Harvey's Garden

Lymphocyte

6 min read

Lymphocytosis

Lymphocytosis: > 33%

Etiology

  • Acute viral infections (e.g., rubella, infectious mononucleosis, mumps)
  • Chronic bacterial infections
    • Bordetella pertussis (Whooping cough)
      • Often causes marked lymphocytosis, particularly in children
      • Can elevate lymphocyte counts to 20,000-30,000/μL or higher
    • Mycobacterium tuberculosis
      • Chronic TB infection can produce lymphocytic responses
      • More common in the later stages of infection
    • Brucella species (Brucellosis)
      • Often presents with relative lymphocytosis
    • Treponema pallidum (Syphilis)
      • Secondary and tertiary syphilis can produce lymphocytosis
    • Borrelia burgdorferi (Lyme disease)
      • Can cause lymphocytosis, especially in later stages
    • Mycoplasma pneumoniae
      • Often associated with atypical lymphocytes
  • Neoplasia (e.g., Hodgkin lymphoma, non-Hodgkin lymphoma, CLL)

Tip

The lymphocyte count may be increased or decreased in lymphoma.

T cell

T cell activation

Mnemonic

  • T cell activation: B7 (CD80/86) on the APC binds CD28 on the T-Cell.
    • Mnemonic: 28 ÷ 7 = 4
      • 28 (on the T cell) divided by 7 (B7 on the APC) equals 4 (reminds you this activates CD4+ T Cells).
  • B cell activation: CD40L on the T-Cell binds CD40 on the B-Cell.

  1. APC ingests and processes antigen, then migrates to the draining lymph node.
  2. T-cell activation (signal 1): exogenous antigen is presented on MHC II and recognized by TCR on Th (CD4+) cell. Endogenous or cross-presented antigen is presented on MHC I to Tc (CD8+) cell.
  3. Proliferation and survival (signal 2): costimulatory signal via interaction of B7 protein (CD80/86) on dendritic cell and CD28 on naïve T cell.
    • Antigen presentation without this co-stimulatory signal will lead to T-cell anergy:
      • Important self-tolerance mechanism
      • The cell will not be activated even though it is exposed to its antigen
    • Superantigens (e.g., toxic shock syndrome toxin 1, enterotoxin B) link MHC II antigen-presenting cells and T-cell receptors on T cells and lead to activation of T cells without a costimulatory signal.
  4. Activated Th cell produces cytokines. Tc cell able to recognize and kill virus-infected cell.

T cell differentiation

CellInduced byInhibited bySecretes
Th1IFN-γ, IL-12IL-4, IL-10IFN-γ, IL-2
Th2IL-2, -4IFN-γIL-4, -5, -6, -10, -13
Th17IL-1, -6, TGF-βIFN-γ, IL-4IL-17, -21, and -22
TregTGF-β, IL-2IL-6TGF-β, IL-10, -35

Mnemonic

  • Th1：你（1）干（γ）吗（α）啊（2）
  • Th2：你是（4）我（5）的，我是（10）你的谁（13）

T-cell development

  • Positive Selection (MHC Restriction)
    • Location: Thymic Cortex. t
    • Interaction: Double-positive thymocytes interact with cortical thymic epithelial cells expressing MHC Class I and II.
    • The Test: “Can you recognize self-MHC?”
    • Outcomes:
      • No/Weak/too strong binding: T-cell undergoes apoptosis (Death by neglect).
      • Moderate binding: T-cell receives survival signal.
    • Lineage Commitment:
      • Binds MHC Class I → Retains CD8, downregulates CD4 (CD8+ Cytotoxic T-cell).
      • Binds MHC Class II → Retains CD4, downregulates CD8 (CD4+ Helper T-cell).
    • Result: T-cells are MHC Restricted (capable of interacting with host MHC).
  • Negative Selection (Central Tolerance)
    • Location: Thymic Medulla. t
    • Interaction: Single-positive (CD4+ or CD8+) thymocytes interact with medullary thymic epithelial cells and dendritic cells presenting self-antigens.
    • The Test: “Do you bind self-antigen too strongly?”
    • Key Mechanism: The AIRE gene (Autoimmune Regulator) allows medullary epithelial cells to express peripheral tissue antigens (e.g., insulin, thyroglobulin) to test T-cells for autoreactivity.
    • Outcomes:
      • High affinity binding: T-cell undergoes apoptosis.
      • Low affinity binding: T-cell survives and matures into a naive T-cell.
    • Result: Central Tolerance (elimination of autoreactive T-cells).

T-cell subtypes

Cytotoxic T cells (killer T cells)

  • Surface markers: CD8
  • Function: Important component of cell-mediated immunity; recognize and kill cells infected with intracellular pathogens (especially viruses) and neoplastic cells; interact with foreign antigens presented via MHC I; induce apoptosis or cell lysis of presenting cells
  • Stimulated by: Macrophages
  • Clinical significance: HIV, Hepatitis B, Adult T cell lymphoma

T-helper cells (Th cells)

Th1 cells

Th2 cells

  • Function: Initiate humoral immune response in cooperation with B lymphocytes; fight extracellular pathogens (especially parasites)
  • Stimulate: Eosinophils, Mast cells, Basophils, B cells (leading to IgE production)
  • Clinical significance: Helminth infections, Type 1 hypersensitivity (asthma, allergic rhinitis)

Th17 cells

  • Function: Regulate tissue inflammation (both proinflammatory and antiinflammatory effects); fight extracellular pathogens
  • Stimulate: Neutrophils
  • Clinical significance: Hyper IgE syndrome

Regulatory T cells (Treg, suppressor T cells)

  • Surface markers: CD4, CD25
  • Function: Limit and protect against excessive immune response; promote immune self-tolerance; prevent formation of autoantibodies
  • Stimulate/suppress: CD4+ and CD8+ T effector cells
  • Clinical significance: sIPEX syndrome

B cell

B cell activation and class switching

  1. Th-cell activation as above.
  2. B-cell receptor–mediated endocytosis.
    • B lymphocytes recognize antigens via their B-cell receptors (membrane‑bound immunoglobulins, IgD or IgM) → B cell receptor-mediated endocytosis of the BCR/antigen complex → breakdown of antigen into small fragments by lysosomal proteases → presentation of antigen fragment via MHC class II receptors on B cell surface to Th cells plus costimulation of B cell CD40 receptor by Th cell CD40L → T cell‑dependent activation of B cells (plasma cells) → immunoglobulin production
    • B cell and T cell need to be activated by the same antigen
  3. Exogenous antigen is presented on MHC II and recognized by TCR on Th cell.
  4. CD40 receptor on B cell binds CD40 ligand (CD40L) on Th cell.
  5. Th cells secrete cytokines that determine Ig class switching of B cells.
    • Th1 (IFN-γ), Th2 (IL-4), Tfh (IL-21), Th17 (IL-21): stimulates class switching to IgG.
    • Th2 (IL-4, IL-13): stimulate class switching to IgE.
    • Th2 (IL-5) + Treg (TGF-β): stimulate class switching to IgA.
  6. B cells are activated and produce IgM. They undergo class switching and affinity maturation.

Lymphatic system

Lymph nodes

Function

  • Nonspecific lymph filtration: macrophages within lymph node
  • Storage and circulation of B cells and T cells
  • Immune system activation: Antigen presentation induces differentiation and proliferation of B lymphocytes and activation of T lymphocytes.

Structure

Histology

  • Cortex (B-cell zone): contains lymphoid follicles, which is the site of B lymphocyte storage, differentiation, and proliferation
    • Secondary lymphoid follicle (active): dense mantle zone surrounding a pale germinal center
    • Primary lymphoid follicle (inactive): dense aggregates of naive B lymphocytes
  • Paracortex (T-cell zone)
    • Region between the cortex and medulla
    • Contains T lymphocytes and high endothelial venules, which allows circulating B and T lymphocytes to enter or leave the bloodstream
    • Site of T-cell activation
  • Medulla
    • Medullary cords: tightly packed with plasma cells and lymphocytes
    • Medullary sinus of the lymph node
      • Composed of macrophages, reticular cells
      • Connected to the efferent lymphatic structures

Clinical significance

NK cells

  • Surface markers
    • Fc receptor (CD16): a membrane receptor protein that recognizes and binds to antibodies that have attached to pathogens
      • Mediates a phagocytic and/or cytotoxic response
      • Found on many immune cells, e.g., NK cells, neutrophils, and macrophages
    • CD56: a neural cell adhesion molecule specific to NK cells

Mnemonic

CD16 for NK cells because when 16 year olds get their driver’s licenses they become killers, naturally.

  • Mechanism of Recognition:
    • Activated by the absence of MHC Class I on target cell surfaces (“missing-self” hypothesis). This is a key mechanism for cells evading cytotoxic T-cells.
    • Can also be activated via Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) by binding to IgG-coated cells.

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