Lab

Lymphocyte Count

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Lymphocyte Count, Lymphocyte, B-Lymphocyte, B-Cell, T-Lymphocyte, T-Cell, Natural Killer Cell, NK cell, Lymphocytosis

  • Characteristics
  1. Forms in Bone Marrow from Lymphoblasts (which are in turn derived from stem cells)
  2. Function: Primary source of viral defense and Antibody
    1. Adaptive Immunity (learned response)
      1. B-Lymphocytes
        1. Humoral Immunity with Antibody against extracellular antigens
      2. T-Lymphocytes
        1. Cellular Immunity via T-Helper/CD4+ Cells and T-Cytotoxic/CD8+ Cells
    2. Innate Immunity
      1. Natural Killer Cells (NK cells)
        1. Lymphocytes providing immediate protection against Intracellular Bacteria, viruses, cancer cells
  3. Morphology on Blood Smear
    1. Mononuclear Leukocytes (same class as Monocytes)
    2. Small cells with minimal cytoplasm
  • Types
  • B-Lymphocytes (B Cells)
  1. B-Cells are responsible for Humoral Immunity
    1. B-Cells are named for where they were first found (Bursa of Fabricus in birds)
    2. Responsible for antigen-specific Antibody (plasma cells) and secondary future responses (memory cells)
  2. Derivation
    1. Fetal Liver
    2. Bone Marrow Pluripotent Stem Cells
  3. Peripheral Migration to Secondary Lymphoid Tissue
    1. Spleen
    2. Lymph Nodes
    3. Peyer's Patches (Small Bowel)
  4. Activation
    1. Recognition
      1. Antigen binds B-Lymphocyte Surface Receptor (BCR)
      2. BCR binding activates B-Lymphocyte
        1. T-Cell Independent Antigen (e.g. inert antigens) alone activate B-Cells
        2. T-Cell Dependent Antigen (e.g. microbes) require added stmulus (e.g. T Cells)
    2. B-Cell Proliferation
      1. Activated Lymphocytes proliferate
    3. B-Cell Differentiation
      1. Plasma Cells (Antibody producing cells)
        1. Survive for days to weeks producing antibodies, and without replicating
      2. Memory Cells
        1. Remain in B-Lymphocyte pool ready to respond to the same antigen in future
        2. Future antigen response is known as secondary immune response
  • Types
  • T-Lymphocytes (T-Cells)
  1. T-Cells are responsible Cell-Mediated Immunity
    1. T-Cells target Intracellular Pathogens (e.g. viruses and Intracellular Bacteria) and cancer cells
  2. T-Cells
    1. Derived in Bone Marrow
    2. Migrate to Thymus
      1. Maturation and Differentiation into two cell lines with different T-Cell Receptors (CD4 and CD8)
    3. Release into peripheral circulation
  3. T-Cell Surface Receptors
    1. T-Cell Receptors (TCR)
      1. Bind the antigen on the antigen presenting cell
      2. TCR Types
        1. TCR-alpha-beta (TCRab+)
        2. TCR gamma-delta (TCRgd+)
    2. T-Cell Co-Receptors
      1. CD4 binds peptide/antigen-MHC class 2 complex on surface of antigen presenting cells
      2. CD8 binds peptide/antigen-MHC class 1 complex on surface of antigen presenting cells
  4. T-Cell Types
    1. Effector Cells
      1. T-Helper Cells (CD4+ Cells)
        1. Releases interferon
          1. Stimulates Phagocytosis by Macrophages
          2. Activates Natural Killer Cells
          3. Suppresses viral replication
        2. Releases interleuken 2
          1. Promotes T-Cell proliferation (esp. memory cells)
          2. Promotes B-Cell proliferation (memory cells and plasma cells)
      2. T-Cytotoxic Cells (CD8+ Cells)
        1. Target and destroy tumor cells and virus-infected cells
    2. Other Cells
      1. Memory Cells
      2. Apoptosis of some cells not otherwise differentiated
  5. Naive T-Cell Activation
    1. T-Cell Receptor (TCR) binds to MHC-Antigen complex on Antigen Presenting Cells
    2. T-Cell Surface CD28 binds to B7 Ligand on antigen presenting cell
    3. T-Cell Surface LFA-1 (Lymphocyte Function Associated Antigen) binds ICAM1 on antigen presenting cells
    4. Interleukin-2 (IL2) produced by naive T Cells
      1. Stimulate T Cell proliferation
  • Types
  • Natural Killer Cells (NK cells)
  1. Lymphocytes providing protection against Intracellular Bacteria and viruses, as well as cancer cells
  2. Part of Innate Immunity in which response is not based on prior exposure to pathogen
    1. Contrast with B-Cells and T-Cells which have a learned pathogen response (Adaptive Immunity)
  3. NK cells bind Major Histocompatibility Complex 1 (MHC-1)
    1. MHC-1 is present on normal cells and it inactivates NK cells
    2. MHC-1 is NOT expressed by infected cells
      1. NK activating receptor Ligand is expressed
      2. NK cells bind infected cells and destroy them
  4. NK cell mechanisms of infected cell destruction
    1. Cytoplasmic granules
      1. Perforin
        1. Generates pores on cells targeted for destruction
      2. Granzyme
        1. Induces programmed cell death (apoptosis) on entry into Target Cells
    2. Cytokines
      1. Interferon-Gamma (IFN-g)
        1. Activates Macrophages for Phagocytosis
  • Labs
  • Normal
  1. Percentage Lymphocytes: 15-40% of White Blood Cells
  2. Total Lymphocytes: 800-2600/mm3
  3. Total T Lymphocytes: 800-2200/mm3
    1. T helper Cells: >400/mm3
    2. T suppressor Cells: 250-750/mm3
    3. Helper Cell to Suppressor Cell ratio: >0.9
    4. CD2 Percentage of Lymphocytes: 65-85%
    5. CD4 Percentage of Lymphocytes: 45-75%
  • Causes
  • Increased (Lymphocytosis)
  1. Increased Absolute Lymphocyte Count (>4500/mm3)
    1. Non-activated Lymphocytes
      1. Influenza
      2. Pertussis
      3. Tuberculosis
      4. Mumps
      5. Varicella
      6. Herpes Simplex Virus
      7. Rubeola
      8. Brucellosis
      9. Fungal infection
      10. Rickettsial infection
      11. Chronic Lymphocytic Leukemia
      12. Acute Lymphoblastic Leukemia
    2. Activated Lymphocytes (Atypical lymphocytes)
      1. Cytomegalovirus Infection
      2. Infectious Mononucleosis
      3. Infectious Viral Hepatitis
      4. Toxoplasmosis
      5. Syphilis
      6. Post-transfusion
      7. Beta Streptococcus
      8. Medication
        1. Mephenytoin
        2. Dilantin
        3. Para-aminosalicylic acid
  2. Increased Relative Lymphocyte Count (>40% of total)
    1. Normal finding in children under age 2 years
    2. Acute stage of viral infection
    3. Connective Tissue Disease
    4. Hyperthyroidism
    5. Addison's Disease
    6. Splenomegaly
  • Causes
  • Decreased
  1. AIDS
  2. Bone Marrow suppression
  3. Aplastic Anemia
  4. Neoplasms
  5. Steroids
  6. Adrenocortical hyperfunction
  7. Neurologic Disorders
    1. Multiple Sclerosis
    2. Myasthenia Gravis
    3. Gullain Barre Syndrome
  • Evaluation
  • Lymphocytosis (Lymphocytes >4500/mm3)
  1. See Leukocytosis
  2. History and potential causes
    1. Contagious contacts
    2. Immunization history
  3. Diagnostics (consider)
    1. Viral specific studies (e.g. Monospot)
    2. Chest XRay