CMB2004/L09 Immunity Against Infection II Flashcards
What are the protective immunities against organisms in interstitial spaces?
Antibodies
Complement
Phagocytosis
Neutralisation
What are the protective immunities against organisms on epithelial surfaces?
Antibodies, especially IgA
Antimicrobial peptides
Give 2 protective immunities against cytoplasmic organisms.
Cytotoxic T cells
NK cells
Give 2 protective immunities against vesicular organisms.
T cell and NK-cell dependent macrophage activation
Give 2 innate defences against viruses.
Interferons
NK cells
Which type I interferons are released in virus-infected host cells?
IFN-a
IFN-B
Describe the series of events that occurs upon release of IFN-a and IFN-B in response to viral infection. (5)
Induce resistance to viral replication by inducing Mx proteins, 2’-5’-linked adenosine oligomers and kinase PKR
Increase MHC class I expression and antigen presentation in all cells
Activate dendritic cells and macrophages
Activate NK cells
Induce chemokines to recruit lymphocytes
How does IFN trigger degradation of viral mRNA? (4)
Induces synthesis of 2’-5’ oligoadenylate synthetase
Adenine trinucleotide synthesised
Activates endonuclease
Degrades viral mRNA
How does IFN inhibit protein synthesis? (3)
Induces synthesis of protein kinase
Phosphorylation and inactivation of eIF-2
Inhibits protein synthesis
Give a type II interferon and explain its effects.
IFNy secreted by T cells and NK cells
Inhibits TH2 response
Promotes TH1
Recruits macrophages
rIFNa can be used to treat which diseases? (2)
Some cancers
Hepatitis B and C
Describe natural killer (NK) cells.
Innate lymphoid cell
Large granular lymphocytes
Recognise structures of viral infected cells
Can recognise stressed cells in absence of Igs and MHC
Kill by extracellular mechanism - perforin and granzyme
What is the role of:
a) activating receptors
b) inhibitory receptors?
a) Recognise carbohydrate ligands, triggers killing
b) recognises MHC class I molecules (no binding, only TCRs can do this)
How are normal cells protected from NK cells? (2)
MHC class I on normal cells recognised by inhibitory receptors that inhibit signals from activating receptors
NK cell does not kill normal cells
Explain how NK cells are triggered to elicit a response. (3)
Missing or absent MHC class I cannot stimulate a negative signal
NK cell triggered by signals from activating receptors
Activated NK cell releases granule contents inducing apoptosis in target cell
Give the 2 components of cell-mediated specific immunity.
Cytotoxic T cells recognise viral peptide + MHC class I
Cytokines with anti-viral activity e.g., IFNy
Describe the 2 mechanisms of cytotoxic T cells inducing apoptosis in the target.
Secretion of cytotoxic granules which polymerise in membrane and granzymes enter cell
Fas ligand on T cell interacts with Fas on target
Describe the mechanism of inducing apoptosis by cytotoxic T cells. (3)
Collision and nonspecific adhesion
Specific recognition redistributes cyto-skeleton and cytoplasmic components of T cell
Release of granules at site of cell contact
Explain the mechanism by which CTLs work. (4)
CTL recognises and binds virus-infected cell
CTL programs target for death, inducing DNA fragmentation
CTL migrates to new target
Target cell dies by apoptosis
Give 3 functions of IFNy.
Inhibits viral replication
Upregulates MHC class I and II expression and antigen presentation
Increases macrophage phagocytosis of dead cells
Promotes NK cell killing activity
Describe antibody and cell-mediated immunity in influenza. (2)
Infection induces antibody and cytotoxic T cell response
Antibody recognises viral haemagglutinin and neuraminidase
High CTL activity correlates with reduced viral shedding
Epidemics arise due to new strains not recognised by antibody
Describe specific immunity against HIV. (2)
Attacks specific immune system
Targets CD4 T cell, macrophages and dendritic cells
Progressive development of AIDS leads to opportunistic infections
Describe the relationship between CTL activity and HIV disease progression.
Higher levels of CTL activity show slower disease progression
Virus mutations that escape CTL recognition may lead to progression to AIDS
Describe the immune response to SARS-CoV-2.
Dampens anti-viral type I interferon - aids viral replication
Viral proteins inhibit RIG1 (PRR)
Viral proteins stimulate NFkB activation - proinflammatory
Antibodies protective and role of cytotoxic T cells
How can the body protect against parasites?
Opsonisation
Complement lysis
ADCC (antibody-dependent cell-mediated cytotoxicity)
Which antibody response is strongly triggered by helminths?
IgE
What is the role of the antibody response against helminths?
Mast cell mediated inflammation
Eosinophil ADCC
Give an example of T cell immunity to Leishmania.
C57BL/6 mice resolve infection
BALB/c mice: fatal progressive disease
Describe the C57BL/6 mouse response to:
a) IFN-y
b) IL-4.
a) +++
b) -
Describe the BALB/c mouse response to:
a) IFN-y
b) IL-4.
a) -
b) ++
Give 2 different effector mechanisms against malaria.
Sporozoite and merozoite susceptible to antibody
Antibody kills infected RBC
Cytotoxic T cells active against infected liver cells