2. WHITE BLOOD CELLS LEUKOCYTES Dr. Taj

3. PLASMA CELLS

4. WHITE BLOOD CELLS ARE VERY IMPORTANT WHY ?

5. PATHOGENS

6. INFECTIONS

7. IMMUNITY Innate immunity (non specific) Examples: Phagocytes Complement Barriers Acquired immunity (specific) Humoral Antibody mediated B lymphocytes Cell mediated T lymphocytes

8. G ranulocytes G ranulocytes Polymorphonuclear leukocytes (PMNs) Polymorphonuclear leukocytes (PMNs) Neutrophils Neutrophils Eosinophils Eosinophils Basophils Basophils Agranulocytes Agranulocytes Lymphocytes Lymphocytes T lymphocyte T lymphocyte B lymphocyte B lymphocyte Monocytes  macrophage system Monocytes  macrophage system TYPES (CLASSIFICATION) Page: 429

9. CLASSIFICATION GRANULOCYTESAGRANULOCYTES

11. CellApproximate Normal range (/µL) Percentage of Total WBC Total WBC4000-11000- - - Granulocytes Neutrophils Eosinophils Basophils 3000-6000 150-300 0-100 50-70 1-4 0.4 Lymphocytes1500-400020-40 Monocytes300-6002-8 Concentration (Normal Counts)

12.  Granulocytes  4-8 hours  Monocytes  10-20 hours  Lymphocytes & macrophages  months & years Life span of leukocytes:

13. FORMATION GENESIS

14. Genesis of blood cells

15. Genesis of white blood cells

16. BARRIERS

17. Lines of Defense Response to Inflammation  1 st line of defense – Tissue macrophages & Physical Barriers  2 nd line of defense – Neutrophil Invasion of the inflamed area  3 rd line of defense – Monocytes –macrophage invasion of inflamed area  4 th line of defense – Increased production of granulocytes and Monocytes by Bone marrow

18. MONOCYTES  No Granules but Vacoules  Size: 15-20 µm  More Efficient than Neutrophils  Life span: 10-20 hours in blood  Two types: Mobile & Fixed

19. RESTING MACROPHAGE ACTIVATED MACROPHAGE

20. ACTIVATED MACROPHAGE

21. Reticuloendothelial System Monocyte/Macrophage System Monocytes Monocytes Mobile macrophages Mobile macrophages Fixed tissue macrophages Fixed tissue macrophages Specialized endothelial cells in bone marrow, spleen and lymph nodes Specialized endothelial cells in bone marrow, spleen and lymph nodes TISSUE MACROPHAGE SYSTEM

22. Reticuloendothelial System Monocytes/Macrophage System Examples are: - 1.Skin and Subc tissues (Histiocytes) 2.Lymph Nodes 3. Alveolar macrophages 4.Liver sinuses (Kupffer Cells) 5.Spleen & Bone marrow 6. Microglia in Brain

23. Tissue macrophages in Liver sinuses

24. Tissue macrophages in Lymph Nodes

25. Tissue macrophages in Spleen

26. NEUTROPHILS Most Abundant WBCs 60-70 % Most Abundant WBCs 60-70 % Size: 15-20 µm Size: 15-20 µm Nucleus: Multilobed 2-5 lobes Nucleus: Multilobed 2-5 lobes Life span: 6-8 hours Life span: 6-8 hours

27. 1. Diapedesis 2. Chemotaxis 3. Opsonization 4. Degranulation 5. Phagocytosis & Digestion DEFENSIVE PROPERTIES OF MACROPHAGES & NEUTROPHILS

33. PMNs Digestive System (Antimicrobial system) ENZYMATICGranules  Heparin  Histamine  Bradykinin  Serotinin  Defensins  Lysosomal enzymes  Slow reacting substance of anaphylaxis of anaphylaxis

34. PMNs Digestive System (Antimicrobial system) NON ENZYMATIC respiratory burst  O2 Free Radicals (O-2, H2O2, -OH)  NADPH-oxidase  Myeloperoxidase  Cl-  HoCl  Hypochlorous acid “very toxic”

35. Feed Back Control of Macrophage & Neutrophil response

36. IMPORTANT TERMS Leukocytosis Leukocytosis Neutrophilia Neutrophilia Pus Pus Leukopenia Leukopenia Leukemias Leukemias

37. Formation of Pus  Dead Neutrophils  Dead Macrophages  Necrotic tissue

38. Inflammation Is an Innate response Is an Innate response When tissue injury occurs by bacteria, trauma, chemical or heat, multiple substances are released by injured tissue that cause dramatic secondary changes in the injured tissue. The entire complex of tissue changes is called Inflammation When tissue injury occurs by bacteria, trauma, chemical or heat, multiple substances are released by injured tissue that cause dramatic secondary changes in the injured tissue. The entire complex of tissue changes is called Inflammation

39. EOSINOPHIL Granules contain arginine rich protein, which take acid dye (eosin) Granules contain arginine rich protein, which take acid dye (eosin) Function: Phagocytosis Function: Phagocytosis Chemotaxis: attracted towards chronic inflammation Chemotaxis: attracted towards chronic inflammation Neutralises allergic products such histamine, 5-HT, Ag-Ab complex, bradykinin (allergic disease of skin &lungs) Neutralises allergic products such histamine, 5-HT, Ag-Ab complex, bradykinin (allergic disease of skin &lungs) Phagocytosis is same as neutrophil, but less efficient Phagocytosis is same as neutrophil, but less efficient

40. Eosinophils cont, High eosinophil count: High eosinophil count: Parasitic (hook worm, ascaris, bilharzia) Parasitic (hook worm, ascaris, bilharzia) Allergic (asthma, rhinitis, drug reaction) Allergic (asthma, rhinitis, drug reaction) Dermatological diseases Dermatological diseases

41. BASOPHILS Weak phagocytic cells Weak phagocytic cells Granules contain polysaccharide granules > base methylene blue color. Granules contain polysaccharide granules > base methylene blue color. Similar to mast cells releases its granules containing heparin, histamine, 5HT. Which causes inflammation reaction Similar to mast cells releases its granules containing heparin, histamine, 5HT. Which causes inflammation reaction

42. IMMUNITY Protect the body against damages caused by foreign organism e.g. bacteria, viruses transplanted incompatible tissue or organs

43. IMMUNE CELLS Cells which recognized foreign organism (antigen) by receptors on its surface and respond to it: Cells which recognized foreign organism (antigen) by receptors on its surface and respond to it: 1. T-Lymphocytes 2. B-Lymphocytes

44. Immune response Lymphocytes respond to antigen either by: Lymphocytes respond to antigen either by: 1. Producing antibodies (B- lymphoctes) to attack foreign antigen (humoral immunity) 2. Cellular killing of foreign invading organism (cellular immunity) by T- lymphocytes

45. Antigens Large > 8000, complex, unique molecule that triggers a specific immune response against itself when it gains entry into body. ENEMIES Bacterias, Viruses, Fungi, Parasites Foreign ness Molecular size Chemical structure Antigenic determinants (Epitopes)

46. Antibody Globulin molecules in plasma which are capable of attacking the invading agent. EXAMPLES: IgG, IgA, IgM, IgD, IgE

47. Types of lymphocytes 1.Helper T-cells. 2.Cytotoxic T-cells. 3.Suppressor T-cells. B-lymphocytes Plasma cells Memory Cells B lymphocytesT lymphocytes

49. Humoral immunity B-lymphocytes recognize foreign organism by its surface receptors B-lymphocytes recognize foreign organism by its surface receptors Interact with antigen>>> proliferation of B-lymphocytes to plasma cells Interact with antigen>>> proliferation of B-lymphocytes to plasma cells Plasma cells secrete the specific antibody to destroy the antigen Plasma cells secrete the specific antibody to destroy the antigen Some of this plasma cells will be kept in marrow as memory cell ready for next exposure to same antigen Some of this plasma cells will be kept in marrow as memory cell ready for next exposure to same antigen

50. Primary immune response The immune response of the body when exposed to antigen for the first time >> antibodies are formed after a latent period (1-2 w), time needed for multiplication and maturation of lymphocytes (vaccination)

51. Secondary immune response Upon the second exposure to the same antigen. immediate production of high titer antibodies immediate production of high titer antibodies Due to the presence of memory lymphocytes (from first exposure) which react immediately when exposed to the same antigen Due to the presence of memory lymphocytes (from first exposure) which react immediately when exposed to the same antigen

54. Cellular immunity T-cell react with antigen > proliferate to give either: T-cell react with antigen > proliferate to give either: Cytotoxic T cells CD8 (Tc) destroy foreign cell, removed by macrophage, monocytes, neutrophils Cytotoxic T cells CD8 (Tc) destroy foreign cell, removed by macrophage, monocytes, neutrophils Helper T cell CD4 (Th) secret lymphokinese to attract macrophages, stimulate B cell to secret antibodies against target cells infected with viruses Helper T cell CD4 (Th) secret lymphokinese to attract macrophages, stimulate B cell to secret antibodies against target cells infected with viruses

55. Helper T-cells Most abundant. Secrete Cytokines (Interleukins) Stimulation of growth and proliferation of cytotoxic T cells and suppressor T cells. Stimulation of B cell growth and differentiation. Activation of macrophage system. Feedback stimulatory effect on helper T cells themselves.

57. Cytotoxic T-cells (Killer cells) Bind with specific antigen Secrete perforins (hole forming proteins) Fluid flows into the cell Cell swells and dissolves

58. Suppressor T-cells Suppress the function of Cytotoxic and helper T cells. Helper and Suppressor T-cells are called regulatory T-cells.

59. Function of Cellular immunity 1. Rejection of transplanted tissues (kidney) 2. Delayed hypersensitivity reaction (tuberculin) 3. Antitumor immunity 4. Cooperation with B cell in humoral immunity

60. Clinical importance The Acquired Immune Deficiency Syndrome (AIDS) AIDS virus selectively attack Th (CD4), reversing Th:Tc ratio 1:2 AIDS virus selectively attack Th (CD4), reversing Th:Tc ratio 1:2 Normal Th (CD4) : Tc (CD8) ratio 2:1 Normal Th (CD4) : Tc (CD8) ratio 2:1 inhibition of immune response inhibition of immune response prone to bacteria/ viruses infection prone to bacteria/ viruses infection Cancer Cancer

61. Immunization Active immunity: Dead organism. Toxins. Live attenuated organism. Passive immunity: Infusion of antibodies, activated T-cells or both.

64. SUMMARY

66. Thank you