Title: Type 1 Diabetes- - IDDM Insulin Dependent Diabetes Mellitus
1Type 1 Diabetes- - IDDMInsulin Dependent
Diabetes Mellitus
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2Contents
Type 1 diabetes(T1D), also named IDDM, is one of
the most common autoimmune disease, affecting
almost 20 million people worldwide.
What is IDDM
? Factors Inducing IDDM
? Immune Mechanism
Manifestations Complications
Therapy
3What 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
4Factors Inducing IDDM
- HLA-DQ ß57
- Asp
- Neutral AA
- HLA-DQ a52
- Arg
- Coxsackie B virus
- Rubella virus
- Mumps virus
- Cytomegalovirus
- Epstein-Barr virus
-
- Etc.
Heredity
Virus
Environment
5Virus 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
Virus host cell have common Ag
6HLA expression
Abnormal expression of Class ? MHC molecules
Class ? MHC molecule
High expression of Class ? MHC molecules
ß cell
ß cell
Virus infection
Environmental influence
7Mechanism of IDDM
? CD4 T cells
Autoimmune response ß cell apoptosis and death
CD8 T cell
Humoral immunity
8CD4 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
9CD4 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
10CD8 T cell response
Perforin - Osmotic lysis
Granzymes - Apoptosis
IFN-? TNF-a - Direct hurt of ßcell
Fas-FasL pathway - Apoptosis
11Pancreatic lymph node
Islet
Tc
Granzyme
Co-stimu- latory signals
Fas FasL
Perforin
APC
?
APC
IL-1ß TNF?
RNIs Apoptosis
O2
NO
?
Th1
MØ
Fas FasL
IFN?
T- and B-cell clonal ex-
pansion
Th1
12Humoral 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)
13Relationship
CD4 T cell response
CD8 T cell response
Humoral immunity
14More 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
15Manifestation
16Complications
Hypoglycemia
Lactic acidosis
Non-ketotic hyperosmolar syndrome
Ketoacidosis
17Complications
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
18Therapy
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
19Thank You !
20(No Transcript)
21Regeneration of ß cells