Connective Tissue Cells & Immune Cells PDF

5 Connective tissue Cells & immune cells ILOs By the end of this lecture, students will be able to 1. Value the significance of stem cell origin of CT cells. 2. Correlate the structure of each cell to its function. 3. Interpret the response of CT cells to physiological...

5 Connective tissue Cells & immune cells ILOs By the end of this lecture, students will be able to 1. Value the significance of stem cell origin of CT cells. 2. Correlate the structure of each cell to its function. 3. Interpret the response of CT cells to physiological & pathological conditions (immune response, hypersensitivity reaction, tissue repair, inflammation) 4. Differentiate types of white blood cells on basis of their origin and histological features. 5. Interpret structural adaptation of immune cells in different medical conditions 6. Interpret stages of lymphocyte maturation & the expression of their receptors What is connective tissue (CT)? Connective tissue, as the name implies, forms a continuum with epithelial tissue, muscle, and nervous tissue, as well as, with other components of connective tissues to maintain a functionally integrated body. ⮚ Origin; Most connective tissues originate from mesoderm, the middle germ layer of the embryonic tissue that contains mesenchymal stem cells (multipotent cells). (Fig. 1) ⮚ Components of the connective tissue; Connective tissue is composed of cells and extracellular matrix consisting of ground substance and fibers. ⮚ Functions of the CT; differ according to the type of CT and its components. Generally, functions include: Providing structural support Serving as a medium for exchange Aiding in the defense and protection of the body Forming a site for storage of fat Classification of CT cells: 1. Fixed cells are a resident population of cells that have developed and remain in place within the connective tissue, where they perform their  functions. The fixed cells are a stable and long-lived population that includes fibroblasts& adipose cells (fat cells). 2. Transient cells (free or wandering cells) originate mainly in the bone marrow and circulate in the bloodstream, where they reach the CT in response to specific signals. These include mast cells and macrophages (the 2 cells may become resident in the CT), plasma cells, Lymphocytes, Neutrophils, Eosinophils, Basophils, monocytes. Structure & function of CT cells: 1. Fibroblasts ⮚ Fibroblasts, the most abundant. ⮚ Function; responsible for synthesis and secretion of extracellular components (fibers & ground substance molecules). ⮚ Functional forms: it may be active fibroblasts with protein synthesis machine, especially when the cell is actively manufacturing matrix, as in wound healing. (Fig 2a) ⮚ Inactive fibroblasts (fibrocytes) are smaller and more ovoid with less organelles. ⮚ Myofibroblasts represent transitional modifications of fibroblasts responding to signalling molecules within a regional intercellular matrix, as in areas undergoing wound healing. They contain actin and myosin filaments thus resembling features of a smooth muscle. Role of myofibroblasts in health and disease Early in process of wound healing, myofibroblasts produce a contractile action to reduce the size of the wound. If the injurious stimulus persists, continuous stimulation of myofibroblasts results in excessive collagen deposition by myofibroblasts with subsequent fibrosis, for example in chronic hepatitis (liver inflammation) and complicated lung infection. 2. Adipose cells ⮚ Adipose cells are fully differentiated and do not undergo cell division. ⮚ They function in the synthesis and storage of triglycerides. ⮚ Types; unilocular fat cells: Cells with a single, large lipid droplet and form white adipose tissue, and multilocular fat cells with multiple, small lipid droplets and form brown adipose tissue. (Fig 2b & c) ⮚ Unilocular fat cells continuously store fat in the form of a single droplet, which enlarges so much that the cytoplasm and nucleus are displaced peripherally against the plasma membrane, thus giving these cells a "signet ring" profile when viewed by light microscopy.  ⮚ Multilocular fat cells are smaller and more polygonal than white fat cells. Multilocular fat cells contain many more mitochondria than unilocular fat cells. 3. Mast cells ⮚ Mast cells are ovoid and possess a centrally placed, spherical nucleus. ⮚ They are characterized by abundant secretory granules that contain different chemical mediators, such as, heparin (Anticoagulant), histamine & Leukotrienes (vasodilators and smooth muscle contractors of bronchi, interleukins (IL-4, IL-5, IL- 6), and tumour necrosis factor-alpha (TNF-α) (enhances the inflammatory response). (Fig 2d) ⮚ Function: They function in the immune system by initiating an inflammatory response known as the immediate hypersensitivity reaction (whose systemic form, known as an anaphylactic reaction, may have lethal consequences). This response commonly is induced by foreign proteins (antigens) such as bee venom, pollen, and certain drugs. (It will be discussed in detail in the following module). Clinical hint Victims of hay fever attacks suffer from the effects of histamine being released by the mast cells of the nasal mucosa, results in feeling "stuffed up" and hinders breathing. (Why?)  Victims of asthma attacks suffer from extra-release of leukotrienes in the lungs and difficulty in breathing (why?). Degranulation of mast cells usually is a localized phenomenon; the typical inflammatory response is mild and site-specific. However, a risk also exists for hyperallergic persons who may experience a systemic and severe immediate hypersensitivity reaction (systemic anaphylaxis) following a secondary exposure to an allergen (e.g., insect stings, antibiotics). (What are the expected signs? and Why?) 4. Macrophages ⮚ Macrophages arise from circulating monocytes, and they are the most abundant phagocytic cells in connective tissue. ⮚ They function in removing cellular debris and in protecting the body against foreign invaders. ⮚ Structure: large cells with irregular surface that show blunt projections or filopodia reflecting cell motility and abundance of lysosomes reflecting active phagocytosis. (Fig 3a) 5. Plasma cells ⮚ Plasma cells are derived from B lymphocytes and manufacture antibodies. ⮚ Their cytoplasm is intensely basophilic (Why?) except in the prenuclear area which appear pale and referred to as a negative Golgi image. (Fig 3 b& c). IMMUNE CELLS Leukocytes (white blood cells) All leukocytes originate in the bone marrow. Leukocytes do not function within the bloodstream but use it as a means of traveling from one region of the body to another. they leave the blood stream by migrating between the endothelial cells of the blood vessels (diapedesis), enter the connective tissue spaces and perform their specific function. (Fig.4) Classification of white blood cells I- Granulocytes, which have both specific granules and non-specific granules (lysosomes) in their cytoplasm 1. Neutrophils 2. Eosinophils 3. Basophils II- Non-granulocytes; which lack specific granules and contain only non-specific granules (lysosomes) 1. Lymphocytes 2. Monocytes. Note: the suffix “ilia” when add to any blood cells means increase in the number of this cells Ex; Neutrophilia means increase in the number of Neutrophils 1. Neutrophils Polymorphonuclear leukocytes (polys, neutrophils) are the most numerous of the white blood cells, constituting 60% to 70% of the total leukocyte population. It is recognized in a blood film by its multilobed nucleus, where lobes are interconnected by chromatin. It has a pale cytoplasm. In females, the nucleus presents a characteristic small appendage. the "drumstick," which contains the condensed, inactive second X chromosome, called the Barr body, which is used for sex identification. (Fig. 5A) Functions They are first line of defence against bacterial infection. They phagocytose and destroy bacteria by the content of their granules. Neutrophils can also migrate through blood capillary wall to reach connective tissue sites where there is bacterial infection to act in phagocytosis. After performing their function, cells die and form pus cells. 2. Eosinophils They are characterized by a bilobed nucleus and eosinophilic granules in cytoplasm. (Fig 5B) Function: Eosinophils phagocytose antigen-antibody complexes and kill parasitic invaders Clinical hint: Connective tissue cells in the vicinity of antigen-antibody complexes release the pharmacological agents histamine and IL-5, causing increased formation and release of eosinophils from the bone marrow. In contrast, elevation of blood corticosteroid levels depresses the number of eosinophils in circulation. 3. Basophils They are characterized by S-shaped nucleus and abundant basophilic granules in cytoplasm. (Fig 5C) Function: They mediate allergic and inflammatory reaction through release of granules content, such as histamine and heparin. Clinical hint In certain hyperallergic individuals, a second exposure to the same allergen may result in an intense generalized response. A large number of basophils (and mast cells) degranulate, resulting in widespread vasodilation and sweeping reduction in blood volume (because of vessel leakiness). Thus, the person goes into circulatory shock. The smooth muscles of the bronchial tree constrict, causing respiratory insufficiency. The combined effect is a life-threatening condition known as anaphylactic shock. 4. Monocytes They are the largest white blood cells in a blood smear and recognized by a large, eccentric and kidney shaped nucleus. It has irregular surface with projection from the cell membrane(filopodia). They possess abundant lysosomes. Monocytes migrate into the connective tissue and become named macrophages. They belong to the mononuclear phagocytic system. They phagocytose and destroy dead and defunct cells (such as senescent erythrocytes) as well as antigens and foreign particulate matter (such as bacteria). The destruction occurs within the phagosomes. Functions Macrophages phagocytose unwanted particular matter. Produce cytokines that are required for the inflammatory and immune responses. Present epitopes (processed foreign antigens) to T lymphocytes, thus acting as antigen presenting cells to elicit an immune response. 5. Lymphocytes They are rounded cells that have a slightly indented, round nucleus that occupies most of the cell. Lymphocytes are subdivided into three functional categories: 1. B lymphocytes (B cells) 2. T lymphocytes (T cells) 3. Null cells The three types are similar morphologically. They are differentiated on bases of their surface receptors. Approximately 80% of the circulating lymphocytes are T cells, about 15% are B cells, and the remainder are null cells. Their life spans also  differ widely: some T cells may live for years, whereas some B cells may die in a few months. Lymphocytes have no function in the bloodstream, but in the connective tissue these cells are responsible for the proper functioning of the immune system To be immunologically competent, they migrate to specific body compartments to mature and to express specific surface markers and receptors. B- cells mature leave the bone marrow as mature cells, while T-cells migrate to the thymus where they become mature and immunocompetent. Once they have become immunologically competent, lymphocytes leave their respective sites of maturation, enter the lymphoid system, and undergo mitosis, forming a group of identical cells, known as a clone. All members of a particular clone can recognize and respond to the same antigen. After stimulation by a specific antigen, both B and T cells proliferate and differentiate into two subpopulations: Memory cells do not participate in the immune response but remain as part of the clone with an "immunological memory," ready to undergo cell division and mount a response against a subsequent exposure to a particular antigen or foreign substance. Effector cells are classified as B cells and T cells (and their subtypes).