Leukocytes & Immune Regulation PDF

Leukocytes & Immune Regulation Content Leukopoiesis Characteristics of Leukocytes Differential Leukocyte Count Alterations in White Cell Count Immune Regulation – Types of immunity & their characteristics – Immunoglobulins Primary and Secondary Immune Response Vaccination Leukocytes (WBCs) Least abu...

Leukocytes & Immune Regulation Content Leukopoiesis Characteristics of Leukocytes Differential Leukocyte Count Alterations in White Cell Count Immune Regulation – Types of immunity & their characteristics – Immunoglobulins Primary and Secondary Immune Response Vaccination Leukocytes (WBCs) Least abundant formed element – 5,000 to 10,000 WBCs/L Protect against infectious microorganisms and other pathogens Conspicuous nucleus Spend only a few hours in the blood stream before migrating to connective tissue Retain their organelles for protein synthesis Granules – all WBCs have lysosomes called nonspecific (azurophilic) granules – inconspicuous so cytoplasm looks clear – granulocytes have specific granules that contain enzymes and other chemicals employed in defense against pathogens Have surface antigens called human leucocyte associated antigen (HLA) unique for each person except identical twins Leucopoiesis lasts between 10-14 days in humans An equal number of cells in the circulating and marginating pools Physiologic leucopoiesis can occur after exercise and adrenaline injection Aplastic anemia – Decreased formation of all mature cell lines (pancytopenia) Could be due to drugs, high radiation, abnormal immune response, idiopathic Individual is susceptible to infection, severe bleeding and anemia Leukemia – Increased number of abnormal cells Can be acute (immature) or chronic (mature) STEM CELLS Pluripotent Stem cells: – Has a diameter of 18 – 23 μ – Give rise to both myeloid and lymphoid series of cells – Capable of extensive self-renewal Myeloid Stem cells - Generate myeloid cells: – Granulocytes: PMNs, eosinophils & basophils. – Thrombocytes – Monocytes Lymphoid stem cells - Give rise only to: – Lymphocytes: T type mainly Colony-Stimulating Factors GM-CSF Has ability to stimulate colonies of neutrophils and macrophagess Acts on many cell types including early multipotential stem cells, megakaryocyte, eosinophil, erythroid and mature neutrophils and macrophages Stimulates cytotoxic and phagocyte activity against bacteria and parasites May also increase the platelet count and possibly the reticulocyte level Hematopoietic Growth Factors GM-CSF: Produced by fibroblasts, stromal cells, T-lymphocytes and endothelial cells Stimulate progenitors for granulocytes, monocytes and erythrocytes G-CSF: LMW glycoprotein Stimulates proliferation and maturation of granulocyte precursors Produced by stromal cells, monocytes, macrophages, and endothelial cells Hematopoietic Growth Factors M-CSF Secreted by stromal cells, macrophages and fibroblasts Heavily glycosylated glycoprotein Potent stimulator of macrophage function and activation Increases the expression of MHC II antigen on macrophages CHARACTERISTICS OF WHITE BLOOD CELLS Chemotaxis (membrane receptors) Phagocytosis (contractile system) Lysis (enzyme granules) DIFFERENTIAL LEUCOCYTE COUNT Neutrophils Caucasians 62% Africans 36% Eosinophils 2.3% 14.5% Basophils 0.4% 0.3% Monocytes 5.3% 4.2% Lymphocytes 30% 45% Leukocyte Life Cycle Leukopoiesis – production of white blood cells – Pluripotent stem cells – (PPSCs) myeloblasts – form neutrophils, eosinophils, basophils monoblasts - form monocytes lymphoblasts - form lymphocytes Red bone marrow stores and releases granulocytes and monocytes Circulating WBCs do not stay in bloodstream – granulocytes leave in 8 hours and live 5 days longer – monocytes leave in 20 hours, transform into macrophages and live for several years – lymphocytes provide long-term immunity (decades) being continuously recycled from blood to tissue fluid to lymph and back to the blood NEUTROPHIL Body’s first line of defense in blood 3 – 5 lobes Ability for chemotaxis and phagocytosis Most frequently occurring white blood cell in the body EOSINOPHIL Nucleus is bi-lobed Coarse granules containing lysosomal enzymes and major basic protein Major basic protein damage helminthic parasites at the larval stage Increase in parasitic infestations and allergic conditions BASOPHIL Nucleus is “S” shaped Rarely seen in normal blood smear Granules contain histamine and heparin Membrane receptors for IgE Move into the tissues to form mast cells LYMPHOCYTE Round nucleus with no visible nucleoli Get larger with a visible nucleoli when metabolically active T and B lymphocytes are morphologically identical Lymphocytes of a specific type are called a “clone” LYMPHOCYTE Metabolically active lymphocyte MONOCYTE Kidney-shaped nucleus Enter the tissues where they form macrophages Powerful phagocytic function May assume specific functions e.g. skin, liver, gut etc. Immune Regulation Complement T cells 70-80% (many years) B cells 20-30% (few months) Characteristics of the Immune System Specificity Memory Discrimination IMMUNITY The capability to resist almost all type of organisms or toxins that tend to damage tissues or organs Immune responses may be either: Innate or non-specific Acquired or adaptive or specific Types of Immunity Innate Immunity Skin Sweat Acid secretions of stomach and digestive enzymes Saliva Mucus Tears Acquired Immunity Caused by immune system that form antibodies and/ or activated lymphocytes that attack and destroy the specific invading organism or toxin Passive immunity - produced by already made antibodies or activated T cells from horse or human serum Active immunity - a person produces an immune reaction in response to the entry of antigens into the body Active Immunity Humoral Immunity B lymphocytes produce gamma globulins called immnoglobulins or antibodies Cell mediated Immunity T lymphocytes become activated Both forms of active immunity are initiated by ANTIGENS – proteins or polysaccharides Different Immunoglobulins Functions of Antibodies Mechanisms of Antibody Action Mechanism of Action By direct attack on invader Precipitation Lysis Agglutination Neutralization By complement system (Lysis) Mechanism of Antibody Action Neutralization: Is the simplest defensive mechanism, occurs when antibodies block specific sites on viruses or bacterial exotoxins (toxic chemicals secreted by bacteria). As a result, the virus or exotoxin cannot bind to receptors on tissue cells. Phagocytes eventually destroy the antigen-antibody complexes. Agglutination: Because antibodies have more than one antigen-binding site, they can bind to the same determinant on more than one antigen at a time. Consequently, antigen-antibody complexes can be cross-linked into large lattices. When cell-bound antigens are cross-linked, the process causes clumping, or agglutination, of the foreign cells. IgM, with 10 antigen-binding sites, is an especially potent agglutinating agent. Mechanism of Antibody Action Precipitation: Soluble molecules (instead of cells) are cross-linked into large complexes that settle out of solution. Like agglutinated bacteria, precipitated antigen molecules are much easier for phagocytes to capture and engulf than are freely moving antigens. Complement Fixation and Activation: This is the chief antibody defense used against cellular antigens, such as bacteria or mismatched red blood cells. When several antibodies bind close together on the same cell, the complement binding sites on their stem regions align. This triggers complement fixation into the antigenic cell’s surface, followed by cell lysis. Additionally, molecules released during complement activation tremendously amplify the inflammatory response and promote phagocytosis via opsonization. This sets into motion a positive feedback cycle that enlists more and more defensive elements. Primary and Secondary Immune Response Primary and Secondary Immune Response Vaccination A preparation containing antigenic material Whole live microorganism Dead microorganism Attenuated (harmless) microorganism Toxoid (harmless form of toxin) Primary and Secondary Response Allergy and Hypersensitivity An inflammatory immune response to a non-pathogenic antigen – allergen Delayed hypersensitivity reaction – mediated by activated T cells e.g. Ivy toxin Immediate hypersensitivity reaction - mediated by Antibodies Anaphylaxis Urticaria Hay fever Asthma