Defense Mechanism PDF

Defense mechanism CIS class-LS101 Introduction to Biology Dr. Mrigya Babuta Assistant Professor Department of Animal Biology, School of Life Sciences  Animal Defense Systems Animal defense systems are based on the distinction between self a...

Defense mechanism CIS class-LS101 Introduction to Biology Dr. Mrigya Babuta Assistant Professor Department of Animal Biology, School of Life Sciences  Animal Defense Systems Animal defense systems are based on the distinction between self and nonself. There are two general types of defense mechanisms: Nonspecific defenses, or innate defenses, are inherited mechanisms that protect the body from many different pathogens. Example: skin Specific defenses are adaptive mechanisms that protect against specific targets. Example: antibodies  Innate Immunity Innate immunity is also called natural or native immunity It provides first line of defense against any microbial infection in human body. It usually involves many cellular and biochemical events that react to microbes and their products in order to clear them from the body. The main components of innate immune system are 1) Barriers 2) Scavenger cells – neutrophils, macrophages, dendritic cell and natural killer cells. 3) Complement system 4) Cytokines 5) Chemical mediators of inflammation  Innate Immunity Microbial agents and pathogens contain some molecules over their surface that act as foreign substance for the body and are collectively called as pathogen associated molecular pattern (PAMP). PAMP’s are recognized by specific proteins and biochemical molecules produced by cells of innate immunity and these recognition molecules are called as pattern recognition receptors. The innate immune responses are produced against the specific structures present over the microbes and are common to many of them. Thus, they cannot distinguish the minute differences among microbes.  Adaptive Immunity Adaptive immunity is stimulated by constant exposure of infectious agents. The most characteristic feature of adaptive immunity is memory against the repetitive exposure of same pathogen. It has a capacity to distinguish between fine differences among microbes and hence also called as specific immunity. As specific immunity is gathered by constant exposure to the foreign agent, it is better termed as acquired immunity.  Adaptive Immunity The central components of adaptive immunity are 1) Lymphocytes and their secreted products e.g. antibodies 2) Foreign substances that trigger specific immune responses and are identified by lymphocytes or antibodies are called as antigens. Graph showing the relation between innate and acquired immunity Common features of Innate and Adaptive immunity  Innate immunity Cells of Innate Immunity: Macrophages and Phagocytes They are present in virtually every tissue and organ of the body and respond instantaneously to the entering pathogens. The job of phagocytic cells involves recruitment of cells at the site of infection, ingestion, and destruction of the pathogens. Neutrophils These are the granulocytes present in the blood stream and are the first line of the defense in the body. They are the most abundant cells present in the blood stream. The nucleus of neutrophils contains 3-5 lobes (polymorphonuclear cells). The cytoplasm of the neutrophils contains the granules that are filled with enzymes like lysozyme, collagenase, and elastase. Cells of Innate Immunity: Monocytes They play a central role in the innate and adaptive immune system. They are about 10-15 µm in diameter and have bean shaped nuclei. Once enter into the circulation they are called macrophages. The major function of macrophage includes following To ingest and kill the microbes. To ingest and clear dead cells and unused cells. They secrete cytokines upon activation. They serve as antigen presenting cells to display the antigens to the T lymphocyte.  Cells of Innate Immunity: Mast cells- These are derived from bone marrow cells and contain histamine and other chemical mediators of allergic diseases. Basophils- They are structurally and functionally similar to mast cells and mediate allergic conditions. The granules of basophils contain acidic proteins which bind to basic dyes (hematoxylin) Eosinophils- They are granulocytes present in the blood and contains the enzyme required to damage the cell wall of the parasite. The granules of the eosinophils contain the basic proteins which bind to acidic dye (eosin). Natural-Killer Cells- The natural killer cells are the third major part of the innate immune system. Their main job is to identify cells that have been infected by a virus, as well as abnormal cells that may turn into (or have turned into) tumor cells Cells of Innate Immunity: Dendritic cells- They are the specialized antigen presenting cells which captures the microbes and microbial antigens, and transport them to lymphoid tissues to be recognized by lymphocytes. They activate the naive T cells and form a bridge between innate and adaptive immune response. They are widely distributed into many organs and epithelial surface.  Adaptive Immunity Cells of Adaptive Immunity Lymphocytes- These are the cells of the adaptive immune system. There are two subsets of the lymphocytes. a) B lymphocyte- Involved in the production of the antibodies. The two major subsets of the B lymphocytes are follicular B cells and marginal B cells. b) T lymphocyte- Involved in the production of cellular immune response. The two major subsets of the T lymphocytes are CD4+ and CD8+ cells. Naïve lymphocytes- The lymphocytes that are not previously encountered with antigens are called as Naïve lymphocytes. They trigger the adaptive immune response after encountering with the antigen  Lymphoid tissue and organs To properly activate the immune system following antigen-antibody interaction, the immune cells need to be localized to a specific area where they properly express the receptors for Antigen (Ag) recognition and attain maturity. Central or Primary Lymphoid organs peripheral or secondary lymphoid organs Central or Primary Lymphoid organs- Bone marrow and thymus Peripheral or secondary lymphoid organs- Spleen and lymph node Primary lymphoid organs are to i) Provide growth factors required for maturation of lymphocytes. ii) Present self antigens for recognition and selection of maturing lymphocytes  Bone Marrow cells are formed in the bone marrow by the process of hematopoiesis by hematopoietic stem cells (HSC) Bone marrow is the major site for the generation of circulating RBC, granulocyte (neutrophils, eosinophils, and basophils), monocytes and B cells.  Bone Marrow Majority of the B cell maturation takes place in the bone marrow, but the final maturation completes in the secondary lymphoid organs (spleen). NK cell maturation occurs entirely in the bone marrow. T cell maturation occurs entirely in the thymus. Thymus The thymus, is the site for maturation of T- lymphocytes, is a lymphoepithelial organ in the upper part of the middle of the chest, just behind the breastbone. Central or Primary Lymphoid organs- Bone marrow and thymus B Cells: Bone marrow site of development T Cells: Thymus site of development  Peripheral or secondary lymphoid organs- Spleen and lymph node Lymphatic system Lymphatic system consists of specialized vessels which drain fluids from tissues and lymph node into the blood circulation. lymphatic system collects the microbial antigens from the entry point and delivers it to the lymph node to activate the adaptive immune response. The antigens are captured and transported to the lymphoid organs during their initial encounter. Antigens are displayed by the antigen presenting cells in the lymphoid tissue and presented to the lymphocytes.  Lymph nodes are the organs that carry the lymph and help in the activation of adaptive immune response. The segregation of B and T lymphocyte depends on the cytokines secreted by the lymph node.  Spleen is also called as graveyard of red blood cells. It is made up of red pulp which is full of blood cells and white pulp rich in lymphocyte. The white pulp helps to stimulate adaptive immune response against blood borne antigens. The white pulp area is divided into T cell and B cell zone.  Other lymphoid tissues Skin, gastrointestinal mucosa, and respiratory epithelium mucosa have their own lymph nodes. The lymphoid tissues associated with the gastrointestinal tract are called gut associated lymphoid tissues (GALT) while bronchial mucosa associated lymphatic tissues are called mucosa associated lymphoid tissues (MALT)  Innate Immunity Innate immunity is also called natural or native immunity It provides first line of defense against any microbial infection in human body. It usually involves many cellular and biochemical events that react to microbes and their products in order to clear them from the body. The main components of innate immune system are 1) Barriers 2) Scavenger cells – neutrophils, macrophages, dendritic cell and natural killer cells. 3) Complement system 4) Cytokines 5) Chemical mediators of inflammation  Innate immunity The main components of innate immune system are 1) Barriers 2) Scavenger cells – neutrophils, macrophages, dendritic cell and natural killer cells. 3) Complement system 4) Cytokines 5) Chemical mediators of inflammation  Barrier immunity The skin acts as a physical barrier to pathogens. Bacteria and fungi on the surface of the body (normal flora) compete for space and nutrients against pathogens. Tears, nasal mucus, and saliva contain the enzyme lysozyme that attacks the cell walls of many bacteria. Mucus and cilia in the respiratory system trap pathogens and remove them. Ingested pathogens can be destroyed by the hydrochloric acid and proteases in the stomach. In the small intestine, bile salts kill some pathogens.  Barrier immunity  Innate immunity The main components of innate immune system are 1) Barriers 2) Scavenger cells – neutrophils, macrophages, dendritic cell and natural killer cells. 3) Complement system 4) Cytokines 5) Chemical mediators of inflammation  Innate immunity Cells of Innate Immunity: Macrophages and Phagocytes They are present in virtually every tissue and organ of the body and respond instantaneously to the entering pathogens. The job of phagocytic cells involves recruitment of cells at the site of infection, ingestion, and destruction of the pathogens. Neutrophils These are the granulocytes present in the blood stream and are the first line of the defense in the body. They are the most abundant cells present in the blood stream. The nucleus of neutrophils contains 3-5 lobes (polymorphonuclear cells). The cytoplasm of the neutrophils contains the granules that are filled with enzymes like lysozyme, collagenase, and elastase. Cells of Innate Immunity: Monocytes They play a central role in the innate and adaptive immune system. They are about 10-15 µm in diameter and have bean shaped nuclei. Once enter into the circulation they are called macrophages. The major function of macrophage includes following To ingest and kill the microbes. To ingest and clear dead cells and unused cells. They secrete cytokines upon activation. They serve as antigen presenting cells to display the antigens to the T lymphocyte.  Cells of Innate Immunity: Mast cells- These are derived from bone marrow cells and contain histamine and other chemical mediators of allergic diseases. Basophils- They are structurally and functionally similar to mast cells and mediate allergic conditions. The granules of basophils contain acidic proteins which bind to basic dyes (hematoxylin) Eosinophils- They are granulocytes present in the blood and contains the enzyme required to damage the cell wall of the parasite. The granules of the eosinophils contain the basic proteins which bind to acidic dye (eosin).  Innate immunity The main components of innate immune system are 1) Barriers 2) Scavenger cells – neutrophils, macrophages, dendritic cell and natural killer cells. 3) Complement system 4) Cytokines 5) Chemical mediators of inflammation  Cytokines Cytokines are the proteins secreted by different cell types and are the regulators of various aspects of innate and adaptive immunity. Many cytokines which were thought to be made by leucocytes are called as interleukins. The productions of cytokines are transient and are not stored for long period of time. Once needed, cytokines are synthesized and secreted out for their biological effect and degraded rapidly upon completion of their assigned job. Cytokines are pleiotropic in nature which means one cytokine can do multiple biological actions. Cytokines may be redundant which means many cytokines can do similar kind of biological activity. Many cytokines act close of their production, either on the same cell called autocrine or to the nearby cells called paracrine action. Cytokines may enter into the circulation from their site of production to act on distant organ; the property is called as endocrine action.  Innate immunity The main components of innate immune system are 1) Barriers 2) Scavenger cells – neutrophils, macrophages, dendritic cell and natural killer cells. 3) Complement system 4) Cytokines 5) Chemical mediators of inflammation  Inflammation Inflammation is the migration of leukocytes, plasma proteins, and blood to the area of breach. They are recruited to the site of injury and destroy the evading pathogens by the help of cytokines and phagocytic cells (neutrophils, macrophages, monocytes). The effect of inflammation in the body has some cardinal features which are described as rubor, calor, dolor, tumor, and functio laesa. Rubor- Redness (because of increased blood supply) Calor-Heat (because of increased blood supply) Dolor- Pain (because of the P substance produced following the secretion of cytokines) Tumor- swelling (due to accumulation of fluid) Functio laesa - Loss of function.  Innate immunity The main components of innate immune system are 1) Barriers 2) Scavenger cells – neutrophils, macrophages, dendritic cell and natural killer cells. 3) Complement system 4) Cytokines 5) Chemical mediators of inflammation  Complement system This system consists of many plasma proteins that help in opsonization of the microbial antigens to promote the recruitment of phagocytic cells. Opsonization is an immune process which uses opsonins to tag foreign pathogens for elimination by phagocytes.  Innate Immunity Microbial agents and pathogens contain some molecules over their surface that act as foreign substance for the body and are collectively called as pathogen associated molecular pattern (PAMP). PAMP’s are recognized by specific proteins and biochemical molecules produced by cells of innate immunity and these recognition molecules are called as pattern recognition receptors. The innate immune responses are produced against the specific structures present over the microbes and are common to many of them. Thus, they cannot distinguish the minute differences among microbes. Recognition system of innate immunity Toll like receptors TLRs are found in the cell surface as well as inside the cells and hence are able to recognize a wide variety of antigens. TLRs to remember: TLR4 TLR3 TLR9  Adaptive Immune Response Adaptive immune responses are of two types Humoral immune response Cell mediated immune response B Cells: The Humoral Immune Response T Cells: The Cellular Immune Response CD4+ T-helper cells and CD8+ T-cytotoxic cells  Different stages of adaptive immune response Steps of adaptive immune response follow a cascade orchestrated by the antibodies and the cells of the adaptive immune system. Step 1 Capture and display of antigens ↓ Step 2 Recognition of antigen by lymphocytes ↓ Step 3 Activation of T lymphocytes ↓ Step 4 Activation of B lymphocytes ↓ Step 5 Production of memory cells  Spleen is also called as graveyard of red blood cells. It is made up of red pulp which is full of blood cells and white pulp rich in lymphocyte. The white pulp helps to stimulate adaptive immune response against blood borne antigens. The white pulp area is divided into T cell and B cell zone. The T cell zone is also the resident area for mature dendritic cells which activates the naïve T cells upon antigen stimulation. Dendritic cells also reside in the B cell zone and activate the humoral immune response. Humoral immune response Humoral immune responses are mediated by the antibodies which are produced by activated B cells. Antibodies recognize the microbial antigen, neutralize the infectivity, and target the microbes to other effector system for degradation. Humoral immunity is the major type of immune response against extracellular microbes and toxins because the secreted form of the antibody can easily bind and eliminate the microbes and toxins. Occasionally antibodies may bind to the microbes to promote their phagocytosis in order to eliminate the infection.  Cell mediated immune response This is also called cellular immunity and is mediated by T lymphocytes. Cell mediated immunity plays an important role against intracellular microbes, viruses, and some intracellular bacteria. The cellular immunity promotes the destruction of microbes by direct killing or phagocytosis of the infected cells.  T cells enter the bloodstream and are carried by the circulation. On reaching a peripheral lymphoid organ they leave the blood again to migrate through the lymphoid tissue, returning to the bloodstream to recirculate between blood and peripheral lymphoid tissue until they encounter their specific antigen. Mature recirculating T cells that have not yet encountered their antigens are known as naive T cells. To participate in an adaptive immune response, a naive T cell must first encounter antigen, and then be induced to proliferate and differentiate into cells capable of contributing to the removal of the antigen. These cells are called as effector T cells because they act very rapidly when they encounter their specific antigen on other cells. The cells on which armed effector T cells act will be referred to as their target cells.  Feature of adaptive immunity The adaptive immunity has some fundamental properties. 1. Specificity 2. Diversity- The ability of lymphocyte repertoire to recognize a wide variety of antigens is called diversity. 3. Memory- The ability of the immune system to remember the antigens and respond again to the same upon exposure is called immunological memory. The immune response against the second exposure of the same antigen or subsequent exposure is usually rapid and larger than the primary immune response Memory response of the adaptive immune system  Specific Defenses: The Immune System Artificial immunity is acquired by the introduction of antigenic determinants into the body. Vaccination is inoculation with whole pathogens that have been modified (weakened or killed) so they cannot cause disease. Immunization is inoculation with antigenic proteins, pathogen fragments, or other molecular antigens. Immunization and vaccination initiate a primary immune response that generates memory cells without making the person ill. Jonas Salk’s polio vaccine. Thanks March of Dimes! http://blogs.cgdev.org/globa lhealth/archive/salk_thm.jpg The English physician Edward Jenner developed vaccine against smallpox. In 1798, intrigued by the fact that milkmaids who had contracted the mild disease cowpox were subsequently immune to the much more severe smallpox, Jenner reasoned that introducing fluid from a cowpox pustule into people (i.e., inoculating them) might protect them from smallpox. To test this idea, he inoculated an 8-year-old boy with fluid from a cowpox pustule and later intentionally infected the child with smallpox. As predicted, the child did not develop smallpox. Louis Pasteur- Story of cholera in chickens Louis Pasteur developed vaccine for Rabies.  Specific Defenses: The Immune System Self/Non-Self: Protecting Ourselves from Our Own Immune System The body is tolerant of its own molecules, even those that would cause an immune response in other individuals of the same species (e.g., blood type; organ transplants) Failure to do so results in autoimmune disease, for example, systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, insulin- dependent diabetes mellitus (type 1 diabetes).