L09 Flashcards
Different effector mechanisms depend on
Type of pathogen, localisation and stage of infection
What type of MHC class would be required for an extracellular infection?
MHC II
What type of MHC class would be required for an intracellular infection?
MHC I
What are the innate defenses against viruses
Interferons and NK cells
What type of interferons are present in responding to a virus
IFN - alpha and beta
How do IFN-alpha and IFN-beta help respond to the virus?
Prevents nucleic acid production/replication
What do chemokines recruit?
Lymphocytes
How does IFN-alpha and IFN-beta prevent viral nucleic acid production/replication
Induce resistance to viral replication in all cells by inducing Mx proteins, 2’-5’ linked adenosine oligomers, and the kinase PKR.
Increase MHC class I expression and AG presentation in all cells
Activate dendritic cells and MQ
Activate NK cells to kill virus-infected cells
Induce chemokines to recruit lymphocytes
What type of interferons are there?
1
How does IFN result in viral mRNA degradation?
2,5’ - oligoadenylate synthetase = adenine trinucleotide synthesis = activates endonuclease = degrades viral mRNA
How does IFN inhibit protein synthesis
Protein kinase = phosphorlyation and inactivation of eIF-2 = inhibits protein synthesis
What cells make IFN alpha and beta?
Infected cell
When is IFN alpha and beta synthesised?
Early response to infection
What cells secrete type II IFN (IFN - gamma)
NK and activated T cells
What does IFN gamma do?
Inhibits TH2 response (Ab), promotes TH1 (NK), recruits Mq
What are the therapeutic use of interferons?
rIFN-alpha - hepatitis B and C, some cancers.
What are the disadvantages of using IFN for therapeutic treatments?
Side effects can be severe
Why can there be severe side effects for therapeutic treatments using IFN?
Cytokine storm -> excessive immune response can damage healthy cells and organs
Are NK cells large granular lymphocytes?
Yes
What are the components of the extracellular mechanism used by NK cells to kill infected cells?
Perforins and granzyme
How do NK cells recognise stressed cells in the absence of Ig and MHC?
Recognise structures on viral infected cells
What are the 2 types of NK cell receptors?
Activating receptors and inhibitory receptors
What do activating receptors do?
recognise carbohydrate ligands = trigger killing of the cell
What do inhibitory receptors do?
recognise MHC class I
What are the only type of receptors on T cells that can perform binding?
TCR
If a virus can reduce MHC expression - what would this result in?
Result in killing of the infected cell
How would reduced MHC result in apoptosis of the infected cell?
There would be no interaction between MHC and inhibitory receptor resulting in the activation of NK = apoptosis
What are the components of cell mediated specific immunity?IF
Cytotoxic T cells (CD8) and cytokines with anti-viral activity
Give an example of a cytokine involved in anti-viral activity and what it does?
IFN gamma - activates Mq
What are the two mechanisms through which cytotoxic T cells induce apoptosis
- secretion of cytotoxic granules
perforin & granzymes - Fas ligand on T cell interacts with Fas on target = apoptosis
How does perforin make pores in the membrane?
Through polymerisation
What cytokines are secreted by CD8?I
IFN gamma
What does IFN gamma result in?
Inhibits viral replication
Upregulates MHC class I and II expression and antigen presentation
Increases macrophage phagocytosis of dead cells
Promotes NK cell killing activity
What is the role of Ab in viral infection responses
Antibodies
Neutralise free virus (prevent entry into and spread between cells)
Can prevent spread within the body (e.g. poliovirus) or protect mucosal surfaces against reinfection (e.g. ‘flu’)
Opsonise to increase phagocytosis
Activate complement leading to lysis (enveloped viruses)
What is the role of Ab in cell mediated immunity in influenza?
Antibody and cell mediated immunity in influenza
Infection induces antibody and cytotoxic T cell (CTL) response
Antibody recognises viral haemagglutinin and neuraminidase
High levels of CTL activity correlates with reduced viral shedding
Epidemics arise due to new strains not recognised by antibody (vaccine strains…….)
How does HIV impact immunity
Attacks specific immune system
Targets CD4 T cell, macrophages and dendritic cells
Progressive development of AIDS leads to opportunistic infections
List examples of opportunistic infections that arise from HIV
Oral candidiasis
Kaposi’s sarcoma
Pneuomcystis pneumonia
Why can’t we develop vaccines against HIV?
Antibodies do not seem to impact HIV
Can infections be controlled by cytotoxic T cell responses?
Potentially
Patients with higher levels of CTL activity show slower disease progression
Virus mutations that escape CTL recognition may lead to progression to AIDS
Describe SARS-COV-2 RNA?
22-32 kilobase ss +ve RNA
What sort of Ig response can helminths induce?
IgE
What is the role of IgE
Mast cell mediated inflammation
Eosinophil ADCC (antibody-dependent cell-mediated cytotoxicity)
Why are cytokines important in a response against parasites?
MQ activation as some protozoa can survive in MQ hidden from Ig
Can differences in T cell responses result in different disease progression?
Yes
What elements of the T cell response is active in C57BL/6 mouse that allows it to survive Leishmania?
TH1
What elements of the T cell response is present in BALB/c mouse that allows it to succumb to Leishmania?
TH2 response
What are the different effector mechanisms that are active at different stages during malaria?
Sporozoite and merozoite may be susceptible to antibody
Antibody may also kill infected red blood cells
Cytotoxic T cells active against infected liver cells
(RTS,S vaccine since 2019)
What is ADCC
Antibody dependent cell cytoxicity
