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Endocrine System > Immunology of Type 1 Diabetes > Flashcards

Immunology of Type 1 Diabetes Flashcards

1
Q

What was the US expenditure in 2022 for diabetes?

A

412.9 billion US dollars

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2
Q

What percentage of the health care dollars goes to care for diabteics?

A

1 in 4 health care dollars, 25%

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3
Q

What are the medical expenditures of diabetic patients like in comparison to non-diabetic patients?

A

2.6 times higher medical expenditures

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4
Q

What is the role of tolerance in preventing autoimmunity?

A

Central and Peripheral Tolerance

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5
Q

What is central tolerance like?

A

Positive and negative selection

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6
Q

What is peripheral tolerance like?

A

Inhibitory cytokines
Anergy
Deletion of Autoreactive T cells
Immune deviation
Active suppression

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7
Q

What are the immune checkpoints that prevent autoimmunity?

A
  1. Central tolerance
  2. Antigen segregation
  3. Active suppression via T-regulatory
  4. Natural or Induced (IL-10 or TGF-beta)
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8
Q

Central tolerance:

A
  1. Central deletion in thymic medulla (T-cells) & Bone marrow (B-cells)
  2. AIRE gene –> which causes defect –> autoimmune polyglandular syndrome (APS) –> TID

Individual organs of the body express tissue-specific antigens (retina or ovaries)
In the thymus, T cells arise capable of recognizing tissue-specific antigens
Under control of the AIRE protein, thymic medullary cells express tissue-specific proteins, leading to deletion of tissue-reactive T cells
In the absence of AIRE, T cells reactive to tissue-specific antigens mature and leave the thymus

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9
Q

Antigen Segregation:

A
  1. B cells with specificity for DNA bind soluble fragments of DNA, sending a signal through the B-cell receptor
  2. The cross-linked B-cell receptor is internalised with the bound DNA molecule
  3. GC-rich fragments from the internalized DNA bind to TLR-9 in an endosomal compartment, sending a co-stimulatory signal

Unmethylated CpG –> TLR-9 (normal in bacteria, expressed in apoptotic cells)

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10
Q

What do cytokines IL10 and TGF-beta inhibit?

A

They inhibit other self-reactive T cells

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11
Q

What is regulatory tolerance?

A

T cells specific for self-antigen recognized in the thymus become a natural regulatory T cell

T cell-specific for self or commensal microbiota antigens recognized in the presence of TGF-beta become induced regulatory T cells

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12
Q

What is autoimmunity like?

A

Multifactorial: genetic factors, infection, and environmental exposure

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13
Q

What are the types of Type 1 diabetes?

A

Type 1A –> immune mediated
Type 1B –> idiopathic loss of insulin secretion-

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14
Q

What is Type 1A Diabetes like?

A

A T-cell mediated disorder, autoimmune destruction of beta cells in the islets of Langerhans of the pancreas

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15
Q

What are the stages of development of Type 1A?

A
  1. Genetic predesposition (HLA-DR3 or DR4)
  2. Precipitating event
  3. Normal insulin release, overt immunologic abnormalities–> variable degree of insulitis
  4. Antibodies against islet cell antigen and glutamic acid decarboxylase, progressive loss insulin release but glucose is normal
  5. Overt diabetes, C-peptide is present
  6. No C-peptide
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16
Q

What are the islets cell cytoplasmic enzymes?

A
  1. Glutamic acid decarboxylase (GAD)
  2. Protein tyrosine phosphatase-related islet antigen 2 (IA-2)
  3. Zinc transporter ZnT8
17
Q

When does GAD present?

A

Years before clinical disease

18
Q

What does the presence of GAD early in life inidcate?

A

Type 1 DM

19
Q

What are the examples of Islet cells antibodies?

A

Islet cells cytoplasmic enymes
Insulin

20
Q

What are the clinical stages of Diabetes?

A

Pre-diabetes: people with islet cell antibodies and normal glucose levels
Overt diabetes: greater than 90% loss of functioning beta cells

21
Q

What are the key steps of Diabetes?

A

Beta cells reactive T cells need to be activated
Response –> pro-inflammatory
Immune regulation failure

22
Q

What are the triggering factors?

A

Molecular mimicry
Dietary Factors

23
Q

What is viral mimicry like?

A

Congenital rubella infections have a direct link
Coxsackie B virus

24
Q

What is the molecular mimicry of Coxsackie B virus like?

A

Sequence similarity between viral protein 2C and glutamic acid decarboxylase binds well to DR3

25
Q

What is the molecular mimicry of mumps and rubella like?

A

Directly lyse beta cells

26
Q

What are the dietary factors that trigger diabetes?

A

Bovine serum albumin –> homologous to islet antigens

27
Q

What causes Th0 to become Th1?

A

IL-12

28
Q

What causes Th0 cells to become Th2 cells?

A

IL-4

29
Q

What is the immunity related to Th1 cells?

A

Cell mediated immunity

30
Q

What immunity is related to Th2 cells?

A

Humoral immunity

31
Q

What are the cytokines released from Th1 cells?

A

IL-2
TNF
IFN

32
Q

What are the cytokines released from Th2 cells?

A

Il-4
IL-5
IL-10

33
Q
A

Endocrine System (10 decks)

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