Autoimmunity and Autoimmune

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Autoimmunity and Autoimmune Disease (AID)
I. Summarization II. Mechanisms
and models of AID III. Nosogenesis of AID
IV. Therapy of AID
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I. Summarization 1. Concepts of Autoimmunity
AID 2. Characters of AID 3. Classification of AID
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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
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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 auto-antibody
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.
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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)

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Rheumatoid arthritis

• Characterized by the presence of rheumatoid
  factor (antibodies against IgG)

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II. Mechanisms and models of AID

• (1)AID caused by type II hypersensitivity
  reactions
• AID with Cell destruction caused by auto-
  antibodies
• AID caused by auto- antibodies against receptors
  on surface of cells
• AID caused by auto- antibodies against extra-cell
  component

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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 extra-cell component
Lung- Kidney syndrome
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(2) AID caused by type III hypersensitivity
reactions IC with auto-antibodies
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SLE(Non-organ specific) many auto-antibodies
anti-nucleus antibodies, anti-DNA, RNA ...
immune destructionLupus cells formation, Joint,
cardiovascular, Kidney, Liver Reasons
(1)   Slow virus continuous infection
(2)   Ag-Ab complex sediment (3)  
Medicine application
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Animal model
Part III
a.Negative b.Homogeneous pattern
c.Peripheral pattern d.Cytoplasmic
pattern e.Nucleolar pattern
f.Cytoplasmicnucleolar pattern
a b c
d e f
Immunofluorescent staining of ANAs(?400)
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Animal model
Part III
a. Negative b. ? 400 c. ? 100 d. ? 40
a b
c d
Immune complexes deposit in glomeruli
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(3)AID caused by type IV hypersensitivity
reactions Inflammatory damage caused by T
cells against self-antigen
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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 infectionInsert DNA, Auto-Ab,
interfere FasL expression, T?B hyperplasia

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1. Self-antigen alteration/associated
antigen 3)   Cross antigen effect A ß
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
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2. Immune regulation abnormity
1)  Alternative activation by multi-clone
stimulator microbes or its
products directly induce B cells to produce
auto-antibodies 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
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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
CD4T cells, help B cells produce antibodies,
without AICD
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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
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6)Others 1     Thymus function
abnormity Tumor, slow virus
infection in thymus
thymus abnormity, thymus hormone
deficiency
Obstruction of thymus T cells differentiation
sthenic B cells function auto-antibodies  
2  Idiotype-anti-idiotype network regulation
abnormity Ab2b, internal
image(antibodies with same effect), Auto-immune
3  Endocrine Child-bearing women E2
4 Heredity
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IV. Therapy of AID           Defend and
control pathogeny infection          
Immunosuppressant           
Anti-inflammation treatment            
Cytokine treatment              Therapy with
specific antibodies            Oral
auto-antigen
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• Grasp characters of AID
• Familiar with mechanisms of AID
• Familiar with nosogenesis of AID
• Know about therapy of AID