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THE IMMUNE 2 SYSTEM by: JPSC  IMMUNE SYSTEM The body’s defense against disease causing organisms, malfunctioning cells and foreign bodies. It plays a very vital role in our body, it protects our body from harmful substances, diseases, viruses, bacteri...

THE IMMUNE 2 SYSTEM by: JPSC  IMMUNE SYSTEM The body’s defense against disease causing organisms, malfunctioning cells and foreign bodies. It plays a very vital role in our body, it protects our body from harmful substances, diseases, viruses, bacteria, and it helps in the removal of foreign bodies and malignant cells from our system that could make us ill. It is made up of various organs, cells, and proteins. It also serves organism by providing natural resistance, recovery, and acquired resistance to infections and diseases. Whereas, on the negative side, immunity may also result in the rejection of a life-saving organ transplant, autoimmune, and immunodeficiency disorders. by: JPSC  FUNCTIONS 1. Defense against infectious agents 2. Homeostasis It is the body’s way or process of maintaining even ranges of body systems such as temperature, hydration, and energy intake. 3. Immune surveillance It can detect and respond to destroy a tumor or neoplastically transform cells before a malignancy can form by activating a stress response. 4. Hypersensitivity or allergy The immune system responds in an abnormal way to a foreign substance thereby potentially harming the body. by: JPSC  5. Production of autoimmune disease In response to an unknown trigger, the immune system may begin to produce antibodies that instead of fighting infections, will attack the body’s own tissues thus producing autoimmune diseases and malignancy. 6. Production of malignancy 7. Immunologic deficiency diseases These are disorders that prevent the body from fighting infections and diseases which makes it easier for us to catch viruses and bacterial infection. by: JPSC  CHARACTERISTICS OF THE IMMUNE SYSTEM 1. Specificity ensures that distinct antigens elicit specific responses. It can distinguish differences among various foreign molecules. 2. Memory leads to enhanced response to repeated exposures to the same antigens. Once the immune system is exposed to an antigen, it exhibits memory and when it will be exposed again to the same antigen, it induces a heightened or enhanced immune response. 3. Replicability increases number of antigen-specific lymphocytes to keep pace with microbe. 4. Mobility increases number of antigen-specific lymphocytes to keep pace with microbe. Enables local reactions to provide systemic protection. by: JPSC  5. Diversity enables immune system to respond to a large variety of antigens. The immune system can respond to different pathogens. 6. Specialization generates responses that are optimal for defense against different types of microbes. 7. Contraction and hemostasis allow immune system to respond to newly encountered antigen. Once an infection has been cleared from the body, the immune system goes back to homeostasis and some of the lymphocytes are no longer stimulated by antigen begins to die, which is called contraction by: JPSC  4. Non-reactivity to self prevents injury to the host during responses to foreign antigens. On the other hand, lymphocytes recognize antigens as something that is not part of the body, but they are still able to recognize and not harm the cells that are part of the body. by: JPSC  Immune system The immune system consists of primary and secondary lymphoid organs, whereas the lymphatic system is part of the circulatory and immune system which is a network of vessels that collect fluid component of blood after it has been drained to tissues, collect antigen from tissues and brings it to secondary lymphoid organs. by: JPSC  LYMPHOID ORGANS The lymphatic system is divided into: 1. Primary lymphoid organs which are the sites for lymphocytes or T and B cell maturation A. bone marrow Found in the center of most bones, red bone marrow is the primary site for the production of all types of blood cells, including lymphocytes. Here, lymphoid stem cells develop into immature B and T lymphocytes. B. thymus The thymus is a soft, lobed gland located in the upper chest, just behind the breastbone. It is responsible for the maturation of T lymphocytes, which are essential for cell- mediated immunity. The thymus involutes (shrinks) with age, and by adulthood, it is much smaller than in a child. by: JPSC  2. SECONDARY lymphoid organs are sites in which further differentiation of lymphocytes occur. A. SPLEEN the largest secondary lymphoid organ located in the upper left quadrant of the abdomen just below the diaphragm, surrounded by a thin connective tissue capsule. It acts as a filter because it removes old, damaged cells, and foreign antigens from the blood. B. LYMPH NODES act as filters and contains different defense cells which trap pathogens and activate the production of antibodies. If lymph nodes become swollen or painful, it can be a sign of an active defense reaction. by: JPSC  D. Others: tonsils, and appendix both act as filters in removing debris and antigen entering the respiratory tract, and the gastrointestinal tract respectively. by: JPSC  PRIMARY LYMPHOID ORGANS 1. Bone marrow sponge-like tissue situated inside the bones (where most defense cells are produced and multiplied) it is the predominant primary lymphoid tissue of the body, because it is the source of all cellular components or cellular elements of the blood, such as erythrocytes, leukocytes, and thrombocytes Once differentiation occurs, mature T and B cells are release from the bone marrow and the thymus. Lymphocyte stem cells are released from the bone marrow and travel to additional primary lymphoid organs where further maturation takes place. by: JPSC  PRIMARY LYMPHOID ORGANS 2. thymus found in the thorax or chest cavity, right below the thyroid gland. It is also called the thymus gland, in which the T cells mature. Unlike most organ that grow until the age of maturity, the thymus enlarges throughout childhood but slowly shrinks from the onset of puberty. As it shrinks its tissues are replaced by adipose tissues which is called the thymic involution by: JPSC  SECONDARY LYMPHOID ORGANS Sites where antigen is trapped and brought into contact with lymphocytes (differentiation). Secondary lymphoid organs provide the environment for the proliferation and maturation of cells, and for filtering and trapping antigens. Antigens in tissues are transported by lymphatic system to secondary lymphoid organs where it is trapped. Newly developed, immunocompetent lymphocytes (T and B) migrate. To secondary lymphoid organs where they interact with antigen, become activated, differentiate, and mutate, divide and multiply Secondary lymphoid organs are distributed throughout the body, and since these organs are responsible for the trapping of antigens. The antigens in tissues are transported with the help of the lymphatic system to the secondary lymphoid organs by: JPSC  FUNCTIONS OF SECONDARY LYMPHOID ORGANS 1 Trapping site of pathogens or antigens. 2 Stand-by areas of T cells, B cells, and phagocytes. Where they become activated and differentiated 3 Place of encounter for pathogens and T cells. by: JPSC  IMMUNE CELLS Several cell types are involved together in the immune system. All the cells that are involved in the immune system arise from the BONE MARROW LYMPHOCYTES Produced by the primary lymphoid organs 20-30% Circulating nucleated cells are lymphocytes and they are classified into 2 categories: Small lymphocytes (T and B lymphocytes) Large granular lymphocytes these lymphoid cells are responsible for the production of immunity and antibodies and include the 3 main types which are B cells, T cells and Natural Killer cells by: JPSC  1. B LYMPHOCYTES 5-15% of circulating lymphocytes; Bursa of Fabricius Can be divided into memory and plasma B cells Classically identified by their cell surface immunoglobulin (Sig) Recognize antigen by means of surface-expressed antigen receptor Distinguishing cell-surface markers include: B220 (CD45), MHC Class Il, CD80 (B7-1) and CD86 (B7-2), CD40, CD19, CD21 by: JPSC  B-cell maturation series Pro-B cell Pre-B cell Immature B cell Mature B cell Activated B cell Plasma cell In the bone marrow the development progresses through the: Pro-B cell --> Pre-B cell --> Immature B cell stages B cells are derived from the multi-potential progenitor cell or the MMP, a lymphoid myeloid precursor Differentiation of pro-B into pre-B cells occurs upon successful rearrangement of heavy chain genes. stromal cells interact directly with pro-B cells and secrete cytokines, hormones, chemokines, and adhesion molecules The Pre-B cell stage begins when the synthesis of the heavy chain part of the antibody molecule occurs. The immature B cells are distinguished by the appearance if complete IgM molecules on the cell’s surface once these rearrangements are completed successfully the transcription begins and the Pre-B cells become Immature B cells and later develop into Mature B cells by: JPSC  The immature B cells exit the bone marrow and enter the blood to complete the maturation program in the secondary lymphoid tissues preferably in the spleen. Mature B cell --> Activated B cell --> Plasma cell develop into either marginal B cells or Follicular B cells and form germinal centers which differentiates into plasma blast and then into plasma cells Plasma cells will migrate to the bone marrow where a subset of them will live for a long time. These plasma cells also provide a source of long-lasting high affinity antibody Humoral immunity is also called Antibody mediated immunity; with the help of T cells, the B cells will differentiate into Plasma B cells that can produce antibodies which are the central elements humoral immunity The antigen recognition molecules of the B cells are the Immunoglobulins. by: JPSC by: JPSC  2. t lymphocytes 70% T cells (5-10%B cells and10-15%are null cells) T cells derive from stem cells in the bone marrow “mature” in the thymus, and then are released into the periphery Primary effectors of “cellular immunity”. Can be divided (broadly) into helper T cells (Th) and cytotoxic T cells (Tc); usually found in a 2:1 ratio. by: JPSC  “cellular immunity” is mediated by the T lymphocytes so in the blood T cells constitute 70% of peripheral lymphocytes and they migrate and mature in the thymus and acquire and express certain surface antigens Each T cell is genetically programmed to recognize a specific cell bound antigen through an antigen specific T cell receptor The T cells functions in the cell mediated immune responses or cellular immunity such as delayed hypersensitivity, graft versus host reactions, and allograft rejection. The Helper T cells are the Th are the most important cells in adaptive immunity where there is a response to a foreign antigenic stimulus which results in the acquisition of immunologic memory and the production of antibodies The T lymphocytes are also associated with cellular immunity so they are responsible for cell mediated immune responses and are divided into several subpopulations with specific functions such as the T helper cells and the cytotoxic T cells. These cytotoxic T cells are effector cells that destroy the virus infected cells, tumor cells, and tissue grafts. T cells have a longer life span compared to B cells which makes it an advantage for the T cells because of their involvement in immunological memory. by: JPSC  Helps the B cell to produce CYtotoxic t-cell antibody response to an B cell differentiation antigen CD4 positive Destroy cells recognized as CD8 positive Secretes lymphotoxins and CYtotoxic t-cell foreign release perforins T Helper cells (Th) Cytotoxic T cells (Tc) glycoprotein found on the surface of T helper cells contains also CD3 that is involved in the activation of is CD4; that’s why T helper cells are CD4 positive cytotoxic T cells (often referred) these cells secrete lymphotoxins which is one of the produces proteins or cytokines that act on B cells tumor necrosis factors that is produces by the T stimulating them to produce antibodies lymphocytes which inhibits or prevents the growth most important cells in adaptive immunity; they do of tumors by causing lysis of cells and blocks the not only help in the activation of B cells to produce transformation of cells. antibodies and macrophages to destroy microbes but release perforins that destroy the targeted cells by also help activate the Cytotoxic T cells to kill infected the formation of holes in the cell membrane to target cells destroy the virus inside the cell by: JPSC  Cytotoxic (killer) t-cell Cytotoxic T cells (CD8+ T cells) attack their target cells (e.g. virally-infected cells) and kill them directly. They are activated in the lymph nodes by dendritic cells. Once they are activated, they are sent out to the site of infection and bind to the cells that express the MHC class 1 that are presenting the foreign antigens by: JPSC  Other similarities between the T and B cells: Both have the same site of origin which is the Bone marrow Both mainly work for protecting the body’s immune system and fight against pathogens Both are involved in adaptive immunity Both have antigen receptors T cell receptors- aka: TCR B cell receptors- aka: BCR t-cell subsets: 1. T HELPER CELLS CD4+; recognize a specific antigen in association with a homologous class II MHC molecule. Act primarily on B cells Th1 mediate functions connected with cytotoxicity and local inflammatory reactions. Th2 direct the immune response toward production of IgE, IgA and IgG1 by: JPSC  2. INDUCER T LYMHOCYTES CD4+ cells that recognize antigens associated with Class I MHC molecules. Activate Th cells, Ts cells and macrophages. 3. SUPPRESSOR T LYMPHOCYTES CD8+ cells that interfere with the development of an immune response by acting directly on the cell or by releasing suppressor factors. 4. DELAYED-TYPE HYPERSENSITIVITY EFFECTOR CELLS CD4+ lymphocytes sub type of Type IV hypersensitivity 5. MEMORY T LYMPHOCYTES CD4+ cells Responsible for anamnestic response and booster immunization by: JPSC  t-cell maturation series Double negative thymocytes Double Activated Sensitized (lymphocyte positive Mature T cell T cell T cell precursors) thymocytes 60 to 80% of circulating lymphocytes in the peripheral blood are T cells and becomes differentiated in the Thymus. The lymphocytes precursors which are called the Thymocytes enter the thymus from the bone marrow the early thymocytes lack CD4 and CD8 markers so these thymocytes are known as double negative thymocytes. Furthermore, they proliferate in the outer cortex under the influence of Interleukin-7. At the second stage the double positive stage the thymocytes can already express both the CD4 and the CD8 antigens so they are now called as the Double positive thymocytes. CD3 TCR is expressed on the cell surface wherein a positive selection process takes place that allows only double positive cells with functional TCR receptors to survive. Functional T cells must be able to recognize foreign antigens along with MHC or the Major histocompatibility complex molecules. by: JPSC  A second selection process takes place among the surviving double positivity cells which is known as Negative selection, this process is very rigorous because only 1 to 2% of the double positive thymocytes in the cortex survive. The cells that survive the selection process exhibit only 1 type of marker either the CD4 or the CD8 --> migrate to the medulla --> 2 major events occur: 1. Development of two distinct T-cell populations; the helper or the inducer cells which are also known as CD4 and the suppressor cytotoxic T cells or the CD 8 2. The loss of TDT enzyme or what we call as the terminal deoxynucleotide transferase by: JPSC  The process assures that most T cells leaving the Thymus will not react to self-antigens, additional proliferation occurs and these cells leave the thymus to proceeds to the secondary lymphoid organs. They recirculate back through the bloodstream and the peripheral organs once every 12 to 24 hours from the T cells to make contact with an antigen. When antigen recognition occurs the T lymphocytes are transformed into large activated cells. T lymphoblast differentiate into functionally active small lymphocytes that produce cytokines which function in assisting B cells to start antibody production killing tumors and other target cells rejecting grafts stimulating hematopoiesis and initiating delayed hypersensitivity reactions this type of immune response is known as the cell-mediated immunity. by: JPSC  Development of Cells Double negative thymocytes (lymphocyte precursor) Double positive thymocytes Mature T cell Activated T cell Sensitized T cell T Cell Receptors CD2 - sheep red blood cell receptor; involved in T cell activation CD3 - part of T cell-antigen receptor complex CD4 - receptor of MHC class I molecule; receptor for HIV CD8 - receptor of MHC class 1 molecule Similarities between T and B cells Antigen receptor on surface (T cell receptor or TCR) Recognize single, specific antigen Expand through clonal selection Some T cells exist as long-lived memories by: JPSC  T-cell B-cell Develop in the thymus Develop in the bone marrow Found in blood (60-80% of circulating lymphocytes), Found in bone marrow, spleen, lymph nodes thoracic duct fluid, lymph nodes Identified by rosette formation with SRBCs Identified by surface immunoglobulin End products of activation are cytokines End product of activation is antibody Antigens include CD2, CD3, CD4, CD8 Antigens include CD19, CD20, CD21, CD40, MHC class Il Located in paracortical region of lymph nodes Located in cortical region of lymph nodes by: JPSC  Location of T and B cells T-cell B-cell Perifollicular and paracortical regions of the lymph Follicular and medullary (germinal centers) of the nodes lymph nodes Medullary cords of the lymph nodes Primary follicles and red pulp of the spleen Periarteriolar regions of the spleen Follicular regions of GALT Thoracic duct of the circulatory system Medullary cords of the lymph nodes by: JPSC  Antigen Processing and Presentation Unlike B cells, T cells cannot recognize “free” antigen Processed (digested) in to smaller fragments within special “antigen presenting cells” (APCs) Presented on the surface of APCs in the context of MHC (major histocompatibility complex) proteins. by: JPSC  null cells Referred to as “Null” cells because they are lymphocytes, but lack typical B cell or T cell markers on their surface Also known as large granular lymphocytes (LGLs) or natural killer (NK) cells Demonstrate cytotoxicity against tumor cells and some virus-infected cells Not specific; do not require antigen stimulation Not phagocytic; but must contact cell in order to lyse it Destroys antigen thru the release of perforin by: JPSC  plasma cells The plasma cells are not normally found in the blood and are derived from B lymphocytes. The plasma cells function in the synthesis and excretion of immunoglobulins or antibodies. They are non-dividing and after several days of antibody production they die without further proliferation. Known as mature antibody-producing cells Contain large inclusion bodies called Russel bodies Derived from B lymphocytes by: JPSC  Monocytes (Peripheral Blood or Macrophage Tissues Monocytes circulate in the blood after leaving the bone marrow and migrate into various tissues and become tissue macrophages. Monocytes that disappear from the blood are not removed from the body but instead, these cells enter the tissues and become macrophages with a longer lifespan. They are involved in phagocytosis and when monocytes become macrophages they are highly motile and they can live for a longer time in tissues. Formed in bone marrow, spleen, and tissues of RES Function in amoeboid movement and phagocytosis (immune response) by: JPSC  GRANULOCYTES Granulocytes are a type of white blood cells that has small granules which contain proteins and with segmented or lobulated nuclei. They play an important role in acute inflammation.. 1. Neutrophils Important in the body’s defense (phagocytosis and destruction of microorganisms) Process facilitated by complement and antibody Comprise majority of white blood cells Multi-lobe nuclei (2-5) Cytoplasmic granules that stain with both acid and basic dyes Play an important role in protection against extracellular microorganism infection Major function: represent about 60-70% of circulating nucleated cells is phagocytosis. Phagocytosis: enhanced when particles or antigens are coated with antibodies by: JPSC  2. Basophils Contains heparin Important in immediate hypersensitivity reactions Found in large numbers in some cell-mediated delayed reactions Bilobed nuclei and cytoplasmic granules Found in low numbers in the blood and act as Mast Cells Involve in allergic reactions particularly the Type I hypersensitivity so when an individual is exposed to an allergen, specific Ig is produced and binds to the surface of the basophils. An increase in the number of basophils in the peripheral blood causes inflammation and may cause immediate hypersensitivity reactions by: JPSC  3. Eosinophils Major affector cells in the immune system Has a specialized role in immunity to helminth and other parasitic infections Can also be damaging to the inflammatory process of allergic disease When triggered, these cells release histamine which can cause asthma and eosinophil count is raised or increased in people with allergic reactions and those who are exposed to parasitic or helminth infections Found in tissues at sites of immune response or reaction that have been triggered by IgE antibodies Attracted to antigen antibody complex and can phagocytize them Interleukin-5 Contain a number of enzymes that can degrade mediators of immediate hypersensitivity Histamine slow reacting substance of anaphylaxis PAF (Platelet Aggregating Factor): control or diminish such hypersensitivity by: JPSC  mast cells Found in a wide variety of tissues, including Skin connective tissues Mucosal epithelial tissues of the respiratory, genitourinary and digestive tracts Heavily granulated Granules contain histamine; degranulation of mast cells results in histamine release, allergic/inflammatory response. Mast cells and basophils have similar characteristics in terms of their function and development. The mast cells have similar importance in allergic reactions as basophils but only found in tissues. by: JPSC  dendritic cells Named as such because when they mature their cytoplasm extends into transient spiny dendrites and sheet like veils These cells function into 3 categories all of which are involved in antigen presentation namely: Antigen presentation and activation of T cells Inducing and maintaining immune tolerance Maintaining immune memory with the B cells Lineage/origin is not entirely understood Express high levels of MHC class II and B7 molecules, making them extremely potent APCs. Multiple different types, based on location (similar to macrophages). Langerhans cells found in skin and mucous membranes. by: JPSC  MONONUCLEAR CELLS Consist of monocytes (in blood) and macrophages (in tissues). Macrophages are larger, more complex, and produce more hydrolytic enzymes Alveolar macrophages lungs Histiocytes connective tissues Kupffer cells liver Mesangial cells kidney Microglial cells brain Osteoclasts bone Splenic macrophages spleen Peritoneal macrophages peritoneal fluid Dendritic cells lymph nodes Langerhans cells skin by: JPSC  cytokines A group of protein or glycoproteins secreted by white blood cells and various cells of the body in response in several stimuli. Their major functions are to mediate and regulate immune response and inflammatory reactions. Interleukins The major cytokines include interleukins that act as mediators between leukocytes and the majority of this are produced by the T helper cells. Endogenous Pyrogen IL-1 substance that originate inside of a body and is capable of inducing fever T cell growth factor CD25 activates antigen presenting cells IL-2 affects the differentiation of B and T cells. considered as the main endogenous pyrogen produced by activated C cells IL-3 Stimulates B cells; potent activator of hematopoietic cells by: JPSC by: JPSC  interferon Proteins produced by virally-infected cells and protect the neighboring cells Which play an important role in the first line of defense against viral infections. tumor necrosis factor Cytotoxic activity against tumor cells and virally infected cells. Which refers to a group of cytokines that can cause cell death or apoptosis TNF plays an important role in tumor cells and virally infected cells because of its cytotoxic activity. by: JPSC  Chemokines Betalysin Enhances motility and promote migration of WBCs Released by platelets during coagulation. Chemokines play a vital role in cell migration and It also has a bactericidal activity that causes lysis the induction of cell movement by enhancing of many gram-positive bacteria motility. by: JPSC