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

Hematopoiesis

Monocyte-macrophage system Reticulo-endothelial System

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

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.

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

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

Lecture # 5 Resistance of the Body to infection Immunity & Allergy 34

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

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

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

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

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

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

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

The bases of Acquired Immunity are Lymphocytes

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)

Hemopoiesis (17.9)

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

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.

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

Lymphocytes T lymphocytes can attack foreign cells directly (17.6)

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

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.

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.

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.

Antibodies (Immunoglobulins-Ig)

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

Antibody

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

Humoral immunity (Acquired immunity) Action of Antibody –Agglutination –Precipitation –Neutralization –Lysis

Antibody –Antigen complex

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

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

Immune response

Cellular Immunity

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)

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

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

Cytotoxic T cells

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

Humoral immunity Allergy Excess Antibody production: hypersensitivity (allergy) Allergins: dust, pollen, drugs.

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

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

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

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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