lecture 10) the innate immune system Flashcards
give 3 basic characteristics of the innate immune system
no immunological memory
non specific
immediate response
what does the hummoral branch of the innate immune system refer to?
complement
enzymes
cytokines
what does the cellular branch of the innate immune system refer to?
phagocytes
natural killer cells
pattern receptors
what is involved in complement immunity?
molecules that aid immunological processes eg clotting, membrane attack
what do phagocytes do?
engulf material
where are the immune cells generally found?
circulation
what are the exceptions of immune cells being found in circulation
alveolar macrophages
M cells
what are alveolar macrophages?
specialised macrophages of the alveoli
what are M cells?
specialised epithelial cells of MALT
transport antigens from lumen to immune cells
name 5 different types of phagocytes
monocytes macrophages dendritic cells neutrophils mast cells
bacteria taken up by what process and where are they destroyed?
taken up by endocytosis
destroyed in the phagolysosome
what is the cytosome and what does it contain?
the cell body excluding the nucleus
contains regulatory compounds
describe the changes in pH down the pathway that bacteria enter and explain the impacts this has on the bacteria
pH decreases down the pathway
becomes a more hostile environment for the bacteria to live in
what enzyme do lysosomes contain and what does this enzyme do?
lysozyme
breaks down peptidoglycan
what happens when lysozyme acts on the bacterial vesicle?
it ruptures and releases the products that can be recognised by the adaptive immune system
what 3 categories of pattern recognition receptors (PRRs) can be engaged during phagocytosis?
PRRs to mediate phagocytosis
PRRs to initiate inflammatory response
PRRs that mediate and initiate
why is it important to have more than one category of PRR?
bacteria have evolved resistant mechanisms againsr PRRs
what does the mannoes receptor recognise?
sugar
what category does the mannose receptor fall into?
mediates phagocytosis
what domain does the mannose receptor have?
carbohydrate domain
give 3 characteristics of the carbohydrate protein domain in the mannose receptor
not much of an intracellular protein domain not involved in signal transduction mostly outside (prob passing through and reaching out)
give an example bacterium that uses the mannose receptor
virulent strains of mycobacterium tuberculosis
no inflammatory response
what does M. tuberculosis do to combat the innate immune system?
sits in early endosome
has proteins that prevent fusion with lysosome
last vesicle will be phagolysosome
what does L. pneumoniae do to combat the innate immune system?
arrests the pathway
what does S. typhimurium do to combat the innate immune system?
decreases pH to prevent fusion
what does F. tularenisis do to combat the innate immune system?
escapes the pathway
what are TLRs?
toll like receptors
what are TLRs used in conjunction with?
mannose receptor
describe the composition of TLRs
dimeric transmembranal
what do TLRs recognise?
different cellular components
what do TLRs do?
transduce the signal through the cell to increase the transcription of certain cytokines by increasing the trancription factor
what are NLRs?
nod like receptors
why type of domain do NLRs have?
nod-like domain
what type of repeats do many NLRs have?
leucine rich repeats
are NLRs found on the membrane?
no, TLRs are found on the membrane to ensure they dont escape
when phagocytes recognise bacterial cells, what do they signal for?
an increase in the production of chemokines and cytokines
what do chemokines and cytokines do when phagocytes have recognised the bacterial cell?
recruit more vigorous immune cells eg killer T cells
how do bacteria counteract recognition and killing?
escape from vacuole to cytoplasm
how do bacteria escape from the vacuole to the cytoplasm when counteracting recognition and killing?
by the action of listeriolysis
where does listeriolysis come from?
listeria monocytogenes, cholesterol dependent cytolysin
name 3 characteristics of M. tuberculosis for the inhibition of phagolysosome fusion
paucity of vacuolar H+ ATPase
inefficient luminal acidification due to less H+
inadequate levels of mature lysosomal hydrolases
what does latent TB do to prevent phagolysosome fusion?
later in life/when immunocompromised, sits asleep in phagosome but will prevent fusion by preventing acidification
what does autophagy target?
portions of cytoplasm, organelles or proteins that have been damaged for lysosome degradation
how does autophagy work?
autophagosome binds with lysosome to break down products that can be reused
when is autophagy beneficial?
when clearing disease
how does autophagy start?
isolation membrane forms, elongates and closes to form double membrane bound vesicle (autophagosome)
autophagosome fuses with lysosome = autolysosome leading to degradation of cytoplasmic contents inside autophagosome
what type of genes are responsibe for autophagy?
ATG genes
how do bacteria cope with autophagy?
selectively target cytosolic molecules/structures eg intracellular pathogens (xenophagy), damaged mitochondria (mitophagy) and protein aggregates (aggrephagy)
what is LLO?
listeriolysin O
how do membranes form?
LC3 - mammalian homologue of atg8
diff molecules embed membrane
protein and ubiquitin stamp protein to signal its damaged
formation of lysosome starts and autolysosome forms
what secretion system does shigella use to induce cell death?
T3SS
what effect of T3SS can repress autophagy?
IcsB
why would a virulence factor like LLO want to elicit autophagy?
upon vascular escape autophagy is an intracellular catabolic process
targets cellular or foreign material
this doubles membrane vacuoles for degradation through fusion with lysosomes
why is listeria at increased risk of running autophagy machinery?
cholesterol dependent
name the 2 possible pathways of autophagy in listeria infections
persistent infections
fusion with lysosome
what type of phagocytosis happens in autophagy of persistent liseria infections?
LC3 associated phagocytosis involving SLAPs
what type of phagocytosis happens in autophagy of liseria infections via fusion with a lysosome?
ActA + Cm
LC3 autophagy
autophagosomes form
describe autophagy in Burkholderia pseudomallei infections
bacteria wants to escape from the vacuole therefore secrete an effector to activate polymerisation so it can spread and create infection/disease
why is diet and health an important influence in immunity?
normally a competition between the host and the bug to see who will win - not usually due to the immune system not working; can be down to the efficacy of the immune system and the bugs defence mechanisms
