IMM 1 immunological mechanisms of diabetes

Question 1

Answer 1

Question 2

changing the concept of T2D

Answer 2

Question 3

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?

Answer 3

Question 4

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?

Answer 4

Question 5

recognized that what two things are causally linked to insulin resistance?

Obesity is characterized by?

Answer 5

Question 6

immune cell infiltration in adipose tissue in obesity

in leanness what cells present? predominates?

in chronic obesity what cells present? predominates?

Answer 6

Question 7

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?

Answer 7

Question 8

Answer 8

Question 9

how do we lose beta cells in T2D?

serum levels?

leads to?

death leads to?

Answer 9

Question 10

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)

Answer 10

Question 11

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?

Answer 11

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

Question 12

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?

Answer 12

Question 13

role of microflora in T2D

and on the horizon?

Answer 13

Question 14

T1D

chronic autoimmune disease characterized largely by?

Answer 14

Question 15

T1D (history)

initiating events in T1D?

insulin target for?

biomarkers for T1D?

later what discovered to have major role?

Answer 15

Question 16

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?

Answer 16

Question 17

physiological contributions to T1D

just waht are three tissues? and main thing that is wrong?

Answer 17

Question 18

environmental factors contributing to T1D?

Concordance rate? suggests?

incidence is? suggests?

type of evidence linking environment and T1D?

incidence by country?

Answer 18

Question 19

T1D

prenatal triggers/ protective factors

postnatal

promoters of progression?

factors slowing progression?

(know the blue)

Answer 19

Question 20

role of infections in T1D

Bacteria?

virus? (3)

virus act by what mechanisms?

Answer 20

adjuvant- agent that modifies the affects of other agents

Question 21

breast-feeding vs cow milk

correlation?

cow milk when may contribute to T1D? what else may result?

what disclaimer?

Answer 21

Question 22

other environmental factors T1D

(3)

Answer 22

Question 23

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?

Answer 23

Question 24

genetic factors contributing to T1D

risk before 20 if sibling affected? general pop?

concordance?

what grouping seen?

Answer 24

Question 25

what genes determine T1D susceptibility T1D and relatives risk for? Specific diabetes gene? how many genes associated with susceptibility? Most significant? (4) what chromosome?

Answer 25

Question 26

negative selection of T cells?

Answer 26

Question 27

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?

Answer 27

Question 28

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?

Answer 28

Question 29

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?

Answer 29

Question 30

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?

Answer 30

Question 31

CTLA-4 gene (\_\_\_\_\_\_) what chromosome? encodes what? that has what function? and binds? CTLA-4 may counter-regulate what? function is? (2)

Answer 31

Question 32

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

Answer 32

Question 33

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?

Answer 33

Question 34

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?

Answer 34

Question 35

Question 36

Functional role of Tregs suggest T1D would not occur in patients with asthma? howerver? common denominator? susceptibility greatly enhanced when? leads to?

Answer 36

Question 37

mechanisms of action of Tregs Tregs become activated by? supress APCs how? Tregs might act directly on? cytokines? decreases what cyto increases what?

Answer 37

Question 38

mechanism of action of Tregs Tregs supress immune responses where? production of what cytokines? reduces ability of what? consumption of?

Answer 38

Question 39

microflora and Tregs in T1D what ratio is important? it affects balance of? where? what defect recently found in T1D patients?

Answer 39

Question 40

antibodies in T1D higher in who? production of autoantibody appears when? presence confirms? specificities of ICA include?

Answer 40

Question 41

pathogenic role of Auto-Abs pathogenic contribution is? why? so what is the pathogenic role of auto-abs in T1D?

Answer 41

Question 42

diagnostic value of autoantibodies presence of 1 vs 2 vs 3 Ab? combined with what it is useful as?

Answer 42

Question 43

T1D on horizon what has been focus of most strategies of immunotherapy? 2 approaches of immunotherapy? most effective? protection seen in? but is?

Answer 43