Hematopoiesis

1. Blood PhysiologyProfessor A.M.A Abdel GaderMD, PhD, FRCP (Lond., Edin), FRSH (London)Professor of Physiology, College of Medicine & King Khalid University HospitalKing Saud UniversityRiyadh

2. Hematopoiesis

3. Monocyte-macrophage system Reticulo-endothelial System

4. Reticuloendothelial System-RES Blood MonocyteTissue macrophage Attached (fixed)Mobile Function is phagocytosis of: • Bacteria • Viruses • Dead tissues • Foriegn particles Immune function

5. Reticuloendothelial System-RES • RES is widespread in the body Cells of the RES: • Monocytes (blood macrophages) • Mobile and fixed tissue Macrophages • Specialiazed endothelial cells in bone marrow, lymph nodes and spleen • Reticular cells of lymph nodes spleen & bone marrow.

6. Reticuloendothelial System-RESCells of the RES - Distribution: • Tissue Macrophages in skin SC tissues • Tisssue Macrophages of lymph nodes • Tissue macrophages in lungs • Macrphages (kupffer cells) in the liver • Macrphages in the spleen and bone marrow

7. Reticuloendothelial System-RES Blood Monocyte Tissue macrophage Attached (fixed) Mobile Function is phagocytosis of: • Bacteria • Viruses • Dead tissues • Foriegn particles Immune function

9. 34 Lecture # 5Resistance of the Body to infectionImmunity & Allergy

10. Lecture # 5 • Immunity-Definition • Antigens • Immune Cells (b- & T- Lymphocytes) • Antibodies and B-Lymphocytes • Cellular Immunity • Clinical Application

11. Immunity? The ability of the body to resist damage (caused by micro-organisms, toxins etc) • Immune system act to maintain health (i.e. homoestatic) • Immunological defenses act against: • foreign organisms e.g. bacteria, viruses • transplanted tissue or organs

12. Immunity -- Types • Acquired immunity: the result of attack by bacteria, viruses etc • e.g.Vaccination • Long lasting (Memory) 2. Innate immunity Non-specific: Examples: • Ingestion of invading organisms (phagocytosis) • Stomach acidity • Skin barrier • Lysozyme • Natural killer lymphocytes

13. Immunity -- Types Acquired immunity: • Specific against individual bacteria, virus, toxin, foreign tissues • Basic types of acquired immunity: Humoral immunity (B-cell immunity) B-LYMPHOCYTES Antibodies Cell-mediated immunity (T-cell immunity) Activated T-LYMPHOCYTES Initiated by antigens

14. Immunity -- Types • Acquired immunity • innate immunity • Non-specific ingestion of invading organisms • No memory cells • Phagocytic cells • Neutrophils • macrophages

15. Antigens

16. Antigens Antigens: • Specific chemical compounds (proteins, polysaccharides) that initiate acquired immunity • High mol. weight (>8000) • Antigenicity due to presence of characteristic epitopes (molecular groups) on its surface

17. Antigens • If mol. Wt <8000 (Haptens), such molecules rarely act as antigens. • Haptens can act as antigens if they combine with a protein and the hapten-protein complex can initiate an immune response • Antigens Recognized either directly by lymphocyte or after being processed by macrophages

18. The bases of Acquired Immunity are Lymphocytes

19. Immune cells Two types: • B-Lymphocytes (Thymus independent, B-lymphocytes) Produce antibodies (Humoral Immunity) 2. T- lymphocytes (Thymus dependent, T-lymphocytes) Cellular mechanisms (Cellular Immunity)

20. Hemopoiesis (17.9)

21. Lymphocytes– cont. Lymphopoiesis Stem cell (thymus, lymphoid tissue & bone marrow) lymphoblast intermediate pyronophilic blast cells lymphocytes

22. B- Lymphocytes(thymus-independents) Found in: • Bone marrow, germinal layer of lymph node, red pulp of spleen • Life span: 2-7 days • Stimulation by antigen  large plasma cell (producers of antibody) • Function: Humoral immunity.

23. Lymphocytes • B lymphocytes transform into plasma cells and secrete antibodies (17.6b)

24. Lymphocytes • T lymphocytes can attack foreign cells directly (17.6)

26. T-Lymphocytes(thymus dependent) Formed in: • bone marrow or lymphoid tissues • migrate to thymus Life span: 100-130 days. Circulate between blood, tissues, lymph.

27. T-Lymphocytes(thymus dependent) Types of T-lymphocytes • T-helper • T-cytotoxic • Natural killer Functions • Cellular immunity • graft rejection • delayed hypersensitivity. • Help in antibody secretion.

28. Helper T Cells • Identified by CD4 coreceptor. • Indirectly participate by regulating the response of both T killer and B cells. • B cells must be activated by helper T cells before they produce antibodies.

29. T Cell Response to a Virus (continued) • Foreign antigens attach to immunoglobulins on B cells. • B cells can present the antigen with class-2 MHC molecules to helper T cells. • Stimulate B cell production, conversion to plasma cells, and antibody production.

30. Antibodies (Immunoglobulins-Ig)

31. Antibodies -(Immunoglobulins-Ig) • Antibody is a gamma globulin produced by plasma cells (B-lymphocytes) • Subdivided into 5 classes: • IgG, • IgM • IgD • IgE • IgA. • Bind specifically to the antigen against which they have been produced

32. Antibody

33. Humoral immunity(Acquired immunity) B-lymphocytes surface receptors interact with antigen B-lymphocytes proliferate to plasma cells Plasma cells secrete specific antibody to destroy the antigen • Some of the stimulated cells do not proliferate stay dormant as memory cells

34. Humoral immunity(Acquired immunity) • Action of Antibody • Agglutination • Precipitation • Neutralization • Lysis

35. Antibody –Antigen complex

36. Immune Responsein humoral immunity The immune response of the body when exposed to antigen • Primary immune response: • first exposure to antigen • antibodies formed after a latent periodone week (time needed for multiplication and maturation of lymphocytes) • e.g. vaccination

37. Immune Responsein humoral immunity 2.Secondary immune response: • second exposure to the same antigen. • immediate production of high titer antibodies • Memory lymphocytes (from first exposure) act immediately when exposed to the same antigen

38. Immune response

39. Cellular Immunity

40. Cellular immunity • T-cell react with antigen by its receptors and proliferate to give either: • Cytotoxic (killer) T cells CD8 (Tc) • Helper T cell CD4 (Th) • Suppressor T cells (Ts)

41. T helper Cell • Most numerous cells • Major regulator of immune system • Secret lymphokinese acts on other cells of immune cells • Stimulate growth of other T-lymphocytes • Stimulate B-lymphocytes growth and maturation into plasma cells • Activation of macrophage system

42. Cytotoxic T cells • T cell directly attack organism, foreign infected cells and destroyed it • Bind to antigen by surface receptors making holes in it membrane • Function: • Rejection of transplanted tissues (kidney) • Antitumor immunity • Cooperation with B cell in humoral immunity

43. Cytotoxic T cells

44. Clinical application • The Acquired Immune Deficiency Syndrome (AIDS) • Normal Th : Tc ratio = 2:1 • AIDS virus selectively attack Th (CD4), ratio =1:2 • Generalize inhibition of immune response • Patient prone to bacteria/ viruses infection & Cancer

45. Humoral immunityAllergy • Excess Antibody production: hypersensitivity (allergy) • Allergins: dust, pollen, drugs.

46. Leucocytosis(Increased WBC Count) Causes: • Physiological • Diurnal: morning  evening • After physical exercise • Stress or Adrenaline injection • Disease (pathological) • Bacterial infections (tonsillitis, appendicitis • Worms infestations

47. Leucopenia(Decreased WBC Count) Causes: • Malnutrition • Typhoid fever • Depressed bone marrow • Deficiency of Vit B12 or folic acid

48. Leukaemia(Cancer of white cells) Causes: • chromosomal abnormality • chemicals, radiation, and viruses WBC:> 50x103 Types of leukaemia • Myeloblast leukaemia  myeloid cells • Lymphoblast leukaemia  lymphocytic cells • Acute or chronic • Accompanied with anaemia, bleeding

49. Functions of Leucocytes- WBC • Defence of the body against infections and foreign invadors Neutrophils & monocytes (Blood macrophages)-Phgaocytosist/ + Immunity Macrophage (RES) system … Phagocytosis + Immunity Lymphcytes ….. IMMUNITY

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