MMI

Question 1

Answer 1

Memorize!

Question 2

Answer 2

Memorize

Question 3

Nf-kB and glucocorticord interaction

Answer 3

Nf-kB activation:

• (P) & removal of IkB inhibitor
• txloc to nucleus
• gene expression

Glucocorticoids:

• induced expression of IkB –> seq NF-kB in cytoplasm
• (-) gene Ts when activated GR (GC receptor) binds directly to NF-kB

Question 4

Answer 4

Memorize

Question 5

catecholamines drive a TH___ shift

Answer 5

Question 6

How dod proinflammatory cytokines are a potently activate the HPA axis.

Answer 6

inflammation –> IL-1, TNF-alpha, IL-6 –> (+) CRH in hypoT –> (+) stress hormones

Question 7

which pituiary hormones are immunostimulatory?

Answer 7

prolactin, GH

Question 8

CD40-CD40L interaction

Answer 8

Th: bind cytokind receptors on B cells –> promote B cell proliferation and Ig production

B: proliferation, synthesis, secretion of Ab

Question 9

autoimmune diseases are characterized by activity of ….

Answer 9

auto-reactive lymphocytes: formation of Ab or activation of effector T cells

• organ specific: chronic T cell or Ab targetting of a particular organ
• systemic: breakdown of immune tolerance to self –> immune complex dmg in several body sites

Question 10

descrbie immuno-pathogenesis in hasimoto thyroiditis

Answer 10

1. inflamm infiltrate of activated: CD8, CD4, B, plasma, macrophages
   * activated CD8 and CD4 –> IFNγ –> MHC II expression by thyrocytes –> CD4 T cell expansion and infiltration in the area
2. delete and replacement of thyroid with above inflamm infiltrate

• CD8: perforin/granzymes or FasL-Fas (CD95L-CD95) pathway
• CD4: IFNγ –> recruitment of macrophages –> cytokine release –> dmg
• anti-thyroid Ab –> bind thyrocytes –> C’ fixation –> ADCC
  
  • TPO
  • TBG
  • TSH receptor

3. thyroid enlargement –> fibrosis

Question 11

PTPN22

Answer 11

Potent inhibitor of the T cell receptor signaling pathway

Question 12

CTLA-4

Answer 12

homologous structure to CD28 on T cells (binds B7 on APC)

fx: (-) T cell activation by counteracting signals DELIVERED by TCR complex and CD28 –> T cell signal termination

Question 13

what could explain why some patients with Graves disease have episodes of hypothyroidism

Answer 13

presence of both stimulating and inhibiting Abs

• TSI
• TSII

Question 14

what HLA is thought to protect pts from developing Graves

Answer 14

HLA DRB1*0701

Question 15

what HLA-DR association with graves disease has been demonstated in caucasians?

Answer 15

HLA-DR3 and -DQA1 *0501

Question 16

neonatal graves disease

Answer 16

transplacental transfer of thyroid-stimulating IgG from mom –> fetus

symptoms of hyperthyroidism

*** spontaneous recovery gradual!

• 2-3 mo as materal IgG metabolized

Question 17

auto-Ag in T1D (4)

Answer 17

glutamic acid decarboxylase (GAD65)

• highly predictive of subseq dev of T1D

insulin

IA-2 (tyrosine phosphatase)

zinc T8 transporter (ZnT8)

Question 18

what is the most important factor in determining disease susceptibility

Answer 18

MHC haplotype

Question 19

2 monogenic syndromes assoc with immune-mediated diabetes-

Answer 19

APS-1 (AIRE) and IPEX (FoxP3)

Question 20

Tregs

Answer 20

differentation & fx requires Foxp3 & production of IL-2

expression: CD4 & CD25 (alpha chain of IL-2 receptor)
fx: (-) activation of naive T cells & fx of effector T cells
* mainly through production of IL-10 & TGF-beta

Question 21

examples of autoimmune disorders associated with type 1A diabetes (5)

Answer 21

1. celiac
2. addison’s
3. autoimmune thyroid disease
4. pernicious anemia
5. vitiligo

Question 23

there is increased _____ in the adipose tissue of obese T2D mice

Answer 23

TNF-alpha

Question 24

elevated lvls of what immune cytokines are predictive of T2D (4)

Answer 24

1. TNF-alpha
2. IL-1
3. IL-6
4. CRP

Question 25

adipokines

Answer 25

Question 26

Hirata disease

Answer 26

Insulin Autoimmune Syndrome * presence of anti-insulin antibodies in a patient who has never been exposed to exogenous insulin * --\> recurrent and spontaneous **hypoglycemia** * DRB1\*0406 * can follow thx with sulfhydryl-containing medication, such as methimazole

Question 27

autoimmune addison's can have concimmitant autoimmunity with what other diseases?

Answer 27

autoimmune polyendocrine syndromes (APS-1 and APS-2)

Question 28

immuno-pathogenesis of autoimmune addison's

Answer 28

**B cells:** * auto-Ab to 21-hydroxylase (in vitro but NOT in vivo) **T cells:** * auto-Ab to IgG1 or IgG2 * T cells reactive to fetal adrenal extracts

Question 29

pts with what diseases should be screened for 21-hydroxylase autoantibodies as a concommitant autoimmunity with Addison's?

Answer 29

1. T1D 2. hypoparathyroidism 3. APS

Question 30

idiopathic hypoparathyroidism may have autoAb to...

Answer 30

1. parathyroid protein: NACHT leucine-rich repeat protein 5 2. CaSR

Question 31

APS-1 major components

Answer 31

1. Chronic mucocutaneous candidiasis (auto-Ab to Th17) 2. Addison’s Disease (AAD) 3. Autoimmmune Hypoparathyroidism: * manifests during childhood * mutation in **AIRE**

Question 32

APS-2 major components

Answer 32

1. T1D 2. Addison’s Disease (AAD) 3. Autoimmmune thyroid disease * **most common** * genetically associated with certain HLA haplotypes & CTLA-4 gene polymorphisms

Question 34

IPEX syndrome

Answer 34

**Mutation in FoxP3 gene --\> absent/dysfunctional Treg** presentation: during first few months of life: * dematitis * growth retardation * multiple endocrinopathies * recurrent infections * overwhelming autoimmunity * T1D (dev as early as 2 DAYS of age) usually die within 2 years: sepsis, failure to thrive

Question 35

Overview of the steps in the maturation of lymphocytes

Answer 35

Question 36

regions of Ag receptor that dtermine Ag specificty are called

Answer 36

variable (V) regions sequence variability within the V regions concentrated in CDRs (complementary determining regions)

Question 38

Steps in the maturation and selection of MHC-restricted T lymphocytes.

Answer 38

recombination done by **RAG-1/2** * beta chain: D --\> J: DJ --\> V: VDJ (variable region that binds to Ag) * alpha chain: V --\> J: VJ mutation in RAG-1/2 --\> **SCID**