Cells of the Innate Immune System PDF

Cells of the innate immune system 1- Agranular leukocytes or Agranulocyts Leukocytes with a single un-lobed nucleus and cytoplasm that contains few, or no granules are known as agranular leukocytes or agranulocytes. A. Monocytes and macrophages: Monocytes spend 1 to 2 days in the circulatio...

Cells of the innate immune system 1- Agranular leukocytes or Agranulocyts Leukocytes with a single un-lobed nucleus and cytoplasm that contains few, or no granules are known as agranular leukocytes or agranulocytes. A. Monocytes and macrophages: Monocytes spend 1 to 2 days in the circulation then cross the endothelium to enter tissues, where they reside for up to several months as macrophages. Both monocytes and macrophages are important for the phagocytosis. B. Dendritic cells: Found throughout the body but mainly in the potential portals (e.g., skin, lung, gastrointestinal tract GIT). Dendritic cells engulf cells and particles by phagocytosis. Acquired its name because it is covered with long membrane extensions that resemble the dendrites of nerve cells. They circulate the blood as immature DCs expressing MHC class II molecules on its surface. Once encounter antigen, DCs capture it and present it on its MHC molecule and become a mature cell. Then it travel to lymph nodes to present these antigens to T cells to start adaptive immunity. They are an antigen presenting cells (APC) as well as macrophages and B cells.  2- Granular leukocytes Granulocytes have multi-lobed nuclei and cytoplasmic granules that contain amines (stained by basic dyes), basic proteins (stained with acidophilic or eosinophilic dyes), or both (neutral staining). A. Neutrophils: Accounts for 60% of the peripheral blood leukocytes (the most numerous leukocyte population). They have variable number of nuclear segments (2 to 5). They are effective in killing bacteria. B. Basophils and mast cells: The acidic cytoplasmic granules of basophils contain amines that cause smooth muscle contraction and are readily stained with “base-loving” dyes. Bilobed cells in which the two lobes of the nucleus are round symmetrical and joined by a thin chromatin strand. These bilobed cells are found in low numbers in the peripheral blood (0-1%) or in their tissue resident form, known as mast cells. Both basophils and mast cells are important in allergic reactions of the adaptive immune response. basophils mast cells  C. Eosinophils: It has this name because of their “eosin-living” granules (eosin is a dye used in histology). They are also bilobed granulocytes with cytoplasmic granules that contain basic proteins. They are active component in both innate and adaptive immune responses to parasitic infections. Molecules of the adaptive immune system Major histocompatibility molecules (MHC) MHC, also called the human leukocyte antigen (HLA) complex. It is a segment of chromosome 6 containing several genes that encode various enzymes and structural molecules needed for the activation and function of B and T cells. They play a major role in considering a transplant tissue as foreign or not (histocompatibility). Although blood group antigen system was already well defined, it became clear that individual tissue type important in determining rate and severity of graft rejection and here where HLA system play important role. The MHC genes exhibit a large difference in the amino acids sequences in different individuals that is known as polymorphism. The structure of HLA molecules HLA class I Expressed on the surface of almost all nucleated cells. Consist of large polypeptide that is α- polypeptide and a small polypeptide known as β2- microglobulin. Can bind to short antigenic peptide in its groove. HLA class II Expressed on the surface of antigen presenting cells (macrophages, dendritic cells, and B cells). Consist of 2 large polypeptide that is α and β polypeptides. Can bind to long antigenic peptide in its open groove. Cluster of differentiation molecules Cluster of differentiation (CD) molecules found on the surfaces of many cell types and often serve as indicators of the functional capacities of leukocytes and other cells. Over 350 CD molecules are identified but in the adaptive immunity three major CD molecules are the most important: CD3: Its functions are to support the TCR and to transduce trans-membrane signaling when the TCR is engaged. CD4 and CD8 Cells of the adaptive immune system Lymphocytes Morphologically, lymphocytes (the major cells of the adaptive immune system) look like cells of the innate immune system but they range in their size from small (4 to 7 µm) to medium (7 to 11 µm) to large (11 to 15 µm). Lymphocytes can be classified according to three general methods: 1. The type of the receptors involved on the surface of the lymphocyte. 2. The place where they undergo the basic training. 3. The type of expression membrane molecules on their surfaces known as cluster of differentiation (CD). Different lineages or maturational stages of lymphocytes can be distinguished by their expression of membrane molecules known as cluster of differentiation (CD). B lymphocytes (B cells) The B lymphocyte derived its letter designation from bone marrow, its major site of maturation, in several mammalian species, including humans and mice. Mature B cells are definitively distinguished from other lymphocytes by their synthesis and display of membrane-bound immunoglobulin (antibody) molecules, its antigen receptors.When naïve B cells first encounter antigen and bind to a specific antibody this cause the cell to divide and differentiate to effector cells (known as plasma cells) and memory cells. 1. B- memory cells Arise from pluripotent Haematopoietic stem cells (HSC) in the bone marrow. They don’t migrate to the thymus but develop within the bone marrow. Each B cell produces a single form of immunoglobulin. 2. Plasma cells They don’t use immunoglobulin as a membrane receptor and instead secrete it into fluids around the cells. They are large sized and active metabolic cells. They produce large quantities of immunoglobulins during short period (< 30 days). T lymphocytes (T cells) T cells are the key players in most adaptive immune system and they are derived from the HSCs in the bone marrow. Immature T cells called prothymocytes migrate to thymus, where, as thymocytes, they develop TCRs and are screened for their ability to distinguish self from non-self. Those which survive the screening process are able to further differentiate into thymus-derived lymphocytes or T cells and enter the circulation. The T-cell receptor (TCR) does not recognize free antigen but recognizes only antigen that is bound to particular classes of self-molecules known as major histocompatibility complex (MHC). CD4+ T cells Is a single chain expressed on the surfaces of ⅔ of mature CD3+ T-cells. CD4+ T cells, also known as helper T (Th) cells. They recognize MHC class II complexes. CD8+ T cells Is a two-chain cell surface expressed on the surfaces of ⅓ of mature CD3+ T cells. CD8+ T cells, also known as cytotoxic T (Tc) cells. They recognize MHC class I molecules and identify and eliminate body cells that are infected with viruses and bacteria.  Natural killer (NK) cells 5-10% of cells which lack either TCR or BCR on their surfaces are known as NK cells. A unique subset of T cells, designated NKT because they share some functional characteristics with NK cells, develop within the thymus and express TCR. However, they do bear another set of receptors called killer activation receptors (KARs) and killer inhibition receptors (KIRs). These cells can kill certain virally infected cells and tumor cells. Immune system organs (Organs of the Lymphatic system) The lymphatic system can be divided to, primary or secondary lymphoid organs. The thymus and bone marrow are the primary or (central), where maturation of lymphocytes takes place. The lymph nodes, spleen, and various mucosal associated lymphoid tissues (MALT) are the secondary or (peripheral) lymphoid organs, which trap antigen and provide sites for mature lymphocytes to interact with that antigen. Primary Lymphoid Organs Thymus The thymus induces the death of those T cells that cannot recognize antigen- MHC complexes and those that react with self-antigen– MHC and pose a danger of causing autoimmune disease. More than 95% of all thymocytes die by apoptosis in the thymus without ever reaching maturity. Aging is accompanied by a decline in thymic function. This decline may play some role in the decline in immune function during aging in humans and mice. Also important to know that thymus reaches its maximal size at puberty. Bone marrow In humans and mice, bone marrow is the site of B-cell origin and development. Arising from lymphoid progenitors, immature B cells proliferate and differentiate within the bone marrow. A selection process within the bone marrow eliminates B cells with self-reactive antibody receptors. Secondary Lymphoid Organs Lymph nodes They are encapsulated bean-shaped structures containing a network packed with lymphocytes, macrophages, and dendritic cells. They are the sites where immune responses are generated to antigens in lymph. A lymph node can be divided into three roughly concentric regions: the cortex, the paracortex, and the medulla, Each of which supports a distinct microenvironment Cortex contains B cells, macrophages, and dendritic cells arranged in primary follicles. After antigenic challenge, the primary follicles enlarge into secondary follicles, each containing a germinal center. Paracortex, contain T lymphocytes and dendritic cells. Medulla, contain plasma cells actively secreting antibody. Spleen The spleen plays a major role in mounting immune responses to antigens in the blood stream. It is a large, ovoid secondary lymphoid organ situated high in the left abdominal cavity. While lymph nodes are specialized for trapping antigen from local tissues, the spleen specializes in systemic infections. Unlike the lymph nodes, the spleen is not supplied by lymphatic vessels. Instead, blood borne antigens and lymphocytes are carried into the spleen through the splenic artery. It consists of a capsule surrounding trabecula. The compartments are of two types, the red pulp and white pulp. Red pulp consists of macrophages and numerous red blood cells (erythrocytes) and few lymphocytes; it is the site where old and defective red blood cells are destroyed and removed. White pulp populated mainly by T lymphocytes.