Professor | Department of Botany and Microbiology "Virology, Immunology and Molecular diagnosis.

Address: Building.5, level 3,Office No. 077. Women Campus, Center for Scientific and Medical Studies | Phone: 8052984

Handout to be discusse between the six groups of the students in each sections

Course: 
451Micro Immunology

Dr.Nagwa Aref
451Micro
II. Cells and Organs of the Immune System
Hematopoiesis

  • Blood cells (both white and red) are formed from hematopoietic stem cells (HSC) by a process known as hematopoiesis
    • HSCs are first formed in the embryonic yolk sac, then migrate to the fetal liver and spleen, which become the major hematopoietic organs during the third-seventh months of embryogenesis
    • Bone marrow becomes the major location of HSC differentiation after the seventh month of embryogenesis, and continues this role throughout life
  • HSC properties
    • HSC are pluripotent ... they can differentiate into a number of different blood cell types, including lymphocytes, granulocytes, monocytes, mast cells, megakaryocytes, and erythrocytes
    • HSC are self-renewing ... they can divide to replenish themselves in their pluripotent (undifferentiated) state
  • Process of hematopoiesis
    • HSC differentiate into either lymphoid or myeloid progenitor cells under the influence of growth factors and cytokines produced in hematopoietic tissues:
      • Interleukin-3 (IL-3) triggers differentiation of HSC into lymphoid progenitor cells
      • Granulocyte-Monocyte Colony Stimulating Factor (GM-CSF) and IL-3 act in combination to trigger differentiation of HSC into myeloid progenitor cells
    • Progenitor cells subsequently differentiate further to form a number of more mature cell types, again under the influence of more growth and differentiation factors
      • Myeloid differentiation ... is triggered by:
        • GM-CSF, IL-3 and IL-6, which act in combination to trigger differentiation of common myeloid progenitor cells into:
          • basophil progenitor cells, which then develop into:
            • basophils ... under the influence of GM-CSF and IL-4
            • mast cells ... under the influence of I9
        • granulocyte-monocyte progenitor cells, which then develop into:
          • Monocytes ... under the influence of GM-CSF and Monocyte Colony Stimulating Factor (M-CSF) ... and later (under the influence of as-yet unknown factors) differentiate into:
            • macrophages when they enter the tissues of the body
            • dendritic cells (the least well-studied of these cells) may differentiate from monocytes (in the tissues) or they may have their own line of differentiation directly from granulocyte-monocyte progenitor cells ... this has not been settled yet
          • Neutrophils ... under the influence of GM-CSF and Granulocyte Colony Stimulating Factor (G-CSF)
      • GM-CSF, IL-3, IL-5 and IL-6, which act in combination to trigger differentiation of common myeloid progenitor cells into:
        • eosinophil progenitor cells, which then develop into eosinophils ... under the influence of GM-CSF and IL-5
      • GM-CSF, IL-3 and Erythropoietin (EPO), which act in combination to trigger differentiation of myeloid progenitor cells into erythroid progenitor cells, which then lose their nucleus as they differentiate into erythrocytes ... under the influence of EPO
      • GM-CSF, IL-3, IL-11 and Erythropoietin (EPO), which act in combination to trigger differentiation of myeloid progenitor cells into megakaryocytes, which then "disintegrate" to form platelets (important for triggering blood clotting) ... under the influence of GM-CSF, EPO and IL-6
    • Lymphocyte differentiation ... is triggered by:
      • IL-3 and IL-7, which act in combination to trigger differentiation of lymphoid progenitor cells into B progenitor cells that subsequently develop into B cells (B lymphocytes) ... under the influence of a combination of IL-2, IL-4, IL-5 and IL-6
      • Unknown factors, which trigger development of the "default" T progenitor cells that migrate (via the bloodstream) to the thymus where they subsequently develop into thymocytes(T lymphocytes) ... under the influence of a combination of IL-2, IL-4, IL-5 and IL-6 and, finally, into:
        • T helper (Th) cells (Th lymphocytes) ... under the influence of IL-2, IL-4 and IL-7 followed by positive and negative selection (more about this later)
        • T cytotoxic (Tc) cells (Tc lymphocytes) ... under the influence of IL-2, IL-4 and IL-7 followed by positive and negative selection (more about this later)
      • Unknown factors, which result in development of natural killer (NK) cells in various tissues of the body

Cells of the Immune System

  • Myeloid Cells
    • Granulocytes
      • General Charactistics
        • comprise 41-81% of blood leukocytes
        • 20-30 µm in diameter
        • have a multilobed nucleus:
          • with loosely packed strands of intensely basophilic chromatin
          • surrounded by a moderate amount of lightly basophilic cytoplasm containing large numbers of granules
      • Types of Granulocytes
        • Neutrophils
          • comprise 40-75% of blood leukocytes
          • contain small, lightly staining granules
          • phagocytic effectors of antibody-mediated immunity and hypersensitivity
        • Eosinophils
          • comprise 1-5%of blood leukocytes
          • contain orange-to-red staining granules
          • help regulate inflammatory responses
          • active in antibody-mediated cytolysis of immature forms of intestinal parasites
        • Basophils
          • comprise 0-1%of blood leukocytes
          • contain large, blue-black staining histamine-rich cytoplasmic granules and FcR that bind IgE molecules
          • help generate inflammatory responses
          • mediators of immediate (type I) hypersensitivity
        • Mast Cells
          • tissue cells with histamine-rich cytoplasmic granules and FcR that bind IgE molecules (~10X more of each than found in basophils)
          • help generate inflammatory responses
          • tissue mediators of immediate (type I) hypersensitivity
    • Monocytes
      • comprise 3-7% of blood leukocytes
      • 20-50 µm in diameter
      • nucleus is large and indented:
        • contains loosely packed strands of intensely basophilic chromatin
        • surrounded by a large amount of lightly basophilic cytoplasm
      • cytoplasm contains numerous granules and occasional vacuoles
      • engulf and digest foreign matter
      • phagocytic effectors of cell-mediated immunity and hypersensitivity
    • Macrophages
      • derived from monocytes after they migrate into tissues (e.g. histiocytes in connecitve tissue, alveolar macrophages in lung, microglial cells in CNS, mesangial cells in kidney, Kupffer cells in liver, osteoclasts in bone, etc.)
      • nucleus is large and indented:
        • contains loosely packed strands of intensely basophilic chromatin
        • surrounded by a large amount of lightly basophilic cytoplasm
      • cytoplasm contains numerous granules and vacuoles, especially when activated by T lymphocyte cytokines, such as interferon-gamma
      • engulf and digest foreign matter
        • active in antigen processing and presentation
        • phagocytic effectors of cell-mediated immunity and hypersensitivity
    • Dendritic Cells are covered with long membrane extensions (that make them look like dendrites in nervous tissues ... hence the name)
      • Circulating dendritic cells
        • constitute 0.1% of blood leukocytes and are also found in lymph ("veiled" cells)
        • develop into mature tissue dendritic cells (?)
      • Interdigitating dendritic cells
        • found in T cell rich regions of secondary lymphoid tissues
        • process and present antigen to T cells
      • Interstitial dendritic cells
        • found in most organs ... lungs, liver, heart, kidney, digestive tract, etc.
        • process and present antigen to T cells
      • Langerhans cells
        • found in epidermis of skin
        • process and present antigen to T cells
  • Lymphoid Cells
    • Comprise 20-45% of blood leukocytes
    • Responsible for immune responses
    • 10-30 µm in diameter
    • Nucleus is nearly round and contains coarse lumps of intensely basophilic chromatin
    • Cytoplasm is lightly basophilic and variable in amount ... less cytoplasm in "resting" lymphocytes and more in "activity" lymphocytes
    • B Lymphocytes develop in bone marrow
      • differentiate into plasma cells, which synthesize and secrete antibody molecules
      • also capable of antigen processing and presentation
    • T Lymphocytes develop in thymus
      • T helper cells (Th) can synthesize and secrete cytokines and function to regulate immune responses (both antibody and cell-mediated) when appropriately stimulated during immune responses
      • T cytotoxic cells (Tc) are mature precursor cells that, as a result of a cell-mediated immune response, differentiate into cytotoxic T lymphocytes (CTL) which mediate cellular immunity vs. virus-infected cells and tumor cells
    • Natural Killer (NK) Cells develop in several lymphoid tissues ... some in thymus, others in bone marrow
      • not antigen-specific, but can recognize "self" cells
      • active in early phases of cell-mediated immune responses ... synthesize and secrete cytokines that promote these responses