HIV Case Study PDF

Human Immunodeficiency Virus Nahima Akthar What this presentation will cover: The origin of B and T cells The activation of B and T cells in adaptive immunity Life cycle of a retrovirus Antibodies and Antigens Diagnosis and monitoring of HIV Opportunistic Infections Tr...

Human Immunodeficiency Virus Nahima Akthar What this presentation will cover: The origin of B and T cells The activation of B and T cells in adaptive immunity Life cycle of a retrovirus Antibodies and Antigens Diagnosis and monitoring of HIV Opportunistic Infections Treatments for HIV What is HIV? A virus that attacks the immune system, specifically targeting and weakening the body's defenses against infections and diseases. It primarily targets CD4 cells (a type of white blood cell), which are crucial for immune function. Over time, if left untreated, HIV can severely damage the immune system and lead to AIDS (Acquired Immunodeficiency Syndrome), the most advanced stage of HIV infection. Clinical Presentation of HIV Acute HIV Infection This is the primary stage of HIV infection, which occurs 2-4 weeks after exposure to the virus and is characterised by flu-like symptoms. Many people are unaware they are infected during this stage because the symptoms resemble a common viral illness. During this stage, the virus is replicating rapidly, and the viral load is very high, but CD4 T-cell counts are still relatively normal. Symptoms: Fever Fatigue Sore throat Clinical Latency This stage can last for many years (10 years or more) and is characterised by a slower progression of the disease. During clinical latency, the virus continues to replicate at low levels, but there may be no noticeable symptoms. If a person is on antiretroviral therapy (ART), they can live in this phase for a longer period without progressing to AIDS. Without treatment, the virus will continue to weaken the immune system, leading to an eventual decline in CD4 count, making the person vulnerable to opportunistic infections. Acquired Immunodeficiency Syndrome (AIDS) AIDS is the most severe phase of HIV infection, occurring when the immune system becomes severely damaged. This stage is diagnosed when the CD4 count falls below 200 cells/µL or when the person develops one or more opportunistic infections or cancers. Symptoms: Severe weight loss (wasting syndrome) Chronic diarrhea Prolonged fever Severe fatigue Night sweats Swollen lymph nodes  Brain lesion typical of toxoplasma Seborrheic dermatitis Oral candidiasis Kaposi’s sarcoma The origin of B and T cells 1. Both B and T cells start in the bone marrow 2. B cells: Stay in the bone marrow and mature. They are then released into the bloodstream, ready to fight infections by producing antibodies. 3. T cells: Travel to the thymus (primary lymphoid organ) to mature. Once mature, they move into the bloodstream and help with various immune functions, like killing infected cells. Explain the activation of B and T cells in the adaptive immune response Activation of B Cells: 1.Detection of Antigen: When a pathogen (like a virus or bacteria) enters the body, it carries foreign molecules called antigens. B cells have special receptors on their surface that can recognise these antigens. 2.Activation by Helper T Cells: Once a B cell detects an antigen, it gets help from T helper cells (which are also activated). The T helper cells send signals to the B cell to help it fully activate. 3.Antibody Production: Activated B cells start to divide and become plasma cells. These plasma cells produce antibodies, which are proteins that can stick to the pathogen and help neutralise it or mark it for destruction. Activation of T Cells: 1.Detection of Antigen: T cells cannot recognise free-floating antigens. Instead, they need antigen-presenting cells (like dendritic cells) to show them the antigens. These cells capture and "present" the pathogen’s antigens on their surface. 2.Activation of Helper T Cells: When a T helper cell binds to an antigen on the presenting cell, it gets activated. Activated helper T cells help coordinate the immune response by signalling other immune cells. 3.Activation of Cytotoxic T Cells: A cytotoxic T cell can be activated by a helper T cell or by directly recognising infected cells that display the pathogen’s antigens. Once activated, cytotoxic T cells can kill infected cells. Use HIV as an example to describe the life- cycle of a retrovirus 1. Attachment: HIV attaches to a CD4+ T cell (a type of immune cell) using a special protein on its surface. 2. Entry: The virus enters the cell by merging its outer layer with the cell membrane. 3. Reverse Transcription: Inside the cell, the virus turns its RNA into DNA with the help of an enzyme called reverse transcriptase. 4. Integration: The viral DNA enters the cell’s nucleus and integrates into the host's DNA, becoming part of the cell’s genetic material. 5. Replication: The host cell starts to make copies of the viral RNA and proteins using its machinery. 6. Assembly: The new viral parts are put together to form new virus particles. 7. Budding: The new viruses leave the infected cell by budding off, ready to infect more cells. 8. Spread: The cycle repeats in other cells, weakening the immune system over time.  1. Attachment 2. Entry 3. Reverse Transcriptase 4. Integration 5. Replication 6. Assembly 7. Budding 8. Spread General structure of an Antibody  Structure of antibodies IgG Most abundant 65%-70% = blood plasma Designed to be a monomer Can activate complement system/opsonisation Neutralisation, precipitation Can pass through placenta into foetus IgA Dimer = two linked together Found in saliva, mucosal lining of GI tract, milk from lactation → passive immunity for baby IgM Pentamer = 5 OR monomer form Made during primary immune response Can bind to protein and activate complement system Agglutination = Type II hypersensitivity IgE Monomer Found in respiratory tract mucosa, GI tract mucosa urogential structures, lymphatic tissues Eosinophil destroys pathogens → IgE antibodies important here Can bind to mast cells and cause inflammatory response, e.g. histamine, leukotriene release + vasoconstriction IgD Monomer B cell receptor Diagnosis Detection of HIV antibody Detection of HIV p24 antigen – Viral protein that lives on the envelope. Used in early and late disease. Test on multiple platforms and diagnose on 2 separate samples to prevent false positives. Routine HIV testing is offered - Antenatal Screening (national policy): all pregnant women are offered HIV testing at their booking visit - Blood/ Organ Donation (national policy): all blood and organ donors are screened, all organ recipients are screened - Emergency Department: all adults having bloods taken are also tested for HIV Monitoring HIV-1 Molecular Testing HIV-1 viral load - Nucleic acid detection. Done by PCR. Marker of HIV replication rate Prior to starting treatment 4 – 6 weeks after starting or changing therapy 6 – 12 monthly when established on therapy Aim of therapy: undetectable viral load / detected < 50 copies/ml Opportunistic infections prevalent in people with advanced HIV (AIDS) Treatment of HIV Anti-Retroviral Drug Groups - Nucleoside Reverse Transcriptase Inhibitors (NRTI) - Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) - Protease Inhibitors (PI) - Integrase Strand Transfer Inhibitors (INSTI/INI)  Nucleoside Reverse Transcriptase Inhibitors (NRTIs) Mechanism of Action Analogues of DNA nucleotides Bind in the DNA chain to stop further polymerisation Competitive Inhibitors Drug Names Tenofovir Abacavir Emtricitabine Lamivudine Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) Mechanism of Action Change structure of the active site of reverse transcriptase so polymerisation stopped Non-competitive inhibition Drug Names Nevirapine Efavirenz Rilpivirine Doravirine Etravirine Protease Inhibitors (PI) Mechanism of Action Viral protein are produced as a polyprotein -> migrate into the virion -> protease breaks up the polyprotein -> this process is called maturation -> protease inhibitors stop maturation -> virion is unable to effectively infect a cell. Drug Names Darunavir + Ritonavir / Cobicistat Atazanavir + Ritonavir / Cobicistat Integrase Strand Transfer Inhibitors (INSTI) Mechanism of Action Double stranded DNA is trapped into nucleus -> integrase intergrates it into human DNA -> integrase inhibitors prevent that from happening -> circularisation of viral DNA -> degraded Drug Names Raltegravir Dolutegravir Elvitegravir Cabotegravir Bictegravir Choosing an ART regime Combination therapy – usually 2 NRTIs + NNRTI/ PI/ INSTI Consider: Patient lifestyle Drug-drug interactions Genetic barrier to resistance