Immune (Lymphatic) System By: Reymond M. Seracarpio II, RN I. Overview/definitions Definition: Immune (Lymphatic) System.

The immune or lymphatic system consists of a complex network of specialized cells and organs designed to protect and defend the body against attacks by "foreign" invaders such as bacteria and viruses. **The cells of this system are known as immunocompetent cells in that they have the capacity to distinguish self from altered self or foreign .  The system has innate components that act rapidly (within hours), but nonspecifically (Innate Immunity - which involves neutrophils and macrophages) and adaptive components that act specifically, but need time to respond (Acquired or Adaptive Immunity -mediated by lymphocytes, initially takes 4-7 days).  The immune system not only protects against extrinsic pathogens but also against intrinsic pathological changes in cells and tissues that result in alterations of cell surface molecules. II. Immune System Components: The immune system consists of specific cells, lymphatic organs and diffuse lymphatic tissue -collections of lymphocytes and other immune cells dispersed in the lining of the digestive and respiratory tracts and in the skin. 1. Cells of the Immune System: originate from precursor cells in the bone marrow and patrol tissues by circulating in either the blood or lymphatics, migrating into connective tissue or collecting in immune organs. a. Lymphocytes one of the most important cells of an immune response; responsible for adaptive immunity; 2 major types: i. B cells-differentiate in the bone marrow of mammals; give rise to plasma cells that secrete antibodies into the extracellular fluid, which bind to antigens. This antibody/antigen complex is more easily recognized by phagocytes. ii. T Cells-differentiate in the thymus, 70-80% of blood lymphocytes; 3 subtypes:  T helper cells -act through secretion of soluble short-range effector molecules, called cytokines that will stimulate B cells and macrophages  T cytotoxic cells- attach directly to target cells to kill them **T helper cells (CD4+) T4; T cytotoxic cells (CD8+) T8

 Natural Killer Cells- lack antigen specific receptors that are typical of B and T cells, play an important role in innate immunity; mechanism similar to T cytotoxic cells, important in elimination of tumors and virus-infected cells. b. Phagocytes - provide innate cellular immunity in tissues and initiate host-defense responses. Three types:  Neutrophils -most numerous of the white blood cells, multilobed nucleus, rapid turnover, work well under ischemic conditions, important in the phagocytosis of pathogens **fags provide the first line of defense against microorganisms Resting Neutrophils - are round with no fibers; Activated Neutrophils - are flat & form fibers Neutrophils generate extracellular fibers called NETS that kill bacteria without the need for phagocytosis. (NETS=neutrophil extracellular traps)  Macrophages--derived from monocytes that enter the tissue from the blood, phagocytose bacteria and tissue debris; release systemic cytokines that
body temp.  Dendritic Cells cells derived from the bone marrow which are found predominately in T-cell areas of lymphoid tissue as well as in the skin. They are phagocytic when they are immature and they take up pathogens. When mature they have the capacity to bind antigens on their surface. **are able to present these antigens to and are effective in activating resting T-cells & initiating adaptive immune responses. c. Other cells/ Component cells Mast Cells this resident connective tissue cell is considered a component of the immune system. It is found near blood vessels and contains lots of basophilic granules, the cells release histamine. **the slow reacting substance of anaphylaxis-->increases vascular permeability-->edema 2. Organs/tissues of the Immune System: Specialized organs and collections of tissue where lymphocytes interact with non-lymphoid cells, which are important either to their maturation or to the initiation of adaptive immune responses.

Classification of Lymphatic tissues: i. Primary (Central) Immune Organs--where stem cells develop and differentiate into mature B-cells and T-cells: Bone Marrow B-cells mature in the bone marrow Thymus a large organ in which T-cells mature **The thymus is located in the cranial chest. B-cells or B- lymphocytes; Tcells or T- lymphocytes; thymocytes ii. Secondary (Peripheral) Immune Organs these organs trap cells or pathogens arriving from sites of infection and antigen is presented to lymphocytes to stimulate adaptive immune responses. y Lymph Node situated along the extensive drainage system of lymph vessels, they serve to filter the lymph fluid before returning it to the bloodstream. Lymph nodes provide an environment in which lymphocytes are able to respond to lymph-borne antigens. **BTW: B cells found in follicles; T-cells located in paracortical areas B cells- B cells are a type of white blood cell (called a b-lymphocyte) that produces antibodies. B cells develop from stem cells in the bone marrow. T cells- The main job of T-cells is to fight infection. There are a number of different types of T-cells that act in many ways to identify, directly attack and destroy infectious agents. Along with other WBCs, they play a major role in the immune system, which guards the body against infection. It also secretes lmphokines (or cytokines) are diverse and potent chemical messengers (inflammatory response)  Spleen serves as a filter for the blood, it is involved in clearance and mounting of immune responses against blood-borne antigens. **An antigen is a substance/molecule that, when introduced into the body triggers the production of an antibody by the immune system, which will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as pollen or cells such as bacteria. The term originally came from antibody generator and was a molecule that binds specifically to an antibody, but the term now also refers to any molecule or molecular fragment that can be bound by a major histocompatibility complex (MHC) and presented to a T-cell receptor. "Self" antigens are usually tolerated by the immune system; whereas "non-self" antigens are identified as intruders and attacked by the immune system. Autoimmune disorders arise from the immune system reacting to its own antigens. 3. Immune tissue associated with various organs:  GALT  MALT  SALT

GALT gut-associated lymphatic tissue; comprised of lymphoid tissue (lymph nodules) in the intestinal wall containing lymphocytes, plasma cells and macrophages. MALT mucosa-associated lymphatic tissue; lymphoid tissue associated with the mucosa of the female reproductive tract, respiratory tract, etc. SALT skin-associated lymphatic tissue; lymphatic tissue associated with the dermis of the skin. III. Primary Lymphatic Organs: Bone marrow The structure and major hematopoietic functions of the bone marrow were covered last semester. It is the second largest organ in aggregate and is the site of B cell development and maturation. Thymus  Function and Origin: y Circulating stem cells migrate to the thymus and differentiate into Tlymphocytes; cells undergo a process of maturation and education prior to release into the circulation. **Embryologically the thymus originates as an epithelial outgrowth of the third pharyngeal pouch. These epithelial cells of the pouch form the epithelial reticular cells of the thymic stroma. (ORIGIN)  Structure: y The thymus is covered by an irregular connective tissue capsule and is divided into lobes that are further separated by thin connective tissue septa into lobules. **The central medulla (core) of each lobule is surrounded by an outer cortex.  Histology: Cortex-consists mainly of star shaped cells called epithelial reticular cells with lymphocytes found between the processes of these cells. Because it is loaded with lymphocytes it stains darkly compared to the medulla. Epithelial reticular cells are connected by desmosomes that maintain the structural integrity of the organ and help form the blood-thymus barrier. **Epithelial reticular cells (or epithelioreticular cells) are a structure in both the cortex and medulla of the thymus. However, histologically, they are more easily identified in the medulla. These cells contain secretory granules which are thought to contain the thymic hormones. **A desmosome (Greek: desmos, band, soma, body), also known as macula adherens (plural: maculae adherentes) (Latin for adhering spot), is a cell structure specialized for cell-to-cell adhesion. A type of junctional complex, they are localized spot-like adhesions randomly arranged on the lateral sides of plasma membranes.

**Desmosomes help to resist shearing forces and are found in simple and stratified squamous epithelium. The intercellular space is very wide (about 30 nm). Desmosomes are also found in muscle tissue where they bind muscle cells to one another. Medulla-has fewer lymphocytes and thus stains lightly. Some epithelial reticular cells in the medulla are larger and form thymic corpuscles. These are comprised of one or several central calcified or degenerated epithelial reticular cells, surrounded by flat keratinized cells in a concentric arrangement.

Aggregated lymphatic nodules of the MALT are prominent in the pharyngeal region where they are referred to as tonsils. They are located adjacent to the lumen of the host organ and are covered by stratified squamous (oropharynx, see below) or pseudostratified columnar (nasopharynx) epithelium

Epithelial Reticular Cells: There are 6 types (Type I-VI); types I-III are found in the cortex and derived from the ectoderm; types IV-VI are found in the medulla and are derived from the endoderm. (Types 4-6 are derived from the 3rd pharyngeal pouch of the endoderm. ) IV. Secondary Lymphatic Organs:  Lymphocytes leave the primary lymphatic organs and seed the secondary lymphatic organs where they first encounter foreign antigens. **Most secondary lymphatic organs are comprised of lymphatic follicles or nodules (consisting of a stromal network of dendritic cells, reticular cells, reticular fibers andntightly packed B-lymphocytes) and diffuse extranodular lymphatic tissue (adjacent to the nodules; contains dense accumulations of small T-cells, macrophages and some lymphoblasts). Immune tissue associated with various organs:  Gut-Associated Lymphatic Tissue (GALT): solitary and aggregated lymphatic nodules associated with the gut. It is especially rich in B-cells and is responsible for localized immunity to pathogens such as bacteria, viruses, and parasites. (e.g., Peyer's patches, mesenteric lymph nodes and the Appendix)  Mucosa-Associated Lymphatic Tissue (MALT): solitary lymphatic nodules or aggregates of nodules commonly found in the subepithelial connective tissue of mucous membranes associated with the female reproductive tract, respiratory tract, and urinary tract.

CLINICAL CORRELATION Abnormalities y Immune Deficiencies Immune deficiency diseases sire a group of disorders in which normal hosts defenses against disease are impaired. **These include defects in non-specific host defenses (e.g., complement deficiency; functional white blood cell disorders), and defects in specific host defenses (e.g., immunosuppression caused by pathogenic bacteria, viruses and parasites; combined immune deficiency; IgA deficiency; growth hormone deficiency). y Cancer- the cancer itself can be profoundly immunosuppressive. The form of immunosuppression usually varies with the tumor type. **For example, lymphoid tumors (lymphomas and leukemia) tend to suppress antibody formation, whereas tumors of T-cell origin generally suppress cell-mediated immunity