Immune System Lecture Notes PDF

What is meant by Immunity? Immunity means being protected from something and being unaffected or not bothered by it. Immunity is the ability of the body to protect itself from any danger whether coming from outside or from inside.  The Immune System The immune system is the set of cells (m...

What is meant by Immunity? Immunity means being protected from something and being unaffected or not bothered by it. Immunity is the ability of the body to protect itself from any danger whether coming from outside or from inside.  The Immune System The immune system is the set of cells (mostly WBCs) and tissues (spleen and lymph nodes) which work to resist infection and harmful effects induced by other living things. The immune mechanisms help the host to identify a pathogen, and neutralize its threat.  The Immune System The immune system can detect and identify many different kinds of agents causing disease e.g. viruses, bacteria and parasites. The immune system can also detect a difference between the body's own healthy cells or tissues, and 'foreign' cells. The Immune System  The Innate Immunity The innate immunity, also known as the non- specific or in-born immunity comprises the cells (Leukocytes) and mechanisms (Inflammation and Phagocytosis) naturally present in all healthy persons to defend them from infection by other organisms. It includes also the natural barriers of infection. Natural Barriers of Infection  Inflammation Inflammation is one of the first responses of the immune system to infection or irritation. Inflammation is stimulated by chemical factors released by injured cells. Inflammation establishes a physical barrier against the spread of infection, and promote healing of damaged tissue following the clearance of pathogens.  Inflammation The process of acute inflammation is initiated by cells already present in all tissues, mainly resident macrophages dendrite cells, histiocytes, and mast cells. At the onset of an infection, burn, or other injuries, these cells release inflammatory mediators (histamine, bradykinin, serotonin and prostaglandins).  Inflammation Those inflammatory mediators sensitize pain receptors, cause local vasodilatation of the blood vessels, and attract phagocytes, especially neutrophils. They are causing the signs of symptoms of inflammation including : pain, swelling, redness, hotness and altered function.  The Innate Immune cells The innate immune cells (leukocytes) differ from other cells of the body in that they are acting as independent, single-cells not tightly associated with a particular organ or tissue.  The Innate Immune cells Leukocytes are able to move and interact with and capture cellular debris, foreign particles, and invading microorganisms. Within the immune system, leukocytes are identifying and eliminating pathogens that might cause infection.  The Innate Immune cells The innate leukocytes include: 1. Natural killer cells, 2. Mast cells, 3. Eosinophils, 4. Basophils; and 5. The phagocytes which include macrophages, neutrophils, and dendritic cells.  Mast Cells They reside in connective tissue and in the mucous membranes. They are associated with wound healing and defense against pathogens, but are also often associated with allergy. When activated, mast cells release histamine. Histamine dilates blood vessels, causing the characteristic signs of inflammation, and recruits neutrophils and macrophages.  Phagocytes These are immune cells that engulf, or 'phagocytose', pathogens or particles. Phagocytes patrol the body searching for pathogens. Phagocytes are able to react to a group of mediators produced by other cells, called cytokines and chemokines that attract and activate phagocytes. The phagocytic cells of the immune system include macrophages, neutrophils, and dendritic cells.  Phagocytosis 1. To engulf a particle or pathogen, a phagocyte extends portions of its plasma membrane, wrapping the membrane around the particle until it is enveloped (becoming inside the cell). 2. Once inside the cell, the invading pathogen is contained inside an phagosome, which merges with a lysosome. 3. The lysosome contains enzymes and acids that kill and digest the particle or organism. Phagocytosis  Phagocytosis Phagocytosis of the hosts’ own cells is a part of regular tissue development and maintenance. When host cells die, phagocytes are responsible for their removal from the affected site. After that growth and development of new healthy cells starts, thus phagocytosis is an important part of the healing process following tissue injury.  Immunity Immunity may be classified into: A. Innate (non specific) immunity and B. Adaptive (specific Immunity).  Acquired (Adaptive) Immunity It is a status of immunity against specific agents to which the body has been exposed. It is different in different persons and in the same person in different times or conditions. It is specific to certain agents not acting against other agents.  Acquired (Adaptive) Immunity Adaptive immunity creates immunological memory after an initial response to a specific pathogen, and leads to an enhanced response to re-infection with that pathogen. It is acquired during life (in utero or after birth). It is classified into passive and active acquired immunity.  Acquired (Adaptive) Immunity  Passive acquired immunity is prepared in a host and transmitted to another one (no active role played by the immune system of the acquiring host).  Active acquired immunity is made by the immune system of a host after stimulation by an infecting or harmful agent.  Both passive and active immunity may be acquired naturally or artificially induced.  Acquired Passive Immunity  Acquired passive natural immunity is represented by immune reactions (antibodies) passing from mother to infant during pregnancy and through lactation.  Acquired passive artificial immunity is represented by antibodies prepared in horse and given to human to protect against tetanus.  Acquired Active Immunity Acquired active natural immunity is represented by immunity acquired against measles after natural exposure to infection. Acquired active artificial immunity is represented by immunity acquired against HBV after vaccination.  What is the first step in phagocytosis? A. Fusion between the lysosome and the vacuole B. Killing the bacteria C. Making a vacuole around the bacteria D. Pseudopodia formation. The Natural barriers of infections include all the following Except: A. Gastric acidity B. Phagocytosis C. Saliva D. Skin.  Passive acquired natural immunity is usually acquired: A. After getting infection B. After vaccination C. By giving antiserum after infection D. From mother to her baby. The Natural barriers of infections include all the following Except: A. Gastric acidity B. Phagocytosis C. Saliva D. Skin.  Skin and mucous surfaces are the only natural barriers of immunity. Cortisone is one of the Chemical mediators of inflammation. Signs and symptoms of inflammation include: pain, hotness and swelling. The last step of phagocytosis is the release of microbial debris.  Skin and mucous surfaces are the only natural barriers of immunity. Cortisone is one of the Chemical mediators of inflammation. Signs and symptoms of inflammation include: pain, hotness and swelling. The last step of phagocytosis is the release of microbial debris. Cells of the Immune System  Cells Involved in Acquired Immunity Acquired immunity needs 2 main types of immune cells: 1.The B lymphocytes or B cells: responsible about antibody production ( Humoral immunity) 2.The T lymphocytes or T cells: responsible about cell-mediated immunity (Cellular immunity). Cells Involved in Acquired Immunity Both cells are produced in bone marrow but they complete their activation and education in different parts: B cells are activated in bone marrow (B) and T cells are activated in the thymus gland (T).  Cluster Designation (CDs)  Each lymphocyte is carrying a molecule indicating its cluster. This molecule is called CD (cluster designation) and is marked by numbers e.g. CD4 or CD8.  CD4 cells are generally having a helper function for other B or T immune cells.  CD8 cells are generally considered cytotoxic cells capable of killing infected or harmful cells.  Cytokines  Cytokines (cyto, from Greek cell" + kines, from Greek "movement") are a group of small proteins (~5–20 kDa) that are important in cell signaling.  Their release has an effect on the behavior of cells around them.  Cytokines are increasing or decreasing some cell count and activity so they are considered immune- modulating agents.  Cytokines Cytokines include interferon, interleukins, lymphokines, and tumor necrosis factors. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B lymphocytes T lymphocytes and mast cells, as well as endothelial cells, fibroblasts. A given cytokine may be produced by more than one type of cell. They act through receptors, and are especially important in the immune system.  Cytokines Cytokines are named according to their functions e.g. interleukins working in communication between leukocytes (IL-1 to IL-28), TNF (tumor necrosis factor) causing necrosis of malignant cells, GCF (granulocyte colony stimulating factor) increasing granulocyte production and IFN (interferon) interfering with viral infections.  Chemokines Chemokines are a family of small cytokines secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines.  Chemokines Types of cells attracted: 1. Monocytes / macrophages 2. T-lymphocytes 3. Mast cells 4. Eosinophils 5. Neutrophils  T helper Cells According to cytokines and chemokines T cells may be sub grouped into Th-1 (T helper type 1) and Th-2 (T helper type 2). Th-1 cells are created by IL-12, IL-2 and they produce IFN-γ. Th-2 cells are created by IL-4 and they produce IL-4, IL-5, IL-9, IL-10 and IL-13.  Major Histocompatibility Complex (MHC) The major histocompatibility complex (MHC) is a set of cell surface proteins essential for the immune system to recognize foreign molecules. The main function of MHC molecules is to bind to antigens derived from pathogens and display them on the cell surface for recognition by the appropriate T-cells.  MHC The MHC determines compatibility of donors for organ transplant, as well as one's susceptibility to an autoimmune disease. The human MHC is also called the HLA (human leukocyte antigen) complex (often just the HLA).  MHC The MHC family is divided into 2 subgroups: MHC-I (class I) and MHCII (class II). Class I MHC molecules have β2 subunits so can only be recognized by CD8 co-receptors. Class II MHC molecules have β1 and β2 subunits and can be recognized by CD4 co- receptors.  T-helper lymphocytes are: A. Produced in the bone marrow and maturated in the bone marrow B. Produced in the bone marrow and maturated in the Thymus gland C. Produced in the bone marrow and maturated in the thyroid gland D. Produced in the Thymus gland and maturated in the bone marrow  To which of the following cells MHC- II presents antigen? A. B lymphocytes B. Cytotoxic T- lymphocytes C. Helper T-lymphocytes D. Phagocytes  B lymphocytes are produced in the bone marrow while T lymphocytes are produced from the thymus gland. CD8 cells are generally considered cytotoxic cells capable of killing infected or harmful cells. Th-1 cells are triggered by IL-12, IL-2 and their effectors cytokine is IFN-γ. MHC class II is found on virtually every cell except RBCs. Antigens and Immunogens Antigens were first defined as foreign materials capable of generating antibodies (Antibody- generating substance). After knowing that immunity is not only antibodies the definition was changed to substance generating immune response and the word used became immunogen.  Antigens and Immunogens An antigen should be: 1. Foreign (non self): If self antigens are changed by infection or degeneration they may become antigenic. 2. Protein in nature: Proteins are potent antigenic substances while lipids or carbohydrates are not. 3. Of big molecular size Antigens and Immunogens The healthy immune system should only react against non-self antigens and the reaction is dependent on the nature of the inducing agent. Foreign antigens should come in an optimal amount: If an antigen is coming in a very low dose it may be neglected and if it is coming in a very large dose it may be tolerated.  Haptens Haptens are small molecular size foreign substances that may be neglected by the immune system unless they are combined to a self protein or being carried by a large molecular size lipid or polysaccharides. The immune reaction will be against the hapten and the carrying protein. Haptens Antibodies (Immunoglobulins) Antibodies were first defined as proteins produced against foreign bodies (Anti- foreign bodies). Later they were proved to be made of gamma globulins and they are produced from special immune cells so they became named Immunoglobulins (Ig). Antibodies (Immunoglobulins) Antibodies are usually produced in response to a specific antigen and they can only react against this antigen both in vivo (inside the body to help removal or destruction of harmful agents) and in vitro (in the lab for diagnosis and identification of different antigens). Antibodies (Immunoglobulins) An antibody is a large Y-shaped glycoprotein molecule produced by activated B-cells and used by the immune system to identify and neutralize pathogens. Antibodies are either secreted into circulation or remain expressed on the surface of the B cell. Antibodies (Immunoglobulins) Antibodies are typically made of two large heavy chains (H chain) and two small light chains (L chain). Both H and L chains are combined by di-sulphide bonds. Each chain has a constant (C) part and a variable (V) part which differs according to the antigen that produced this antibody. V parts are sometimes called Fab (fraction antigen-binding).  Types of Immunoglobulins IgA: It is called secretory antibody and is present in saliva, breast milk and other body secretions. It is resistant to digestion by proteolytic enzymes found in the gastrointestinal mucosa. It is responsible for local immunity. Types of Immunoglobulins IgD: It functions mainly as an antigen receptor on B cells that have not been exposed to antigens. It activates basophils and mast cells to produce antimicrobial factors. It has a minor role in immune reactions.  Types of Immunoglobulins IgE: It binds to allergens, triggering histamine release from mast cells and basophils. Also protects against parasitic worms. It is the antibody that is increased in allergy or hypersensitivity.  Types of Immunoglobulins IgG: It provides the majority of antibody-based immunity against invading pathogens. It is the only antibody capable of crossing the placenta to give passive immunity to fetus, and can activate the classical complement system. It the antibody mostly detected in immune reactions as it is the most abundant antibody in the blood.  Types of Immunoglobulins IgM: Expressed on the surface of B cells (monomer) and in a secreted pentamer with very high avidity. Eliminates pathogens in the early (primary immune response) before there is sufficient IgG. Like IgG, it can also activate the classical complement system. Its presence indicates early or active infection. Types of Immunoglobulins Primary and Secondary Immune Response  How many Heavy Chains are present in a molecule of IgM? A. 2 Heavy chains B. 4 Heavy chains C. 5 Heavy Chains D. 10 Heavy chains  Which of the following cells are producing antibodies? A. Mast cells B. Phagocytes C. Plasma cells D. T helper cells. A true antigen should be foreign protein of good molecular size. Hapten is not antigenic alone. Hapten combined to a body protein may stimulate immune system to produce antibodies against both of them. Antibodies are immunoglobulins produced from activated T cells. Each molecule of immunoglobulin-D has 2 heavy chains and 2 light chains.  Immune Reactions Immune reactions are those occurring between immunogen (antigen) and its specific antibody. It can occur both in vivo and in vitro. These reactions are known to be: Specific: each antibody can react only with one antigen. This is a base for using immune reactions to identify an unknown antigen by reaction with its specific antibody and vice versa.  Immune Reactions O It needs optimum temperature: usually 37 C. It can be seen only if the concentrations of both antigen and antibody are equivalent. If one of them is much higher the other the reaction occur but cannot be seen. The result of immune reaction is dependent on the nature of the antigen.  Agglutination Reaction If the antigen is cellular or particles; the reaction will lead to agglutination of these particles. The best example of this type is the test done for blood grouping (A, B, AB or O). Agglutination may be done in a tube (tube agglutination) or on a slide (slide agglutination). Sometimes the soluble antigen is carried on inert particle (latex) and then tested by agglutination (passive agglutination). Tube Agglutination Test Passive Agglutination  Precipitation Reaction If the antigen is soluble reaction will lead to precipitation making it detectable and easy to remove. It can be done in tubes (Tube precipitation or Ring Test). It can also be done on transparent agarose plates making lines or rings of opaque precipitation (radial immundiffusion). Tube precipitation (Ring Test)  Immune Reactions in vivo 1. Toxin neutralization: blocking the action of toxins 2. Virus neutralization: coating the viruses to prevent them from binding to cells and preventing infection. 3. Opsonization: coating slippery (capsulated) bacteria to facilitate the action of phagocytes. 4. Agglutination of bacteria to make it easier to immune cells to remove them. 5. Precipitation of soluble antigens to make it easier for kidney or liver to remove them from the blood.  Tube agglutination test is done mainly to: A. Detect soluble antigens B. Fix complement C. Know blood group of patient D. Know the amount of antibodies in serum of a patient. Radial immune diffusion is a type of: A. Agglutination reactions B. Complement fixation reactions C. Precipitation reactions D. Toxin neutralization reactions Agglutination is an immune reaction in which the antigens are soluble. Tube agglutination is used to determine blood groups. In tube agglutination we can know the amount of the antibody in serum of infected persons. Sometimes the soluble antigen is carried on inert particle (latex) and then tested by agglutination (passive agglutination). Precipitation reaction done in tubes is called ring test. Radial immune diffusion is a precipitation reaction done on transparent agarose plates. The complement is a part of natural innate immunity. Complement triggers inflammation, Phagocytosis and membrane attack. Opsonization is an example of immune reactions in vitro.