1. HIV/AIDS HIV/AIDS Rate per 100,000 people Plan for Tonight Unit 6 and 7 Work Immune Response HIV’s Interaction with the Immune System Difficulties with HIV Treatment/Vaccines Highly Active Antiretroviral Treatment (HAART) New Promising Treatments

2. Immune Response: Initial Infection Pathogens (disease-causing bacteria or viruses or other organisms), for example HIV, invade your body Antigens (proteins on the surfaces of pathogens that can be recognized by antibodies)

3. Immune Response Step 1: Initial Recognition of Infection Cell-Mediated ResponseAntibody-Mediated Response Macrophage B Cell # 146,883 B Cell# 34,599 MACROPHAGE are white blood cells that gobble up foreign invaders. MHC Protein B CELLS are white blood cells that produce antibodies. Each person can produce hundreds of millions of different B Cells. Each type of B cell is genetically-unique and produces a unique antibody. Two B cells(out of hundreds of millions) are shown here. ANTIBODIES are Y-Shaped proteins. The ends of the arms of the Y have antigen-binding sites. Each different type of antibody has a uniquely shaped antigen-binding site.

4. Immune Response Step 2: Phagocytosis of Pathogen Cell-Mediated ResponseAntibody-Mediated Response Macrophage MACROPHAGE engulf (phagocytize) the pathogenic invader. After this, the macrophage kills and breaks down the pathogen into pieces. The B CELL that has an antibody that binds to antigen engulfs(phagocytizes) the antigen- antibody complex. After this, the B cell kills and breaks down the pathogen into pieces. B Cell # 146,883

5. Immune Response Step 3: Antigen-Presenting Cells Cell-Mediated ResponseAntibody-Mediated Response Antigen-Presenting Cell Antigen-Presenting Cell MACROPHAGE display parts of the pathogen alongside the MHC protein. At this point, the macrophage is called an Antigen-Presenting Cell (or APC). The B CELLdisplays parts of the pathogen alongside the MHC protein. At this point, this B cell is called an Antigen- Presenting Cell (or APC).

6. Immune Response Step 4: Helper T Cell-APC Interaction Cell-Mediated ResponseAntibody-Mediated Response Antigen-Presenting Cell Antigen-Presenting Cell T Cell # 2,888,124 T Cell #492 HELPER T CELLS are another kind of white blood cell. There are hundreds of millions of different kinds of T Cells. Each is genetically unique and each displays a unique form of the protein called T Cell Receptor protein. Shown here are two of the hundreds of millions of different kinds of T Cells in a persons body.

7. Immune Response Step 5: Helper T Cell Stimulation Cell-Mediated ResponseAntibody-Mediated Response Antigen-Presenting Cell Antigen-Presenting Cell T Cell # 2,888,124 Binding of Helper T Cell to APC stimulates the APC to secrete Interleukin. Interleukin stimulates Helper T cells to rapidly reproduce. Since Helper T Cell # 2,888,124 is locked on, it will be in an area of high Interleukin concentration. So among all the Helper T Cells floating around the body, Helper T Cell # 2,888,124 will be the one to reproduce rapidly and repeatedly.

8. Immune Response Step 5: Helper T Cell Proliferation Cell-Mediated ResponseAntibody-Mediated Response Antigen-Presenting Cell Antigen-Presenting Cell T Cell # 2,888,124 Huge numbers of T Cell # 2,888,124 are produced. T Cell # 2,888,124

9. Immune Response Step 6: Helper T Cell Differentiation Cell-Mediated ResponseAntibody-Mediated Response Antigen-Presenting Cell Antigen-Presenting Cell T Cell # 2,888,124 Cytotoxic T Cells kill body cells infected by the pathogen. MEMORY T Cell # 2,888,124 CYTOTOXIC T Cell # 2,888,124 HELPERT Cell # 2,888,124 CYTOTOXIC T Cell # 2,888,124 MEMORY T Cell # 2,888,124 HELPERT Cell # 2,888,124 Memory T Cells are fairly inactive. They reproduce at a steady pace. Helper T Cells interact with other white blood cells to propagate the immune response.

10. Immune Response Step 7: Helper B Cell Stimulation Cell-Mediated ResponseAntibody-Mediated Response Antigen-Presenting Cell Antigen-Presenting Cell T Cell # 2,888,124 HELPERT Cell # 2,888,124 HELPER T CELL #2,888,124 binds to the antigen-presenting B cell (#146,883) since this B cell displays the same antigen-MHC complex. This binding stimulates Helper T Cell to secrete Cytokines. Cytokines stimulate B cells to rapidly reproduce. Since B cell 146,883 is locked on, it will be the one to rapidly reproduce. Thus, the B Cell that produces the antibody that binds to the current infectious agent is the one that proliferates.

11. Immune Response Step 8: Helper B Cell Proliferation Cell-Mediated ResponseAntibody-Mediated Response Antigen-Presenting Cell Antigen-Presenting Cell T Cell # 2,888,124 HELPERT Cell # 2,888,124 Many copies of B Cell 146,883 are produced. B Cell # 146,883

12. Immune Response Step 9: Helper B Cell Differentiation Cell-Mediated ResponseAntibody-Mediated Response Antigen-Presenting Cell HELPERT Cell # 2,888,124 Plasma B Cells produce and secrete large quantities of antibodies. This helps to fight the current infection. Memory B Cell # 146,883 Plasma B Cell #146,883 Plasma B Cell #146,883 Plasma B Cell #146,883 Plasma B Cell #146,883 Plasma B Cell #146,883 Plasma B Cell #146,883 Memory B Cell # 146,883 Memory B Cell # 146,883 Memory B Cell # 146,883 Memory B Cell # 146,883 Memory B Cell # 146,883 Memory B Cells are fairly inactive. They reproduce at a steady rate and will be present if the body is ever re-infected with the same pathogen.

13. Immune Response Step 10: Immunity Memory B Cell # 146,883 Memory B Cell # 146,883 Memory B Cell # 146,883 Memory B Cell # 146,883 Memory B Cell # 146,883 Memory B Cell # 146,883 If the body is ever again infected with the same pathogen, then the particular Memory T Cells and Memory B Cells that specifically recognize and bind this pathogen are already present. So steps 1-5 and 7-8 won’t have to happen. This makes for a faster immune response upon re- infection (so you don’t feel like you’re sick). MEMORY T Cell # 2,888,124

14. Human Immunodeficiency Virus Cell-Mediated ResponseAntibody-Mediated Response Antigen-Presenting Cell Antigen-Presenting Cell T Cell # 2,888,124 HELPERT Cell # 2,888,124 HIV infects Helper T Cells. When HIV infects a person’s body, that stimulates an immune response. This causes an increase in Helper T Cells. But this increase in Helper T Cells is an increase in hosts as far as HIV is concerned.

15. HIV Multiplication T Cell # 2,888,124 1. HIV attaches to the T Cell Receptor T Cell # 2,888,124 2. HIV penetrates into host cell T Cell # 2,888,124 3. HIV’s RNA genome is liberated. T Cell # 2,888,124 4. cDNA of the HIV genome is made by the enzyme Reverse Transcriptase T Cell # 2,888,124 5. Viral proteins are made and must be cut apart by Protease Enzymes to be activated. T Cell # 2,888,124 6. Many new viral particles are produced. Some are mutants. 4a. HIV cDNA can insert into host chromosome

16. Difficulties with HIV Treatment/Vaccines T Cell # 2,888,124 4. cDNA of the HIV genome is made by the enzyme Reverse Transcriptase T Cell # 2,888,124 6. Many new viral particles are produced. Some are mutants. Reverse transcriptase has a very high mutation rate. Drug-resistant and vaccine-resistant strains develop rapidly. Random mutations occur. Among these mutants a few may be resistant to an anti-HIV drug. When that drug is used, non-resistant strains will be killed off and that will leave the drug-resistant strain as the survivor.

17. Highly Active Antiretroviral Drug Therapy (HAART) One or two different nucleoside analogs that inhibit the action of Reverse Transcriptase AND One or two different protease inhibitors that inhibit the action of retroviral protease enzyme. Pros: Highly effective. Unlikely that a cell will incur enough random mutations that make it resistant to all of the drugs all at once. Cons: Expensive. Difficult dosage regimen that many people fail to maintain (missed doses increase risk of drug-resistant HIV strains). Some have side effects.

18. New Promising Treatment T Cell Mutant A few rare mutant people appear to have T Cell Receptors that HIV cannot attach to. Bone marrow from mutant person was transplanted into an HIV-infected person. After two years, the bone marrow recipient appears to be HIV-free.

19. New Promising Treatment: Next Step T Cell Mutant A few rare mutant people appear to have T Cell Receptors that HIV cannot attach to. Transfuse genetically-altered bone marrow stem cells back into the bones of the HIV-infected patient. Should be a “permanent” treatment with little risk of immunological rejection since they are the person’s own cells. Isolate gene for mutant T Cell Receptor. Introduce mutant T Cell Receptor gene into bone marrow of HIV-infected people (must also remove the native T Cell Receptor gene).