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Type 1 Diabetes- - IDDM Insulin Dependent Diabetes Mellitus

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Title: Type 1 Diabetes- - IDDM Insulin Dependent Diabetes Mellitus


1
Type 1 Diabetes- - IDDMInsulin Dependent
Diabetes Mellitus
  • TEAM - ?? ??? ?? ??? ??? ???

2
Contents
Type 1 diabetes(T1D), also named IDDM, is one of
the most common autoimmune disease, affecting
almost 20 million people worldwide.
What is IDDM
  • IDDM

? Factors Inducing IDDM
  • Insulin

? Immune Mechanism
  • Dependent

Manifestations Complications
  • Diabetes

Therapy
  • Mellitus

3
What is IDDM
Factors
Self Ag changes
Immune Response
  • Heredity
  • Virus Infection
  • Environmental
  • Factors
  • Recognition of
  • specific self islet
  • ßantigens
  • Effects of
  • immune cells
  • molecules

Disease
Breaking
Type 1 Diabetes Or IDDM. NOD Children
Adolescent Insulin-dependent
  • Breaking of
  • Immune
  • tolerance
  • Autoimmune
  • disease

4
Factors Inducing IDDM
  • HLA-DQ ß57
  • Asp
  • Neutral AA
  • HLA-DQ a52
  • Arg
  • Coxsackie B virus
  • Rubella virus
  • Mumps virus
  • Cytomegalovirus
  • Epstein-Barr virus
  • Etc.
  • Chemicals
  • Medicament

Heredity
Virus
Environment
5
Virus Infection
  • Changes of self-Ag into non-self-Ag

Host cells become target cells
Initiate immune response
  • Changes of host cell immune system function

Ab Cytokines Immune tolerance Th1/Th2
  • Cross reaction

Virus host cell have common Ag
6
HLA expression
Abnormal expression of Class ? MHC molecules
Class ? MHC molecule
High expression of Class ? MHC molecules
ß cell
ß cell
Virus infection
Environmental influence
7
Mechanism of IDDM
? CD4 T cells
Autoimmune response ß cell apoptosis and death
CD8 T cell
Humoral immunity
8
CD4 T cell response
Th1/Th2 unbalance Th0 Th1
  • MHC ? abnormal
  • expression
  • Host cell turns into
  • APC
  • MHC ? Self-Ag
  • Activate CD4 T cell

Cytokine secretion Th1 IFN-? TNF-a Macrophage
IL-1ß TNF-a
Apoptosis Fas-FasL pathway
9
CD4 T cell related response
  • Th0 cells mainly differentiate into Th1 cells,
    causing Th1/Th2 unbalance.
  • Th1 cells produce IFN-? TNF-a, inducing
    expression of Fas protein on islet ßcell, and
    FasL expression on CTL or macrophage(IL-1ß , NO,
    RNIs).
  • IFN? can activate NK cell ,which then hurt the
    target cells (ß cell) with specific Ag .
  • IL-2 IL-12
  • Th2 antagonizes Th1 effects.
  • IL-4 and IL-10 can strongly inhabit Th-1 to
    produce IFN-?, which can decrease the level of
    isletitis and improve ß cells to produce insulin,
    to decrease the morbidity of IDDM

10
CD8 T cell response
Perforin - Osmotic lysis
Granzymes - Apoptosis
IFN-? TNF-a - Direct hurt of ßcell
Fas-FasL pathway - Apoptosis
11
Pancreatic lymph node
Islet
Tc
Granzyme
Co-stimu- latory signals
Fas FasL
Perforin




APC











?




APC




IL-1ß TNF?
RNIs Apoptosis
O2
NO


?

Th1












Fas FasL
IFN?
T- and B-cell clonal ex-
pansion
Th1
12
Humoral Immunity
  • Insulin Insulin Ab (IA)
  • Insulin receptor Anti-insulin receptor Ab
  • Islet cell surface Ag (ICA)- Islet cell surface
    Ab
  • Glutamate decarboxylase (GAD)
  • Anti-glutamic acid decarboxylase Ab (GADA)

13
Relationship
CD4 T cell response
CD8 T cell response
Humoral immunity
14
More non-self-Ag - More HLA expression of
residual ß cells
More T cells response - More destruction of ß
cells
ß cells destruction - HSP GM ICA
Further destroy
Residual cells
Cell lysis
15
Manifestation
16
Complications
Hypoglycemia
Lactic acidosis
Non-ketotic hyperosmolar syndrome
Ketoacidosis
17
Complications
Skin infection
Mucosa infection
Chronic Complications
Alzheimers disease
Diabetic neuropathy
Numbness Foot infection
Large blood vessels problem
Small blood vessel problem
Diabetic retinopathy (Blindness) Diabetic
nephropathy (Albuminuria Kidney Failure )
Heart disease (Myocardial
infarction) Stroke
18
Therapy
Gene therapy
Islet transplantation
Insulin therapy
  • Subcutaneous injection (Lifetime)
  • Intravenous injection (Emergency)
  • Gene vector
  • Insulin-like substance
  • Transgenic mice model
  • stem cell
  • Islet ß cell transplantation
  • Islet-Kidney united transplantation

19
Thank You !

  • Dec. 7th, 2007

20
(No Transcript)
21
Regeneration of ß cells
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