Chapter 10 Immunology vol.5

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.