IMM 1 immunological mechanisms of diabetes Flashcards
changing the concept of T2D
T2D: key concepts
caused by? where?
characterized by what?
Deleterious complications that arise from elevated blood sugar?
what factors contribute to development of T2D?
T2D prevalence rises with what? so that means a role of?
threat to global health why?
insulin sensitivity in health
lean insulin-sensitive individuals, normal secretion is sufficient to? (3)
adipose macrophages and kupffer cells do what?
resulting serologic state characterized by what serum concentrations?
recognized that what two things are causally linked to insulin resistance?
Obesity is characterized by?
immune cell infiltration in adipose tissue in obesity
in leanness what cells present? predominates?
in chronic obesity what cells present? predominates?
Factors regulating macrophage polarity and insulin resistance
in leanness- adipocyte secretes what? these promote? what type are these? which secrete what? may secrete? FFAs present?
Obesity- induces changes in what? resulting in? FFAs present? will also cause the release of what?
what cell is activated by this? produces what? induces what state?
how do we lose beta cells in T2D?
serum levels?
leads to?
death leads to?
pathogenic role of M1 M in islet inflammation and beta cell dysnfunction
what long chain fatty acid induces b-cell dysfunction? via?
b-cells sense this FA via what pathway? this recruits what? to where? how?
newly recruited ____ differentiate into ____ that play pivotal role in b- cell dysfunction via (3)
Genetics of T2D
T2D multifactorial disease arising from the presence of what? where? and what else?
risk if in family?
Concordance rate?
what population has a much higher prevalence of T2D than general population?
concordance rate is showing in twins the prevalence of the disease in both twins. if 100 % then it is entirely genetic. but since its not then there are other factors. Since dizygotic twins have a lower concordance rate then that means the genes do play a role
environmental factors in T2D
twin studies show important role in what two things (non genetic) in development of T2D
B- 2 things that increase T2D
E- what factor would increase risk?
role of microflora in T2D
and on the horizon?
T1D
chronic autoimmune disease characterized largely by?
T1D (history)
initiating events in T1D?
insulin target for?
biomarkers for T1D?
later what discovered to have major role?
What is T1D
characterized by? resulting in?
patients with T1D are prone to?
most cases are characterized by (immunological)
type 1 diabetes is what mediated?
at time of clinical symptoms of T1D how much b cells destroyed?
onset of T1D associated with infiltration of what by?
infiltrate is termed?
physiological contributions to T1D
just waht are three tissues? and main thing that is wrong?
environmental factors contributing to T1D?
Concordance rate? suggests?
incidence is? suggests?
type of evidence linking environment and T1D?
incidence by country?
T1D
prenatal triggers/ protective factors
postnatal
promoters of progression?
factors slowing progression?
(know the blue)
role of infections in T1D
Bacteria?
virus? (3)
virus act by what mechanisms?
adjuvant- agent that modifies the affects of other agents
breast-feeding vs cow milk
correlation?
cow milk when may contribute to T1D? what else may result?
what disclaimer?
other environmental factors T1D
(3)
role of microflora in T1D
major evidence supporting connection is represented by?
important what was or wasnt well represented in gut biota in T1D patients?
this explains what symptoms?
genetic factors contributing to T1D
risk before 20 if sibling affected? general pop?
concordance?
what grouping seen?
what genes determine T1D susceptibility
T1D and relatives risk for?
Specific diabetes gene?
how many genes associated with susceptibility?
Most significant? (4) what chromosome?
negative selection of T cells?
mechanisms of thymic (central) tolerance
takes place when?
what mechanisms lead to suboptimal expression of islet cell auto-Ags and lead to?
alternative mRNA splicing results in? of what?
thymic presentation of self-molecules mediated by what cells? transcribe self-molecule genes under direction of?
suboptimal tolerization to islet cell allows for maturation of? results in?
AIRE control Auto-Ag expression where? how?
role of AIRE in T1D
AIRE critical factor in?
what is controlled by AIRE?
malfunction leads to?
this leads to?
insulin gene (______)
Mapped to a region containing?
VTNR polymorphism categorized into?
which class can be affected leading to lower insulin mRNA synthesis? this results in?
Central tolerance broken with what alleles?
Role of HLA in T1D
what are the high risk alleles? found in what percentage of individuals with T1D
most prevalent in children diagnosed prior to 5?
HLA class II? molecules that lack what are found on individuals with T1D?
what confer protection?
CTLA-4 gene (______)
what chromosome?
encodes what? that has what function? and binds?
CTLA-4 may counter-regulate what?
function is? (2)
mechanisms of CTLA-4
engagement of CTLA-4 expressed on surface of T effector may?
CTLA-4 on responding Teff cells or Treg cells or?
does what to APCs? this does what
intrinsic vs extrinsic
immunopathogenesis of T1D
B-cell death in islets can occur both?
DCs present where? take up what?
release of what as a result of infection or stress may activate? and promote?
T cells activated where?
once activated islet specific T cells do what?
immunopathogenesis of T1D
what plays important role in the pathogenesis of T1D?
these APCs activate? which further stims?
IFN-gamma ingibits? and enhance? which are toxic to?
Functional role of Tregs
suggest T1D would not occur in patients with asthma?
howerver?
common denominator?
susceptibility greatly enhanced when?
leads to?
mechanisms of action of Tregs
Tregs become activated by?
supress APCs how?
Tregs might act directly on?
cytokines?
decreases what cyto increases what?
mechanism of action of Tregs
Tregs supress immune responses where?
production of what cytokines?
reduces ability of what?
consumption of?
microflora and Tregs in T1D
what ratio is important? it affects balance of? where?
what defect recently found in T1D patients?
antibodies in T1D
higher in who?
production of autoantibody appears when?
presence confirms?
specificities of ICA include?
pathogenic role of Auto-Abs
pathogenic contribution is?
why?
so what is the pathogenic role of auto-abs in T1D?
diagnostic value of autoantibodies
presence of 1 vs 2 vs 3 Ab?
combined with what it is useful as?
T1D on horizon
what has been focus of most strategies of immunotherapy?
2 approaches of immunotherapy?
most effective?
protection seen in? but is?
