Chapter 18 Autoimmune Diseases 1. 1.Immunological homeostasis: To self Ag, our immune system is in tolerance and immune response won’t take place. Immune.

Chapter 18 Autoimmune Diseases

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1.Immunological homeostasis: To self Ag , our immune system is in tolerance and

immune response won’t take place.

Immune tolerance broken up

Anti self T cell Anti self B cell

Autoimmunity

Autoimmune Diseases2

2.Autoimmune Diseases(AID)

Overview• Autoimmunity: is that immune system plays

response to self cells and tissues. This can take place in all the individuals.

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• Autoimmune diseases: Under certain internal and external factors,

immune tolerance is broken up and durative autoimmunity produces abnormal immune response to autoantigen that caused self cells and tissue damage or dysfunction. We call this clinical symptoms of autoimmune diseases.

Short time autoimmunity response is ubiquitous and can not induce durative damage.

Section I. Induced factors and mechanism of autoimmune diseases

We still don’t know the definite etiological factor.

FactorsI. Aspect of Ag

1. Ag of immunologically privileged site releasing

sympathetic ophthalmia

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2. Change of self Ag rheumatoid arthritis abnormal IgG (Ag) anti IgG Ab( IgM,rheumatoid

factor) ICIC deposit at synovium of small joints flare, distortion, anchylose, lose motor function.

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3. Molecular mimicry:

there are some common epitopes between microbes and human cells. When these microbes invade human, immune response can be induced to elimiante them and damange self cells and tissues.

post-streptococcal glomerulonephritis

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4.Epitope spreading:

Dominant epitope and cryptic epitope

After immune system play response to a dominant epitope, it may play response to cryptic epitope. This is epitope spreading.

如 SLE- Histon ( H1) - DNA

RA ， MS10

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II. Genetic aspect 1. Genotype of HLA is relative with autoimmune

disease.

①HLA molecule coded by differential HLA gene can not supply Ag for T cell negative selection.

②HLA molecule coded by differential HLA gene can present pathogen, which is similar with self Ag, preferably. Immune diseases can be induced by molecular mimicry.

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Relation between autoimmune diseases with MHC

diseases genotype of HLA relative risk

ankylosing spondylitis B27 87.4

Acute anterior uveitis B27 10.04

Goodpasture’s syndrome DR2 15.9

MS DR2 4.8

Graves’ disease DR3 3.7

MG DR3 2.5

SLE DR3 5.8

IDDM DR3/DR4 3.2

rheumatoid arthritis DR4 4.2 13

2.Others gene relative with autoimmune diseases.

C1q , C4 , DNA enzyme , CTLA-4 et al.

III. Other aspects

1.Sex and autoimmune diseases.

MS and SLE ： female 10-20 fold to male

ankylosing spondylitis ： male 3 fold to female

2.Age: old age

3. Environmental : cold \moisture\sunshine

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Mechanism

1.autoreactive T cell clone delection abnormal

2.Immune ignorance broken up

3.Lympocytes polyclone activation

4.Activated induced cell death (AICD) disorder

5.Regulation T cell abnormal

6.MHC II molecule abnormal expression

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Section II .Immunological injury mechanism

and typical diseases

Etiological factor:

anti self Ab and anti self T cell.

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•Hypersensitivity:

as soon as immunity response eliminate Ag, host’s tissue appears physiologic function disorder or even damaged by the response.

•Autoimmune diseases: hypersensitivity diseases to self Ag. Pathogenesis is same as hypersensitivity.

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Autoimmune diseases and hypersensitivity

I. Autoimmune diseases induced by Self Ab

1.Self Ab on cell membrane or adhered on membrane induced autoimmune diseases.

• Complement activation,• Splenic phagocytes phagocytosis, • ADCC,• Neutrophil activation

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2. Autoimmune diseases induced by anti cell surface receptor Ab.

（ 1 ） Diseases mediated by stimulating auto-antibodies

Graves’ disease

• Anti- TSHR IgG• Effect fetus• Plasma exchange

transfusion

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（ 2 ） Diseases mediated by blocking auto-antibodies

myasthenia gravis, MG

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Myasthenia gravis (MG)(anti-AchR, blocking antibodies) In myasthenia gravis the antibodies bind the acetylcholine receptor and blocks the normal binding of acetylcholine , and cause it to be cleared from the surface of the muscle .

In addition, the anti-AChR activates complement, which damages the muscle end-plate; the number of acetylcholine receptors declines as the disease progresses.

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3. Diseases mediated by ICSystemic lupus erythematosus, SLE

Anti-dsDNA Ab

Anti-ssDNA Ab

Anti-nucleoprotein Ab

Anti-histone Ab

Anti-RNA Ab

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II. Disease mediated by anti self T cellsInsulin-dependent diabetes mellitus, IDDM ： CD8+CTL damage pancreatic islets β cells

Multiple sclerosis, MS

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Section III.

Classification and features of Autoimmune disease

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• Organ specific autoimmune disease

Graves disease

IDDM

Myasthenia Gravis (MG)

• Systemic autoimmune disease

RA

SLE

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Classification of Autoimmune disease

2.Features of autoimmune disease

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1. Autoantibody and autoreactive T cell can be detected in patients.

2. Autoantibody and autoreactive T cell playing response to self cells and tissues that induce dysfunction.

3. The recover of patients has relationship with intensity of autoimmune response.

4. The diseases tissues have Ig deposition or lymphocytes infiltration.

5. The diseases can be passive transfered by serum or lymphocytes

Section IV. Preventive and controlling principle of autoimmune disease

1. Prevent and control microbes infection

2. Immunodepressant utilization

Cytokines and CR blocking agent

Rheumatoid Arthritis: anti TNF-αmonoclonal Ab (infliximab)

3.Rebulid immunological tolerance to self antigen

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Exercise

• Concept:

Autoimmune

Autoimmune disease • Classification and Features of autoimmune diseases.• Preventive and controlling principle of autoimmune

disease

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