Immunopathology and HIV

Flashcards covering immunopathology, primary and secondary immunodeficiencies, HIV structure, infection mechanisms, treatments, and related opportunistic infections

What is immunopathology?

The study of immune system imbalances, where the system is either too weak (hypo-reactive) or too strong (hyper-reactive), leading to health problems.

What happens in hypo-reactivity?

The immune system doesn’t respond well enough, leading to immunodeficiencies and difficulty fighting infections.

What are the potential consequences of hyper-reactivity in the immune system?

Hyper-reactivity (too strong) can cause allergies, autoimmunity, and transplant rejection.

What is Primary Immunodeficiency (PID)?

A group of disorders where parts of the immune system are missing or not working properly from birth, affecting adaptive or innate immunity which includes humoral B cell defects, combined B and T cell defects, phagocytic defects, cellular T cell only defects, and complement system defects.

How does PID aid scientific understanding?

PID helps scientists understand the functions of individual immune cells and can range in severity from mild to fatal, predisposing individuals to infections, autoimmune diseases, and allergies.

Explain Severe Combined Immunodeficiency (SCID)

A serious PID where T cells, B cells, and sometimes NK cells don’t work properly or are missing; patients are highly vulnerable to infections from birth and often need urgent treatment like bone marrow transplants.

What are Secondary Immunodeficiencies?

Immunodeficiencies that occur after birth due to external factors, not inherited genetic issues, such as acquired hypogammaglobulinemia, AIDS, or agent-induced immunodeficiency.

How does AIDS affect the immune system?

AIDS, caused by HIV, destroys helper T cells (CD4+) and weakens immune defense, leading to high susceptibility to infections and cancer.

What global impact has AIDS had?

Approximately 37.9 million people worldwide are currently infected; over 25 million have died from AIDS-related causes; racial and ethnic minorities are disproportionately affected; 63% of people receive antiretroviral therapy; and AIDS-related deaths have significantly dropped due to new drug therapies.

What are the two main strains of HIV?

HIV-1, the most common worldwide, is highly aggressive and more likely to cause AIDS, while HIV-2 is found mainly in West Africa and is less aggressive, HIV-1 Group M is responsible for majority of the global pandemic.

How does HIV enter and spread in the body?

HIV enters through mucosal surfaces or directly into the bloodstream; dendritic cells capture HIV and transport it to lymph nodes, where it infects CD4+ T helper cells and replicates rapidly, spreading the infection.

What makes HIV difficult to fight?

High mutation rate: HIV changes its structure quickly and genome integration: HIV inserts its genetic material into host DNA, forming a permanent infection.

How does HIV lead to immunodeficiency?

HIV gradually destroys CD4+ T cells, leading to immunodeficiency, progressing to AIDS if untreated.

What is HAART and how does it combat HIV?

HAART (highly active anti-retroviral therapy) blocks entry into cells, prevents integration into DNA, and inhibits replication of new virus.

Describe the structure of the HIV-1 virion

Envelope: outer layer made from host cell membrane; Gp120: surface protein that binds to the CD4 receptor on human T helper cells; Gp41: fusion protein that helps fuse the HIV and host cell membranes; P24: capsid protecting the HIV RNA; ssRNA: HIV genetic material; reverse transcriptase (p64) converts HIV RNA into DNA; p32 integrase helps insert the HIV DNA into the host’s genome; p10 protease processes viral proteins.

What are the functions of gp120 and gp41?

Gp120: head portion that binds to the CD4 receptor, has a glycan shield that hides it from the immune system; gp41: stem that stays embedded in the membrane, responsible for fusing the virus with the host cell.

What is a provirus?

The form HIV takes after integrating its DNA into the host's genome, with LTRs at both ends controlling transcription, integration, and recombination.

What are HIV's structural genes and regulatory genes?

Structural genes: Gag (codes for nucleocapsid proteins), Pol (codes for enzymes like protease, reverse transcriptase, integrase), Env (codes for envelope glycoproteins like gp120 and gp41). Regulatory genes: Tat, Rev, Nef, Vpu, Vif, Vpr for modulating function and immune evasion.

How is HIV-1 spread?

Via intimate contact with infected body fluids, such as vaginal/anal intercourse, receipt of infected blood/blood products, or passage from mother to infant.

What role do dendritic cells play in HIV infection?

Dendritic cells in virus-exposed areas take up and harbor viruses and pass it to CD4+ T cells, acting like Trojan horses unintentionally delivering HIV directly to its main target.

What determines HIV's tropism?

Tropism is determined by a protein on the virus called gp120, which attaches to receptors on host cells, such as CCR5 (helps HIV establish itself) and CXCR4 (faster progression in AIDS).

Infection phases: Acute phase

First few weeks, Rapid spike in viral load (HIV in blood), Strong immune response kicks in [CD8+ T cells kills infected cells, CD4+ T cells orchestrate response, anti-HIV antibodies are made], Viral load drops but isn’t eliminated

Infection phases: Asymptomatic phase

Can last for years, CD4+ T cells slowly decline, though person may still feel well, Viral load slowly rises again, HIV mutates and escapes immune detection, Replicates silently and depletes T cells [Dormant memory CD4+ T cells, Proliferating T cell pools]

Infection phases: AIDS

CD4+ T cells drop below 200/mm3 ,Viral load spikes again, Person becomes severely immunocompromised, susceptible to infection and cancer, Making HIV harder to fight and Kills 1-2 billion CD4+ T cells a day during latency

What are the four specific criteria for frank AIDS?

Evidence of infection with HIV-1 (proven by blood test), <200 CD4+ T cells/μL of blood, Impaired/absent DTH reactions, Occurrence of opportunistic infections.

What are common co-morbidities associated with AIDS?

Opportunistic infections (fungal, viral, bacterial, parasitic, cancerous), and wasting syndrome.

What are the stages of HIV infection and CD4+ depletion?

HIV virion enters CD4+ T cell, pre-integration phase: viral RNA is inside but not yet part of the host's DNA, after integration, the virus becomes a provirus, DNA is embedded into the host cells DNA.

What are the different paths the infected cell can take?

Active infection - Virus replicates [Apoptosis, osmotic lysis, virus hijacks the cell, target of HAART], Abortive infection - Virus starts replication but doesn’t complete it [Causes pyroptosis], Silent infection (dormant) - Virus is dormant [Creates reservoirs that hide from treatment and immunity, Can later reactivate making it hard to fully cure HIV]

Why the gut is a major site of HIV replication and CD4+ T cell loss?

Gut cells express CCR5 and CXCR4, these receptors are used by HIV to enter cells. Massive depletion of CD4+ T cells occur in the gut-associated lymphoid tissue contributing to immunodeficiency, The innate immune response is also impacted like dendritic cells stop working properly.

Explain HAART

HAART is a combination of anti-retroviral drugs used to suppress HIV replication and key features are: Uses multiple drugs with diff mechanisms of action(Targets virus at various stages of its life cycle, Makes it hard for HIV to develop resistance) and Effectiveness lowers viral load to undetectable levels ( Improves immune function and slows progression to AIDs) but no a cure and Early treatment = better long-term outcomes.

Therapeutic agents that inhibit retrovirus replication - Chemokine receptor antagonists

The therapeutic agents inhibit retrovirus replication working by block the virus from attaching and is a CCR5 blocker.

Therapeutic agents that inhibit retrovirus replication - Fusion inhibitors

The therapeutic agents inhibit retrovirus replication working by stopping the virus from merging with cell.

Therapeutic agents that inhibit retrovirus replication - Reverse transcriptase inhibitors

The therapeutic agents inhibit retrovirus replication working by using Nukes – faulty DNA building blocks [stop DNA chain] or Non-nukes – block RT enzyme directly.

Therapeutic agents that inhibit retrovirus replication -Integrase inhibitors

The therapeutic agents inhibit retrovirus replication working by block viral DNA from entering host genome.

Therapeutic agents that inhibit retrovirus replication - Protease inhibitors

The therapeutic agents inhibit retrovirus replication working by preventing new viruses from maturing properly.

How do certain drugs block DNA fusion and entry into host cells?

Ibalizumab binds to CD4 receptor, preventing conformational changes; Maraviroc binds to CCR5, blocking HIV from attaching; Enfuvirtide (T-20) mimics HR2 domain, preventing HR1-HR2 interactions and blocking fusion.

How does reverse transcriptase inhibitors (RTIs) interrupt polymerization?

HIV reverse transcriptase builds viral DNA from RNA using normal nucleotides; NRTIs like AZT mimic normal nucleotides, inserting into the chain but lacking a necessary OH group, causing chain termination, stops DNA synthesis by HIVs reverse transcriptase.

How do integrase and protease inhibitors work?

HIV integrase inhibitors block HIV DNA from integrating into host DNA; HIV protease inhibitors bind to the active site of HIV protease, blocking it and preventing viral proteins from becoming functional ultimately stopping viral maturation.

What are the adverse effects of different HIV drug classes?

NRTIs: mitochondrial toxicity, bone marrow suppression; NNRTIs: rash, hepatitis; Protease inhibitors: hepatotoxicity, insulin resistance; Integrase inhibitors: dizziness, sleep issues; Fusion inhibitors: injection site reactions; CCR5 antagonists: dizziness, liver issues.

What causes HIV fitness and viral drift?

RT is error prone and causes frequent mutations during replication, leading to genetic diversity, ability to escape immune detection, resistance to drugs, and difficulty in developing a universal vaccine; HIV is the fastest mutating virus.

How do microorganism suppress the the immune system?

Lepratomous leprosy skews immune response, bacterial superantigens leads to massive T cell activation then temp immune suppression, measles virus suppresses IL-2 production, Epstein-barr virus infects B cells which activates CD8+ T cells to kill infected cells then adaptive immunity is temp deactivated.

HIV Transmission, Disease Progression, and Clinical Management: Explain this case study

Martin, a 42-year-old police officer, was diagnosed with early-stage AIDS after routine testing revealed a low CD4+ T cell count and high viral load. He reported night sweats and unexplained weight loss, began HAART, viral load dropped to undetectable levels, and CD4 count increased. Early diagnosis and adherence to therapy were critical for long-term survival.

Explain key takeaways from HAART

HIV infects CD4+ T cells, using gp120 and co-receptors (CCR5, CXCR4). Progressive loss of CD4+ T cells leads to immunodeficiency, allowing opportunistic infections and cancers. HAART effectively reduces viral load and can restore CD4+ counts. Early diagnosis and adherence to therapy are critical for long-term survival. Prevention of transmission and ongoing monitoring remain vital.