Lecture 4 Blood - PDF

White blood cell leukocytes Tripoli university Department of medical physiology By dr Aisha Alkilani White blood cells (leukocytes) Total count 4000—11000 /3mm Site of formation: granulocytes + monocytes in bone marrow, but lymphocytes formed in lymphatic tissue L.N, spleen...

White blood cell leukocytes Tripoli university Department of medical physiology By dr Aisha Alkilani White blood cells (leukocytes) Total count 4000—11000 /3mm Site of formation: granulocytes + monocytes in bone marrow, but lymphocytes formed in lymphatic tissue L.N, spleen, liver Life span: 1. granulocytes: 5 hrs in the blood 5 days in the tissues 2. Monocytes: 10 hrs in the blood long time in the tissues (months to years) 3. Lymphocytes few hrs in the blood long time in the tissues  Types of leukocytes (wbcs) Types of leukocytes Non Granular Granular leukocytes leukocytes contains granules in no granules in their cytoplasm their cytoplasm Neutrophils Lymphocytes Eiosinophils monocytes basophils ‫طكطك‬ Neutrophils (microphages): they form about 60% of total ‫كط‬ WBCs, its surface membrane contains receptors for IgG Function: potent phagocytes… attack and destroy the invading bacteria and foreign substances by 6 mechanisms: 1. Margination 2. Diapedesis 3. Ameboid movement..,,,,foot like extension ( pseudopodia ) like ameba 4. Chemotaxis by chemical substances e.g. toxins 5.Phagocytosis nutrophil can phagocytose 5—20 bacteria Mechanisms by which neutrophils invading bacteria and foreign substances Eosinophil : 3% of total WBCs its surface membrane contain receptors for IgG, IgM and IgE. Function of eosinophils: 1.Weak phagocytes 2.Defense against parasites by diapedesis, ameboid movement and chemotaxis….to ward the tissue invaded by parasites. NO of eosinophil increase in parasitic infection 3.Slow and modulate allergic reactions by preventing spread of local inflammation through ***Detoxifying the inflammation inducing substances released by mast cells and basophils e.g. histamine ***Phagocytose and destroy Ag-Ab complex Basophils : 1% of total WBCs its surface membrane contain receptor for IgE Share with Mast cells the following functions: 1. Synthesize and liberate the heparin 2. play an important role in allergic reaction Ag-Ab reaction +++mast cell and basophil to release histamine bradykinin serotonin, lysosome enzymes which cause local vascular and tissue reactions which cause the allergic manifestation  Non granular leukocytes 4. Lymphocytes : 30% of total WBCs count 2 types B-LYMPHOCYTES T-LYMPHOCYTES BOTH are responsible for acquired immunity. Can not be identified morphologically.  Origin and differentiation of lymphocytes They originate from bone marrow stem cell Differentiated in two sites before going to lymphoid tissue: B lymphocytes:- Differentiated in Liver and bone marrow circulation Lymphoid tissue. T lymphocytes:- differentiated in thymus gland Circulation lymphoid tissue 5. Monocytes (Macrophage): 6% of total WBCs count Function : 1. Phagocytosis (show the character of neutrophil in phagocytosis BUT??) 2. Help the function of B and T lymphocytes by presenting the antigen to them. 3. Release many chemical substances which increase the inflammatory reactions and immune response to invading organism  Monocytes macrophage Killing invading microorganisms by 1. direct killing 2. stimulate synthesis and release of neutrophils, monocytes and lymphocytes, 3. stimulate release of histamine from mast cells and basophils Differences between the microphages and macrophages Microphages Macrophages Neutrophils Monocytes Engulf small particles Engulf large particles e.g. RBCs Engulf 5—20 bacteria Engulf up to 100 bacteria Less powerful More powerful phagocytosis phagocytosis  Tissue macrophage system (reticuloendothelial system) they are macrophages present in the tissues ( liver, spleen, lymph nodes, lung, skin)… They are either ****Free macrophage ready for phagocytosis in tissue spaces ****fixed macrophage attached to the specific tissues where they are. according to the its sites, there are different macrophages: kuppfer cells in the liver Alveolar macrophage in the lung Histocytes in the skin Osteoclasts in the bone Microglia in the brain Mesengial cells in the kidney  Inflammation Secondary changes occur after infection , trauma, heat, chemical injury…. 1. Local capillaries vasodilatation……. redness 2. Capillary permeability…… oedema 3. Clotting of fluid in tissue spaces ….stop spreading These changes due to inflammatory substances e.g. histamine which released from destroyed cells.  Inflammation Who is response to this inflammation ???? Neutrophil and macrophage response to inflammation as defense lines. First defence line tissue macrophage within one hr Second defence line neutrophil invasion within few hrs Third line monocyte macrophage invasion after 12 hrs Immunity  IMMUNITY Definition: ability of our body to resist organisms or toxins that tend to damage the tissues and organs Types 2 types 1. Non specific (innate) 2. specific (acquired) immunity immunity Does not depend on the Develop specifically nature of invading against the Ag after it substance invades the body 1. Non specific (innate) 2. specific (acquired) immunity immunity Humoral immunity Cellular immunity  Non specific immunity It includes 1. Skin barrier resist invasion 2. Acidity of stomach 3. Phagocytic cells 4. Natural killer cells (non T non B Lymphocytes) 5. Substances in the blood: 1. Interferon 2. Properding system 3. Complement system  INF PROPERDING SYSTEM COMPLEMENT SYSTEM Substances in the blood Definition Glycoprotein Plasma globulins Plasma Proteins C1—C9 Origin and activation released from viral By Immunological 1.Direct pathogen Infected Cells defensive mechanism invasion 2.Ag-Ab reaction 3. Properding system Function 1. Protect non infected 1. Activation the 1.Stimulation cell against viruses complement phagocytosis 2. Protect the body 2. Stimulate 2. Neutralization of from cancer cells phagocytosis Ag 3. Lysis invading organism 4. Release hydrolytic enzymes 5. Increase capillary permeability 6. Anti inflammatory function (Acute phase proteins ‫مصور المعتمد‬CRP)  Definitions Opsonization : it is an immune process which uses opsonins to promote uptake of the pathogen by the macrophage and get eliminated by phagocytes. Antigen: it is a foreign large MW substance, when introduced to the body initiate immune response Hapten : it is a foreign small MW substance which initiate immune response only after binding to the tissue proteins  Definitions Humoral acquired immunity: it is responsibility of B lymphocytes which lead to formation of circulating Abs Cellular acquired immunity: it is responsibility of T lymphocytes which when activated circulate and attack the Ags Clones of lymphocytes: when a group of B and T lymphocytes react against to specific Ag.. called the specific clone Specific acquired immunity 1. Humoral immunity Humoral immunity (antibody mediated immunity) it is immunity mediated by the circulating antibodies The cell responsible is B lymphocytes Mechanism of humoral immunity 1. Activation of B lymphocytes 2. Formation of plasma cell and Abs 3. Formation of memory cell 4. Inhibition of AB production by suppressor cells Antibodies  Antibodies … gamma globulins secreted by plasma cell in lymphoid tissue. Called immunoglobulins (Ig) Each Ab is specific to certain Ag Types…..5 types 1. Immunoglobulin G (IgG) the smallest MW ,highest concentration 75%, cross the placenta, passive immunity, Rh antibodies are IgG 2. Immunoglobulin M (IgM) the largest MW, can not pass placenta, ABO antibodies are IgM 3. Immunoglobulin A (IgA) topical local immune system, called secretary Ig, or cytophilic Ig 4. Immunoglobulin D (IgD) act as Ag receptors on the surface of lymphocytes 5. Immunoglobulin E (IgE) usually attached to the basophil and mast cell surfaces +++their secretions.e.g. histamine  Composition of antibodies **IgG, IgA, IgD and IgE are Y shaped **Y shaped Igs consist of 4 polypeptide chain 2 light chains, and 2 heavy chain connected by disulphide bonds ** the Ag binding site lies between heavy and light chains. **IgM consist of 5 units (pentamer) it has 10 Ag binding sites. Ig m composition  Mechanism of action of immunoglobulins Direct action: Indirect action Ab directly attack the By activation the complement invading agent and system and yhen inactivate the inactivate it invader through: by one of these mechanisms: 1. agglutination 2. Opsonization 1. agglutination (agglutinin) 3. Neutralization 2. Precipitation (precipitins) 4. lysis 3. Neutralization (antitoxin) 4. Lysis (lysins) N.B All Igs can activate the complement except Ig A Thanks for listening