2C: Immune System



Antigens: Molecules (proteins) that generate immune response, on surface of cells. Foreign antigens not found in body immune system (IS) responds to. Allows IS to respond to:

Pathogens: Organisms that cause disease (bacteria, viruses, fungi). All have antigens on surface, identified as foreign by IS, which respond to destroy pathogen.

Abnormal body cells: Cancerous, pathogen-infected cells, abnormal antigens on surface trigger IS.

Toxins: Poison molecules, some produced by bacteria. IS responds, and to pathogens releasing.

Cells from other individuals of same species: Organ transplant, blood transfusion, cells have antigens different to self, triggers IS. Leads to rejection of transplanted organs if drugs arent taken to suppress IS. If donated blood doesnt contain antigens recognised by IS, generates IS.

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Immune Response

Phagocytosis: Phagocyte (e.g macrophage) white blood cell carries out phagocytosis. In blood and tissues. Recognises foreign antigens on pathogen. Cytoplasm of phagocyte engulfs it. In phagocytic vacuole in cytoplasm of phagocyte. Lysosome fuses with phagocytic vacuole, lysozymes break down pathogen. Presents pathogens antigens on surface to activate IS cells. 

T-Cells: White blood cell. Receptor proteins on surface bind to complementary antigens presented by phagocytes. Activates. TH cells release chemical signals that activate/stimulate phagocytes, cytotoxic T cells, which kill abnormal/foreign cells. Also B-cells.

B-Cells: White blood cell. Covered with antibodies, proteins bind to antigens to form antigen-antibody complex. each has different shaped antibody on membrane, different ones bind to different antigens. When antibody on surface meets complementary antigen, binds to it. Clonal selection. Activated B cell divides into plasma cells.

Antibody production: Plasma cell clones of B cell. Secrete antibodies specific to antigen. Monoclonal antibodies. Bind to antigens on surface of pathogen forming antigen-antibody complexes. 2 binding sites, bind 2 pathogens at once. Pathogens clumped together, agglutination. Phagocytes bind to antibodies and phagocytose many pathogens at once. 

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Immune Response (2)

Antibodies: Proteins, chains of amino acids, specificity depends on variable regions which form antigen binding sites. Each variable region has unique tertiary structure complementary to one specific antigen. All have same constant regions. 2 light chains, 2 heavy, disulfide bridges.

Cellular Response: T-cells, other IS cells. E.g. phagocytes

Humoral: B-cells, clonal selection, production of monoclonal antibodies

Primary response: Antigen enters body for 1st time and activates IS. Slow bc not many B-cells to make antibody needed to bind to it. Eventually body produces enough antibody to overcome infection. Infected persons shows symptoms. After exposure, B, T cells produce memory cells, remain in body for long time, remember specific antigen and recognise it 2nd time. Record specific antibodies needed to bind to antigen. Now immune, IS responds quickly to 2nd infection.

Secondary Response: If same pathogen enters body again, IS produces stronger, quicker response. Clonal selection happens faster. Memory B-cells activated, divide into plasma cells that produce right antibody to antigen. Memory T-cells activated , divide into correct T-cells to kill cell carrying antigen. Gets rid of pathogen before signs of symptoms.

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Immunity and Vaccines

Active Immunity: IS makes own antibodies after being stimulated by antigen. Natural: Become immune after catching disease. Artificial: Vaccination. Long-term, memory cells produced, takes a long time to come into effect, requires exposure to antigen.

Passive Immunity: Immunity from antibodies from different organism. Natural: Baby receives antibodies from mother through placenta, breast milk. Artificial: Injected with antibodies from someone else. Tetanus can be injected with antibodies against tetanus from blood donations. Short term bc antibodies broken down, no memory cells, immediate protection, no exposure.

Vaccinations: Contain antigens cause body to produce memory cells against particular antigen, without disease, symptoms. Reduce occurence of disease, not vaccinated less likely to catch disease, herd immunity. Antigens may be free/attached to dead/attenuated pathogen. Injected or taken orally. Oral could broken down by enzymes in gut/molecules too large to be absorbed into blood. Boosters given later to make sure more memory cells produced.

Ethics: Animal testing/animal based substances, testing on humans is risky, risk of side effects, who is first to receive in an epidemic of new disease, cost, should people be forced

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Antigenic Variation

Antigenic variation: After exposure to antibodies, pathogens can change their surface antigens. Different antigens formed due to changes in genes. When infected again, memory cells do not recognise different antigens. Primary response has to start again, and takes time, so become ill again. Makes it difficult to develop vaccines against some pathogens. HIV, influenza.

Influenza: Flu vaccine changes every year. Antigens on surface of flu change regularly, forming new strains of virus. Memory cells produced from vaccination with 1 strain will not recognise other strains. New vaccine developed, 1 chosen every year that is most effective against recently circulating virus. Government, health authorities implement programme of vaccination using most suitable vaccine.

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Antibodies in Medicine

MA: Produced from group of genetically identical B-cells. All identical in structure. Specific bc binding sites have unique tertiary structure that only antigen with complementary shape fits into

Anti-cancer drugs: Cancer cells have antigens, tumour markers, not found on normal body cells. MA can be made to bind to tumour markers. So drug only accumulates where cancer cells are. Side effects of antibody-based drug lower than other drugs bc accumulate near specific cells.

Pregnancy tests: Detect hormone human chorionic gonadotropin (hCG) found in urine of pregnant women. Application area contains antibodies complementary to hCG protein, bound to blue bead. When urine applied, hCG binds to antibody on bead, forms antigen-antibody complex. Urine moves to test slip, carrying beads with it. Test slip contains antibodies to hCG immoblised. hCG present, blue, bc immobilised antibody binds to hCG. If no hCG, beads pass through test area  without binding to anything, so wont turn blue.

Enzyme-linked immunosorbent assay (ELISA): Allows to see if patient has antibodies to certain antigen or vice versa. Used in medical diagnosis to test for pathogenic infections, allergies, etc. Antibody has enzyme attached to it, reacts with substrate to produce coloured product. Causes solution in reaction vessel to change colour. Demonstrates antigen/antibody present in sample. In some, quantity of antigen/antibody can be worked out from intensity of colour change.

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Antigens from patient sample bound to inside well in well plate. Detection antibody with attached enzyme complementary to antigen is added. If present, immobilised on inside surface of well, detection antibody binds. Well washed to remove unbound antibody, substrate solution added. Detection antibody present, enzyme reacts for colour change, positive.

Indirect ELISA: HIV antigen bound to bottom of well in well plate. Blood plasma contains several different antibodies, added. If HIV specific antibodies in plasma, bind to HIV antigen at bottom of well. Well washed to remove unbound antibodies. Secondary antibody has specific enzyme attached, added. Binds to HIV specific antibody. Washed out to remove unbound secondary antibody. No primary antibody, secondary washed away bc nothing to bind to. Solution with substrate added, reacts with enzyme attached to secondary antibody, produces coloured product. Colour change, HIV-specific antibodies in blood, infected with HIV.

Ethics: Animal rights issues, animals (mice) used to produce cells from which MA produced.

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HIV and Viruses

Human immunodeficiency virus affects human immune system, leads to aquired immune deficiency syndrome (AIDS). IS deteriorates and eventually fails, susceptible to other infections.

HIV host cells: Infects anf kills TH cells, host cells for virus. TH send signals activate phagocytes, TC cells, B-cells, without IS unable to respond to infections bc IS cells not activated. HIV > AIDS when TH cells critically low.

Initial Infection: HIV replicates rapidly, infected have flu symptoms, After, HIV replication lower. Latency period. Can be years. No symptoms.

AIDS: 1st: Minor infections of mucous membranes, recurring respiratory infections. 2nd: IS cells decreases further. Serious infections. TB, chronic diarrhoea, severe bacterial infections. 3rd: Very serious. Toxoplasmosis of brain, candidiasis of respiratory system. Survival time depends on existing infections, HIV strain, age.

HIV structure: Spherical structure, core containing genetic material (RNA), proteins (reverse transcriptase, integrase), around is coating of protein (capsid), lipid envelope made of stolen membrane of previous host, sticking out are attachment proteins that help HIV attach to host.

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HIV and Viruses (2)

HIV replication: 1. Attachment protein attaches to CD4 glycoprotein on cell membrane of host TH cell. Capsid released into cell, uncoats, releases RNA into cell cytoplasm. Reverse transcriptase used to make complementary strand of DNA from viral RNA template. Double-stranded DNA made, inserted into human DNA. Host cell enzymes used to make viral proteins from viral DNA in human DNA. Viral proteins assembled into new viruses, bud off, infect other cells, takes some of host's lipid envelope too, causes TH cell to die.

Antibiotics and viruses: Kill bacteria by interfering with metabolic reactions, target bacterial enzyme, ribosomes, different from humans. Antibiotics designed to only target bacterial so dont damage human ones. Virus uses hosts enzymes, ribosomes, so antibiotics cant inhibit bc cant target human processes. Antivirals target virus-specific enzymes.

No cure for HIV. Antivirals slow it down. So control the spread through sex, infected bodily fluids, mother to baby. Taking antivirals during pregnancy reduces chance of baby being HIV positive.

HIV retrovirus bc stores genetic information using RNA instead of DNA, so need to 'make' DNA in human cell to make new copies of themselves.

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