Chapter10 今日のメモ☆
Immunology第五回目はGraft rejection（移植片拒絶）とVaccination（ワクチン接種）に関して。
HLA incompatibility
-
human leukocyte antigen (HLA) : HLA［ヒト白血球抗原］適合性, 白血球の血液型のようなもの
-
histocompatibility type : 組織適合性
identical twins : 100% , siblings : 25%
exact HLA match is approximately 1/10 million
HLA-DR, HLA-B maching :
renal &
cardiac graft
HLA matching is NOT important :
liver transplantation
-
Hyperacute rejection
ABO mismatches. within
2 days. untreatable.
-
Acute rejection
T cell-macrophage-mediated attack, based on
HLA and other
tissue antigen mismatches.
in
10-14 days. necrose if untreated.
-
Chronic rejection
several
months to years.
fibrosis（線維症）, occlusion of small arteries（動脈閉塞） in the kidneys
atherosclerosis（アテローム性動脈硬化） in the heart.
success rate after 5 years is
50% even though MHC-matched(HLA-matched)
treatment with
corticosteroids can be helpful.
Bone marrow transplantation
immunodeficiency diseases, aplastic anemia, some leukemias, genetic diseases
-
graft-versus-host (GVH) disease（移植片対宿主病）
graft
T cell recognition of the host is important
HLA matching is important
clinical symptoms : skin (rash), GI tract (pain, vomiting, bleeding), liver (necrosis, serum bilirubin↑)
Prophylaxis and treatment
- immunosuppression of the graft recipient
*
Corticosteroids : just before the transplantation.
combination w/ azathioprine, cyclosporine, antilymphocyte globulins/ antithymocyte globulins
*
Azathioprine : before the transplantation, maintainance doses are given afterward
*
Methotrexate : primarily for bone marrow transplantation
combination w/ antilymphocyte globulins/ antithymocyte globulins(ALGs/ATGs)
- Specific suppression of T cells
*
Cyclosporine A : used as prophylaxis
inhibit T
H cell secretion of IL-2, prevent complete T cell activation
side effect : nephrotoxicity（腎毒性）
*
Tacrolimus (FK-506)
same way as cyclosporine A, but NOT used together
*
Rapamycin
inhibit T
H cell response to IL-2, prevent complete T cell activation
different way as two drugs above
*
ALG, ATG : use prophylactically and therapeutically
antisera derived from animal. against T cell antigens
*
Moromonab-CD3(OKT3) : use
therapeutically
mouse monoclonal antibody for CD3 antigen of peripheral T cells.
opsonization of T cell for phagocytosis.
side effect : high fever, chills, blood pressure changes, vomiting, diarrhea, respiratory distress
contraindicate: in patients who have fluid overload because of
edema
※
monoclonal antibodies are used to mask HLA antigens on the graft tissues
Vaccination（ワクチン接種）
Passive vaccination（不活化ワクチン）
intramuscular, intravenous injection
limited to several weeks to months
- Prophylaxis of infectious disease
*
Tetanus（破傷風）immunoglobulin(
TIG)
*
Hepatitis B immunoglobulin(
HBIG)
- Prophylaxis or therapy
* varicella zoster immunoglobulin (VZIG) （水痘帯状ヘルペス）,
rubella（風疹） for pregnant women
- Treatment of antibody deficiency
* intravenous immunoglobulin (IVIG), intramuscular immunoglobulin (IGIM)
- Other situation
* IVIG : idiopathic thrombocytopenia purpura（突発性血小板減少症紫斑病）
* Intramuscular Rh immunoglobulin : prophylaxis for RH disease
*
Muromonab-CD3 : acute renal graft rejection
Active vaccination（生ワクチン,弱毒化ワクチンetc）
intramuscular, subcutaneousm（皮下）, intradermally, intranasally, oral introduction
immunity is long lasting(some elicit lifelong immunity)
the first vaccination for infants and children should be after
6 weeks.(some may be given immediately after birth)
- Live, attenuated vaccines
* [MMR] measles（はしか）, mumps（おたふく）, rubella（風疹） : lifelong immunity, school entry
* oral
polio（ポリオ） : school entry
- Subunit vaccines
* [DTP] Diphtheria（ジフテリア）, tetanus（破傷風）, pertussis（百日咳） : 1st dose at shool entry
* [Td] Tetanus and diphtheria toxoids : 2nd dose in 4-8 weeks & 3rd dose 6 months later
※ Tetanus-prone wound
for
deep puncture, uncertain about vaccination or after 10 years : tetanus immunoglobuline
(TIG) & Tetanus and diphteria toxoids
(Td)
for a
clean & minor wound, uncertain about vaccination or after 10 years :
Td is administered.
※ sometimes passive and active vaccines are used together (ex. Rabies（狂言病）)
Immunomodulation（免疫修飾・修復）
- Fab antidigoxin antibody : reversal of toxicity associated with toxic
digoxin serum level.
- monoclonal antibodies :
hybridoma(cancerous plasma cell with activated mouse B cell) has immortality characteristic of the myeloma（骨髄腫）
*
muromonab-CD3 : treat acute graft rejection
* other monoclonal antibodies : treat breast, colon cancer and leukemias
- immunostimulation
* IFN-α : hairy cell
leukemia,
kaposi sarcoma(AIDS), genital warts（生殖器いぼ）
at
low doses : IFN stimulate immune cellular function (T cells, NK cells, macrophages)
at
high doses : immunosuppressive
* IFN-γ : macrophage-activating factor in chronic granulomatous disease（慢性肉芽腫性疾患）
combined use of IFN-α & IFN-γ has better results
* IL-2 : melanoma（黒色腫）
* levamisole (Sulfur-containing compounds) : colon cancer with fluorouracil
Today's question
- Vacctination(ワクチン接種)の問題
Q: Which is a valid comparison of live, attenuated and killed , inactivated active vaccine.
(A) Replication of the organisms in a live attenuated vaccine increases the stimulation of the immune system and a lower dose is often required.
(B) Attenuated vaccines often require multiple doses.
(C) A killed, inactivated vaccine probably produces lifelong immunity in one or two doses.
A: (A)
Live, attenuated vaccines introduce organisms that are competent to replicate. This replication stimulates the immune response. For this and probably other easons, a live, attenuated vaccine (but not a killed, inactivated vaccine) probably provides lifelong immunity in one or two doses.
