Defense against infectious disease Topics 6.3 and 11.1

Assessment Statements Define pathogen Explain why antibiotics are effective against bacteria but not against viruses Outline the role of skin and mucous membranes in defence against pathogens Outline how phagocytic leucocytes ingest pathogens in the blood and in body tissues Distinguish between antigens and antibodies Explain antibody production Outline the effects of HIV on the immune system Discuss the cause, transmission and social implications of AIDS.

Pathogen Any living organism or virus that is capable of causing a disease Include: –Viruses –Bacteria –Protozoa –Fungi –Worms Exposure to vast majority does not result in disease Why not?

Why are antibiotics effective against bacteria but not against viruses? Bacteria background –Prokaryotic –Different kind of protein synthesis –Cell wall Antibiotics are chemicals which take advantage of differences between prokaryotic and eukaryotic cells Categories: –Selectively blocks protein synthesis –Inhibits the production of a new cell wall, thus blocking their ability to grow and divide Virus background –Make use of our body cells’ metabolism –Any chemical that could inhibit this would also damage our cells

Role of skin Barrier to infection Two layers –Dermis (sweat glands, capillaries, sensory receptors and dermal cells which give structure and strength to the skin) –Epidermis (constantly being replaced as underlying dermal cells dies and are moved upwards) As long as are skin stays intact, we are protected from most pathogens entering living tissue

Role of stomach acid Kills most of ingested particles

Role of mucus Area with mucous membrane What it is and does TracheaTube which carries air to and from the lungs Nasal passagesTubes which allow air to enter the nose and then the trachea UrethraTube which carries urine from bladder to the outside VaginaReproductive tract leading from uterus to the outside

Role of phagocytic leukocytes A.k.a. white blood cells Found in bloodstream Macrophage –Type which gets involved early in the process of fighting off a pathogen –Large wbcs that are able to change their cellular shape to surround an invader and take it through the process of phagocytosis –Often referred to as amoeboid motion –Can squeeze in and out of small blood vessels

When a macrophage meets a cell Recognizes ‘self’ cells from ‘not-self’ Recognition based on the protein molecules that make up part of the surface of all cells and viruses If the proteins are ‘self’, then the cell is left alone If the proteins are ‘not-self’, the macrophage engulfs the invader by phagocytosis Lysosomes within the macrophage chemically digest whatever has been engulfed Type of response is non-specific b/c the identity of the pathogen has not been determined at this point

Antibodies Protein molecules that we produce in response to a specific type of pathogen Each type of antibody is different Each pathogen is made up of either cells with cell membranes or, in the case of a virus, a protein coat Cellular invaders have proteins called antigens that are embedded into their outer surface Most pathogens have several different antigens on their surface and therefore may trigger the production of many different types of antibodies

Each antibody is a protein that is Y shaped At the end of each of the forks of the Y is a binding site The binding site is where the antibody attaches itself to an antigen b/c the antigen is a protein on the surface of a pathogen, the antibody thus becomes attached to the pathogen

Typical immune response 1.A specific antigen type is identified (e.g. a particular cold virus) 2.A specific B lymphocyte (leukocytes that produce antibodies) is identified that can produce an antibody which will bind to the antigen. 3.The B lymphocyte and several identical B lymphocytes clone themselves to rapidly increase the number of the same type of B lymphocytes 4.Newly formed ‘army’ begins antibody production

Video 5.Newly released antibodies circulate in the bloodstream and eventually find their antigen match 6.Using various mechanisms, the antibodies help eliminate the pathogen –bind themselves directly to the pathogen, which cuts off the pathogen's ties with other cells in the body –bind and cover the pathogen so phagocytic cells can recognize it 7.Some of the cloned antibody-producing lymphocytes remain in the bloodstream and give immunity from a second infection by the same pathogen. They are called memory cells.

How HIV damages the immune system Human immunodeficiency virus (HIV) is the virus that eventually results in the set of symptoms collectively called acquired immune deficiency syndrome (AIDS) All viruses must find a type of cell in the body that matches their own proteins in a complementary way Helper-T cell is a communicator cell that HIV infects HIV has a latency period that may be several years long

Helper-T cells communicate which cells need to undergo cloning process and begin antibody production When the helper-T cells begin to die, the communication ceases and antibodies do not get produced At this stage, the individual no longer fights off pathogens as they did before and the symptoms of AIDS start to appear

Issues related to AIDS Hard to find a vaccine or cure b/c it ‘hides away’ for years It is waiting for some chemical signal to become active It also mutates very quickly The body’s immune responses or vaccines may not even recognize HIV after it has mutated several times Initially it was difficult to get funding due to the association of HIV with sexual activity and drug abuse

Enzyme-linked immunosorbent assays (ELISA) are often used to detect the presence or absence of a particular protein –Newly infected people will initially produce antibodies against HIV –ELISA detects them HIV is transmitted person to person by body fluids Blood is now routinely tested for the presence of blood-borne diseases and immediately destroyed if pathogens are found

Originally labeled as a disease affecting homosexuals and drug abusers Now know that it is rapidly spreading by heterosexual encounters Those diagnosed may be discriminated The Ray Brothers Until a cure is found, we continue to lengthen the life-span of those infected and to educate people on how to decrease their risk of exposure to HIV Vaccine trial

Defence against infectious disease Topic 11.1

Assessment Statements Describe the process of blood clotting Outline the principle of challenge and response, clonal selection and memory cells as the basis of immunity Define active and passive immunity Explain antibody production Describe the production of monoclonal antibodies and their use in diagnosis and in treatment Explain the principle of vaccination Discuss the benefits and dangers of vaccination.

Why does blood clot? When small blood vessels get broken, blood escapes from the closed circulatory system Our bodies create a clot which ‘seals’ the damaged blood vessels preventing excessive blood loss and helping to prevent pathogens from entering the body Prothrombin and fibrinogen are plasma proteins which circulate in the blood Platelets are cell fragments which also circulate

Blood clotting sequence Blood vessel is damaged Damaged cells release chemicals which stimulate platelets to adhere to the damaged area Other platelets begin adhering to those platelets To strengthen the plug, the damaged tissue and platelets release chemicals called clotting factors which convert prothrombin into thrombin Thrombin is an active enzyme which catalyses the conversion of soluble fibrinogen into the relatively insoluble fibrin Fibrin is a fibrous protein which forms a mesh-like network that helps to stabilize the platelet plug More cellular debris gets trapped in the fibrin mesh and soon a stable clot has formed preventing both further blood loss and entry of pathogens

Hemophilia Inherited blood disorder which is sex- linked Most are male People born with hemophilia have little or no clotting factor

Antibody production The bloodstream contains many different types of B lymphocytes or B cells Each type is capable of synthesizing and secreting a specific antibody which binds to a specific antigen Problem: there isn’t enough room to have enough of each type of B cell for the amount of antibody secretion that may be needed at various times Leukocytes represent roughly 1% of all the cells in your bloodstream Cellular communication methods lead the cloning of the appropriate B cell type for antibody synthesis when needed

1.Macrophage encounters a foreign antigen and engulfs the possible pathogen by phagocytosis 2.Antigens of the invader are displayed on the cell membrane of the macrophage – this is known as antigen presentation 3.Leukocytes known as helper-T cells chemically recognize the antigen being presented and become activated 4.Helper-T cells chemically communicate with the specific B cell type (which has also come in contact with the antigens) that is able to produce the antibody needed 5.animationanimation

Cell cloning When a helper-T cell activates a specific B cell, the activated B cell type begins a series of cell division known as cell cloning Types –Antibody-secreting plasma cells – secrete antibodies immediately and help to fight off the primary infection –Memory cells – do no secrete antibodies during the primary infection, but are long-lived cells which remain circulating in the bloodstream waiting for a subsequent infection

Principles of true immunity Challenge and response –Immune system challenged by an antigen during 1 st infection in order to develop an immunity –Macrophages, helper-T cells, B cells Clonal selection –Identification of plasma B cells –Multiple cell divisions to build up #s of same cell Memory cells –Provide long-term immunity

Types of immunity Active –Always leads to the production of memory cells –Provides long-term immunity Passive –When an organism acquires antibodies which were produced in another organism –Only the organism which produces the antibodies has the memory cells –Mother to fetus through placenta –From mother’s colostrum –Injection of antibodies in antisera (antivenoms produced for treatment of poisonous snake and spider bites)

Polyclonal antibodies Primary immune response Pathogen is being recognized as many antigens and not just one Each of the protein types can cause an immune response and thus several different kinds of plasma B cells undergo clonal selection, so several different kinds of antibodies are produced and several different kinds of memory cells remain after the infection It is difficult to separate the different kinds of antibody that have been produced

Monoclonal antibodies Researchers have developed a clever and unique procedure for forming many antibodies, all of the same type Procedure: –Inject an antigen into a laboratory animal –Animal is given time to go through a primary immune response –Response is polyclonal –Spleen is harvested to gain access to many blood cells –B cells kept alive by fusing them with cancerous (myeloma) cells –When B cells and myeloma cells are grown together a few of the cells fuse together and become a cell called a hybridoma

–These hybrid cells produce antibodies of a particular type and they are very long lived (as are all cancer cells) –Individual hybridomas transferred and cultured in separate containers –Each container is tested for the presence of a particular antibody by use of the ELISA test –Enzyme-linked immunosorbent assay test identifies which containers hold a pure colony of B cells which are producing the type of antibody desired –These cells are cultured for a very long period of time –animationanimation

Uses of monoclonal antibodies Diagnosis –Pregnancy testing which detects human chorionic gonadotrophin (HCG) –Anti-HCG antibodies are chemically bonded to an enzyme which catalyses a color change when the antibody encounters HCG molecules Treatment –Monoclonal antibodies that target the cancer- cell antigens –Antibody could be chemically modified to carry with it a toxin specific for this type of cancer –Antibody could contain a radioisotope for pin- point radiation therapy

How does a vaccine result in immunity? One cannot be immune to a pathogen before being exposed to it at least once For many diseases, vaccines have been developed that act as the first exposure to the pathogen Vaccine is developed by weakening a pathogen and then injecting the pathogen into the body Methods: –Selecting a weak strain –Heating the pathogen –Chemical treatment of pathogen Infection is not prevented, but the secondary immune response is quicker and more intense than the primary response

Benefits and dangers of vaccination BenefitDanger Possible total elimination of the disease (ex. Smallpox) Prior to 1999, many vaccines contained thimerosal, a mercury-based preservative. Mercury has been shown to be a neurotoxin. Decrease in spread of epidemics and pandemics 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 Anecdotal evidence suggested that MMR vaccine may have a link the onset of autism (no support from clinical studies) Each vaccinated individual benefits b/c 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