a series of enzymes normally circulating in an inactive form May be activated by the classical or alternate pathways Can result in lysis or enhanced phagocytosis of cells Lysozyme, a hydrolytic enzyme in mucous secretions and in tears, can cleave the peptidoglycan layer of bacterial cell wall. Interferon, proteins produced by virus-infected cells . Has many functions including ability to bind to nearby cells and induce a generalized antiviral state. cont…

36. C-Reactive Protein Normally trace levels in serum Early acute inflammation indicator: Increases within 4-6 hrs of infection or trauma 100 to 1000 fold increase serum concentration concentration drops rapidly in serum when stimulus removed Enhances opsonization , agglutination, precipitation, and classical pathway complement activation – enhances removal of irritant cont…

37. Phagocytosis Phagocytic cells Chemotaxins such as Complement components Coagulation cascade proteins Bacterial and viral products Attract phagocytic cells including: Mast cell, lymphocyte, macrophage, neutrophil Physical contact between phagocytic cell and foreign object results in Formation of phagosome Formation of phagolysosome Digestion Release of debris cont…

38. Phagocytosis Is a form of endocytosis. Important body defense mechanism in which specialized cells engulf and destroy foreign particles such as microorganisms or damaged cells. Macrophages and segmented Neutrophiils are the most important phagocytic cells. cont…

39. Can be divided in to several stages: chemotaxis – attraction of leukocytes or other cells by chemicals Movement of neutrophils is influenced by chemotaxins – chemical messengers Complement, proteins from coagulation, Products from bacteria and viruses, Secretions from mast cells, lymphocytes, macrophages, and other neutraphils cont…

40. Phagocytosis ... Adherence – binding of organism to the surface of phagocytic cell. Engulfment :- is the injestion of m/os and formation of phagosomes. Digestion – after the foreign particle or m/os is ingested, cytoplasm lysosome fuse with phagosome The enzymes of lysosome then contribute to microbial killing and lysis. cont…

41. Phagocytosis ... cont… Source : Kuby immunology 2007, 5 th ed

42. 1.5. The adaptive immune system

43. 1.5. The adaptive immune system

44. 1.5. Adaptive Immunity Specific Third line of defense Repeated exposure - augmented – memory More vigorous response Longer lasting response Anamnestic Components Cells (Cell mediated) =CMI Soluble Factors ( Humoral immunity) = HI 1.5. The adaptive immune system

45. Capable of recognizing and selectively eliminating specific foreign microorganisms and molecules(i.e., foreign antigens). Unlike innate immune responses, adaptive immune responses are reactions to specific antigenic challenges Different populations of lymphocytes and their products are the major actors together with accessory cells – Antigen presenting cells (APCs) Cardinal features are : Specificity Diversity , Memory, 1.5. The adaptive immune system

46. Cardinal Features of adaptive Immune Responses Specificity – Insures that distinct antigens elicit specific responses. for different structural components of a single complex protein, polysaccharide, or other macromolecules. Portions of such antigens recognized by individual lymphocytes are called determinants or epitopes . This fine specificity exists because individual lymphocyte express membrane receptors able to distinguish subtle (slight) differences in structure between distinct antigens. 1.5. The adaptive immune system

47. Diversity - total number of antigenic specificities of the lymphocytes in an individual, called the lymphocyte repertoire, is extremely large. estimated mammalian immune system can discriminate 10 9 to 10 11 distinct antigenic determinants. This property of the lymphocyte repertoire is called diversity . It is the result of variability in the structures of antigen- binding sites of lymphocyte receptors for antigens . 1.5. The adaptive immune system

48. Memory- Enhances the ability to respond in a more rapid , aggressive and qualitatively different manner from the primary exposure to that antigen. Specialization: Generates responses that are distinct to different microbes, maximizing the efficacy of antimicrobial defense mechanisms. Non-reactivity to self: Ability to recognize , respond and eliminate many non-self antigens while not reacting harmfully to self antigens . This immunological unresponsiveness is referred as t olerance. Abnormalities in the induction or maintenance of self-tolerance lead to immune responses against self-antigens resulting disease conditions called Autoimmune diseases 1.5. The adaptive immune system

49. An effective immune response involves three major groups of cells: Cellular Immunity ( T lymphocytes), Humoral Immunity (B cells), and Accessory cells ( antigen-presenting cells). The two major populations of lymphocytes— B lymphocytes (B cells) of Humoral immunity and T lymphocytes (T cells) of Cellular Immunity provide us with our specific adaptive immunity 1.5. The adaptive immune system

50. Self –limitation- All normal immune responses returning the immune system to its resting or basal state with time after antigen stimulations, process called homeostasis . 1.5. The adaptive immune system

51. Innate Immunity Adaptive Immunity Comparison of Innate and Adaptive Immunity No memory No time lag Not antigen specific A lag period Antigen specific Development of memory Summary of innate and adaptive immunity

52. Defense mechanisms against infections

53. Links b/n Adaptive & Innate IR Innate and adaptive immune responses function cooperatively . The innate immune response to microbes stimulates adaptive immune responses. Adaptive immune responses use many of the effector mechanisms of innate immunity to eliminate microbes

54. Adaptive and Innate - Interactions Infectious Exposure Innate Immunity holds Innate Immunity Fails Disease Adaptive Immune system Recovery Second Infectious Exposure Same organism Adaptive Immunity Specific memory No Disease Summary of innate and adaptive immunity

55. Review questions Define the term immunity and immunology? Describe the historical events of immunology and its development. What is the difference between innate and adaptive immunity in terms of components and type of immune response. Explain major defense mechanism of innate immunity and adaptive immune system

56. Reference Kuby; Goldsby et. al. Immunology. 2007 (5 th ed) Tizard. Immunology an introduction,4 th edition ,Saunders publishing,1994 Naville J. Bryant Laboratory Immunology and Serology 3 rd edition. Serological services Ltd.Toronto,Ontario,Canada,1992 Abul K. Abbas and Andrew H. Lichtman. Cellular And Molecular Immunology 2008, 5 th edition Mary T. Keogan, Eleanor M. Wallace and Paula O’Leary Concise clinical immunology for health professionals , 2006 Ivan M. Roitt and Peter J. Delves Essential immunology 2001, 3 rd ed Reginald Gorczynski and Jacqueline Stanley, Clinical immunology 1990.