viruses and parasites Flashcards
lecture 9
Why are viruses classified as obligate intracellular parasites?
Viruses depend on host cells for replication but may also exist extracellularly during some stages of infection.
What are the key innate immune defences against viruses?
Type I Interferons (IFN-α and IFN-β):
Prevent viral replication and protect non-infected cells.
Natural Killer (NK) Cells:
Recognise and kill infected or stressed cells using perforin and granzyme.
What are the functions of interferons in viral defence?
IFN-α and IFN-β (Type I): Early response to viral infection, prevent viral replication, protect neighbouring cells.
IFN-γ (Type II): Secreted by T cells and NK cells, inhibits TH2 responses, promotes TH1, recruits macrophages.
How are interferons used therapeutically?
Recombinant IFN-α treats hepatitis B, hepatitis C, and some cancers.
Severe side effects may limit their use.
How do natural killer /NK cells identify and kill target cells?
Recognise stressed or infected cells via activating receptors.
Use perforin to create pores in target membranes and granzymes to induce apoptosis.
What distinguishes infected cells from normal cells for NK cells?
Activating receptors: Trigger killing by recognising carbohydrate ligands.
Inhibitory receptors: Bind to MHC class I molecules to prevent killing.
Viruses that reduce MHC class I expression make cells more susceptible to NK cells.
How do cytotoxic T cells (CD8+) kill virus-infected cells?
Granule Secretion: Perforin forms pores, allowing granzymes to enter and induce apoptosis.
Fas-Fas Ligand Interaction: Induces apoptosis via death receptor signalling.
What cytokines do CTLs secrete, and what are their effects?
IFN-γ:
Inhibits viral replication.
Increases MHC class I and II expression.
Enhances macrophage phagocytosis.
Boosts NK cell activity.
How do antibodies defend against viruses?
Neutralise free virus and prevent cell entry.
Opsonise viruses for enhanced phagocytosis.
Activate complement to lyse enveloped viruses.
What immune mechanisms are involved in influenza defence?
Antibodies neutralise haemagglutinin and neuraminidase.
CTLs reduce viral shedding.
Epidemics occur due to new strains escaping antibody recognition.
How does HIV evade the immune system?
Targets CD4+ T cells, macrophages, and dendritic cells.
Mutates to escape CTL recognition.
Leads to opportunistic infections like oral candidiasis and Kaposi’s sarcoma in AIDS.
What immune responses and complications occur in severe COVID-19 cases?
Immune dysregulation: Cytokine storm leads to acute respiratory distress syndrome (ARDS).
Severe cases: Lymphopenia, eosinopenia, extensive pneumonia, multiple organ failure.
What immune responses are critical against parasites?
Antibodies: Opsonisation, complement lysis, and ADCC (e.g., IgE response to helminths).
Cell-mediated Immunity: TH1 cytokines activate macrophages against protozoa like Leishmania.
How does T cell immunity determine the outcome of Leishmania infection?
C57BL/6 Mice (TH1): Strong IFN-γ response resolves infection.
BALB/c Mice (TH2): High IL-4 levels lead to progressive disease.
What immune mechanisms target malaria?
Antibodies: Neutralise sporozoites and merozoites, kill infected RBCs.
CTLs: Target infected liver cells.
Why is understanding immune responses critical for vaccine development?
Vaccines must induce the right immune response for each pathogen and stage of infection.
How do Type I interferons (IFN-α and IFN-β) protect against viral infections?
Induce an antiviral state in neighbouring cells.
Increase killing activity of NK cells by 20-100 fold.
Suppress viral nucleic acid production and replication.
What is the role of IFN-γ in viral immunity?
Promotes TH1 responses, enhancing cell-mediated killing.
Recruits macrophages to infection sites.
Inhibits TH2 responses, reducing reliance on antibodies.
Why can interferons have severe side effects in therapeutic use?
They can induce systemic inflammatory responses, leading to symptoms such as fatigue, fever, and muscle pain.
How do NK cells kill target cells without involving antibodies or MHC?
Use activating receptors to identify stressed cells.
Release perforin to create membrane pores and granzyme to induce apoptosis.
Act rapidly to control infections.
Why do viruses that downregulate MHC class I expression become more susceptible to NK cell killing?
MHC class I molecules inhibit NK cell killing. Without them, inhibitory signals are lost, allowing NK cells to attack the infected cell.
Why are cytotoxic T cells (CTLs) referred to as “serial killers”?
CTLs can kill multiple infected cells in succession without releasing viruses or causing inflammation.
What ensures CTL killing is highly specific?
Recognise viral peptides presented by MHC class I on infected cells.
Release granules in a polarised manner directly onto the target cell.
How does complement activation aid in viral defence?
Causes lysis of enveloped viruses.
Enhances phagocytosis through opsonisation.
Promotes inflammation, aiding immune cell recruitment.
Why do antibodies against HIV not provide effective protection?
HIV rapidly mutates, escaping antibody recognition, and targets CD4+ cells, crippling the immune system.
How does CTL activity correlate with HIV disease progression?
Higher CTL activity is associated with slower progression to AIDS, as CTLs control viral replication.
How does SARS-CoV-2 evade the immune system?
Suppresses Type I interferon production to aid viral replication.
Viral proteins inhibit RIG-1 (a pattern recognition receptor) and stimulate pro-inflammatory NF-κB.
What causes cytokine storms in severe COVID-19 cases?
Dysregulated immune responses lead to excessive cytokine release, causing acute respiratory distress syndrome (ARDS), lung damage, and multi-organ failure.
Why do helminths often induce a strong IgE antibody response?
IgE triggers mast cell-mediated inflammation.
Facilitates eosinophil ADCC, important for targeting large parasites.
What is ADCC, and how does it help in parasite defence?
Antibodies bind to parasite surfaces, recruiting immune cells like eosinophils, which release toxic granules to kill the parasite.
What determines whether mice resolve or succumb to Leishmania infection?
C57BL/6 mice (TH1): Strong IFN-γ response resolves infection.
BALB/c mice (TH2): High IL-4 response leads to fatal disease progression.
: Which immune mechanisms target malaria at different stages?
Antibodies neutralise sporozoites and merozoites.
Cytotoxic T cells target infected liver cells.
Why is it challenging to develop vaccines for diverse pathogens?
Different pathogens and infection stages require distinct immune responses, and vaccines must mimic these effectively.
Why is global data sharing critical during pandemics like COVID-19?
It enables rapid identification of effective treatments, tracking of mutation rates, and global coordination for vaccine development.
