mechanisms Flashcards
in one phrase, how does our modern lifestyle contribute to inc NCD risk
they induce inflammation and altered immune function
how does the intestinal barrier contribute to tissue repair/damage - 3
chemical barrier - antimicrobial secretions
physical barrier - mucus layers and epithelial cells with tight junctions
immunological barrier - immune cells, antibodies (IgA) and cytokines
impact of high fat/ high sugar diet on barrier function
damage intestinal barrier causing leaky gut, disrupts tight junctions in epithelial cells
thus, driving inflammatory mechanisms
strangers release
PAMPs - from pathogens, initiate sig cascades and chronification of inflammatory response
dangers release
DAMPS , initiate sig cascades and chronification of inflammatory response
features of inflammation
swelling, redness, pain, respiratory tract issues, heat
how is inflammation resolved
resolution - macrophages esp
unless chronification of inflammation occurs
what can cause chronic inflammation
autoimmunity
genetics
ongoing barrier disruption e.g. eczema
skin barrier dysfunction is known as
eczema
drivers of eczema - 6
pollutants
changes in microflora
scratching
allergens
stress
genetic polymorphisms causing L skin barrier
what is filaggrin deficiency
correlates with eczema risk, genetic polymorphism
role of filaggrin
skin barrier formation and hydration
low filaggrin expression results in inc -7
staphylococcal infection
viral replication
risk of asthma
severity of eczema
dry skin and protease activity
early onset and persistent eczema
risk of food allergy and allergic sensitisation
what is eosiophilic esophagitis
GI disease, infiltration of eosinophils
eosiophilic esophagitis medication
proton pump inhibitors
proton pump inhibitors in pts with lower filaggrin expression
didnt respond well
what type of stuff causes acute inflammation
infection, wound, trauma, allergen, burn, pollutants, frostbite, chemicals
what type of stuff causes chronic inflammation
type 2 diabetes, pregnancy, respiratory disease, obesity, cancer, cardiovascular disease rheumatoid arthritis, neurological disease
what do epigenetic modifications do
alter DNA accessibility and chromatin structure to regulate patterns of gene expression - heritable, not due to change in DNA sequence
exogenous factors can influence this
long term modifications usually dna methylation and short term modifications usually histone modifications
what is chromatin
complex of chromosomal DNA associated with proteins in nucleus
chromatin and histone modifications
histones can be post translationally modified to restructure chromatin
via phosphorylation, sumoylation, ubiquitination, methylation, acetylation (best studied and promotes transcription)
malaria prevention - 3
vector control, preventative chemotherapy, vaccine
what occurs when mosquitos interact with malaria, and when carrying malaria interact with humans
parasite sucked by malaria
parasite developed in GI of mosquito
sporosites migrate to salivary glands
stings person
releases sporosites into blood, rbc, repeats
when did the relevant new world mosquito appear
anophelin mosquito - 95 million years ago
when did plasmodium falciparum malaria begin to infect humans
8000 - 3000 BC
whats making malaria more likely
inc global warming
sickle cell anemia, genetics, and malaria
areas of malaria overlap with areas of sickle cell anemia geographically
if homozygous to specific allele, u develop sickle cell anemia
if heterozygous, u are resistant to malaria
what is the mutation for sickle cell anemia
GAG to GTG
thus
GLU to VAL
what occurs to sickle cell blood cell when infected with malaria/ plasmodium parasite
changes partial pressure of oxygen in cell
thus
dec parasite growth and maturation
inc uptake my macrophages
dec adherence to endothelium
why homo sickle cell bad
all rbcs change partial pressure n cause blockage n die
what occurs in DNA methylation
methyl group covalently attached to cytosine residue in CpG dinucleotide sequences - ensures repression of transciption by blocking DNA recognition for transcription binding. other factors might preferentially bind
natural cortisol cycle
highest when waking up, fluctuate throughout day
tissues more sensitive to cortisol as cortisol declines
effected by chronic stress - lots of tissues sensitive to glucocorticoids. fluctuation in cortisol no longer fluctuating or adaptive
