L2 - Intracellular immunity (Mtb) Flashcards
What are the pros of an intracellular pathogen?
access to protected environment
Protection from immune response
Protection from bacterial competitors
nutrient rich environment
What are the cons of intracellular pathogen?
overcome barriers
resist phagocytosis
resist adaptive immunity
adapt to hostile environment
What are the 2 types of intracellular pathogen?
obligate
facultative
What is the coherent immune response?
Constant cross communication between cells and tissues of innate and adaptive immune system
What are the risk factors for Mtb?
Congregate settings
poverty/unemployment
homelessness
drug abuse
HIV co-infection
immunosuppression (steroid/biologic)
What is the pathology of Mtb?
Cachexia
respiratory failure
dissemination
haemoptysis
What does Mtb infect?
lung resident phagocytes
What does FAP of Mtb do?
engages with macrophages - induces endocytosis
What are the antimicrobial activities of the macrophage phagolysosome?
Lactoferrin (deprivation) defensives (permeable) hydrolases ROS acidification
How does Mtb evade macrophage killing?
arrests phagosome maturation at early stage
no phagolysosome formation
proteins rewire macrophage
How do APCs detect Mtb?
APCs express PRRs
PRRs localised in best place to encounter PAMPs
produce antibacterial peptide CATHELICIDIN
TLRs
Which TLRs detect Mtb in macrophages?
TLR2 - lipoprotein
TLR4 - LPS
TLR9 - hypomethylated DNA
What are the RECEPTORS involved in macrophage activation
MHCI/MHCII
CD40/B7
TNF/IFNg
Fas
What are the CYTOKINES involved in macrophage activation?
IL-12
TNF
IL-1
IL-18
What are the ANTIMICROBIAL FUNCTIONS involved in macrophage activation?
Toxic oxygen radicals
Lysosomal enzymes
numbers of granules
What do macrophages recruit to the site of infection?
NK cells
supply cytokines
positive feedback loop of activation
What is the positive feedback loops of NK cell and macrophages?
IFNg activates macrophages
IL-12 activates NK cells
keeps further activating both as more cytokines produced
How do macrophages and dendritic cells differ in MHC properties
dendritic MUCH better at loading antigens on MHC molecules
this is ESSENTIAL for APC to activate adaptive immunity
How do dendritic cells initiate adaptive immunity?
dendritic detect Mtb in the alveoli
Detect PAMPs
MHC presentation
lymph node - APC scans T cells that recognised MHC
What are CD4 protein type cells
T helper cells (Th1)
What are CD8+ protein type cells?
Cytotoxic killer cells
How do CD4 cells specialise
IFNg, IL-12 = Th1
IL-4 = Th2
Why does the Th2 response to M. leprae have severe consequences?
high infectivity
low/absent T-cell responsiveness
What is the granuloma?
aggregates of immune cells that surround foci of infected tissues
encased by gunk of necrotic tissue
dynamic
How many people manage to effectively clear a granuloma?
70%
granuloma - stale-mate,
