Lesson3 - SZL2111 HIV/AIDs LESSON 3 The Immune system...

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Unformatted text preview: SZL2111 HIV/AIDs LESSON 3 The Immune system Learning outcomes SODeL JKUAT Upon completing this topic, you should be able to : ˆ Have an overview of the Human Immune system(IS) ˆ Understand various types of immunity ˆ Describe various stages of immune response ˆ What is immunodeciency? ˆ Various disorders and diseases associated with immune system JJ II J I J DocDoc I Back Close 1 SZL2111 HIV/AIDs 3.1. Overview of the Immune System Immune system is a system of biological structures and processes within an organism that protects against diseases by identifying and killing pathogens and tumor cells. The immune system SODeL JKUAT is made up of organs that are involved in ghting invasion by foreign bodies. They include; 3.1.1. The bone marrow The bone marrow is the production site of the white blood cells(WBC) involved in immunity WBC involved includes the B-lymphocytes (B cells) and the T lymphocytes (T cells). The B-lymphocytes mature in the bone marrow and then enter the JJ II J I J DocDoc I Back Close circulation. T lymphocytes move from the bone marrow to the thymus, where they mature into several kinds of cells capable 2 SZL2111 HIV/AIDs of dierent functions Lymphoid organs The Lymphoid tissues include the thymus gland, the spleen, the lymph nodes, the tonsils and adenoids, and similar tissues in the gastrointestinal, respiratory, and reproductive systems The lymph nodes are SODeL JKUAT distributed throughout the body. They are connected by lymph channels and capillaries, which remove foreign material from the lymph before it enters the bloodstream. The lymph nodes also serve as centers for immune cell proliferation. The remaining lymphoid tissues, such as the tonsils and adenoids and other mucoid lymphatic tissues, contain immune cells that defend the body against microorganisms JJ II J I J DocDoc I Back Close 3 SZL2111 HIV/AIDs 3.1.2. Types of Immunity • Innate/ Inborn/Natural/Non-specic immunity; Present at birth Provide non-specic immunity to any foreign invador regardless of invadors' composition. Operates under cer- SODeL JKUAT tain mechanisms or factors ˆ Physical/mechanical barrier  Skin protects from entry of pathogens to our body  Respiratory tracts- the hairs /cilia along the tract leads to coughing & sneezing in presence of microorganism hence act as lters to clear the pathogens from upper respiratory tract. JJ II J I J DocDoc I Back Close ˆ Biochemical factors Acidic gastric juices e.g. Hydrochloric acid in the stomach. Enzymes present in sweat, saliva and 4 SZL2111 HIV/AIDs breast milk respond by destroying invading microorganisms. Blood protein factors e.g. interferons, compliments, acute phase proteins destroy by puncturing holes in the body. SODeL JKUAT ˆ Genetic - control People may become carriers but not sick ˆ Cellular factors - WBCs participate both in natural & acquired immune responses. The cells ght invading foreign bodies by releasing cell mediators. Other cells (nongranular) e.g. monocytes & macrophages are phagocytic i.e. engulf, digest &kill microorganism Inammatory responses. The inammatory response is a major function of the natural (nonspecic) immune system elicited in re- JJ II J I J DocDoc I Back Close sponse to tissue injury or invading organisms. Chemical mediators assist this response by: Minimizing blood loss 5 SZL2111 HIV/AIDs Walling o the invading organism. Activating phagocytes and promoting formation of brous scar tissues. Regeneration of injured tissue. • Acquired/ Adaptive / Specic Immunity SODeL JKUAT Immunologic responses are acquired during life. Are not present at birth. They develop as a result of immunization/vaccination. Also developed after contracting a disease i.e. weeks or months after exposure to the disease, the body produces an IR sucient to defend against re-infection. The two types of acquired immunity: active and passive. In active acquired immunity, the immunologic defenses are developed by the person's own body. JJ II J I J DocDoc I Back Close This immunity generally lasts many years or even a lifetime. Passive acquired immunity is temporary immunity transmitted 6 SZL2111 HIV/AIDs from another source that has developed immunity through previous disease or immunization. For example, gamma-globulin and antiserum, obtained from the blood plasma of people with acquired immunity, are used in emergencies to provide immu- SODeL JKUAT nity to diseases when the risk for contracting a specic disease is great and there is not enough time for a person to develop adequate active immunity. Both types of acquired immunity involve humoral and cellular (cell-mediated) immunologic responses. It's divided into 2 forms 1. Humoral immunity (AMI) Involves antibodies produced by B cells The antibodies recognize & bind specically to JJ II J I J DocDoc I Back Close foreign antigens & may cause one of the following: -Break/ splitdown the membrane of Ag (lysis) -Coat the Ag mak7 SZL2111 HIV/AIDs ing it easier for phagocytosis (opsonization) -Neutralize activities of toxins/ virus/ bacteria (neutralization) -Direct killing of foreign Ag ( cytotoxicity / cell killing) -Clump parasites together (agglutination) SODeL JKUAT 2. Cell mediated immunity (CMI) - Two most important T cell subtypes are involved in CMI T helper and T killer cells • Cells of the Immune System 1. T-Cells  T lymphocytes are divided into two major subsets that dier in functions and identity (functionally and phenotypically (identiably) dierent). JJ II J I J DocDoc I Back Close (a) The T helper subset, (CD4+ T cell) - The main function is to augment or potentiate immune responses by 8 SZL2111 HIV/AIDs the secretion of specialized factors that activate other WBCs to ght o infection. They interact with B cells or T killer cells & help them respond to foreign agents. T helper1-controls intracellular pathogens SODeL JKUAT (CMI) (b) T helper2 - controls extra cellular pathogens (AMI) b)T killer/suppressor subset (CD8+ T cell). These cells are important in directly killing certain tumor cells, viral-infected cells and sometimes parasites. They directly bind to foreign agents, attack & kill those cells thus eliminating them from the body. The CD8+ T cells are also important in down-regulation of im- JJ II J I J DocDoc I Back Close mune responses. 9 SZL2111 HIV/AIDs NB: Both types of T cells can be found throughout the body. They often depend on the secondary lymphoid organs (the lymph nodes and spleen) as sites where activation occurs, but they are also found in other tissues of SODeL JKUAT the body, most conspicuously the liver, lung, blood, and intestinal and reproductive tracts. 2. Natural Killer Cells (NK) Are similar to the killer T cell subset (CD8+ T cells). They directly kill certain tumors such as melanomas, lymphomas and viral-infected cells, most notably herpes and cytomegalovirus-infected cells. NK cells, unlike the CD8+ (killer) T cells, kill their targets without a prior sensitization. But kill more eectively JJ II J I J DocDoc I Back Close when activated by T h cell. 3. B Cells  The major function of B lymphocytes is the 10 SZL2111 HIV/AIDs production of antibodies in response to foreign proteins of bacteria, viruses, and tumor cells. Antibodies are specialized proteins that specically recognize and bind to one particular protein that specically recognize and bind to SODeL JKUAT one particular protein. Antibody production and binding to a foreign substance or antigen, is critical as a means of signaling other cells to engulf, kill or remove that substance from the body. 4. Granulocytes or Polymorphonuclear (PMN) Leukocytes It is a group of WBCs. Granulocytes are composed of three cell types identied as neutrophils, eosinophils and basophils, based on their staining characteristics with cer- JJ II J I J DocDoc I Back Close tain dyes. These cells are important in the removal of bacteria and parasites from the body. They engulf these 11 SZL2111 HIV/AIDs foreign bodies and degrade them using their powerful enzymes. (a) Neutrophils -a/c60% - complete dvpt in the BM enter blood & remain incirculation for 10hours - leave SODeL JKUAT thro capillary wall & enter connective tissue - after a day or 2 they enter the digestive tract or urinary tract & are swept out of the body by waters. (b) Eosinophils a/c 3% of circulating WBCs - help control allergic reactions & helminth infections (c) Basophils- a/c less than 1% - controls allergic reactions, inammatory reactions, clotting process & fat metabolism JJ II J I J DocDoc I Back Close 5. Macrophages  They are often referred to as scavengers or antigen-presenting cells (APC). This is because they pick 12 SZL2111 HIV/AIDs up and ingest foreign materials and present these antigens to other cells of the immune system such as T cells and B cells. This is one of the important rst steps in the initiation of an immune response. Stimulated macrophages SODeL JKUAT exhibit increased levels of phagocytosis and are also secretory. Monocytes - they cross capillary wall, enter tissue & dierentiate to macrophages, - destroy bacteria, dead cells and other matters - Are CD4+ 6. Dendritic Cells  Dendritic cells function as APCs. In fact, they are more ecient APCs than macrophages. These cells are usually found in the structural compartment of the lymphoid organs such as the thymus, lymph nodes and JJ II J I J DocDoc I Back Close spleen. They are also found in the bloodstream and other tissues of the body. It is believed that they capture anti13 SZL2111 HIV/AIDs gen or bring it to the lymphoid organs where an immune response is initiated. They are extremely hard to isolate. Recent nding is that dendritic cells bind high amount of HIV, and may be a reservoir of virus that is transmitted SODeL JKUAT to CD4+ T cells during an activation event. Cells that possess CD4 markers include: ˆ T helper cells ˆ Macrophages ˆ Monocytes ˆ Colon cells ˆ Dendritic cells ˆ Retinal cells JJ II J I J DocDoc I Back Close NB: HIV attaches to any CD4+ cell. Immune response to invasion 14 SZL2111 HIV/AIDs When bacteria, viruses or other pathogens overcome the body's natural immunity and gain entry into the blood system, three specic mechanism of acquired immunity are initiated. They include: SODeL JKUAT ˆ The phagocytic immune response ˆ The humoral or antibody immune response ˆ The cellular or cell mediated immune response 1. Phagocytic immune response ˆ The rst line of defense, the phagocytic immune re- sponse, involves the WBCs (granulocytes and macrophages which have the ability to ingest foreign particles. These JJ II J I J DocDoc I Back Close cells move to the point of attack, where they engulf and destroy the invading agents. 15 SZL2111 HIV/AIDs 2. Humoral or Antibody immune response ˆ The humoral response is characterized by production of antibodies by the B-lymphocytes in response to a specic antigen. Although the B-lymphocyte is ulti- SODeL JKUAT mately responsible for the production of antibodies, both the macrophages of natural immunity and the special T-cell lymphocytes of cellular immunity are involved in recognizing the foreign substance and in producing antibodies. 3. Antigen recognition ˆ The part of the invading or attacking organism that is responsible for stimulating antibody production is JJ II J I J DocDoc I Back Close called an antigen (or an immunogen). For example, an antigen can be a small patch of proteins on the 16 SZL2111 HIV/AIDs outer surface of the microorganism. A single bacterium, even a single large molecule, such as a toxin (diphtheria or tetanus toxin), may have several such antigens, or markers, on its surface, thus inducing SODeL JKUAT the body to produce a number of dierent antibodies. Once produced, an antibody is released into the bloodstream and carried to the attacking organism. There it combines with the antigen, binding with it like an interlocking piece of a jigsaw puzzle . 3.1.3. Stages in an immune response • Recognition stage JJ II J I J DocDoc I Back Close ˆ The immune system's ability to recognize antigens as foreign, or non-self, is the initiating event in any immune 17 SZL2111 HIV/AIDs response (g 2.2). The body must rst recognize invaders as foreign before it can react to them. The body accomplishes recognition using lymph nodes and lymphocytes for surveillance. Lymph nodes are widely distributed in- SODeL JKUAT ternally and externally near the body's surfaces. They continuously discharge small lymphocytes into the bloodstream. These lymphocytes patrol the tissues and vessels that drain the areas served by that node. ˆ Lymphocytes are found in the lymph nodes and in the circulating blood. The volume of lymphocytes in the body is impressive. These lymphocytes recirculate from the blood to lymph nodes and from the lymph nodes back into the JJ II J I J DocDoc I Back Close bloodstream, in a never-ending series of patrols. Some circulating lymphocytes can survive for decades. Some of 18 SZL2111 HIV/AIDs these small, hardy cells maintain their solitary circuits for the lifetime of the person. ˆ The exact way in which circulating lymphocytes recognize antigens on foreign surfaces is not known; however, the- SODeL JKUAT orists think that recognition depends on specic receptor sites on the surface of the lymphocytes. Macrophages play an important role in helping the circulating lymphocytes process the antigens. When foreign materials enter the body, a circulating lymphocyte comes into physical contact with the surfaces of these materials. Upon contact, the lymphocyte, with the help of macrophages, either removes the antigen from the surface or in some way picks JJ II J I J DocDoc I Back Close up an imprint of its structure, which comes into play with subsequent re-exposure to the antigen. 19 SZL2111 HIV/AIDs ˆ In a streptococcal throat infection, for example, the streptococcal organism gains access to the mucous membranes of the throat. A circulating lymphocyte moving through the tissues of the neck comes in contact with the organ- SODeL JKUAT ism. The lymphocyte, familiar with the surface markers on the cells of its own body, recognizes the antigens on the microbe as dierent (non-self) and the streptococcal organism as antigenic (foreign). This triggers the second stage of the immune responseproliferation. • Proliferation stage ˆ The circulating lymphocyte containing the antigenic mes- JJ II J I J DocDoc I Back Close sage returns to the nearest lymph node. Once in the node, the sensitized lymphocyte stimulates some of the resident 20 SZL2111 HIV/AIDs dormant T and-lymphocytes to enlarge, divide, and proliferate. T lymphocytes dierentiate into cytotoxic (or killer) T cells, whereas-lymphocytes produce and release antibodies. Enlargement of the lymph nodes in the neck SODeL JKUAT in conjunction with a sore throat is one example of the immune response. • Response stage ˆ In the response stage, the changed lymphocytes function either in a humoral or a cellular fashion. The production of antibodies by the-lymphocytes in response to a specic antigen begins the humoral response. Humoral refers to JJ II J I J DocDoc I Back Close the fact that the antibodies are released into the bloodstream and so reside in the plasma (uid fraction of the 21 SZL2111 HIV/AIDs blood). ˆ With the initial cellular response, the returning sensitized lymphocytes migrate to areas of the lymph node (other than those areas containing lymphocytes programmed to SODeL JKUAT become plasma cells). Here, they stimulate the residing lymphocytes to become cells that will attack microbes directly rather than through the action of antibodies. These transformed lymphocytes are known as cytotoxic (killer) T cells. The T stands for thymus, signifying that during embryologic development of the immune system, these T lymphocytes spent time in the thymus of the developing fetus, where they were genetically programmed to be- JJ II J I J DocDoc I Back Close come T lymphocytes rather than the antibody-producinglymphocytes. Viral rather than bacterial antigens induce 22 SZL2111 HIV/AIDs a cellular response. This response is manifested by the increasing number of T lymphocytes (lymphocytosis) seen in the blood smears of people with viral illnesses, such as infectious mononucleosis. SODeL JKUAT ˆ Most immune responses to antigens involve both humoral and cellular responses, although one usually predominates. For example, during transplantation rejection, the cellular response predominates, whereas in the bacterial pneumonias and sepsis, the humoral response plays the dominant protective role. • Eector stage JJ II J I J DocDoc I Back Close ˆ In the eector stage, either the antibody of the humoral response or the cytotoxic (killer) T cell of the cellular re23 SZL2111 HIV/AIDs sponse reaches and couples with the antigen on the surface of the foreign invader. The coupling initiates a series of events that in most instances results in the total destruction of the invading microbes or the complete neutraliza- SODeL JKUAT tion of the toxin. The events involve interplay of antibodies (humoral immunity), complement, and action by the cytotoxic T cells (cellular immunity). Production of B-Lymphocytes ˆ B-lymphocytes stored in the lymph nodes are subdivided into thousands of clones, each responsive to a single group of antigens having almost identical characteristics. When the antigenic message is carried back to the lymph node, JJ II J I J DocDoc I Back Close specic clones of the-lymphocyte are stimulated to enlarge, divide, proliferate, and dierentiate into plasma cells capa24 SZL2111 HIV/AIDs ble of producing specic antibodies to the antigen. Otherlymphocytes dierentiate into-lymphocyte clones with a memory for the antigen. These memory cells are responsible for the more exaggerated and rapid immune response SODeL JKUAT in a person who is repeatedly exposed to the same antigen. 3.1.4. Role of antibodies in Humoral Immune Responses ˆ Antibodies are large proteins called immunoglobulins because they are found in the globulin fraction of the plasma proteins. Each antibody molecule consists of two subunits, each of which contains a light and a heavy peptide chain. The sub-units are held together by a chemical link com- JJ II J I J DocDoc I Back Close posed of disulde bonds. Each subunit has a portion that serves as a binding site for a specic antigen referred to 25 SZL2111 HIV/AIDs as the Fab fragment. This site provides the "lock" portion that is highly specic for an antigen. An additional portion, known as the Fc fragment, allows the antibody molecule to take part in the complement system. SODeL JKUAT ˆ Antibodies defend against foreign invaders in several ways, and the type of defense employed depends on the structure and composition of both the antigen and the immunoglobulin. The antibody molecule has at least two combining sites, or Fab fragments. One antibody can act as a crosslink between two antigens, causing them to bind or clump together. This clumping eect, referred to as agglutination, helps clear the body of the invading organism by JJ II J I J DocDoc I Back Close facilitating phagocytosis. Some antibodies assist in removing oending organisms through opsonization. In this 26 SZL2111 HIV/AIDs process, the antigenantibody molecule is coated with a sticky substance that also facilitates phagocytosis. ˆ Antibodies also promote the release of vasoactive substances, such as histamine and slow-reacting substance, two of the SODeL JKUAT chemical mediators of the inammatory response. In addition, antibodies are involved in activating the complement system. 3.1.5. Types of Immunoglobulins The body can produce ve dierent types of immunoglobulins. (Immunoglobulins are commonly designated by the abbreviation Ig.) Each of the ve types, or classes, is identied by a specic JJ II J I J DocDoc I Back Close letter of the alphabet (IgA, IgD, IgE, IgG, and IgM). Classication is based on the chemical str...
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