Lecture 28 HIV Progression of AIDS Cell Types Infected by HIV Innate Immune System Macrophage and Natural Killer Cell Adapted immune system Helper T Cell and Natural Killer T Cell These cells have 3 receptors in common CD4 and CCR5 CXCR4 HIV uses these 3 receptors to enter hosts therefore HIV can infect all 4 of these cell types T Helper Cells CD4 Cells commanding officer and central to the activity of the adaptive immune response Key in responding to antigen presenting cells and identifying and eliminating foreign invaders antibodies Activates B cells to differentiate into Plasma cells and produce antigen specific Activator Killer T cells which go off and hunt and kill infected cells cytotoxic T cells cell killing T cells Killer T cells Fighting HV Macrophage engulfs HIV and presents the HIV antigen gp120 to CD4 helper cell to show it does not belong T helper cell activates B cells and they create antibodies to go and attack and destroy anything that the antibodies go to Killer T cell destroys any cell even helper cells within the body that has been effected by the HIV virus Helper T cell is central to the immune response to an infection target of HIV so their numbers will go down which will effect how much the body fights back HIV s Path to Immune System Destruction 1 Primary infection Dendritic cells deliver HIV to CD4 cells 2 Establishment of infection in lymphoid tissue 3 Massive amount of HIV in bloodstream 4 Wide dissemination to lymphoid organs lymph nodes 5 Trapping of virus and establishment of chronic persistent infection 6 Inflammation occurs and CD4 cells are called in via cell signaling for an immune response leading to more infection 7 Partial immunological control of virus accelerated virus replication Rapid CD4 T cell turnover 8 Destruction of immune system Infected T cells go to the lymph nodes and therefore can infect cells within the lymphnodes VIRENIA Massive amount of HIV virus in the bloodstream How Does HIV Destroy CD4 Cells Killing of CD4 cells Lysis of budding virus particles Killing of CD4 cells Syncytium formation of large clumps of helper cells cells fuse together infected CD4 positive and uninfected CD4 negative they lose function 95 CD4 cells in lymphoid tissue Cell undergoes programmed cell death Syncytium can mean a rapid progression to AIDS The fusion of CD4 cells target cells due to some cells expressing gp120 protein HIV Induced Syncytia on plasma membrane Progression to AIDS Primary infection Acute HIV syndrome Wide dissimilation of virus Seeding of lymphoid organs Weight loss fevers fatigue and malaise chills night sweats and decreased appetite Constitutional syndrome Opportunistic disease KS pneumocystis pneumonia cervical cancer Death Can be infected with HIV for ten years with little to no symptoms The CDC s Definition of AIDS All HIV infected people with fewer than 200 CD4 T Cells per cubic millimeter of blood compared with CD4 T Cells counts of about 1 400 for healthy people Or If their CD4 T Cells counts lower than 14 of all lymphocytes And being diagnosed with at least one or more of the two dozen AIDS associated conditions that result from HIV s attack on the immune system Normal people usually have 1400 CD4 The Stages of HIV Infection Stage 1 Primary HIV Infection Short flu like illness large amounts of HIV in the peripheral blood seroconversion HIV antibodies and cytotoxic lymphocutes 3 weeks post infection can have fungus in mouth fevers weight loss rash nausea vomiting Stage 2 Clinically Asymptomatic Stage Lasts for an average of ten years free from major symptoms there may be swollen glands HIV level in peripheral blood drops to very low levels patient remains infectious T helper cell infection Stage 3 Symptomatic HIV Infection Over time the immune system loses the struggle to contain HIV lymph nodes and tissues become damaged HIV mutates and becomes more pathogenic T helper cell destruction emergence of opportunistic infections such as Hairy cell leukoplakia Stage 4 Progression from HIV to AIDS As the immune system becomes more and more damaged theillnesses presented become more and more severe leading eventually to an AIDS diagnosis CD4 cell count below 200 mm3 opportunist infections Immune Response and Stage of Infection Stage 1 Acute infection Stage 2 Virus drops down HIV antibodies go up Stage 3 antibody levels drop and virus goes up Stage 4 Very low levels of antibodies and high levels of the virus Rapid Progression to AIDS Progression to AIDS is more rapid under the following circumstances When syncytia forming HIV is present When acute infection is symptomatic When HIV infection occurs with a drug resistant strain When a higher setpoint of viral load follows initial viremia after infection antibodies present body begins to fight the infection When patient smokes When opportunistic infections or neoplasms cancerous growths are present When in congenital cases there are signs of infection less than 3 months of age HIV Progression Viral Load Set Point Infected with HIV Set Point point at which antibodies have been produced and the body begins to Lower set point slow rate of progression High set point faster rate of progression effective treatment decrease the fight the infection viral load Viral Load and Progression to AIDS Relation between baseline viral load setpoint and median survival rate 10 years with 4530 molecules of HIV viral load 7 7 with 4531 13020 molecules of HIV 5 3 with 13021 36270 molecules of HIV 3 5 with 36270 molecules of HIV Viral Load and CD4 Cell Count If your CD4 cell count is HIGH and your viral load is LOW your medicines are doing a good job of controlling the virus If your CD4 cell count is LOW and your viral load is HIGH your medicines are not doing a good job of controlling the virus CD4 Cell Count Predicts likelihood of developing AIDS Many diseases are possible to develop if CD4 count is 200 or below Questions Which of the following does NOT represent a condition that leads to rapid HIV progression to AIDS Syncytia forming HIV is present HIV infection caused by a drug resistant strain A bad turkey bite The patient smokes Other factors virus Signs of infection within 3 months of age Immune system is weak before invasion of the virus Primary infections results in symptoms skipped the no symptoms section of the What is the combination of viral load and CD4 cell count would you mostl mikely find in an individual who has been diagnosed with AIDS Syncytia causes the depletion of functioning immune
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