09. Immune System - Lymphoid Organs

The overlapping part of the Venn diagram includes components that are involved in both innate and adaptive immunity, such as Dendritic cells and Monocyte-macrophages which play roles in antigen presentation and immune response activation.

The physical barriers involved in innate immunity include the skin and mucous membranes of the gastrointestinal, respiratory, and urogenital tracts.

Neutrophils are responsible for removing bacteria, fungi, and parasites from the body.

NK cells destroy various unhealthy host cells, including those infected by viruses, bacteria, and tumorigenic cells.

High endothelial venules (HEVs) are significant in the paracortex as they facilitate the migration of lymphocytes from the bloodstream into the lymph node, playing a crucial role in immune response.

Medullary sinuses are spaces lined by discontinuous endothelium that separate the medullary cords. They are continuous with the cortical sinuses and converge at the hilum. Their lumen contains a meshwork of processes from reticular cells, serving as a final lymph filter, which includes many macrophages and neutrophils if the node is draining an infected area.

Medullary cords are branched, cordlike masses of lymphoid tissue that extend from the paracortex. They contain T and B lymphocytes as well as many plasma cells.

• Contains the largest single accumulation of lymphoid tissue
• Involved in filtration of blood
• The main site of old erythrocyte destruction

The spleen is surrounded by a capsule of dense connective tissue that gives rise to trabeculae which penetrate the splenic pulp. These trabeculae carry branches of the splenic artery, vein, lymphatics, and nerves into the splenic pulp.

The white pulp consists of:

1. Periarteriolar lymphoid sheaths (PALS): These surround the central arterioles, which are branches of the splenic artery.
2. Lymphoid nodules: These are filled with B-cells and are involved in the immune response.

The splenic cords, also known as Billroth's cords, consist of a network of reticular cells and fibers, T and B lymphocytes, macrophages, other leukocytes, and red blood cells.

Splenic sinusoids are characterized by elongated endothelial cells called stave cells, which are oriented parallel to blood flow. They have a highly discontinuous basal lamina and are sparsely wrapped with reticular fibers.

Toll-like receptors (TLRs) on leukocytes allow for the recognition and binding of surface components of pathogens.

Leukocytes and other cells produce several antimicrobial chemicals, including:

1. Hydrochloric acid (HCl) and organic acids
2. Defensins
3. Lysozyme
4. Complement
5. Interferons

Cytokines are small secreted proteins that facilitate cell-to-cell communication during immune responses, influencing the behavior of various immune cells.

Chemokines induce directional movement of leukocytes, a process known as chemotaxis, guiding immune cells to sites of infection or inflammation.

Interleukins are produced by leukocytes and play a crucial role in stimulating or suppressing lymphocyte activities in adaptive immunity, thereby regulating immune responses.

Cytokines stimulate phagocytosis or directed cell killing by innate immune cells and increase mitotic activity in certain leukocytes, enhancing the immune response.

The main types of lymphocytes involved in adaptive immunity are:

• B lymphocytes
• T lymphocytes
• Memory lymphocytes

An antigen-presenting cell (APC) is an immune cell that:

• Detects infections
• Engulfs pathogens
• Informs the adaptive immune response about the infection

Hematopoietic stem cells are the precursors that give rise to all blood cells, including lymphocytes. They differentiate into common lymphoid progenitor cells, which then develop into either T or B lymphocytes depending on their location in the body.

T lymphocytes differentiate in the thymus, while B lymphocytes differentiate in the bone marrow. T lymphocyte progenitors migrate to the thymus, whereas B lymphocyte progenitors remain in the bone marrow to mature.

B lymphocytes develop from hematopoietic stem cells in the bone marrow, progressing to common lymphoid progenitor cells, then to immature B cells, and finally to plasma cells, often involving the spleen in the process.

The thymus is crucial for the maturation of T lymphocytes, where progenitor cells develop into thymocytes and eventually mature T cells, which are essential for the adaptive immune response.

Lymphocytes are identified by surface proteins called clusters of differentiation (CD). T cells express T-cell receptors (TCRs), while B cells express B-cell receptors (BCRs).

The two main types of T lymphocytes are:

1. Helper T lymphocyte: Involved in cell-mediated immunity.
2. Cytotoxic T lymphocyte: Also involved in cell-mediated immunity.

Each T lymphocyte has approximately 100,000 receptors on its surface.

B lymphocytes are primarily involved in humoral immunity.

Antigens are molecules that trigger an immune response. They can be soluble molecules or components of intact cells such as bacteria, protozoa, and tumor cells. Epitopes are the small molecular domains of the antigens that are recognized by the immune system.

MHC class I molecules present peptides from intracellular sources to cytotoxic T cells (CD8+ T cells).

MHC class II molecules are mainly expressed on antigen-presenting cells (APCs) such as dendritic cells, macrophages, and B cells, and they present peptides from extracellular sources to helper T cells (CD4+ T cells).

The interaction between an antigen-presenting cell presenting an antigen via MHC class II and a CD4+ T cell leads to the maturation of the T cell into a helper T cell (Th1 or Th2), which then releases granules.

When a CD8+ T cell interacts with an antigen-presenting cell presenting an antigen via MHC class I, it matures into a cytotoxic T cell (Tc), which also releases granules.

The two main types of adaptive immune responses are humoral immunity and cell-mediated immunity.

B cells are responsible for producing antibodies that defend against extracellular pathogens. They differentiate into plasma cells and memory B cells upon activation.

T cells, specifically Tc cells, are involved in cell-mediated immunity. They interact with infected cells and can differentiate into active Tc cells and memory Tc cells to eliminate infected cells, cancers, and transplant tissues.

Humoral immunity is triggered by the presence of intact antigens, which activate B cells to produce antibodies.

TH cells (T helper cells) play a crucial role in the adaptive immune response by facilitating the activation of B cells and Tc cells, enhancing the overall immune response.

An antibody is a glycoprotein of the immunoglobulin family secreted by plasma cells that interacts specifically with an antigenic determinant. Its primary function is to bind to antigens, aiding in the immune response.

Antibodies can accumulate in the blood plasma and in the interstitial fluid of tissues.

Antibodies are transported across epithelia into the secretion of glands such as mucous, salivary, and mammary glands.

On the surface of B lymphocytes, antibodies act as membrane proteins, playing a crucial role in the recognition of antigens and the initiation of the immune response.

• Highest opsonization and neutralization activities.
• Classified into four subclasses: IgG1, IgG2, IgG3, and IgG4.

• Produced first upon antigen invasion.
• Increases transiently during the initial immune response.

• Expressed in mucosal tissues.
• Forms dimers after secretion, enhancing its function in mucosal immunity.

• Acts as antigen receptors in triggering B-cell activation.

• Involved in allergic reactions and responses.

The Fc region of the antibody binds to complement proteins, leading to the activation of the complement system, which helps to eliminate pathogens.

Opsonization occurs when the Fc region of an antibody binds to receptors on phagocytic cells, facilitating the engulfment and destruction of pathogens by these immune cells.

The activation of NK cells is triggered when the Fc region of an antibody binds to a receptor on the NK cell, leading to the release of cytotoxic chemicals such as perforin and granzymes, which induce apoptosis in virus-infected cells.

The primary lymphoid organs where lymphocytes are formed are the thymus and bone marrow.

The secondary lymphoid organs involved in lymphocyte activation and proliferation include the lymph nodes, spleen, and mucosa-associated lymphoid tissue (MALT) found in the digestive system.

The thymus is a primary lymphoid organ responsible for the maturation of T lymphocytes (T cells), which are crucial for adaptive immunity.

Lymphoid tissue is primarily composed of reticular connective tissue produced by fibroblastic reticular cells.

The main types of cells found in lymphoid tissue include:

1. Lymphocytes
2. Reticular cells
3. Antigen-Presenting Cells (APCs)
4. Plasma cells

Lymphoid tissue can be organized in two ways:

• Diffuse within areas of loose connective tissue
• Surrounded by capsules, forming discrete secondary lymphoid organs

The two types of lymphoid nodules are primary lymphoid nodules (containing immature B-lymphocytes) and secondary lymphoid nodules (which include a germinal center with lymphoblasts and a follicular mantle with non-proliferating B cells).

Lymphoid nodules are primarily located in the digestive, respiratory, and urogenital mucosae.

The germinal center in secondary lymphoid nodules is where lymphoblasts proliferate, indicating an active immune response and the maturation of B-lymphocytes.

The thymus is responsible for the production and maturation of T lymphocytes.

The two main regions of the thymus are:

1. Cortex: The outer region that contains darkly basophilic thymocytes.
2. Medulla: The inner region that is more lightly stained compared to the cortex.

With aging, the thymus undergoes thymic involution, which is characterized by an increase in adipose tissue and a decrease in the number of thymocytes.

The cortex of the thymus contains an extensive population of T lymphoblasts (thymocytes).

Thymic epithelial cells exhibit features of both epithelial and reticular cells, characterized by:

1. Squamous cells that contribute to the blood-thymus barrier.
2. Stellate cells that form a cytoreticulum.
3. Squamous cells that form a sheetlike structure contributing to the corticomedullary barrier.

The cortex of the thymus also contains numerous macrophages that play a role in the immune response and maintenance of the thymic environment.

Hassal corpuscles are large aggregates of thymic epithelial cells (TECs) that are sometimes concentrically arranged. They secrete several cytokines that control the activity of local dendritic cells, including factors that promote the development of regulatory T cells for peripheral tolerance.

T lymphoblasts do not yet express CD4, CD8, or a TCR (T Cell Receptor).

Positive selection allows cells whose receptors bind to self-HLA molecules to survive, ensuring that T cells can recognize self-MHC molecules.

T cells that do not interact with HLA molecules undergo apoptosis (programmed cell death).

Negative selection leads to the apoptosis of cells with high-affinity receptors for self-HLA and self-antigens, preventing autoimmunity.

The final result is the maturation of T cells into either CD4+ or CD8+ T cells, which are essential for adaptive immunity.

1. Mucosa-associated lymphoid tissue (MALT)
2. Lymph node
3. Spleen

Mucosa-associated lymphoid tissue (MALT) is found in the mucosa or inner lining of the digestive, respiratory, and urogenital tracts, constituting a larger lymphoid organ (70%).

The mucosal connective tissue of MALT contains large collections of lymphocytes, Ig-A secreting plasma cells, antigen-presenting cells (APCs), and lymphoid nodules.

The large structures associated with MALT include the tonsils, Peyer's patches in the ileum, and the appendix.

Lymphoid tissue in the tonsils is closely associated with the surface epithelium, allowing for efficient antigen capture and the initiation of immune responses when encountering antigens entering the mouth and nose.

The palatine tonsils are covered by stratified squamous epithelium.

Tonsillar crypts are 10-20 deep invaginations in the palatine tonsils that increase the surface area and are densely infiltrated by lymphocytes and other leukocytes, playing a crucial role in immune response.

The dense connective tissue acts as a partial capsule for the palatine tonsils, providing structural support.

Many secondary lymphoid nodules are found around the tonsillar crypts, which are clusters of immune cells involved in the immune response.

The lingual tonsils are covered by stratified squamous epithelium.

The pharyngeal tonsil is covered by pseudostratified ciliated columnar epithelium, lacks crypts but has shallow infoldings, contains diffuse lymphoid tissue, and has a thin underlying capsule.

No, the lingual tonsils lack a distinct capsule.

Lingual tonsils are covered by stratified squamous epithelium, while pharyngeal tonsils are covered by pseudostratified ciliated columnar epithelium.

The mucosa of the pharyngeal tonsil contains diffuse lymphoid tissue.

Peyer's Patches are large aggregates of lymphoid nodules located in the mucosa and submucosa of the ileum, part of the gastrointestinal tract.

The lymphoid nodules of Peyer Patches are covered by simple columnar epithelium.

Peyer's Patches do not have an underlying connective tissue capsule.

M cells have large epithelial structures with apical microfolds instead of the typical brush border found in neighboring enterocytes. They also feature a porous basement membrane that contains a transient population of lymphocytes and dendritic cells.

M cells are responsible for transporting antigens across the epithelial layer. They uptake antigens and facilitate the secretion of IgA on both sides of the epithelial layer, interacting with underlying immune cells such as dendritic cells, helper T lymphocytes, B lymphocytes, and plasma cells.

The appendix plays a key role in monitoring intestinal contents for antigens.

The mucosa of the appendix is almost completely filled with lymphoid tissue.

The appendix is a short, small diameter projection from the cecum.

Lymph nodes act as inline filters of lymph, defending against the spread of microorganisms and tumor cells, and providing environments for antigen presentation and the development of plasma cells.

Lymph nodes are typically bean-shaped and measure about 10mm by 2.5cm in size.

There are typically 400-450 lymph nodes distributed throughout the body along the lymphatic vessels.

The main structural components of a lymph node include the capsule, cortex, and medulla.

Lymph nodes are roughly kidney bean shaped and consist of several main structural components:

• Dense connective tissue capsule: Surrounds the lymph node.
• Trabeculae: Extensions of the capsule that branch internally.
• Cortex: Contains the germinal center for B cell proliferation.
• Medulla: Contains plasma cells.
• Paracortical area: The site for T cells.
• Afferent lymphatic vessels: Enter at the convex surface.
• Efferent lymphatic vessels: Leave at the concave hilum along with arteries, veins, and nerves.

Valves in the lymphatics ensure unidirectional lymph flow, preventing backflow and maintaining the proper direction of lymph movement through the lymphatic system.

Afferent lymphatic vessels enter the lymph node at the convex surface, while efferent lymphatic vessels leave at the concave surface (hilum), along with the artery, vein, and nerve that penetrate the organ.

The cortex contains lymphoid nodules, which may have germinal centers. It also features a subcapsular sinus that receives lymph from afferent lymphatics, and cortical sinuses that branch among the lymphoid nodules along trabeculae.

The paracortex is a deeper extension of the cortex that lacks lymphoid nodules. It is rich in T cells and contains high endothelial venules (HEVs), which are key features of this region.