Lecture #2

Cells and Tissues of the Immune System

  • Different Types of Blood Cells:

    • Red Blood Cells

    • Eosinophils

    • Monocytes

    • Neutrophils

    • Basophils

  • Learning Objectives

  • List types of white blood cells, their approximate percentages, and half-lives.

  • Explain the role of endothelial cells in immune responses.

  • Know where different types of immune cells originate and mature.

  • List primary and secondary lymphoid tissues.

  • Describe the distribution of lymphocytes in the body.

  • Explain overall lymphatic circulation.

Blood Cells Terminology

  • Leukocyte: Any white blood cell (WBC)

  • Lymphocyte: A type of WBC (includes T cell, B cell, and NK cell)

  • Granulocyte: Also known as polymorphonuclear cells, includes neutrophils, eosinophils, basophils

  • Mononuclear cells: Includes lymphocytes or monocytes

Blood Cell Percentages and Half-Lives

  • Capillary lymphocyte:

    • < 0.5%

    • Half-Life: 100 days

  • Eosinophil:

    • 1 - 3% of WBCs in circulation

    • Half-Life: 30 minutes

  • Monocyte:

    • 3 - 7% in circulation

    • Half-Life: 1 - 2 days

  • Neutrophil:

    • 55 - 90% of WBCs in circulation

    • Half-Life: 8 to 10 hours

  • Basophil:

    • 0.5% of WBCs in circulation

    • Half-Life: 120 days

  • Platelets: Important in blood clotting

  • Red Blood Cells (RBCs).

Specific White Blood Cells

Basophil

  • Accounts for 0.5% of WBCs in circulation.

  • Contains granules that stain basophilic with contents such as histamine and serotonin.

  • Plays an important role in allergies and parasitic infections, usually after eosinophils.

  • May differentiate into tissue mast cells.

Eosinophil

  • Comprises 1 - 3% of WBCs in circulation with a half-life of 30 minutes.

  • Contains granules that stain eosinophilic filled with major basic protein and eosinophilic cationic protein, which are potent against parasites.

  • Eosinophils circulate for about 30 minutes in the bloodstream, migrate to tissues (primarily under epithelial surfaces) where they can survive for a couple of weeks.

  • Important for controlling extracellular parasites.

  • Eosinophilia may occur in some parasitic infections and allergic reactions.

Monocyte

  • Comprises 3 - 7% in circulation, circulates for 1 - 2 days before migrating to tissues to differentiate into macrophages.

  • Macrophages are crucial for immune responses, performing functions such as:

    • Phagocytosis and killing of bacteria

    • Presentation of antigen on MHC II

    • Secretion of cytokines, playing a major role in inflammation and immune response.

  • Monocytes/macrophages appear at infection sites after neutrophils, indicating chronic infection when accumulated.

Neutrophil

  • Comprises 55 - 90% of WBCs in circulation, with a very short lifespan; survives about 1-2 days.

  • Half-life in blood is about 8-10 hours; neutrophils are replaced 2.5 times a day.

  • Functions as first responders in bacterial infections, arriving in substantial numbers (within 4 hours) at infection sites.

  • They exit the bloodstream and accumulate where they ingest and kill pathogens.

  • Bone marrow increases neutrophil production in response to infections, leading to neutrophilia (elevated neutrophil counts).

  • Failure to produce enough neutrophils results in neutropenia, often due to viral infections.

Lymphocyte

  • Comprises between 20 - 35% in most animals, which includes B cells, T cells, and NK cells.

  • Typically circulate for about 4 months between blood and lymphoid tissues, uniquely capable of reentering blood after tissue migration.

  • Naïve B and T cells cannot be distinguished morphologically; both are vital for adaptive immunity.

  • They circulate to find specific antigens and die if they do not encounter them, but if they do recognize an antigen, they get activated and differentiate into memory cells.

Endothelial Cells

  • Endothelial cells line blood and lymph vessels, crucial for regulating leukocyte traffic.

  • They have adhesion molecules called addressins that help leukocytes identify their location in the body.

  • Addressins are upregulated during infections, facilitating the binding of neutrophils to endothelial cells and their exit to the infection site.

Origin of Immune Cells

  • All immune cells originate from bone marrow, categorized into three lineages:

    • Erythroid: Produces RBCs and platelets

    • Myeloid: Produces monocytes, neutrophils, eosinophils, basophils, some dendritic cells, and mast cells

    • Lymphoid: Produces B cells, T cells, NK cells, and some dendritic cells

Maturation of Immune Cells

Myeloid Cells

  • Granulocytes are released in a mature state into the circulation.

  • Dendritic cells migrate to tissues to mature, functioning as sentinel and antigen-presenting cells, vital for initiating adaptive immunity.

  • Mast cell precursors leave the bone marrow to mature in tissues, surviving weeks to months; important in combating parasitic infections and allergies.

Lymphoid Cells: T Lymphocytes

  • T lymphocytes are released as immature pre-T cells from the bone marrow, maturing in the thymus, where they undergo DNA rearrangement to generate T-cell receptors.

  • If these receptors recognize self-antigens, the T cells are eliminated; if they recognize MHC molecules but not antigens, they mature and move to secondary lymphoid tissue.

Lymphoid Cells: B Lymphocytes

  • B lymphocytes are released as immature pre-B cells from the bone marrow, maturing in primary lymphoid tissues such as:

    • Birds: Bursa of Fabricius

    • Mammals: Bone marrow, Peyer’s patches in some species (e.g., ruminants)

  • During maturation, B cells develop their B cell receptors (BCR). If they recognize an antigen during this development, they are eliminated; if not, they mature and migrate to secondary lymphoid tissues.

Lymphoid Cells: NK Cells

  • Natural Killer (NK) cells are released from the bone marrow in a mature state, ready to function immediately.

  • NK cells are part of innate immunity, non-specific, and lack memory functions unlike B and T cells.

Lymphocyte Differentiation and Activation

  • Upon encountering their specific antigen in secondary lymphoid organs, clonal expansion occurs—mitosis of lymphocytes increases their numbers.

  • B cells differentiate into effector plasma cells that secrete antibodies or form memory cells, which are long-lived clones.

  • T cells differentiate into effector cells or memory cells in response to their antigens.

Distribution of Lymphocytes in Secondary Lymphoid Tissues

  • Lymph Nodes: 40%

  • Spleen: 2%

  • Intestine: 10%

  • Bone Marrow: 10%

  • Other Tissues: 25%

Primary and Secondary Lymphoid Tissues

Primary Lymphoid Tissues

  • The maturation of lymphocytes occurs in these tissues, including:

    • For T cells: Thymus

    • For B cells:

      • Birds: Bursa of Fabricius

      • Mammals: Bone marrow; in ruminants, Peyer’s patches.

Secondary Lymphoid Tissues

  • Large quantities of lymphocytes reside in these tissues awaiting contact with antigens, thus increasing the likelihood of meeting their targets:

    • Lymph Nodes: Where adaptive immune responses to lymph-borne antigens begin.

    • Spleen: Involved in adaptive immune response to blood-borne antigens.

    • MALT: Mucosal associated lymphoid tissue, serves similar roles for mucosal surface antigens.

Structural Features of Lymph Nodes

  • B Cell Zone: Follicle

  • T Cell Zone: Parafollicular cortex

  • Medulla: Contains lymphatic sinuses and vessels

Morphology of the Spleen

  • Red Pulp: Area containing blood

  • White Pulp: Contains B cell (follicles) and T cell (periarteriolar lymphoid sheaths) zones.

Lymphatic Circulation

  • Naive lymphocytes follow a specific circulation path, while primed lymphocytes take a different route back to tissues.

Key Concepts

  • Key Concept 1: All blood cells originate from the bone marrow.

  • Key Concept 2: White blood cells play significant roles in immunity.

  • Key Concept 3: B and T lymphocytes are central to adaptive immune responses.

  • Key Concept 4: B and T cells mature in primary lymphoid organs; T cells mature in the thymus while B cells mature in the bursa, bone marrow, or Peyer's patches, dependent on species.

  • Key Concept 5: Lymphocytes with receptors for self-antigens are eliminated before leaving primary lymphoid organs.

  • Key Concept 6: Mature lymphocytes migrate to secondary lymphoid organs where they encounter foreign antigens.

  • Key Concept 7: Major secondary lymphoid organs include lymph nodes, spleen, bone marrow, and Peyer’s patches within the intestine.