Topic 2C - Cells and the Immune System

Topic 2C - Cells and the Immune System

1. The Immune System

   • ANTIGENS are MOLECULES (usually proteins) that can generate an immune response when detected by the body. They are USUALLY DOUND ON THE SURFACE OF CELLS and are used by the immune system to detect PATHOGENS (organisms that cause disease) ABNORMAL BODY CELLS (eg cancerous cells that have abnormal antigens on their surface) TOXINS and CELLS FROM OTHER INDIVIDUALS OF THE SAME SPECIES (eg organ transplants)
   • Phagocytosis
     • A PHAGOCYTE is a type of WHITE BLOOD CELL that carries out PHAGOCYTOSIS (ENGLUFING OF PATHOGENS) They are found in the BLOOD and TISSUE & are the FIRST CELLS TO RESPOND to an immune system trigger
       • 1) A PHAGOCYTE recognises FOREGIN ANTIGEN of the PATHOGEN & the CYTOPLASM OF THE PHAGOCYTE MOVES AROUND THE PATHOGEN, ENGLUFING IT.
         • 2) The pathogen is now contained in a PHAGOCITIC VACUOLE in the cytoplasm of the phagocyte.
           • 3) A LYSOSOME (an organelle containing enzymes lysozymes) FUSES WITH THE PHAGOCYTIC VACUOLE & the LYSOZYMES BREAK DOWN THE PATHOGEN
             • 4) A phagocyte then presents the PATHOGENS ANTIGEN - it sticks it on its surface to activate other responses
   • T-Cells (T lymphocytes) - Cell mediated response in the THYMUS
     • 1) Another type of RED BLOOD CELL. it has RECEPTOR PROTEINS on its surface that BIND to COMPLEMENTORY ANTIGENS presented to it by PHAGOCYTES
       • 2) RECEPTORS on a specific T HELPER CELL fit exactly onto these antigens
         • 3) This attatchments activates T cells to DIVIDE RAPIDLY by mitosis and form a CLONE of IDENTICAL CELLS
           • 4) The cloned T cells -
             • Develop into MEMORY CELLS that enable a rapid response to future infections from the same pathogens
             • Stimulates PHAGOCYTES to engulf PATHOGENS by PHAGOCYTOSIS
             • Stimulate B cells to divide and secrete their ANTIBODY
             • Activate CYTOTOXIC T CELLS to kill infected cells by making holes in their cell surface membrane as the cell becomes fully permeable
   • B-Cells (B lymphocytes) - Humoral responsein the bone marrow
     • 1) The surface antigen of an invading pathogen is taken up by a B CELL, which PROCESES the antigen and PRESENTS THEM ON ITS SURFACE
       • 2) HELPER T CELLS attatch to the ANTIGEN ON THE B CELL, this activates the B celll to DIVIDE BY MITOSIS to give a clne of PLASMA CELLS
         • 3) The plasma cells PRODUCE AND SECRETE the specific antibody that fits the antigen of the pathogen. The antibody attaches to the antigen and DESTROYS THEM
           • Some B CELLS develop into memory cells that can respond to future infections of the pathogen by dividin rapidly and developing into plasma cells
   • Plasma cells make more antibodies to a specific antigen
     • Plasma cells are identical to B-CELLS, they secrete antibodies to specific antigens, they are called MONOCLONAL ANTIBODIE. An antibody has 2 binding sites so can bind to 2 pahtogens at the same time meaning they become clumped together called - AGGLUTINATION
       • Antibodies are PROTEINS made up of amino acids, their SPECIFICITY depends on its VARIABLE REGIONS which forms the ANTIGEN BINDING SITE each antibody has a unique variable region with a specific tertiary structure which is complementory to a specifc antigen. All antibodies have the SAME CONSTANT REGION
     • PLASMA CELLS - SECRETE ANTIBODIES, SURVIVE ONLY A FEW DAYS, LEAD TO THE DISTRUCTION OF PATHOGENS - PRIMARY IMMUNE RESPONSE
     • MEMORY CELLS - LIVE LONER THAN PLSMA CELLS, DO NOT PRODUCE ANTIBODIES DIRECTLY WHEN THEY ENCOUNTER THE SAME ANTIGEN AGAIN THEY DIVIDE RAPIDLY INTO PLASMA CELLS SO HAVE LONG TERM IMMUNITY - SECONDARY IMMUNE RESPONSE
   • Split into TWO parts
     • CELLULAR - The T-CELLS & other immune system cells they interact with (eg phagocytes)
     • HUMOURAL - B-CELLS, CLONING & the production of MONOCLONAL ANTIBODIES
     • Each part is needed to remove pathogens from the body e.g t-cells activate b-cells
   • PRIMARY IMMUNE RESPONSE - When an antigen enters for the first time it activates the immune system, the PRIMARY IMMUNE RESPONSE., the PRIMARY REPONSE is SLOW because they're AREN'T MANY B-CELLS that can make the antibody. Eventually, the body will produce enough to overcome the infection, MEANWHILE THE PERSON WILL SHOW SYMPTOMS. After being exposed B & T-CELLS MAKE MEMORY CELLS these stay in the body for a long time. The person is now IMMUNE - their immune system has the ability to overcome a second infection quickly
   • SECONDARY IMMUNE RESPONSE - if the same pathogen enters the body again the immune system will produce a QUICKER, STRONGER immune response. B-CELLS ARE ACTIVATED AND DIVIDE INTO PLASMA CELLS THAT PRODUCE ANTIBODIES. The secondary immune response often gets rid of the pathogen BEFORE THE PERSON INFECTED SHOWS ANY SYMPTOMS

2. Immunity and vaccines

   • Vaccines can protect individuals and populations against disease.. While B-cells are dividing to help deal with the pathogen, you suffer from diseases. Vaccination can help deal with this. Vaccines contain antigens that cause the body to create memory cells against a pathogen without it causing disease. This m,eans they become immune witout any symptoms
     • Vaccines protect those who have them but as they redce the occurance those that haven't had the vaccine are less likely to catch the disease (because there are fewer people to catch it from_ - HERD IMMUNITY
       • Vaccines always contain antigens, either FREE or ATTATCHED to a DEAD or WEAKENED PATHOGEN. Vaccines can be INJECTED or taken ORALLY., the disadvantage of taking it orally is that it can be broken down by enzymes in the gut or the molecules of the vaccine may be TOO LARGE to dissolve into the blood. Sometimes BOOSTER VACCINES aregiven later on to make sure memory cells are produced
   • Antigenic variation
     • 1) Antigens on the surface of pathogens activate the primary response. When youre infected a second time by the same pathogen with the same antigens on it they activate the SECOND RESPONSE and don't get ill. Some PATHOGENS can CHNAGE THEIR ANTIGENS - ANTIGEN VARIATION (different antigen on the pathogen due to changes in genes)
       • 2) This means if youre infected A SECOND TIME the memory cells produced from the first infection WILL NOT RECOGNISE THE ANTIGENS so the immune response has to start again and carry out the PRIMARY RESPONSE.. The primary response takes time to get rid of the infection so we get ill again. This makes it hard to produce vaccines against these pathogens such as influenza, HIV and the common cold.
     • 1) The flu virus changes every year because the antigen on the surface changes regularly forming new strains of the virus
       • 2) Memory cells produced from vaccination with one strain of the flu will not recognise the different antigens and become - IMMUNIOGICALLY DISTINCT
         • 3) Every year they're are different strains of the virus circulating so a different vaccine has to be made. New vaccines are developed and one a year is chosen as the most effective against the recent circulating antigen
           • 4) The government then implement a programme of vaccinations
   • ACTIVE
     • The type of immunity where you're immune system MAKES ITS OWN ANTIBODIES after being STIMULATED BY AN ANTIGEN
       • NATURAL - Where you become immune after CATCHING A DISEASE
         • ARTIFICIAL - where you become immune after BEING GIVEN A VACCINATION containing a harmless antigen
     • REQUIRES EXPOSURE to antigen
       • TAKES A WHILE for protection to develop
         • Memory cells PRODUCED
     • Protection is LONG TERM because the antibody is produced (after activating memory cells) in response to complimentory antigens
   • PASSIVE
     • Where immunity is recieved by being GIVEN ANTIOBODIES BY A DIFFERENT ORGANISM. You're immune system doesn't make its own antibodies
       • NATURAL - when a BABY becomes IMMUNE due to ANTIGENS FROM ITS MOTHER through the PLACENTA & BREAST MILK
         • ARTIFICIAL - When you become IMMUNE BY BEING INJECTED WITH ANTIBODIES FROM SOMEONE ELSE.. E.g the tetnus toxin collected by blood donations
     • DOESN'T REQUIRE antigen EXPOSURE
       • Protection is IMMIDIATE
         • Memory cells ARENT PRODUCED
           • Protection is SHORT TERM because antibodies given are broken down

3. Antibodies in medicine

   • Monoclonal antibodies
     • MONOCLONAL ANTOBODIES are ANTIBODIES PRODUCED FROM A SINGLE GROUP OF GENTICALLY IDENTICAL B-CELLS this means they're all IDENTICAL. ANTIBODIES are very SPECIFIC because their binding sites have a UNIQUE TERTIARY STRUCTURE that only a complimentory antigen will fit
     • You can make monoclonal antibodies that CAN BIND TO ANYTHING YOU WANT e.g cell antigen or other substance and they will only bind to that molecule
     • Targeting drugs to a particular cell type - cancer cells
       • 1) Different cells in the body have different antigens, CANCER CELLS have antigens named TUMOUR MARKERS that are not found in normal body cells
       • 2) Monoclonal antibodies can be made that will bind to tumour markers you can also attatch ANTI-CANCER DRUGS to the ANTIBODIES
         • 3) When the ANTIBODIES come INTO CONTACT with CANCER CELLS they will BIND TO TUMOUR MARKERS. This means the drug will only accumulate in the body where they're are cancer cells. So side effects of the antibody based drug are lower than other drugs because they accumulate near specific cells
     • Targeting a particular substance for medical diagnosis - Pregnancy testing
       • Pregnancy tests detect the hormone HUMAN CHORIONIC GONADOTROPIN (hCG) that's found in URINE of pregnant women
         • 1) The application area contains ANTIBODIES FOR hCG bound to a coloured bead (blue) When urine is applied to the application area and hCG WILL BINDTO THE ANTIBODY on the beads FORMING AN ANTIGEN-ANTIBODY COMPLEX
           • 2) The urine moves up the stick to the test strip carrying any beads with it. The TESP STRIPCONTAINS ANTIBODIES TO hCG which are stuck in place(immobalised)
             • 3) If there is hCG PRESENT the test strip TURNS BLUE because the immobalisedANTIBODY BINDTO hCG - CONCENTRATING THE hCG ANTIBODY COMPLEX with BLUE BEADS attached. If NO hCG is present, the BEADS WILL PASS THROUGH THE TEST AREA WITHOUT BINDINGTOANYTHING, AND WONT GO BLUE
     • The ELISA test for HIV
       • The ENZYME-LINKED IMMUNOSORBANT ASSAY allows you to see if a patient has CERTAIN ANTIBODIES TO ANTIGENS or CERTAIN ANTIGENS TO ANTIBODIES. It can be used for pathogenic infections, allergies such as nuts and anything you can make an antibody for
       • In an ELISA TEST an ANTIGEN IS USED WHICH HAS AN ENZYME ATTATCHED TO IT. This ENZYME REACTS with a SUBSTRATE TO PRODUCE A COLOURED PRECIPITATE. If there is a colour change it demonstattes that the antibody or antigen being tested in present. In some types of ELISA the quantity of the antibody/antigen can me judged by te intensity of the colur change.
       • DIRECT ELISA - uses a SINGLE antibody that is compllimentory to te antigen or INDIRECT ELISA that uses TWO ANTIBODIES
       • 1) An INDIRECT ELISA can test if indoviduals have ANTIBODIES to the HIV VIRUS. The HIV ANTIGEN is BOUND TO THE BOTTOM OF THE WELL IN A WELL PLATE. Asample of the patients BLOOD PLASMA which may contain several antibodies is ADDED TO THE WELL. If there are any HIV SPECIFIC ANTIBODIES they will BIND TO THE ANTIGEN The well is then WASHED OUT to remove unbound antibodies
         • 2) A SECOND ANTIBODY with a specific ENZYME ATTATCHED is ADDED to the well. The SECONDARY ANTIBODY CAN BIND TO THE FIRST ANTIBODY (primary antibody) The well is WASHED to remove any unbound secondary antiodies . IF THERE IS NO PRIMARY ANTIODY ATTATCHED ALL THE SECONDARY WILL BE WASHED AWAY
           • 3) A SOLUTION IS ADDED TO THE WELL. This contains a SUBSTRATE which CAN REACT WITH THE ENZYME ON THE SECONDARY ANTIBODY & produce a COLOURED PRODUCT. IF THE SUBSTRATE PRODUCES A COLOUR IT INDICATES THE PATIENT HAS HIV ANTIBODIES AND IS INFECTED WITH HIV
   • Ethical issues with vaccines
     • All vaccines are TESTED ON ANIMALS before testing on humans - some people disagree with animal testing. Also, ANIMAL BASED SUBSTANCES may be produce a vaccine which people also disagree with
       • TESTING VACCINES ON HUMANS CAN BE TRICKY - (volunteers may put themselves at an unnecisary risk of contracting a disease because they think they are protected, e.g they might have unprotected sex because they've had a HIV vaccine and think they're protected where it may not work properly)
     • Some people don't want to take the vaccines because of the SIDE EFFECTS, but they are still protected because of HERD IMMUNITY which others think this is unfair
       • If there was an EPEDEMIC OF A NEW DISEASE there woudl be a rush to recieve the vaccine and difficult decisons about WHO will recieve vaccines first
   • Ethical issues with monoclonal antibody therapy
     • ANIMALS ARE USED TO PRODUCE THE CELLS from which the ANTIBODIES ARE PRODUCED. Some people disagree with the use of animals in this way

4. HIV & Viruses

   • HIV (Human Imminodeficency Virus) is a virus that effects the immune system. It eventually develops into Aquired immune deficency syndrome (AIDS) Aids is a condition where THE IMMUNE SYSTEM DETERIORATS and eventually FAILS. This makes suffers of aids more suseptible to other infections
     • People with HIV are classed as having aids when symptoms of A FAILING IMMUNE SYSTEM APPEARS or A LOW COUNT OF T HELPER CELLS. People with AIDS often contact diseases that wouldnt cause serious problems to people with a normal immune system. The length of time between HIV and AIDS varies but without treatment usually 10 years
       • 1) The simple symptoms of aids include minor infection of mucous membrances (eg nose, ears & genitals) & reccuring respiratory problems
         • 2) As aids progreses the number of immune cells decreases, patient becomes more suseptible to more serious infectons such as chronic diarrohea
           • 3) During later sstages of aids patients have a very low number of immune cells and can develop a range of different infections such as TOXOPLASMOSIS ON THE BRAIN Its these serious conditions that kill the patient not HIV itself
           • Underlying infections, type of HIV, AGE and ACCESS TO MEDICAL CARE effects the length of time people urvive
   • HIV INFECTS & eventually KILLS T Helper cells, which act as HOST CELLS. The T-Cells send signals to activate phagocytosis, activate T-cytotoxic cells and B-cells so are HUGLEY IMPORTANT IN THE IMMUNE SYSTEM. Without T-cells the immune system if unable to respond to infections. Suffers of HIV get AIDS when the number of T-cells reaches a citical LOW
   • A CORE that contians GENTIC INFORMATION (RNA) and some PROTEINS (including REVERSE TRANSCIPTASE needed for virus replication)
   • An OUTER COATING of PROTEIN called a CAPSID
   • An EXTRA OUTER LAYER called an ENVELOPE. This is made of a membrane stolen from the cell membrane of a previous host cell
   • STICKING OUT OF THE ENVELOPE are loads of copies of an ATTATCHEMENT PROTEIN that helps HIV attatch to the T-cells
   • HIV (and all other viruses) replicates inside the cells of the organisms its infected
     • HIV replicated inside the T HELPER CELLS of the host, it doesnt have the 'equptment' such as enzymes or ribosones to replicte on its own
       • 1) The ATTATCHMENT PROTEINS attatch to the RECEPTOR MOLECULE on the cell membrane of the T helper cell. The CAPSID IS RELEASED INTO THE CELL, where it UNCOATS and releases the genetic information (RNA) INTO THE CYTOPLASM
         • 2) Inside the cell REVERSE TRANSCRIPTASE is used to make a COMPLIMENTORY STRAND OF DNA from the RNA TEMPLATE, From this DOUBLE STRANDAD DNA IS MADE and insrted into the HUMAN DNA
           • 3) Human enzymes are used to make VIRAL PROTEINS from VIRAL DNA found in the HUMAN DNA The VIRAL PROTEINS are assembled into new viruses and go on to infect other cells
             • During the initial infection period, the HIV REPLICATES RAPIDLY and the infected may experience servere flu like symptoms. After this replication drops, this is the LATENCY PERIOD, during this period the infected wont experience any symptoms
   • Antibiotics DONT work against HIV
     • 1) Antibiotics KILL BACTERIA by interupting their METABOLIC REACTIONS. They TARGET BACTERIAL ENZYMES AND RIBOSOMES used in these reactions
       • 2) BACTERIA ENZYMES AND RIBOSOMES are DIFFERENT TO HUMANS. ANTIBIOTICS ONLY KILL BACTERIAL ONES so they dont damage HUMAN CELLS
         • 3) VIRUSES DONT HAVE THIER OWN ENZYMES AND RIBOSOMES - they use the HOST CELLS. So, because human viruses use human enzymes and ribosomes ANTIBIOTICS CANT INHIBIT them because they dont target human processes
           • 4) MOST ANTIVIRAL DRUGS are designed to target few VIRUS-SPECIFIC ENZYMES (enzymes that only the virus uses) (E..g HIV USES REVERSE TRANSCIPTASE, Humans dont use this enzyme so drugs can be developed to inhibit it without harming the host cell REVERSE TRANSCRIPTASE INHIBITORS)
     • There's currently NO CURE FOR HIV but ANTIVIRAL DRUGS CAN SLOW DOWN THE PROGESSION AND DEVELOPMENT OF AIDS
       • The best way to control HIV is by reducing its spread. HIV can be spread by UNPROTECTED SEX, INFECTED BODILY FLUIDS AND FROM A HIV POSITIVE MOTHER TO HER FEAUTUS

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