Defense against infectious disease HL

Cut in blood vessel Blood escapes Body works to “seal” the cut Describe the process of blood clotting

Blood clotting Clotting proteins prothrombin & fibrinogen PlateletsErythrocytes & Leucocytes

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Here’s how it works Damaged blood vessel Chemicals released Platelets adhere to damaged areas Chemicals convert prothrombin into thrombin Thrombin (enzyme) catalyses soluble fibrinogen into insoluble fibrin

Outline the principle of challenge and response, clonal selection and memory cells as the basis of immunity

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The Immune Response Early on the immune system cannot differentiate between disease invaders & transplanted kidney – “self” or “not-self” Remember, “not-self” = antigen All our body cells have same membrane proteins

Antibody production Leococytes have different types of B cells Each B cell can synthesize & secrete a specific antibody which binds to a specific antigen You don’t have enough of each type B cell for the amount of secretion that may be needed an one time Leucocytes represent about 1% of all the cells in your bloodstream

Antibody production Macrophage encounters an antigen Phagocytosis (partial digestion) Molecular pieces of invader are displayed on the cell membrane (antigen presentation) Leucocytes (helper T- cells) are activated

Antibody production Helper T-cells turn the immune response from non-specific to antigen specific as the identity of the antigen is now determined Helper T-cells chemically communicate with (activate) the specific B cell type that can produce antibody needed

Cell cloning When Helper T-cell activates a specific B cell, the B cell begins dividing Known as cell cloning – All daughter cells produce same antibody 2 types of cloned B cells

Antibody-secreting plasma cells Secrete antibodies immediately & help fight off the 1 st (primary) infection Memory cells Cells do not secrete antibodies during the 1 st infection, but are long-lived cells which remain circulating in the bloodstream for secondary infection

During the time it takes to activate the system the pathogen is causing damage & producing symptoms Staphylococcus Aureus

Subsequent infections Memory cells produced at 1 st infection are floating in bloodstream Long-lived cells, now in large numbers, are capable of responding to the same pathogen very quickly

Principles of Immunity Challenge & response: immune system must be challenged by an antigen during the 1 st infection in order to develop immunity Clonal selection: the identification of the leucocytes that can help with a specific pathogen & the multiple cell divisions Memory cells: cells that provide long-term immunity. You must have experienced the pathogen to produce these cells.

Define active & passive immunity Active immunity: the events previously described represent active immunity Passive immunity: when an organism acquires antibodies which were produced in another organism – only the organism which produced the antibodies has the memory cells & thus gains full long-term immunity – Therefore – short –term benefits

Examples of Passive Immunity Transfer of antibodies from mother to fetus through the placenta. Memory cells aren’t transferred. Acquisition of antibodies from the mother’s colostrum (breast mild produced in late pregnancy and the 1 st few days after birth). Injection of antibodies in antisera (antivenoms produced for treatment of posonous snake and spider bites.)

Describe the production of monoclonal antibodies and their use in diagnosis and in treatment.

Polyclonal Antibodies A primary immune response = polyclonal response – Pathogen is being recognized as many antigens & not just one – Once a polyclonal immune response has occurred, it is very difficult to separate the different kinds of antibody that have been produced

Monoclonal Antibodies Begin with the injection of an antigen into a lab animal (mouse) Mouse is given time to go through primary immune response (polyclonal) Spleen of the mouse is harvested in order to gain access to many blood cells Some of the leucocytes cloned for the antigen will be a part of the cellular population within the spleen

Monoclonal Antibodies Mouse injected with a chosen antigen Mouse spleen harvested days later Leucocytes removes Fused with myeloma cells to form hybridoma cells Hybridomas grown in separate cultures ELISA test used to identify cultures secreting desired antibodies Antibody purified from cell culture Antibodies can be uses for variety of diagnostic purposes

Monoclonal antibodies Myeloma cells = cancerous cells Hybridoma cells = B cells & myeloma cells fused together Hybridoma cells produce specific antibodies & are very long lived Moved to environment that kills B cells & myeloma cells that didn’t fuse ELISA = enzyme-linked immunosorbent assay

Monoclonal antibodies Test for specific antibodies using ELISA ELISA test identifies which containers hold a pure colony of B cells which are producing the type of antibody desired

Uses of monoclonal antibodies Embryo produces hormone – human chorionic gonadotrophin (HCG). Shows up in mother’s urine Diagnosing pregnancy The monoclonal antibodies could be chemically modified to carry a specific toxin or a pin-point radiation therapy Cancer treatment

Explain the principle of vaccination You cannot be immune to a pathogen before being exposed to it Vaccines developed as the 1 st exposure Vaccine composed of weakened pathogen – Select a “weak” strain – Heat the pathogen – Chemically treat the pathogen

Vaccines Leucocytes recognize weakened pathogen as “not-self” Primary immune response takes place – Memory B cells made Vaccines don’t prevent infections - secondary immune response is quicker - secondary response is more intense

Discuss the benefits & dangers of vaccination Some diseases have been eliminated (smallpox) Some vaccines are required by the government for entering school – MMR – Polio – DPT

BenefitDanger Possible total ellimination of the disease. This has occurred with smallpox & many believe it is possible to eradicate polio & measles Prior to 1999, many vaccines contained thimerosal, a mercury-based preservative. Mercury is a neurotoxin to which infants & young children are particularly susceptible Decrease in spread of epidemics & pandemics. Increased international travel has made this more important than ever. The perception exists that multiple vaccines given to children in a relatively short period of time may ‘overload’ their immune system Preventative medicine is typically the most cost-effective approach to healthcare. Costs associated with vaccination programs are small compared to the costs Anecdotal evidence suggested that MMR vaccine may have a link to the onset of autism. Clinical studies have not supported this. Each vaccinated individual benefits because the full symptoms of the disease do not have to be experienced in order to gain immunity Cases have been reported of vaccines leading to allergic reactions and autoimmune responses