VII. Overview of the lymphoid immune system

• A. Lymphocytes evolve from pluripotent stem cells located in the bone marrow, and differentiate into two major functional cell types:
  • 1. B lymphocytes, comprising the humoral immune system, whose ultimate function is the production of antibodies
  • 2. T lymphocytes, comprising the cellular immune system, whose functions include
    • a. Direct killing of foreign or intracellularly infected cells, cytotoxic T cells
    • b. Fine control of the immune response through the secretion of cytokines, helper and suppressor T cells.
• B. The anatomical organization of the lymphoid immune system can also be divided into two major functional groups:
  • 1. The primary immune organs, which are the sites of initial maturation from immature precursors into immune competent cells:
    • a. B cells- bone marrow
    • b. T cells- thymus
  • 2. The secondary immune organs, which are the sites of antigen driven replication and differentiation into committed effector cells
    • a. Lymph nodes
    • b. Spleen
    • c. Mucosal Associated Lymphoid System (MALT)-lymphoid cells lining the respiratory and gastrointestinal tracts
    • d. Everywhere else
• C. The lymph nodes, in their totality, are the largest of the secondary immune organs, and the site of the majority of lymphoid pathology.

VIII. Lymph node anatomy

To recognize lymph node pathology, one has to be familiar with normal lymph node anatomy and cytology

Figure 1: Picture of lymph node

• A. The lymph node has 7 major subdivisions.
  • 1. The lymph node capsule, which surrounds the lymph node
  • 2. The subcapsular sinus- the initial entryway of lymphatic fluid into the node via afferent lymphatics
  • 3. The lymph node cortex- beneath the subcortical sinus-the location of primary and secondary lymphoid follicles
    • a. In the absence of immune stimulation, the cortical lymphoid follicles are primary follices, composed of small B lymphocytes which may be virgin B lymphocytes or recirculating memory B cells. There is also a fine meshwork or dendritic reticulin cell cytoplasm, which is invisible without special immunolabelling techniques
    • b. With antigenic stimulation, antigen recognizing B cells are stimulated to replication and differentiation. This converts the primary follicle into a secondary follicle or germinal center, surrounded by a mantle zone of transient small lymphocytes, and a central area containing replicating "follicular center cells" and their differentiating progeny- see below.
  • 4. The paracortex- the region surrounding and beneath the germinal centers
  • 5. The medulla- deep to the cortex/paracortex, and composed of medullary cords and medullary sinuses
  • 6. Medullary vessels- artery and vein
  • 7. Afferent and efferent lymphatic vessels
• B. After initial maturation in the primary immune organs, "virgin" B and T lymphocytes are released into the peripheralblood and home to specific sites within the lymph node (and theother secondary organs), controlled by incompletely understood homing receptors. Hence these regions are enriched for one type of lymphocyte, T or B. The separation of B and T lymphocytes is not absolute however, and both cell types are present throughout the lymph node, necessary for coordinated lymphoid immune response.
• C. The sites of B cell homing include:
  • 1. The primary and secondary follicles of the lymph node cortex-the sites of antigen presentation to B cells, and subsequent proliferation and differentiation in response to same
  • 2. The medullary cords, where plasma cells aggregate, and release their immunoglobulins into the efferent lymph
• D. The site of T cell homing is the paracortex.
• E. Normal lymphocytes recirculate, passing from blood into and through the lymph nodes, and then into efferent lymphatics, surveilling for the presence of the antigen for which they have a unique and specific receptor on their surface. If this antigen is not present, the lymphocytes leave the node.
• F. Virgin lymphocytes have a finite lifespan, numbered in weeks, unless they come in contact with antigen.
  
  

IX. Cytology of the lymph node

• A. The lymph node is thus a dynamic organ, composed of transient B and T lymphocytes, antigen processing and presenting cells, replicating B and T lymphocytes (in response to antigen), persistent and transient final effector cells. Some of these functional subgroups are cytologically unique, and others are cytologically indistinguishable. The ultimate microscopic impression, with practice, is one of cytologic heterogeneity, and histologic organization.
• B. Cell types:
  • 1. Small lymphocytes
    • a. Small round dark blue dots. Round nucleus, clumped chromatin, small or absent nucleolus.
    • b. The dullest looking cells hiding the greatest level of functional heterogeneity. Can be T or B cell, virgin (unexposed to antigen) or differentiated effector/memory cell. Most likely lineage guessed by location within the node, but lineage and state of differentiation must be confirmed by immunologic/molecular techniques
    • c. Locations:
      • (1) B cells- primary follicles, mantle zone of secondary follicles, medullary cords
      • (2) T cells- paracortex, minor population within germinal center.
    • d. Kinetically, clumped chromatin tells us that the cell is nonproliferating- not activated to enter the cell cycle and replicate
      
      
      
      
      
      
  • Figure 2: Follicular center cell types
  • 2. Follicular (germinal) center cells- replicating and post-replicating B cells.
    • a. Noncleaved cells, large and small
      • (1) Replicating populations within the germinal center-expanding the number of cellsreactive with entrapped antigen.
        • (a) Have round nuclei like small lymphocytes, but larger, with open or vesicular chromatin pattern, and recognizable nucleoli. Nucleus clear because genetic material unwound for replication. Size, large or small based on comparison with nucleus of macrophage.
    • b. Cleaved cells, small (and large)- post mitotic memory cell or plasma cell precursors
      • (1) Clumped chromatin like small lymphocytes, but irregular folded and cleaved nuclear profiles.
      • (2) Nonproliferating population
  • 3. Immunoblasts- Proliferating large cells found outside the germinal centers. May be of B or T cell type. Again have characteristics of replicating lymphocytes- vesicular chromatin, nucleoli
  • 4. Accessory cells
    • a. Antigen processing cells-process and present antigen to B and T lymphocytes- invisible innormal lymph node
      • (1) T cell paracortex- interdigitating reticulin cells
      • (2) B cell germinal centers- dendritic reticulin cells
    • b. Macrophages (histiocytes)-
      • (1) Tingible body macrophages of germinal centers
      • (2) Main cells of medullary sinuses- Abundant pale cytoplasm, oval nucleus, single small nucleolus
        

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