Ms. S. Scott Human Health and Physiology J205 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. Clotting System:       Platelets : Circulate with the erythrocytes and the leukocytes in the plasma Process: Release of clotting factors from damaged tissue cells or from platelets Semi-solid liquid formed to prevent entry of pathogens 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 In the last reaction Fibrogen, a soluble plasma protein is altered by the removal of sections of peptide that have many negative charges. Polypeptide bind to others, forming long protein fibers called fibrin. Fibrin forms a mesh across wounds Through clotting system, thrombin formed from prothrombin.  Thrombin acts on soluble fibrinogen in tissue fluid plasma to produce insoluble strands of fibrin and fibrnopeptides.  The insoluble fibrin strands crisscross one another forming a clot which serves as a barrier to the spread of infection.  This mechanism is referred as “walling off” reaction.  The fibrnopeptides act inflammatory mediators inducing increased vascular permeability and neutrophil chemotaxis. Fibrinolytic System:             Fibrinolytic system removes clot. The end product of this pathway is the enzyme plasmin, which is formed from plasminogen.  Plasmin breaks down fibrin clots into degradation products that are chemotactic for neutrophils.  Plasmin also contributes to the inflammatory response activating the classical complement pathway.  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. Blood clotting is made possible by a number of plasma proteins and cell fragments called platelets. 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 Blood clotting is made possible by a number of plasma proteins and cell fragments called platelets. 11.1.1

Process 2: Blood Clotting Blood clotting is made possible by a number of plasma proteins and cell fragments called platelets. Platelets build up at wound and seal off small breaks in blood vessels 11.1.1

Process 3: Blood Clotting Blood clotting is made possible by a number of plasma proteins and cell fragments called platelets. 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. Blood clotting is made possible by a number of plasma proteins and cell fragments called platelets. 11.1.1

Fibrin + RBC = Clot Blood cells are caught in the mesh and soon form a semi-solid clot. Exposed to air, semi-clot forms a protective scab, remains until wound has healed 11.1.1

11.1.2 Challenge and Response When the body is challenged by a foreign pathogen it will respond with both a non-specific and specific immune reaction The body is capable of recognizing invaders as they do not possess the molecular markers that designated all body cells as 'self' (MHC class I) Non-specific immune cells (macrophages) present the foreign antigens to lymphocytes as examples of 'non-self' (on MHC class II) These lymphocytes can then respond with the production of antibodies to destroy the foreign invaders 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) Glycoproteins that identify cells are known as the Major Histocompatability Complex (MHC) There are genes on our 6th chromosome that code for our MHC. Thus, our MHC is genetically determined. Each of us as a unique MHC on our cells membrane. 11.1.2

Clonal Selection The majority of B cell clones will differentiate into antibody-producing plasma cells, a minority will become memory B cells (BM cells) Because the adaptive immune response is dependent on clonal expansion to create sufficiently large amounts of antibodies, there is a delay between initial exposure and the production of antibodies. When a B cell does divide and differentiate into antibody-secreting plasma cells, a small proportion of clones will differentiate into memory cells Each B lymphocyte has a specific antibody on its surface that is capable of recognizing a specific antigen 11.1.2

Polyclonal Selection Because the adaptive immune response is dependent on clonal expansion to create sufficiently large amounts of antibodies, there is a delay between initial exposure and the production of antibodies. When a B cell does divide and differentiate into antibody-secreting plasma cells, a small proportion of clones will differentiate into memory cells Because pathogens may contain several antigenic determinants, several B cell clones may become activated (polyclonal activation) 11.1.2

Infection and Immune Response Memory cells remain in the body for years (or even a lifetime) If a second infection with the same antigen occurs, the memory cells react faster and more vigorously than the initial immune response, such that the symptoms of the infection do not normally appear Because the individual no longer presents with the symptoms of infection upon exposure, the individual is thus said to be immune 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

Definitions of Immunity 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 Macrophages take in antigen by endocytosis Antigen Macrophage 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. receptor Helper T-cell Helper T-cell binds to macrophage presenting the antigen 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 Inactive B-cell Antibody Antigens bind to the antibodies in the surface membranes of B-cells Antigen 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 Macrophage Antigen Activate B-cell Helper T-cell Activate Clone Antibody Production: Summary Memory Cell Antibodies Plasma Cell 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 Antigens that correspond to desired antibody are injected into an animal (usually a mouse) 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 Tumour cells are obtained. These cells grow and divide endlessy. B-Cells from above animals are fused with tumour cells, producing a cell called a hybridoma. These hybridoma divide endlessly and produce a lot of the desire antibodies. The hybridoma cells are culture & the antibodies they produce are purified and extracted 11.1.5

Monoclonal Antibody Production Monoclonal antibodies are prepared by fusing immortal myeloma cells with the spleen cells, B cells, derived from a mouse that has been immunized with the intended antigen to produce monoclonal antibody-producing cells, hybridomas. Hybridomas have the characteristics of the two different types of cells, and are able to both produce antibodies and reproduce infinitely. 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 V= Vaccination I=Infection Sometimes two or more vaccinations are needed to stimulate the production of enough antibodies to fight off a disease. There are many diseases in which the primary infection stage can do considerable damage to the body. Some of these are serious enough to be fatal. Vaccination (immunization) uses modified pathogens (Antigen) which have significantly reduced pathogenicity. The pathogen organism in some vaccines is dead and in others is weakened (attenuated). These vaccines carry the pathogen antigen (epitope) and therefore stimulate clonal selection and the development of immunological memory but without developing the disease symptoms or signs 11.1.6

Vaccination and the Immune System V= Vaccination I=Infection The first vaccination causes little antibody production and the production of some memory cells. 11.1.6

Vaccination and the Immune System V= Vaccination I=Infection The second vaccination, called a booster shot causes a response from the memory cells & therefore a faster & greater production of antibodies. 11.1.6

Benefits and Dangers of Vaccination Elimination of disease Neurotoxic side effects due to mercury-based 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