lec 10-11 innate/adaptive immune response Flashcards
innate immune response
non-specific
immediate
no immunological memory
includes physical barriers such as skin, chemicals in the blood, and immune system cells that attack foreign cells in the body.
adaptive immune response
acquired immune system
specific to antigen
lag time from exposure to response
immunological memory after exposure
composed of highly specialised, systemic cells and processes that eliminate pathogens or prevent their growth
innate humoral response
chemicals circulating in the blood
complement system
membrane attack complex
adaptive cell-mediated response
mediated by t-cells
- regulate activity of b-cells
professional phagocytes
monocytes macrophages neutrophils tissue dendritic cells mast cells
when bacteria are taken up by an endosome
pH of phagosome drops
environment becomes more hostile for bacteria
- signalling pathways triggered
- fusion with lysosome to form phagolysome
phagolysosome
lysosome contains potent chemicals to destroy bacteria e..g lysozyme (antibacterial agent)
action of lysozyme on phagolysosome
vesicle ruptures and releases
damage signal recruits other immune cells
how do innate immune cells detect viral infection
pattern recognition receptors (PRRs)
- present on cell surface or in intracellular compartments
types of PRRs
TLRs
NLRs
receptor kinases
how do TB pathogens prevent normal immune pathways
use mannose receptors no inflammatory response initiated sits in early endosome produce proteins that prevent fusion with lysosome no phagolysosome formation
toll-like receptors
membrane spanning both intra and extra cellular portions come as pairs (dimeric) e.g. TLR1 pairs with TLR2 recognise and bind to ligands of microbes
recognise PAMPs
TLRs activate immune response when they bind
recruit adaptor proteins within cytosol
antigen-induced signal transduction pathway
nod-like receptors
cytoplasmic bound - not membrane
pick up bacteria if escaped from endosome
recognise presence of PAMPs
NOD - nucleotide-binding oligomerization domain
LRRs - leucine rich repeats
Pathogen Associated Molecular Patterns -PAMPs
activate innate immune responses
- protect host from infection
elevate protein levels
transduce signals through cell to increase transcription of cytokine
examples of PAMPs
flagellin
peptidoglycan
lipoprotein
bacteria aim to escape the vacuole
bacteria secrete toxin called cytolysin - lyses membrane
cytolysin is cholesterol dependent - attacks hosts membranes
listeria secretes listeriolysin extracellularly
lower pH causes more listeriolysin to be produced
phagosome ruptures
bacteria becomes intracellular and spreads
recruits actin tails for movement
produces a phospholipase
process of Salmonella
use TLRs to ensure they get to protected environment:
- taken up and recognised by TLRs
- bacteria hijacks TLRs
- signalling creates acidic pH of vacuole
reaches salmonella-containing vacuoles(SCV) - protective niche
then secrete proteins into the cell to prevent further damage:
secreted effector proteins
prevent fusion with lysosome
process of shigella
- enters M cells (sensory gut molecules)
- enters into macrophage
- induces cell death (secretion of effector proteins into cytoplasm -T3SS)
- recognised by intracellular NLRs
- plasma membrane ruptures
- bacteria escape and enter neighbouring cells
T3SS
type 3 secretion system
used by pathogenic gram-ve bacteria
detect eukaryotic organisms
secrete effector proteins that help bacteria infect cells
autophagosome formation
LC3 (myosin light chain 3) and ubiquitination come together on membrane
membrane ‘isolation’ sac elonagtes anf close forming double membrane vesicle
autolysosome formation
- outer membrane fuses with a lysosome
- degradation of cytoplasmic contents
- broken down products can be re-used e.g. amino acids
autophagy
intracellular degradation system
targets portions of cytoplasm and delivers cytoplasmic constituents to the lysosome
beneficial for clearing infectious diseases
control of autophagy
Type 3 secretion system - T3SS
IcsB - intracellular spread
pro-inflammatory cytokines
interleukins
interferons
tumour necrosis factor (TNF-alpha)
process of phagocytosis
bacteria taken up by phagocytosis
bacteria destroyed within phagolysosome
phagocytes act as APCs - antigen presenting cells
parts of bacteria (antigens) appear on the surface of the phagocyte
presented to a helper T cell
helper T cell activated
antigens present to..
MHC molecules
tri-molecular complex
key in recognition
made up of :
- MHC
- peptide
- T cell receptor
where are peptides held
in the grooves of the MHC I and II molecules
CD1 molecule
MHC-like structure present glycolipids (not peptides) to natural killer t cells
CD8+ T cells recognise antigens presented by …
MHC I molecules
CD4+ t cells recognise antigens presented by …
MHC II molecules
structure of MHC I
2 polypeptides and a beta-2 microglobulin component
antigens presented by MHC I originate from the …
cytosol
antigens processed by proteosomes in the cytosol are loaded…
through the endoplasmic reticulum onto antigen presenting cells (MHC I)
when CD8+T cells are stimulated…
memory cells are activated
CD8 releases perforin molecules and granzymes which attack infected host and destroy
2 killing mechanisms by cytotoxic t cells
perforin
CD95 or FasL pathway
perforin pathway
perforin molecules delivered from cytoplasmic granules
fuse with membrane of APC
pores form allowing granzymes to enter infected cell
cause apoptosis
CD95 or FasL pathway
recognition system of cell death molecules FasL expression increases on CTL binds to Fas on the APC Generation of proteases apoptosis initiated
structure of CD4 cells
2 polypeptides
groove for peptide to sit in
no beta-2 microglobulin
lots of co-receptors in addition to tri-molecular complex
CD4 T cells recognise antigens that originate directly from …
the phagosome
CD4 T cells
helper T cells
produce many cytokines - depending on how they are activated
help Cd8 T cells
affect B cells - antibody production
production of cytokines and chemokines
modulates an immune response
after exposure to TB, if innate immunity is inadequate then
infection occurs
if TB infection occurs and adaptive immunity is inadequate then
latent infection occurs
bacteria is contained in a granuloma
process of infection with TB
TB taken up by macrophages
immune cells recruited by chemokines e.g. neutrophils
innate granuloma - TB is surrounded by immune cells
inflammatory cytokines recruit D cells e.g. TNF-alpha
immune granuloma - chronic granuloma
chronic granuloma
fibrotic capsule
surrounded by fibroblasts
if CD4 levels are low…
then probably immunocompromised
proteins in membranes of vacuoles
MHC I and II
