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Autoimmune Hemolytic

Anemia (AIHA)05 级临六三班

曲玉娟 杨亭亭 叶 青 丁 盛 刘 扬 王占奎

• 1. Introduction of AIHA• 2. Mechanism and pathogenesis• 3. Treatment

What is AIHA?

• Autoimmune hemolytic anemia (AIHA) is a disease in which the body attacks its own red blood cells (RBC).

Abnormal RBC

AIHA/IMHA is a life threatening immune disease because ：

• Causing Hypoxia• Result in blood clotting disorders and

systemic inflammation syndrome

Clinical Manifestations Acrocyanosis( 手足发绀 ),fever, shivering, hemoglobinuria,

pallor and jaundice dark red/ black urine etc

MECHANISM

Abnormal of T cell immunological tolerance

Immunological regulation disturbance

After-Abs regulation disturbance

Abnormal of T cell immunological tolerance

І T cell alternation activation pathway

Ⅱ DC mediated T cell immunological tolerance disturbance

Ⅲ Inhibition of activated T cell abnormal

Abnormal of T cell immunological tolerance

І Normally, there are little soluable self-antigens in the organism.they can induce T cell immunological tolerance but the B call immunological tolerance.

little dose soluble self-antigens

B cellautoimmune B cell lack

of Th cell

self-tolerance T cell

T cell

B cell

Inactivated B cell

T cell alternation activation pathway• Self antigens abnormal• virus infection. Drugs effection etc.

• Cross Reaction • molecular mimicry:• some microbe antigens have the similarities with self antig

ens ,the microbe antigens activate T cells ,then autoimmunity occur.

Abnormal of T cell immunological tolerance

Ⅱ DC mediated T cell immunological tolerance disturbance In normal condition,there is an equilibrium between DC and T cell in lymph nodes

Abnormal of T cell immunological tolerance

T cell

CTL CTL

Th cell

Th cell ApoptosisAICD

DCBystander killing

ApoptosisAICD

• Under pathogenic condition,this equilibrium is disturbed,amount of autoimmune Th cells and CTL released into blood,then autoimmune dieases ocuur--AIHA

Abnormal of T cell immunological tolerance

• Fas gene absence

• CTLA-4 gene mutant

Abnormal of T cell immunological tolerance

Ⅲ Inhibition of activated T cell abnormal

AICD effect doesn't work

Immunological Regulation Disturbance

• Th1/Th2 disequilibrium and CKs network

• Treg abnormal

Th1/Th2 disequilibrium and CKs network

ThP

Th1

Th2

APC

IL-12

IL-4

IL-2 、 IFN-γ 、 TNF-γ

IL-4 、 5 、 6 、 7 、 8 、 9 、10

Th0

AIHA

Th2

Th1

DC subgroup disequilibrium, Treg abnormal etc.

Immune surveillance

Th1

Cellular immunity

Anti-virus Anti-mutation Eliminate the decrepit and dead cells

Antibodies

Th2Humoral immunity

Anti-infection immunity

Th2 production increased IL-4 、 5 、 6 、 7 、 8 、 9 、 10 secretion increased Improve humoral immunity, B cells are activated excessively

IL-10IL-10 is secreted by many kinds cells: activated thymocytes, B cell, CD45RA+ naive T cell, macrophages etc.

IL-10 bcl-2 telomerase Lifespan of B cell

IL-10 Proliferation of B cellIL-2,IL-4

IL-10 + Differentiation of B cell and type switching from IgG1 to IgG3

T reg abnormal

CD4+CD25+T cells are 10% ～ 15% of all the T cells, they have higher affinity to self-peptide in thymus than the common T cells, and their function is not affected by APC

Ag CD25-CD25+

IL-10

TGF-β

Co-stimulate factors on APC

After-Abs regulation disturbance

• CONCEPT: After-Abs regulation refers to the

regulation of other regulators, such as Fc, complements and co-stimulators followed by the effects of Abs. including:

• Fc and Fc-receptor regulation

• Complement regulation

Fc and Fc-receptor regulation

• FcγRⅡ is a inhibiting receptor on the surface of MΦ .

• While FcγRⅠand FcγRⅢ are activating receptors on the surface of MΦ

Fc and Fc-receptor regulation

Ca²+

FcγRⅱ

Tyr residues

FcγRi

FcγRiii

immunity-FcR.html

Fc and Fc-receptor regulation

Ca²+

FcγRⅱ

Tyr residues

FcγRi

FcγRiii

hemolytic RBC

Complement regulation

• Complement receptor type1(CR1)• DAF

Inhibit the activation of the complements by deactivating the C3/C5convertase in the classic pathway and alternate pathway

The classical pathway

C3

C2

C4 C4b

C2aC3 convertase

C3bC5 convertase

C5 C5b MAC

CR1 DAF

CR1 DAF

No homelysis of RBC

Complement regulation

Genes of CR1 or DAF are lost or deficiency, the excessive activation of complements may attack self-RBC, and AIHA probably occurs.

The classical pathway

C3

C2

C4 C4b

C2aC3 convertase

C3bC5 convertase

C5 C5b MAC

CR1 DAF

CR1 DAF

The homelysis of RBC

Treatment

• Hematopoietic stem cells transplantion

• Monoclonal Ab treatment• Peptide segment binding self-Ab

competitively• CKs treatment• New immune inhibitor• Liposome clodronat

The mechanism of AIHA is rather complicated, immune tolerance 、 immune regulation and after-Ab regulation etc are abnormal. Clearance of the relationship between these disturbance and development of AIHA, will provide new methods for diagnosis and treatment.

THANK YOU!

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