The Organs of the Immune System

• The immune system recognizes and responds to non-self antigens in a coordinated manner
• Diseased, damaged, distressed, or dying cells are eliminated
• The immune system has two complementary arms: innate and adaptive
• The immune system consists of organs, tissues, cells, and molecules

Immune System Organs

• Primary immune organs are the bone marrow and thymus
  • Bone marrow is responsible for immune cell production, including B cell maturation
  • The thymus is responsible for T cell maturation
• Secondary immune organs include the spleen, lymph nodes, tonsils, Payer's patches, and mucosal-associated lymphoid tissues (MALT)
• Secondary organs allow immune cells to interact with antigens

Lymph Nodes

• Lymph nodes are secondary lymphoid organs
• Lymph nodes conduct non-specific filtration via macrophages, store B and T cells, and activate immune responses
• The follicle in the lymph node is the site of B-cell localization and proliferation.
• The medulla contains reticular cells and macrophages
• The paracortex houses T cells
• Paracortex enlargement indicates an extreme cellular immune response, like with EBV or other viral infections, potentially leading to paracortical hyperplasia and lymphadenopathy

Immune System Cells

• Multipotent stem cells differentiate into lymphoid and myeloid cells in response to cytokines and growth factors
• The common lymphoid progenitor cell becomes B lymphocytes, T lymphocytes, and natural killer (NK) cells
• The common myeloid progenitor cell becomes erythrocytes, megakaryocytes/thrombocytes, mast cells, eosinophils, basophils, neutrophils, monocytes/macrophages, and dendritic cells

Lymphoid Progenitor Cells (Lymphocytes)

• Lymphocytes are located in the bloodstream and secondary lymphoid tissues
• Surface markers of Lymphocytes include: B lymphocytes (CD19, 20, 21), T lymphocytes (CD3) and Helper T cells (CD4), and CTLs (CD8)
• Different maturational stages of lymphocytes can be distinguished by the expression of membrane CD molecules (Cluster of Differentiation (CD)
• Lymphocytes have no function until activated in secondary lymphoid tissues for adaptive immunity
• When stimulated by an antigen, lymphocytes enlarge, becoming lymphoblasts that differentiate into effector or memory cells like plasma cells, T-helper cells, and T-cytotoxic cells
• Memory cells are long-lived, residing in the Go phase of the cell cycle until reactivated by a secondary encounter with the same antigen

Natural Killer Cells

• Natural killer cells are located in the bloodstream
• They have surface markers CD16 and CD56
• They constitute 10-15% of peripheral T cells
• Their number is not increased by immunization
• Natural killer cells are not MHC restricted
• They lack most surface markers of T and B cells
• They are activated by IFN-γ, IL-2, and IL-12
• Natural killer cells kill virally infected cells and tumor cells

Myeloid Progenitor Cells

• Neutrophils, or polymorpho-nuclear (PMN) cells, circulate with segmented, lobular nuclei (3–5 lobes) and cytoplasmic granules
• Neutrophils are the most abundant circulating blood cell
• They conduct phagocytic activity aimed at killing extracellular pathogens
• The phagosome fuses with granules to destroy internalized pathogens, resulting in an oxygen-dependent respiratory burst
• Neutrophils do NOT function as antigen-presenting cells (APCs)
• Neutrophils are the first cells to arrive at a site of inflammation
• Monocytes circulate in the blood
• Monocytes are agranulocytes with a bean or kidney-shaped nucleus
• Monocytes are precursors to tissue macrophages
• Macrophages reside in all tissues
• Macrophages are agranulocytes with ruffled cytoplasmic membranes, cytoplasmic vacuoles, and vesicles
• Macropahges function as phagocytes and professional antigen-presenting cells for T-cell activation
• Dendritic cells reside in epithelial and lymphoid tissue
• Dendritic cells are agranulocytes with thin, stellate cytoplasmic projections
• Dendritic cells function as phagocytes and professional antigen-presenting cells for T-cell activation
• Eosinophils circulate and are recruited into loose connective tissue of the respiratory and GI tracts
• Physical features of eosinophils include granulocytes with bilobed nuclei and large pink cytoplasmic granules
• Eosinophils eliminate large extracellular parasites and contribute to Type I hypersensitivity
• Basophils are low frequency circulating blood cells; they are granulocytes with bilobed nuclei and large blue cytoplasmic granules
• Basophils function in eliminating large extracellular parasites and mediate Type I hypersensitivity

Mast Cells

• Reside in most tissues adjacent to blood vessels
• Granulocytes with small nuclei and large blue cytoplasmic granules
• Assist in the elimination of large extracellular parasites and Type I hypersensitivity

Immune System Cell Classification

• Phagocytic cells
• Antigen-presenting cells
• Lymphocytes

Phagocytic Cells

• Neutrophils
• Macrophages
• Dendritic cells
• Eosinophils

Professional Antigen-Presenting Cells

• Macrophages
• Dendritic cells
• B lymphocytes

Lymphocyte Circulation

• Naive lymphocytes (T & B cells) mature in bone marrow & thymus but have not encountered antigens
• After maturation, T & B cells continuously migrate from blood into peripheral lymphoid tissues and back via lymphatic vessels
• Homing & trafficking: Lymphocytes migrate between lymphoid (lymph nodes, spleen) & non-lymphoid tissues, homing to specific sites
• Homing & trafficking are regulated by cell surface adhesion molecules and chemokines