1. Blood Physiology Professor A.M.A Abdel Gader MD, PhD, FRCP (Lond., Edin), FRSH (London) Professor of Physiology, College of Medicine & King Khalid University Hospital King Saud University Riyadh

2. Hematopoiesis

3. Monocyte-macrophage system Reticulo-endothelial System

4. Reticuloendothelial System- RES Blood Monocyte Tissue 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, ly mph nodes and spleen –Reticular cells of lymph nodes spleen & bone marrow.

6. Reticuloendothelial System- RES Cells 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. Lecture # 5 Resistance of the Body to infection Immunity & Allergy 34

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 1.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 1.Acquired immunity 2.innate immunity –Non-specific ingestion of invading organisms –No memory cells –Phagocytic cells Neutrophils macrophages

15. Antigens

16. 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 Response in humoral immunity The immune response of the body when exposed to antigen 1.Primary immune response: –first exposure to antigen –antibodies formed after a latent period one week (time needed for multiplication and maturation of lymphocytes) –e.g. vaccination

37. Immune Response in 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 –S–Stimulate growth of other T-lymphocytes –S–Stimulate B-lymphocytes growth and maturation into plasma cells –A–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 immunity Allergy 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: > 50x10 3 Types of leukaemia –Myeloblast leukaemia  myeloid cells –Lymphoblast leukaemia  lymphocytic cells Acute or chronic Accompanied with anaemia, bleeding

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

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