Topic 11.1 – Defense Infectious Against Disease Ms. S. Scott Human Health and Physiology J205 Higher Level Assessment Statements 11.1.1 Describe the process of blood clotting 11.1.2 Outline the principle of challenge and response, clonal selection and memory cells as the basis of immunity 11.1.3 Define active and passive immunity 11.1.4 Explain antibody production 11.1.5 Describe the production of monoclonal antibodies and their use in diagnosis and treatment 11.1.6 Explain the principle of vaccination 11.1.7 Discuss the benefits and dangers of vaccination 11.1 Clotting is triggered very rapidly following tissue injury and limit spread of invading pathogens into the blood stream. The body has an internal mechanism to slow bleeding and begin healing. Bleeding stops because blood has the ability to form a clot. . Blood clotting is made possible by plasma proteins and platelets. 11.1.1 Overall Reaction of Blood Clotting Clotting Factors Activator Fibrin + RBC = Clot 11.1.1 Process 1: Blood Clotting When we cut ourselves, we cut small blood vessels. When this happens, our body forms a clot. A clot stops us from losing blood and from a foreign pathogen from entering into our body. 11.1.1 Process 1: Blood Clotting A wound triggers a cascade of events by which a blood clot is formed. First platelets collect at the site of the wound. Platelets are small disc shaped cell fragments Platelets do not contain a nucleus 11.1.1 Process 2: Blood Clotting Platelets build up at wound and seal off small breaks in blood vessels 11.1.1 Process 3: Blood Clotting 11.1.1 Process 4: Blood Clotting Fibrin proteins form a mesh of fibres which traps red blood cells. These dry and become a scab which closes the wound. 11.1.1 Fibrin + RBC = Clot 11.1.1 Challenge and Response When the body is challenged by a foreign pathogen it will respond with both a non-specific and specific immune reaction 11.1.2 Lymphocytes Recognize Self • Cells are identified by specific molecules lodged in the outer surface of the cell (plasma) membrane. • These molecules are called glycoproteins ( a molecule that contains a carbohydrate and a protein) 11.1.2 Clonal Selection The majority of B cell clones will differentiate into antibodyproducing plasma cells, a minority will become memory B cells (BM cells) Each B lymphocyte has a specific antibody on its surface that is capable of recognizing a specific antigen 11.1.2 Polyclonal Selection 11.1.2 Infection and Immune Response 11.1.2 Types of Immunity Passive immunity is due to the acquisition of antibodies from the mother via the placenta and milk. Also antibodies can be received by injections. 11.1.3 Types of Immunity Active immunity is due to the production of antibodies by the organism, after the body’s defense have been exposed to antigens. 11.1.3 Types of Immunity • Active Immunity – - develops when a person is exposed to microorganisms or foreign substances and the person’s immune system responds. • Passive Immunity – - is acquired when antibodies are transferred from one person to another. - The recipients do not make the antibodies themselves 11.1.3 Types of Immunity 11.1.3 Types of Immunity Definitions of Immunity Active Production of antibodies by organism itself after the body defense mechanism have been stimulated by an antigen Passive Acquisition of antibodies from another organism in which active immunity has been stimulated Artificial The antibodies are produced elsewhere and injected Natural Your body produces its own antibodies 11.1.3 Review Active & Passive Immunity • Is this active or passive immunity? – Antigen enters body….the body produces antibodies to neutralize antigen. – NATURALLY ACQUIRED --- ACTIVE IMMUNITY Review Active & Passive Immunity • Is this active or passive immunity? – Antibodies passes from mother to fetus during pregnancy – NATURALLY ACQUIRED --- PASSIVE IMMUNITY Review Active & Passive Immunity • Is this active or passive immunity? – Weakened or dead fragments of a microbe are injected into the body….the body produces antibodies to neutralize microbe – Artificially ACQUIRED --- Active IMMUNITY Review Active & Passive Immunity • Is this active or passive immunity? – Antibodies in a serum (i.e. antivenom used to treat snake bites) are introduced to the body…… – Artificially ACQUIRED --- PASSIVE IMMUNITY Antibody Production: The Primary Response Step 1: Antigen Presentation Antigen Macrophage Macrophages take in antigen by endocytosis The macrophage processes the antigen and attaches it to a membrane protein called a MHC protein The MHC protein is moved to the cell surface membrane by exocytosis so that the antigen is displayed on its surface. MHC protein 11.1.4 Antibody Production: The Primary Response Step 2: Activation of Helper T-cell Helper T-cells have receptors on their cell surface membranes which can bind to antigens presented by macrophages. Helper T-cell binds to macrophage presenting the antigen receptor Helper T-cell Macrophage sends a signal to activate the helper T-cell 11.1.4 Antibody Production: The Primary Response Step 3: Activation of B-lymphocytes B-cells have antibodies in their cell surface membranes Antigens bind to the antibodies in the surface membranes of B-cells Antigen Inactive B-cell Antibody 11.1.4 Antibody Production: The Primary Response An activated helper T-cell with receptors for the same antigen binds to the B-cell SIGNAL The helper T-cell sends a signal to the B-cell, activating the B-cell. 11.1.4 Antibody Production: The Primary Response The activated B-cell starts to divide by mitosis to form a clone of plasma cells. Plasma cells are activated B-cells with a very extensive network of rough endoplasmic reticulum. Plasma cells synthesis large amounts of antibody, which they excrete by exocytosis. 11.1.4 Antibody Production: Summary Antigen B-cell Clone Memory Cell Antigen Activate Activate Helper T-cell Macrophage Antibody Production: Summary Plasma Cell Antibodies 11.1.4 Monoclonal Antibody Production • Antibody produced by a single clone (type) of B lymphocytes • It consists of a population of identical antibody molecules. A monoclonal antibody has many uses in medicine because: They are stable molecules They can be used over a long period of time 11.1.5 Monoclonal Antibody Production 1. Antigens that correspond to desired antibody are injected into an animal (usually a mouse) 2. B-cells are produce by the above animal and the antibodies produced by B-cells are removed. They are made from genetic engineering using mouse cells. 11.1.5 Monoclonal Antibody Production 3. Tumour cells are obtained. These cells grow and divide endlessy. 4. B-Cells from above animals are fused with tumour cells, producing a cell called a hybridoma. 5. These hybridoma divide endlessly and produce a lot of the desire antibodies. 6. The hybridoma cells are culture & the antibodies they produce are purified and extracted 11.1.5 Monoclonal Antibody Production 11.1.5 11.1.5 Uses of Monoclonal Antibodies Determine/ diagnose pregnancy – Pregnant women produce a urine with high concentration of human chorionic gonadotrophin (HCG) – Monoclonial antibodies that bond with HCG have been engineered to also carry color granules. – Thus a change in color in a pregnancy test confirms pregnancy. 11.1.5 Uses of Monoclonal Antibodies Treatment of Disease – Cancer cells carry specific tumour-associated antigens (TAA) on the cell (plasma) membrane – Monoclonial antibodies to TAA have been produced…. – These antibodies as carry drugs to kill the cancer cell 11.1.5 Principles of Vaccination A weakened pathogen is injected into the body to generate an immune response and produce memory B cells. Vaccines don’t prevent infections, but on subsequent exposure to the pathogen the secondary immune response is faster. 11.1.6 Vaccination and the Immune System B. V= Vaccination I=Infection Level of antibody • Sometimes two or more vaccinations are needed to stimulate the production of enough antibodies to fight off a disease. Time V I D. 11.1.6 Vaccination and the Immune System B. V= Vaccination I=Infection Level of antibody • The first vaccination causes little antibody production and the production of some memory cells. Time V I D. 11.1.6 Vaccination and the Immune System B. V= Vaccination I=Infection second vaccination, called a booster shot causes a response from the memory cells & therefore a faster & greater production of Time antibodies. Level of antibody V • The I D. 11.1.6 Benefits and Dangers of Vaccination Benefits Dangers Elimination of disease Neurotoxic side effects due to mercurybased preservatives Decreased spread of epidemics Overload of immune system Cost-effective preventative medicine Anecdotal evidence of autism associated with MMR Decrease in symptoms associated with disease Allergic reactions and autoimmune responses 11.1.7