The Immune System PDF

2 THE IMMUNE SYSTEM by: JPSC IMMUNE SYSTEM FUNCTIONS The body’s defense against disease causing organisms, 1. Defense against infectious agents malfunctioning cells and foreign bodies....

2 THE IMMUNE SYSTEM by: JPSC IMMUNE SYSTEM FUNCTIONS The body’s defense against disease causing organisms, 1. Defense against infectious agents malfunctioning cells and foreign bodies. It plays a very vital role in our body, it protects our body 2. Homeostasis from harmful substances, diseases, viruses, bacteria, and It is the body’s way or process of maintaining even ranges of it helps in the removal of foreign bodies and malignant cells body systems such as temperature, hydration, and energy from our system that could make us ill. intake. It is made up of various organs, cells, and proteins. 3. Immune surveillance It also serves organism by providing natural resistance, recovery, and acquired resistance to infections and It can detect and respond to destroy a tumor or neoplastically diseases. Whereas, on the negative side, immunity may also transform cells before a malignancy can form by activating a result in the rejection of a life-saving organ transplant, stress response. autoimmune, and immunodeficiency disorders. 4. Hypersensitivity or allergy The immune system responds in an abnormal way to a foreign substance thereby potentially harming the body. by: JPSC by: JPSC  5. Production of autoimmune disease In response to an unknown trigger, the immune system may CHARACTERISTICS OF THE IMMUNE SYSTEM begin to produce antibodies that instead of fighting infections, 1. Specificity will attack the body’s own tissues thus producing autoimmune ensures that distinct antigens elicit specific responses. diseases and malignancy. It can distinguish differences among various foreign molecules. 6. Production of malignancy 2. Memory leads to enhanced response to repeated exposures to the same antigens. 7. Immunologic deficiency diseases 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 These are disorders that prevent the body from fighting enhanced immune response. infections and diseases which makes it easier for us to catch viruses and bacterial infection. 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 by: JPSC 5. Diversity 4. Non-reactivity to self enables immune system to respond to a large variety of antigens. prevents injury to the host during responses to foreign antigens. The immune system can respond to different pathogens. 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. 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 by: JPSC  Immune system LYMPHOID ORGANS The lymphatic system is divided into: 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 1. Primary lymphoid organs been drained to tissues, collect antigen from tissues and brings it to secondary 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 by: JPSC 2. SECONDARY lymphoid organs D. Others: tonsils, and appendix are sites in which further differentiation of lymphocytes both act as filters in removing debris and antigen entering the respiratory tract, and the gastrointestinal occur. tract respectively. 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 by: JPSC  PRIMARY LYMPHOID ORGANS PRIMARY LYMPHOID ORGANS 1. Bone marrow 2. thymus sponge-like tissue situated inside the bones (where most found in the thorax or chest cavity, right below the thyroid defense cells are produced and multiplied) gland. it is the predominant primary lymphoid tissue of the body, It is also called the thymus gland, in which the T cells mature. because it is the source of all cellular components or cellular elements of the blood, such as erythrocytes, leukocytes, and Unlike most organ that grow until the age of maturity, the thrombocytes thymus enlarges throughout childhood but slowly shrinks from the onset of puberty. Once differentiation occurs, mature T and B cells are release from the bone marrow and the thymus. As it shrinks its tissues are replaced by adipose tissues which is called the thymic involution Lymphocyte stem cells are released from the bone marrow and travel to additional primary lymphoid organs where further maturation takes place. by: JPSC by: JPSC SECONDARY LYMPHOID ORGANS FUNCTIONS OF SECONDARY LYMPHOID ORGANS Sites where antigen is trapped and brought into contact with 1 Trapping site of pathogens or antigens. lymphocytes (differentiation). 2 Stand-by areas of T cells, B cells, and phagocytes. Where they Secondary lymphoid organs provide the environment for the become activated and differentiated proliferation and maturation of cells, and for filtering and 3 Place of encounter for pathogens and T cells. 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 by: JPSC  IMMUNE CELLS 1. B LYMPHOCYTES 5-15% of circulating lymphocytes; Bursa of Fabricius Several cell types are involved together in the immune system. All Can be divided into memory and plasma B cells the cells that are involved in the immune system arise from the Classically identified by their cell surface immunoglobulin (Sig) BONE MARROW Recognize antigen by means of surface-expressed antigen receptor LYMPHOCYTES Distinguishing cell-surface markers include: B220 (CD45), Produced by the primary lymphoid organs MHC Class Il, CD80 (B7-1) and CD86 (B7-2), CD40, CD19, 20-30% CD21 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 by: JPSC B-cell maturation series The immature B cells exit the bone marrow and enter the blood to complete the maturation program in the secondary Pro-B Pre-B Immature Mature Activated Plasma lymphoid tissues preferably in the spleen. cell cell B cell B cell B cell cell Mature B cell --> Activated B cell --> Plasma cell develop into either marginal B cells or Follicular B cells In the bone marrow the development progresses through the: and form germinal centers which differentiates into Pro-B cell --> Pre-B cell --> Immature B cell stages plasma blast and then into plasma cells B cells are derived from the multi-potential progenitor cell Plasma cells will migrate to the bone marrow where a or the MMP, a lymphoid myeloid precursor subset of them will live for a long time. These plasma Differentiation of pro-B into pre-B cells occurs upon cells also provide a source of long-lasting high affinity successful rearrangement of heavy chain genes. antibody stromal cells interact directly with pro-B cells and secrete Humoral immunity is also called Antibody mediated cytokines, hormones, chemokines, and adhesion molecules immunity; with the help of T cells, the B cells will The Pre-B cell stage begins when the synthesis of the differentiate into Plasma B cells that can produce heavy chain part of the antibody molecule occurs. antibodies which are the central elements humoral The immature B cells are distinguished by the appearance if immunity complete IgM molecules on the cell’s surface The antigen recognition molecules of the B cells are once these rearrangements are completed successfully the the Immunoglobulins. transcription begins and the Pre-B cells become Immature B cells and later develop into Mature B cells 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 by: JPSC “cellular immunity” is mediated by the T lymphocytes so in the blood T cells constitute 70% of peripheral Helps the B cell to produce lymphocytes and they migrate and mature in the thymus and acquire and express certain surface antigens CYtotoxic t-cell antibody response to an B cell differentiation antigen CD4 positive Each T cell is genetically programmed to recognize a specific cell bound antigen through an antigen specific T cell receptor CYtotoxic t-cell Destroy cells recognized as CD8 positive Secretes lymphotoxins and foreign release perforins The T cells functions in the cell mediated immune responses or cellular immunity such as delayed hypersensitivity, graft versus host reactions, and allograft rejection. T Helper cells (Th) Cytotoxic T cells (Tc) 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 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 The T lymphocytes are also associated with cellular immunity so they are responsible for cell mediated immune (often referred) these cells secrete lymphotoxins which is one of the responses and are divided into several subpopulations with specific functions such as the T helper cells and the produces proteins or cytokines that act on B cells tumor necrosis factors that is produces by the T cytotoxic T cells. 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 These cytotoxic T cells are effector cells that destroy the virus infected cells, tumor cells, and tissue grafts. 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 T cells have a longer life span compared to B cells which makes it an advantage for the T cells because of their also help activate the Cytotoxic T cells to kill infected the formation of holes in the cell membrane to involvement in immunological memory. target cells destroy the virus inside the cell by: JPSC by: JPSC  Other similarities between the T and B cells: Cytotoxic (killer) t-cell Both have the same site of origin which is the Bone marrow Both mainly work for protecting the body’s immune system Cytotoxic T cells (CD8+ T cells) attack their target cells (e.g. virally-infected cells) and kill them directly. 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 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 Th1 mediate functions connected with cytotoxicity and local inflammatory reactions. Th2 direct the immune response toward production of IgE, IgA and IgG1 by: JPSC by: JPSC 2. INDUCER T LYMHOCYTES CD4+ cells that recognize antigens associated with Class I t-cell maturation series MHC molecules. Double negative Activate Th cells, Ts cells and macrophages. thymocytes Double positive Mature T cell Activated Sensitized (lymphocyte precursors) thymocytes T cell T cell 3. SUPPRESSOR T LYMPHOCYTES CD8+ cells that interfere with the development of an immune 60 to 80% of circulating lymphocytes in the peripheral blood are T cells and becomes differentiated in the response by acting directly on the cell or by releasing Thymus. The lymphocytes precursors which are called the Thymocytes enter the thymus from the bone marrow suppressor factors. 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. 4. DELAYED-TYPE HYPERSENSITIVITY EFFECTOR CELLS At the second stage the double positive stage the thymocytes can already express both the CD4 and the CD8 CD4+ lymphocytes antigens so they are now called as the Double positive thymocytes. sub type of Type IV hypersensitivity CD3 TCR is expressed on the cell surface wherein a positive selection process takes place that allows only double 5. MEMORY T LYMPHOCYTES positive cells with functional TCR receptors to survive. CD4+ cells Responsible for anamnestic response and booster immunization Functional T cells must be able to recognize foreign antigens along with MHC or the Major histocompatibility complex molecules. by: JPSC by: JPSC  A second selection process takes place among the surviving double positivity cells which is known as Negative The process assures that most T cells leaving the selection, this process is very rigorous because only 1 to 2% of the double positive thymocytes in the cortex Thymus will not react to self-antigens, additional survive. proliferation occurs and these cells leave the thymus to The cells that survive the selection process exhibit only 1 type of marker either the CD4 or the CD8 --> migrate proceeds to the secondary lymphoid organs. They to the medulla --> 2 major events occur: recirculate back through the bloodstream and the peripheral organs once every 12 to 24 hours from the 1. Development of two distinct T-cell populations; the helper or the inducer cells which are also known as CD4 T cells to make contact with an antigen. 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 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 by: JPSC Development of Cells T-cell B-cell Double negative thymocytes (lymphocyte precursor) Develop in the thymus Develop in the bone marrow Double positive thymocytes Mature T cell Found in blood (60-80% of circulating lymphocytes), Found in bone marrow, spleen, lymph nodes Activated T cell thoracic duct fluid, lymph nodes Sensitized T cell Identified by rosette formation with SRBCs Identified by surface immunoglobulin End products of activation are cytokines End product of activation is antibody T Cell Receptors Antigens include CD2, CD3, CD4, CD8 Antigens include CD19, CD20, CD21, CD40, MHC class Il CD2 - sheep red blood cell receptor; involved in T cell activation CD3 - part of T cell-antigen receptor complex Located in paracortical region of lymph nodes Located in cortical region of lymph nodes 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 by: JPSC  Location of T and B cells Antigen Processing and Presentation Unlike B cells, T cells cannot recognize T-cell B-cell “free” antigen Perifollicular and paracortical regions of the lymph Follicular and medullary (germinal centers) of the Processed (digested) in to smaller nodes lymph nodes fragments within special “antigen Medullary cords of the lymph nodes Primary follicles and red pulp of the spleen presenting cells” (APCs) Periarteriolar regions of the spleen Follicular regions of GALT Presented on the surface of APCs in Thoracic duct of the circulatory system Medullary cords of the lymph nodes the context of MHC (major histocompatibility complex) proteins. by: JPSC by: JPSC null cells plasma cells Referred to as “Null” cells because they are lymphocytes, but lack typical B cell or T cell markers on their surface The plasma cells are not normally found in the blood and are derived from B lymphocytes. The plasma cells Also known as large granular lymphocytes (LGLs) or natural killer (NK) cells function in the synthesis and excretion of immunoglobulins or antibodies. They are non-dividing and after several Demonstrate cytotoxicity against tumor cells and some virus-infected cells days of antibody production they die without further proliferation. Not specific; do not require antigen stimulation Known as mature antibody-producing cells Not phagocytic; but must contact cell in order to lyse it Contain large inclusion bodies called Russel bodies Destroys antigen thru the release of perforin Derived from B lymphocytes by: JPSC by: JPSC  Monocytes (Peripheral Blood or Macrophage Tissues GRANULOCYTES Monocytes circulate in the blood after leaving the bone marrow and migrate into various tissues and become Granulocytes are a type of white blood cells that has small granules which contain proteins and with segmented tissue macrophages. Monocytes that disappear from the blood are not removed from the body but instead, these or lobulated nuclei. They play an important role in acute inflammation.. 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. 1. Neutrophils Formed in bone marrow, spleen, and tissues of RES Important in the body’s defense (phagocytosis and Function in amoeboid movement and phagocytosis (immune response) 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 by: JPSC 2. Basophils 3. Eosinophils Contains heparin Major affector cells in the immune system Important in immediate hypersensitivity reactions Has a specialized role in immunity to helminth and other parasitic Found in large numbers in some cell-mediated delayed reactions infections Bilobed nuclei and cytoplasmic granules Can also be damaging to the inflammatory process of allergic disease Found in low numbers in the blood and act as Mast Cells When triggered, these cells release histamine which can cause Involve in allergic reactions particularly the Type I hypersensitivity so asthma and eosinophil count is raised or increased in people with when an individual is exposed to an allergen, specific Ig is produced allergic reactions and those who are exposed to parasitic or and binds to the surface of the basophils. helminth infections An increase in the number of basophils in the peripheral blood Found in tissues at sites of immune response or reaction that have causes inflammation and may cause immediate hypersensitivity been triggered by IgE antibodies reactions 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 by: JPSC  mast cells dendritic cells Found in a wide variety of tissues, including Named as such because when they mature their cytoplasm Skin extends into transient spiny dendrites and sheet like veils connective tissues Mucosal epithelial tissues of the respiratory, genitourinary and digestive tracts These cells function into 3 categories all of which are involved in antigen presentation namely: Antigen presentation and activation of T cells Heavily granulated Inducing and maintaining immune tolerance Granules contain histamine; degranulation of Maintaining immune memory with the B cells mast cells results in histamine release, allergic/inflammatory response. Mast cells and basophils have similar Lineage/origin is not entirely understood characteristics in terms of their function and Express high levels of MHC class II and B7 molecules, making development. them extremely potent APCs. The mast cells have similar importance in allergic Multiple different types, based on location (similar to reactions as basophils but only found in tissues. macrophages). Langerhans cells found in skin and mucous membranes. by: JPSC by: JPSC MONONUCLEAR CELLS cytokines A group of protein or glycoproteins secreted by white blood cells and various cells of the body in response in Consist of monocytes (in blood) and macrophages (in tissues). several stimuli. Their major functions are to mediate and regulate immune response and inflammatory reactions. Macrophages are larger, more complex, and produce more hydrolytic enzymes Interleukins Alveolar macrophages lungs The major cytokines include interleukins that act as mediators Histiocytes connective tissues between leukocytes and the majority of this are produced by the T helper cells. Kupffer cells liver Mesangial cells kidney Endogenous Pyrogen Microglial cells brain IL-1 substance that originate inside of a body and is capable of inducing fever Osteoclasts bone T cell growth factor CD25 Splenic macrophages spleen activates antigen presenting cells Peritoneal macrophages peritoneal fluid IL-2 affects the differentiation of B and T cells. Dendritic cells lymph nodes considered as the main endogenous pyrogen produced by activated C cells Langerhans cells skin 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 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