Download 幻灯片 1

Autoimmunity and Autoimmune
Disease (AID)
I.
Summarization
II.
Mechanisms and models of AID
III. Nosogenesis of AID
IV. Therapy of AID
I. Summarization
1. Concepts of Autoimmunity & AID
2. Characters of AID
3. Classification of AID
1. Concepts of Autoimmunity & AID
Autoimmunity:
Inappropriate response of the immune system against
self-components
Autoimmune disease, AID:
Diseases induced by inappropriate response of the
immune system against self-components
2. Characters of AID
1 High titer auto-antibody in serum and self-reactive T cells
against self-components
2 Damage to organs and tissue destruction caused by autoantibody & self-reactive T cells
3 close relationship between disease prognosis and auto-immune
4 Repeat,chronic persistent
5 Animal model replication and adoptive transfer
6 Inherited tendency, female susceptible
7 No reasons
Among them, no.1 and no.2 could not be absent.
3. Classification of AID
• Organ specific
• Hashimoto's thyroiditis
• Primary myxoedema thyrotoxicisis
• Insulin-dependent diabetes mellitus
• Non-organ specific
• Systemic lupus erythematosus (SLE)
• Rheumatoid arthritis (RA)
Rheumatoid arthritis
Characterized by the
presence of rheumatoid
factor (antibodies against
IgG)
II. Mechanisms and models of AID
（1）AID caused by type II hypersensitivity
reactions
1.
AID with Cell destruction caused by auto- antibodies
2.
AID caused by auto- antibodies against receptors on surface of
cells
3.
AID caused by auto- antibodies against extra-cell component
1 ） AID caused by auto- antibodies against cell
surface antigen
immunologic thrombocytopenic purpura, ITP
2） AID caused by auto- antibodies against
receptors on surface of cells
toxic diffuse goiter、myasthenia gravis
myasthenia gravis：
（1） thymocyte pathological changes
（2） IgG increase, Auto-antibody to AChR
3） AID caused by auto- antibodies against extracell component
Lung- Kidney syndrome
（2） AID caused by type III hypersensitivity
reactions
IC with auto-antibodies
SLE（Non-organ specific）
many auto-antibodies: anti-nucleus antibodies, anti-DNA,
RNA ...
immune destruction：Lupus cells formation, Joint,
cardiovascular, Kidney, Liver …
Reasons：
（1） Slow virus continuous infection
（2） Ag-Ab complex sediment
（3） Medicine application
Animal model
a b c
d e
f
Part III
a.Negative b.Homogeneous pattern c.Peripheral pattern
d.Cytoplasmic pattern e.Nucleolar pattern
f.Cytoplasmic+nucleolar pattern
Immunofluorescent staining of ANAs(400)
Animal model
a
b
c
d
Part III
a. Negative
b.  400
c.  100
d.  40
Immune complexes deposit in glomeruli
（3）AID caused by type IV hypersensitivity
reactions
Inflammatory damage caused by T cells
against self-antigen
Activated CNS-specific T cells infiltrate the
CNS,
Become reactivated and Contribute to MS
B7-1 CD28
autoreactive
MBP
or
mimic
CD28 B7-1
autoreactiv
eTh1
autoreactiv
eTh1
IL-12
BBB
III. Nosogenesis of AID
1. Self-antigen alteration/associated antigen
1） covert antigen release（lens, sperm, hypothyroid）
2） self-antigen alteration
Ag denaturalization, Metabolization alteration, Ag expression
alteration, Medicine effect
a-methyldopamine: RBC membrane e antigen, anti-RBC Ab,
autoimmune hemolytic anemia
Hydrazinebenzenepyridazine: Alter nuclear component,
Anti-nucleus Ab, SLE-like syndrome
Virus infection：Insert DNA, Auto-Ab, interfere FasL
expression, T、B hyperplasia
1. Self-antigen alteration/associated antigen
3） Cross antigen effect:
A β Hemolytic streptococcus vs. human cardiac muscle Ag
type 12 streptococcus vs. glomerulo basement membrane
4） Molecule mimic effect: the similar Aa sequence between pathogen and
human
5） Determinant Spreading
Dominant Epitope
Epitope in primary immune response
Cryptic Epitope
Epitope in continuous immune response
2. Immune regulation abnormity
1） Alternative activation by multi-clone stimulator :
microbes or its products directly induce B cells to produce autoantibodies
2） MHC II expression abnormity:
IFN-g、IL-1、IL-2、 MHCII
3） Assistant stimulator expression abnormity:
4） Th ratio or function unbalance:
Th1/Th2 deviation
5） Fas、FasL expression abnormity:
Diseases caused by Fas/FasL abnormity
lpr(lymphoproliferation)
gld(generalized lymphorpoliferative disease)
Lymphadenopathy and spleen swell, many IgG and IgM, including anti-DNA antibodies
and rheumatoid factor
Immune complex glomerulonephritis and arthritis five months after animals born, many
auto-reactive CD4+T cells, help B cells produce antibodies, without AICD
Autoimmune Lymphoproliferative Syndrome and Perforin
Rieux-Laucat, F., Le Deist, F., De Saint Basile, G.,
Clementi, R., Ferrarini, M., Bregni, M. (2005).
Autoimmune Lymphoproliferative Syndrome and
Perforin. N Engl J Med 352: 306-307
6）Others
1
Thymus function abnormity
Tumor, slow virus infection in thymus
thymus abnormity,
cells function
2
thymus hormone deficiency
Obstruction of thymus T cells differentiation sthenic B
auto-antibodies
Idiotype-anti-idiotype network regulation abnormity
Ab2b, internal image(antibodies with same effect), Auto-immune
3
Endocrine
Child-bearing women： E2
4
Heredity
IV. Therapy of AID
Defend and control pathogeny infection
Immunosuppressant
Anti-inflammation treatment
Cytokine treatment
Therapy with specific antibodies
Oral auto-antigen
•
•
•
•
Grasp characters of AID
Familiar with mechanisms of AID
Familiar with nosogenesis of AID
Know about therapy of AID