Immunity to Pathogens Flashcards
for a successful invasion of the host, the pathogen must overcome both the…
innate and adaptive immune responses
Innate immunity to viral infections is largely though the induction of?
Type I interferons (IFN-α and IFN-β)
How are IFN-α and IFN-β induced?
via Toll-like receptors (TLRs) that detect viral dsRNA in infected cells
what 3 things are induced by IFN-α/β receptor signaling?
- Mx proteins
- Rnase L
- Protein kinase R
What do Mx proteins do?
inhibit virus transcription and assembly
What does Rnase L do?
degrades viral mRNA
What does protein kinase R do?
blocks protein translation
What happens when IFN-α and IFN-β bind to the appropriate receptor on NK cells?
induces lytic activity
What further enhances the lytic activity of the NK cells in response to IFN-α and IFN-β ?
IL-12 produced by innate immune cells such as dendritic cells
What 4 methods does antibody use to contain the spread of viruses?
- block viral attachment to host cells
- preventing fusion of viral envelope with host cell membrane
- agglutination and opsonization
- activation of classical complement pathway
What occurs after antibody activates the classical complement pathway in terms of viral killing?
opsonization of viral particles by C3b and lysis of enveloped virus by the membrane attack complex
Cell-mediated immunity is responsible for eliminating viruses once…
cells have already become infected
What 4 things are involved in cell mediated viral clearance
- IFN-γ secreted by CD4+ Th1 cells and CD8+ CTL has direct antiviral activity
- CTLs target and kill virus infected cells
- NK cells are directly lytic for infected cells and also kill by ADCC
- Macrophages are activated by IFN-γ and kill by ADCC
What are 6 ways in which viruses can evade the immune response (briefly)
- evade action of IFN-α and IFN-β
- inhibit viral antigen presentation (3 ways)
- Constant alteration of viral antigens
- Modulation by capping and shedding
- Interfering with complement function
- Suppression of Antiviral immune responses (3 ways)
How do viruses evade IFN-α and IFN-β action?
by blocking or inhibiting the action of dsRNA-dependent protein kinase R
what are the three ways in which viruses inhibit viral antigen presentation?
- down regulating class I MHC
- Inhibiting TAP transporter
- Down regulating class II MHC expression on APCs
what are the two ways in which viruses can alter their antigens?
- genetic drift through point mutations in the genome
2. genetic shift through exchange of genetic material with viral reservoirs in other hosts
What are two examples of ways in which viruses can interfere with complement function ?
- production of a C3 binding protein that increase decay of C3 convertase
- inhibits alternative pathway - C4b binding protein that inhibits classical pathway
What are three ways in which viruses can suppression immune responses
- activating Treg cells
- Altering the Th1/Th2 balance
- destroying essential lymphoid tissues
through what two means to bacteria invade the body?
Mucosal surfaces or breaks in the skin
What 4 things are requires to establish a bacterial infection?
- attachment to host cells
- Proliferation
- invasion of tissue
- damage to host cells (sometimes due to toxins)
Low level infections can be controlled by..
the innate response - primarily phagocytosis by neutrophils
Immunity to extracellular bacteria is achieved largely through..
production of antibody by plasma cells in regional lymph nodes and submucosa
What are the 4 roles of antibody in terms of extracellular bacterial infection?
- Prevent attachment + colonization
- Neutralize bacterial exotoxins or endotoxins
- Opsonize for phagocytosis
- Activate classical complement pathway
What are the 4 results of activating complement for fighting extracellular bacteria infection?
- lysis of gram negative bacteria by MAC
- production of C3b opsonin
- production of anaphylatoxins - cause mast cells to degranulate
- chemotactic factors produced to attract neutrophils and macrophages
Briefly, what are the 6 ways in which extracellular bacteria can evade the immune system?
- Production of cell surface appendages
- Secretion of proteases that cleave secretory IgA
- Changes in amino acid sequence of key cell surface structures
- Expression of surface structures like capsules
- Toxin production
- Interfering with complement system
How do surface appendages help bacteria avoid the immune response?
enhance ability to attach to mucosal epithelium
How do proteases help bacteria avoid the immune response?
reduce half life of secretory IgA and prevent IgA mediated agglutination of bacteria
How does changing the amino acid sequence of surface structures help bacteria avoid the immune response?
allows them to evade the IgA response
How do surface structures like capsules help bacteria avoid the immune response?
inhibit phagocytosis
How does toxin production help bacteria avoid the immune response?
interfere with phagocytosis by killing leukocytes
what are 4 ways in which extracellular bacteria interfere with the complement system
- Capsules fail to stabilize C3 convertase - inhibits alternative pathway
- Resistance to MAC with capsules
- Secrete decoy proteins that deviate from the normal complement activation site
- acceleration of complement breakdown by secreted enzymes
What are the 3 ways in which intracellular bacteria colonize phagocytic cells?
- inhibiting lysozome fusion
- Resisting oxidative/lysosomal attack
- Escaping the phagosome following phagocytosis
What form of cell mediated immunity protects against intracellular bacterial infections?
A DTH response
Th1 cells release __ that activates macrophages and increases phagocytic ability/activity
IFN-y
What else do Th1 cells activate? what does this achieve?
CTLs kill infected macrophages, releasing bacteria, which are then phagocytosed and killed by activated uninfected macrophages
What is formed in response to persistent bacterial infection/cell mediated response?
granuloma and extensive tissue necrosis due to accumulation of lysosomal enzymes
What parasite has cell surface antigens that go though various maturational stages?
Plasmodium sp
What parasite has a large repertoire of genes coding for variable surface glycoprotein that can be expressed sequentially?
Trypanosoma
How is protection to helminths achieved?
both humoral and cell-mediated immunity
What special adaptations do Schistosoma have that help them avoid the immune response?
- decreased expression of antigens
- antigen masking with host ABO
- Induces strong Th2 response which downregulates Th1 required for clearance
What do worm antigens in the gut cause?
IgE-sensitized mast cells in the lining of the gut to degranulate
What does mast cell degranulation in the gut cause?
Increased vascular permeability and the secretion of eosinophil chemotactic factor that allows worm-specific IgG and eosinophils to reach worm
What do eosinophils do when they reach the worm?
Bind to IgG coated worm and release granule contents including major basic protein (MBP)
What causes the worm to be expelled?
Smooth muscle contraction stimulated by histamine
What else is important in maintaining acute inflammatory responses to helminths?
Activation of tissue mast cells by anaphylatoxins (C3a and C5a) generated by complement breakdown
