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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.
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