Lecture 3: Innate Sensing by the Immune System Flashcards
Why do we have response against virus with spike protein but not spike protein alone?
Virus has PAMPs along with spike protein antigen –> virus serves as adjuvant
do we mount immune response against an adjuvant? why?
yes –> adjuvant acts as PAMP or DAMP to trigger immune response
difference btwn PAMP/DAMP and epitope that T cells recognize
T cells recognize PEPTIDES that have been processed by DCs
PAMP is usually not a peptide
role of epigenetics in innate immunity?
epigenetics allows for trained immunity by altering gene expression in a way that is long-lasting
what is trained innate immunity?
due to epigenetic changes, the cell can react differently than the first exposure
difference btwn trained innate immunity and adaptive memory
trained innate immunity is NOT specific
what is sterile inflammation? example?
sterile inflammation = inflammation that occurs in the absence of microbial stimuli
ex. lesion on internal organ
does sterile inflammation support Janeway’s hypothesis or Matzinger’s theory?
Matzinger’s theory (DAMPs)
advantage of having lots of non-lymphoid tissue-resident cells?
centralized location
disadvantage of having lots of non-lymphoid tissue-resident cells?
can have non-specific hyperinflammatory response leading to unnecessary tissue damage
2 examples of how our immune system could have evolved from pre-existing program to ensure tissue development and/or proper tissue physiology
- macrophages initially undergoing efferocytosis to clean up dead cells during development
- type 2 immune response evolved for tissue repair, rather than immunity
3 ways in which “form follows function” impacts the activation of our immune system
- DC has dendrites to reach out into environment
- PRRs on outside vs inside of cell depending on pathogen
- MHC interacting with TCR for specificity
describe the cells of gut villi
bottom of crypts has proliferating stem cells that migrate up villi to make the rest of the differentiated epithelial cells with specialized functions
how do proliferation and differentiation change further up the villi?
proliferation decreases, differentiation increases
describe “form follows function” in the context of gut villi
- stem cells are protected in the crypt
- easier to dispose of dead cells in lumen rather than crypt
describe our skin cells
proliferating basal cells at the bottom rise up to differentiate
top cells are superficial skin layer –> cells die and lose everything except lipids to create a seal and make us waterproof
what do we see when looking at the gut microscopically?
can see villi projections covered in dead cells, mucous, food, bacteria, fungi, viruses
what do we see when looking at the gut histologically?
villi acts as sieve
what does DAPI stain?
nuclei
what does UEA1 label?
mucous
what does DCLK label?
subset of cells that produce IL-25 to activate innate immune response
all PRR signaling pathways converge at:
MyD88 and NFkB conserved signaling pathway
describe the MyD88 and NFkB signaling pathway
MyD88 adaptor protein recruits other proteins to activate NFkB pro-inflammatory TF
if all PRR pathways converge at MyD88 and NFkB, how can we differentiate btwn diff pathogens and allow specificity? (4)
- location
- Magnitude of response
- Certain cell types mount response against certain PAMPs due to epigenetics
- Other adaptor proteins involved that activate and recruit other TFs
