Human Physiology: Lymphatic System

Lymphatic System

• The lymphatic system is responsible for fluid balance, fat absorption, and defense.

Components of the Lymphatic System

• Primary lymphoid organs:
  • Bone Marrow
  • Thymus
• Secondary lymphoid organs:
  • Lymph nodes
  • Spleen
  • Tonsils
  • Aggregates of lymphocytes and antigen-presenting cells in the lung (BALT) and the mucosa of the digestive tract (GALT), including Peyer’s patches

Types of Immunity

• Innate or Natural Immunity:
  • Provides immediate defense against infection
  • Physical barriers: skin, mucous membranes, and tears
  • Chemical barriers: HCl, organic acids, defensins, and lysozyme
  • Cellular barriers: neutrophils, natural killer cells, and toll-like receptors
• Adaptive Immunity:
  • Acquired gradually by exposure to microorganisms
  • More specific and slower to respond
  • T cell immunity: cellular mediated immunity and cytokine production
  • B cell immunity: humoral immunity and antibody production

Innate Immunity

• Physical barriers:
  • Skin and mucous membranes
  • Tears, saliva, and urine
• Chemical barriers:
  • HCl and organic acids
  • Defensins and lysozyme
• Cellular barriers:
  • Neutrophils and natural killer cells
  • Toll-like receptors

Adaptive Immunity

• T cell immunity:
  • Cellular mediated immunity
  • Cytokine production
  • Uptake of a pathogen by phagocytes
  • Passive and active immunity
• B cell immunity:
  • Humoral immunity
  • Antibody production
  • Antigen exposure

Antigens and Antibodies

• Antigen:
  • A molecule recognized by cells of the adaptive immune system
  • Examples: foreign matter, bacteria, and viruses
• Antibodies:
  • Proteins produced by plasma cells in response to antigens
  • Examples: IgG, IgA, IgM, IgE, and IgD

Classes of Antibodies

• IgG: most common antibody in the blood
• IgA: found in mucosal surfaces
• IgM: first antibody produced in response to an infection
• IgE: involved in allergic reactions
• IgD: found on the surface of mature B cells

Antigen Presentation

• Major Histocompatibility Complex (MHC):
  • A group of genes that code for proteins found on the surfaces of cells
  • Helps the immune system recognize foreign substances
  • Also known as Human Leukocyte Antigen (HLA)
• Two classes of MHC:
  • CLASS 1: found on all nucleated cells
  • CLASS 2: found on antigen-presenting cells

Cells of Adaptive Immunity

• Antigen-presenting cells:
  • Detect, engulf, and inform the adaptive immune response about an infection
  • Examples: dendritic cells, macrophages, monocytes, and thymic epithelial cells
• Lymphocytes:
  • Regulate and carry out adaptive immunity
  • Found in the bone marrow and lymphoid tissues
  • Have specific receptors on their surface

Lymphocytes

• T lymphocytes:
  • Recognize antigenic epitopes via surface protein complexes termed T-cell receptors (TCRs)
  • Types:
    • Helper T cells (CD4 T lymphocytes)
    • Cytotoxic T cells (CD8 T cells)
    • Regulatory T cells (Tregs or suppressor T cells)
    • γδ T lymphocytes
• B lymphocytes:
  • Recognize specific antigens via surface protein complexes termed B-cell receptors (BCRs)
  • Produce antibodies in response to antigens

Lymphoid Tissue

• Reticular connective tissue is filled with large numbers of lymphocytes
• Lymphoid tissue packed with lymphocytes usually stains dark blue in hematoxylin and eosin
• Reticular fibers are found in lymphoid tissue### Thymic Epithelial Cells (TECs)
• TECs are epithelial reticular cells with oval nuclei and lightly stained cytoplasm with processes.
• They play a crucial role in the development of T cells in the thymus.

Blood-Thymus Barrier

• The blood-thymus barrier exists in the cortex of the thymus, making it an immunologically protected region.
• The barrier consists of:
  • Endothelium of the thymic capillaries and the associated basal lamina.
  • Perivascular connective tissue and cells (e.g., pericytes and macrophages).
  • Type I epithelial reticular cells and their basal laminae.

Thymus

• The thymus is a primary lymphoid organ where T cells develop and mature.
• T lymphoblasts, or thymocytes, attach to a cytoreticulum composed of interconnected TECs.
• TECs secrete many cytokines, compartmentalize the thymus into a cortex and a medulla, and surround blood vessels in the blood-thymus barrier.
• Developing T cells with nonfunctional TCRs are detected and removed in the thymic cortex by a process of positive selection.
• Cells with functional TCRs move into the thymic medulla, where they undergo negative selection, leading to central immune tolerance.

Thymic Medulla

• The thymic medulla contains Hassall corpuscles, which are aggregates of TECs that promote the formation of regulatory T cells.
• Regulatory T cells form in the thymic medulla upon interacting with dendritic cells presenting self-antigens.

Secondary Lymphoid Organs

• Secondary lymphoid organs include lymph nodes, spleen, tonsils, Peyer's patches, and mucosa-associated lymphoid tissue (MALT).

Mucosa-Associated Lymphoid Tissue (MALT)

• MALT is found in the mucosa of most tracts, including the palatine, lingual, and pharyngeal tonsils, Peyer's patches, and the appendix.
• MALT is composed of dispersed aggregates of non-encapsulated organized lymphoid tissue within the mucosa.

Types of MALT

• Tonsils: large, irregular masses of lymphoid tissue in the mucosa of the posterior oral cavity and nasopharynx.
• Peyer's patches: clusters of subepithelial, lymphoid follicles found in the intestine.
• Appendix: a short, small-diameter projection from the cecum, filled with lymphoid tissue.

Lymph Nodes

• Lymph nodes filter lymph and provide a site for B-cell activation and differentiation to antibody-secreting plasma cells.
• Each lymph node has three functional but not physically separate compartments: an outer cortex, an underlying paracortex, and an inner medulla.

Lymph Node Cortex

• The cortex is the outer region of the lymph node, where B cells encounter antigens, proliferate, and then move into the deeper regions of the lymph node.
• The cortex contains lymphoid nodules, which are organized around the long, interdigitating processes of follicular dendritic cells (FDCs).

Lymph Node Paracortex

• The paracortex is the region between the cortex and medulla, characterized by the lack of nodules.
• The paracortex contains specialized post-capillary venules called high endothelial venules (HEVs), which are an important entry point for most circulating lymphocytes into lymph nodes.

Lymph Node Medulla

• The medulla is the inner region of the lymph node, adjacent to the hilum and efferent lymphatic.
• The medulla contains medullary cords, which are branched cordlike masses of lymphoid tissue, and medullary sinuses, which are dilated spaces lined by discontinuous endothelium.

Spleen

• The spleen is a large lymphoid organ without a cortex/medulla structure, instead, it has two intermingled but functionally different regions: white pulp and red pulp.
• White pulp is secondary lymphoid tissue associated with small central arterioles, enclosed by periarteriolar lymphoid sheaths (PALS) of T cells.
• Red pulp filters blood, removes defective erythrocytes, and recycles hemoglobin iron, and consists of splenic cords with macrophages and blood cells of all kinds, and splenic sinusoids.