Autoimmune of Endocrine

Question 1

Cytokines such as IL-1, IL-6, and TNF-α act as auto/paracrine or endocrine factors to

Answer 1

increase the activity of the hypothalamus-pituitary adrenal (HPA) axes

Question 2

Cortisol, the stress hormone from adrenal gland, can modulate the

Answer 2

immune system

Question 3

In physiologic amounts, cortisol boosts

Answer 3

immunity and limits inflammation

Question 4

Endocrine autoimmune disorders are

Answer 4

organ specific and sometimes cell type specific

Question 5

Endocrine autoimmune diseases generally involve

Answer 5

chronic T cell or antibody targeting of a particular organ or cell type

Question 6

What cells maintain and amplify the inflam reactions?

Answer 6

Th17

Question 7

What cells fail to keep auto reactive clones in check?

Answer 7

Tregs

Question 8

What is the central mechanism associated with the development of many autoimmune disorders, either as a failure of elimination of autoreactive lymphocytes or as the means of mediating tissue damage

Answer 8

Apoptosis

Question 9

What autoimmune disease is hyperthyroidism?

Answer 9

Graves

Question 10

What autoimmune disease is hypothyroidism?

Answer 10

Hashimotos

Question 11

What disease is from adrenal deficiency?

Answer 11

Addisons

Question 12

What 2 autoantibodies are associated with Hashimotos?

Answer 12

Thyroid peroxidase (90%)
Thyroglobulin antibodies (50%)

10% will be nagative for both

Question 13

What are manifestations of hashimotos?

Answer 13

• Goiter in front of neck
  -Oral: Large tongue, thick lip, low salivary gland, dysphagia
• Weight gain, dry skin, thin hair
• Depression
• Myxedema
• Kidney dysfunction

Question 14

What is Myxedema?

Answer 14

Skin swelling due to increased glycosaminoglycan deposits

Question 15

What does PTPN22 affect in Hashimotos?

Answer 15

The threshold for T cell activation, influencing immune tolerance and autoimmunity

Question 16

What does CTLA-4 do in Hashimotos?

Answer 16

Checkpoint inhibition impaired the regulation of immune responses, making the tissue more susceptible to attack

Question 17

What does FOXP3 do in Hashimotos?

Answer 17

Transcription factor of regulatory T cells, helping prevne tautoimmune reactions

Question 18

In Hashimotos, the thyroid gland is intensely filled with

Answer 18

lymphocytes and plasma celsl

Question 19

First stage of Hashimotos involves accumulation of macrophages and dendritic cells. Macrophages produced IL-B and IL-18 that activate inflammasome and trigger

Answer 19

cell death

Question 20

Hashimotos: IFN-y and TNF-a trigger

Answer 20

thyrocyte apoptosis

Question 21

Hashimotos: Dead cells, reciprocally, activate production of autoantibodies against

Answer 21

thyroid peroxidase and thyroglobulin

Question 22

What environmental factors are linked to Hashimotos?

Answer 22

• Infections, smoking
• Radiation
• Medicine (Antiarrhythmics and interferon)
• Nutrition

Question 23

What nutrition factors are associated with Hashimotos?

Answer 23

• Idoine intake (can stim thyroid peroxidase and trigger flare up)
• Selenium def (disrupts balance of Th1 and Th2)
• Iron def
• Vit D def (increased diff of B lymph into plasma cells)
• Magnesium and zinc def

Question 24

What are treatments for Hashimotos?

Answer 24

• Thyroxine replacement therapy
• Possibly selenium and Vit D supplements

Question 25

In Hashimotos, if serious illness involving damage to internal organs, then what should be used?

Answer 25

High doses of corticosteroids in combo with immune suppressants

Question 26

In Hashimotos, if serious brain or kidney disease, what should be done?

Answer 26

Plasmapheresis to remove antibodies from blood to suppress immunity

Question 27

What are symptoms of Graves?

Answer 27

- Goiter - Proptosis (bulging eyes) - Afib - Shortness of breath - Proximal muscle weakness - Nervousness - Hyperpigmented and itchy skin lesion on dorsum of feet and legs

Question 28

What is the autoantibody in Graves?

Answer 28

TRAb (TSH receptor)

Question 29

What does TRAb mimic?

Answer 29

The action of TSH; it stimulates TSH receptor on thyroid follicular cells

Question 30

Graves: Folluclar celsl hypertrophied with active thyroglobulin production and accumulate intracellular _________ containing _______

Answer 30

colloid droplets; thyroglobulin

Question 31

TSH receptor autoantibodies are typically of what isotope?

Answer 31

IgG

Question 32

What3 polymotrphisms are shared between Hashimotos and Graves?

Answer 32

- PTPN22 gene - CTLA-4 gene - FOXP3 gene

Question 33

What genetic components are associated with Graves?

Answer 33

- HLA - TSHR - PTPN22 - CTLA-4 - FOXP3 - IL-2RA - CD40

Question 34

Describe immune pathogenesis of Graves

Answer 34

- Breach in immune tolerance allows auto T and B cells to survive - Dysfunction or insuff in Tregs allows autoimmunity to persist - T and B cells infiltrate thyroid glands - Induces HLA class II antigens and they express follicular thyroid cells presenting TSH-R - Chronic stim and presentation of thyroid antigens perpetuate autoimmune cycle

Question 35

What are extrathyroidal manifestationf of Graves?

Answer 35

- Bulging eyes - Pretibial myxedema (swelling of shins)

Question 36

What environmental factors are linked to Graves?

Answer 36

- Microbial infections - Smoking - Excessive iodine intake - Thyroid autommunity in Celiac children

Question 37

What are the microbial infectiosn that have a link to Graves?

Answer 37

- Yersinia Enterocolitica - EBV - Hep C - HSV and CMV

Question 38

What are treatments for Graves?

Answer 38

- Radioactive iodine - Anti-thyroid drugs - Surgery

Question 39

What are symptoms of T1D?

Answer 39

- Polyuria - Polydipsia - Polyphagia - Weight loss - Fatigue - Blurry Vision

Question 40

What autoantibodies are linked to T1D?

Answer 40

- Islet cell antibodies - Antibodies to glutamic acid decarboxylase (GAD-65) - Insulin autoantibodies - IA-2A to protein tyrosine phosphatase I2A

Question 41

What are genetic factors linked to T1D?

Answer 41

- HLA-D - HAving high number of tandem repeated regions in insulin

Question 42

T1D is a ___________ immune-mediated disease

Answer 42

T cell dependent

Question 43

At onset of T1D, elevated levels of

Answer 43

insulin specific T follicular helper and increased IL-21

Question 44

What is the autoantibody in Addisons?

Answer 44

21-hydroxylase which damages the cortex of adrenal gland

Question 45

What is Addisons disease characterized by?

Answer 45

Adrenal cortex fails to produce hormones like cortisol and aldosterone

Question 46

What are manifestations of Addisons?

Answer 46

- Dark hyperpigmentation in lips and mouth and areas of friction - Salt craving - Women lose pubic hair - Other signs: Hypoglycemia, hyponatremia, hyperkalemia, anemia, lymphocytosis and eosinophilia

Question 47

What are environemtnal factors linked to Addisons?

Answer 47

- Molecular mimicry - In past, TB was major cause and still is in some areas, less common causes include fungal - Hemorrhage into adrenal gland - Abnormal accumulation of fatty substance in adrenals

Question 48

In Addisons, the cortisol deficiency can lead to

Answer 48

reduced responsiveness to catecholamines in blood vessels

Question 49

What is treatment of Addisons Disease?

Answer 49

Replacing deficient hormones Hydrocortisone for cortisol and Fludrocortisone for aldosterone

Question 50

What are symptoms of APECED?

Answer 50

- Hypoparathyroidism - Adrenocortical insufficiency - T1D - Chronic candidiasis - Ectodermal dystrophy