6. Transplantation Medicine Flashcards
(49 cards)
Transplantation medicine
• Organ transplantation is the effective restoration of vital organ functions in end-stage organ disease
• Underlying principles:
– Immunology of proper donor and recipient ____
– Immunosuppressive therapy for ____ and management of graft rejection
• Comprehensive dental ____ prior to transplantation reduces risks of infections
• Post-transplantation oral health considerations
– Immunosuppressive ____
– ____-term immunosuppression
– Complications of ____
• Dental risk assessment and dental planning vital
matching
preventation
screening
medications
long
graft-versus-host disease (GVHD)
Organ Procurement and Transplantation Network U.S. Department of Health & Human Services
Just by sitting here, in just ____ minutes someone in the country will have end stage organ disease and need a transplant. So they will be added to the waiting list. By the end of today, about ____ people will have undergone organ tissue or cell transplant. When someone is listed as an organ donor, they have the ability to help ____ people.
10
95
8
WHY? Look at how many candidates are on the waiting list. ____ total.
Notes ____ and liver are high. Why is kidney #1? (couldn’t hear, but he hints kidney disease is common), indirectly hepatitis, BUT IMPORTANTLY: Kidney is high because these people don’t die immediately so people can wait on ____. 2 kidneys they can live on ____. Even if both are affected, they can stay on dialysis a long time.
____- lots of alcohol abuse, hepatitis.
113,000 kidney dialysis one liver
When you get organ transplant, they are able to survive. Within the first year, ____% survival. For kidney its ____%! High percent they will survive and live longer, even in the 90’s after 3 years for adult and pediatric patients. Good chance you will have patients needing or have received organ transplantations.
70-90
96.7
Classification/Types of Transplantation
Graft: A transplanted cell, tissue or organ
Based on type of tissue transplanted
• ____ organ/tissue transplantation (virtually all ____ of organs/tissues)
• ____ transplantation (____ components)
A graft is any cell tissue or organ that is transplanted from one site to another.
What are they types? Based on the type of tissue: Solid organ transplant (heart, liver kidney). Almost all types of organs and tissues can be transplanted.
Hematopoietic cell transplantation is the transplant of bone marrow components for whatever reason they may be needed.
solid
types
hematopoietic cell
bone marrow
Classification/Types of Transplantation
Based on genetic relations of tissue to recipient
• ____ transplantation: a graft to and from one’s self (____)
• ____ transplantation: a graft from one identical twin (identical genetic make-up) to another (____)
The other one is based on the genetic relations. For example, if you have a graft from one side of the mouth to the other (self to self) thats autologous transplantation. Also would be when you take then fibula to the jaw. From one part of the body to the other. This is an autograft.
Isogenic or syngeneic is transplant form identical ____. Easy to do because of identical genetic make up. High probability that this will work.
Allogenic transplantation: donor to a non identical recipient. Members of the same ____. Mr. Smith to Mr. Jones. Xenograft from one ____ to another. Monkey to human. All these are important terms. Most used is allogenic.
autologous
autograft
isogeneic or syngeneic
isograft
twin
species
species
Classification/Types of Transplantation
Based on genetic relations of tissue to recipient
• ____ transplantation: a graft from donor to a non-genetically identical recipient (____)
• ____ transplantation: a graft from donor of one specie to recipient of another specie (____)
allogeneic
allograft
xenogeneic
xenografts
Indications for transplants
This chart emphasizes the need for organ transplantation. Many indications: ____ or something more limited.
Long list. He reads a few of them like ____ transplantation (from one person to someone with a tumor)
TAKE A LOOK PLAYA
multi organ transplantation
allogenic
Transplantation antigens: MHC Major Histocompatibility Complex (MHC)
- 1967: Discovery of the human MHC revolutionized organ transplantation
- Histocompatibility antigens are tissue ____ antigens
- Induce immune response in a genetically dissimilar (____) recipient – Rejection
- 1968: WHO Nomenclature Committee designated the leukocyte antigens controlled by the closely linked human MHC genes as ____.
- Genes (>200) that encode histocompatibility antigen reside in the MHC region on the ____ arm of human ____
- The genes and their encoded cell-surface and soluble protein products are divided into 3 classes (____) based on tissue ____, ____, and ____.
- All share important roles in immune function
These antigens are very important. They are the Major Histocompatibility Complex also called hemoleukocyte antigens. Discovered in 1967 and they changed everything. Every cells have something different on their surface that allows the cell to be “self.” They do some sort of immune reaction when taken from one person to another then genetically dissimilar. These genes are close to HLA (human leukocyte antigen) so they use both terms.
MHC region on chromosome 6. three types based on distribution, structure and function
cell-surface allogeneic HLA short chromosome 6 I, II, and III distribution structure function
The Human Leukocyte Antigen System
Looking at chromosome six we can see the MHC region. There you have three classes where III is between
1 and 2. Different genetic regions or loci responsible for immune reaction or histocompatibility. HLA ____ are really the important ones for transplant medicine.
Important to know they’re on the short arm of chromosome #6.
2 and 1
The Human Leucocyte Antigen System
Class I MHC antigens
• Present on all ____ cells and red blood cells
• Composed of ____ chain protein encoded by genes of the HLA-A, HLA-B, or HLA-C loci on chromosome 6 and associated noncovalently with ____, encoded by a gene on chromosome ____
Class II MHC antigens
• Expressed only on ____ which include B lymphocytes, activated ____ lymphocytes, monocytes, ____, Langerhans cells, dendritic cells, endothelium, and ____ cells.
• Heterodimer composed of noncovalently associated ____ chains proteins encoded by genes of the ____ region
Klein and Sato, N Engl J Med. 2000 Sep 7;343(10):702-9.
Class III MHC genes
• Located between the ____ and ____ loci
• Determine the structure of ____, C4, and ____ in the complement system
Class I are on all nucleated cells and red blood cells and are labeled A B and C that are associated with the class I. Looks at the structure on the right: Its a heterodimer that is associated with a macro globulin (?), just FYI Class II also a heterodimer. But only present on the antigen presenting cells. Also another heterodimer. HLA = D (Dq Dp Dr, etc) All of these must be matched together to be a good match.
Class III is less important. Located between B and D on the chromosome 6. Involved in complement activation
nucleated
heavy
B2-microglobulin
15
antigen presenting cells (APC) T macrophages epithelial alpha and beta HLA-D
HLA-B
HLA-D
C2
factor B
Transplantation antigens: MHC Class I
Every ____ has these antigens on their surface (all nucleated cells and RBCs)
cell
Transplantation antigens: MHC Class II
Class II MHC self-marker protein: present only in ____ cells
Class II is only on APCs. Antigen presenting cells process anything ____. They digest and put them in the lysosome and put them on the surface so they become antigenic so antibodies can be produced against them. APCs are also nucleated so they will express class I as well as class II.
antigen presenting cells
foreign
Transplantation antigens: ABO system
ABO Compatibility
• Less important than ____ compatibility in graft survival.
- ABO incompatibility: rejection of primarily vascularized grafts (____)
- ABO blood group antigens are highly expressed on kidney and cardiac grafts (especially patients with blood group ____ antigen)
- Preformed naturally occurring antibodies to blood group substances are present in ____ recipients
- Can be tempered with ____ therapies
Also considered is the ABO (but less important) especially when it comes to ____ transplants. This is easily tempered by immunosuppressive medication. No match, transplant will still go on because this can always be suppressed but still something to look at.
Two tests are done to test matches. ____ is the DNA typing to see what antigens are expressed by the donor. All the calculations are done especially of class I and II to see if the match would work. If a perfect match, the match would go on.
HLA kidney and heart substances mismatched immunosuppressive vascularized HLA
Donor-Recipient Matching
Pairing of donors to recipients: Two laboratory tests
- ____: determination of HLA antigens on donor and recipient leukocytes
- ____: measures response of immunocompetent cells from the recipient to donor cell antigens (or donor immune response to recipient cell antigen for HCT)
Functional test is when they take the cells of the donor and recipient to see if there is a reaction. Especially important with hematopoietic stem cell transplantation.
serologic or DNA typing
functional test
Graft rejection
What if there’s not a good graft. ____ will be 100%, will not be rejected.
But taking from B to A and don’t match the HLA, the graft will be ____ by host immunity.
Someone from B to donate to someone with complex A and B will still be ____ because only B genes are going in.
If we take someone with complex A and B and put in someone with B it will ____ because of the A.
Highly complex… Match and keep a record. Better with ____ but still need to match HLA. Can match with non family with same HLA and perhaps trade with another persons relative.
autograph
destroyed
accepted
reject
relatives
Graft Rejection
- Donor antigen reacts with recipient ____ cell receptors: T cell response
- Recipient APC: activates ____ cell response
- Production of ____, lymphokines: activation of cytotoxic T cells, B cells and NK cells, macrophage activation
- Direct ____ damage
- Damage to ____ endothelium of graft
- Graft ____
- In HCT: mature lymphocytes in graft can react with recipient antigen = ____
Graft rejection will activate a cells response. APC will realize it is foreign and activate the T cell to release cytokines. Activation of B cells and NK cells that will target the tissues and destroy the endothelium of the graft to destroy the grafts access to blood flow leading to rejection.
GVHD- lymphocytes in the graft can react with the host cells. We will talk more about this soon.
T T cytokine tissue vascular rejection GVHD
Graft Rejection
1. End-organ damage: re-manifestation of the various ____ of the specific nonfunctioning organ.
2. Clinical presentation (organ specific):
• Increased ____ (rejection of liver),
• Decreased metabolism of medications (rejection of liver/kidney)
• Complete ____ and death (rejection of lung/heart).
3. Need for re-____ to prevent death (except for kidney failure)
HLA matching is VERY important. Graft rejection will happen when this goes wrong. Kidney is put in and if rejected will go back to the disease state that initially became the indications for the graft. Clinical presentation will vary.
If kidney, inability to metabolize medication. Lung and heart, this is life threatening leading to organ failure and death. Take out the organ and retransplant immediately to avoid death.
complications
bleeding tendency
organ failure
transplantation
Graft rejection
Hyperactive
• Common in ____ organ rejection
• Occurs within ____ hours of surgical anastomosis
• Mediated by ____ antibodies and complements
• Requires ____ graft removal
Acute rejection
• Mediated by ____ cells and antibodies
• Occurs within first ____ days after transplantation
• Responds to high-dose ____ and antilymphocyte therapies
Chronic rejection
• ____ and insidious
• Primarily ____ mediated
• ____ but ____ cell-mediated toxicity resulting in vascular
endothelial damage of transplanted organ
• Generally ____ even with immunosuppressive medications
solid
48
preformed
immediate
T
90
steroids
slow antibody continuous muted irreversible
Immunosuppressive medications
- ____ are used a lot because they can temper the action of the antigen presenting cells and T cells.
- Calcineurin inhibitors like ____ are used to block the activation of T cells
- ____ are mTOR inhibitors that block the proliferation of T cells.
- This cartoon is showing that these medications are actually tempering the activation or activity of T cells
steroids
cyclosporine and tacrolimus
sirolimus and everolimus
“I’m not going to go over this long list. This is for you to study.”
Lists all the medications that are used. Shows the classification and indications for each
____ is highly used as a broad acting immunosuppressant. Also used after organ transplantation for ____ action to prevent rejection.
All drugs have their ____ and nephrotoxic side effects. Also shows dental implications for each
____ is involved in gingival hyperplasia.
____ medications are antagonized.
____ is known to called pyogenic granuloma-like lesions ____ inhibitors are associated with aphthous lesions or ulceration
cyclosporine
prophylactic
hepatoxic
cyclosporine
P450
tacrolimus
MTOR
• Steroids have a lot of ____. When patients are on steroids, need to know all the different side effects of corticosteroids.
side effects
Corticosteroids Corticosteroid Side-Effect Profile • Induces \_\_\_\_ • Induces muscle weakness • Induces osteoporosis • Alters fat metabolism and distribution • Induces \_\_\_\_ • Induces electrolyte imbalances • Induces central nervous system effects, including psychological changes • Induces \_\_\_\_ changes—cataracts, glaucoma • Aggravates high blood pressure • Aggravates congestive heart failure • Aggravates \_\_\_\_ disease • Aggravates underlying infectious processes (e.g. tuberculosis) • Suppresses the pituitary-adrenal axis, resulting in adrenal atrophy • Suppresses the stress response
• This is a list of the side effects of corticosteroids
• Patients on long-term corticosteroids are susceptible to developing ____, myopathies, muscle weakness
• Patients might be taking additional medications like parathyroid hormone or bisphosphonates which will
also affect how you treat your patients dentally.
• Patients might have ____ deposition, puffiness, hyperlipidemia, electrolyte imbalance, psychotic effect,
cataracts, high blood pressure, peptic ulcer
- All these are things you have to be concerned about with patients on immunosuppressants, especially ones taking corticosteroids.
- ____ infections (like tuberculosis) can be re-activated by these meds.
- ____ is important. These drugs suppress the stress response
diabetes
hyperlipidemia
ocular
peptic ulcer
DM
fat
chornic
stress
Hematopoietic Cell Transplantation
• Autologous HCT: no ____ required
• Allogeneic HCT:
– Requires “conditioning” with cytotoxic ____ or radiation
– To eradicate residual ____ prior to infusion of the hematopoietic stem cells
– Donor T cells react against and kill residual tumor cells to induce a ’____’ effect (GVT)
- Most of the things we talked about apply more to organ transplantation. How let’s look at hematopoietic cell transplantation.
- Autologous HCT: from self to self, does to need immunosuppression. Blood is taken out and re-____ back into the same person.
- Allogeneic HCT: requires a conditioning regimen. The patient is given some form of chemo or radiation (especially patients with leukemia) to kill the tumor cells before they transplant the stem cells.
- The goal is to eradicate the tumor so when the stem cells are transplanted, they have the ability to kill any residual tumor cells (Graft vs Tumor effect)
immunosuppression
chemotherapy
tumor
graft-v-tumor
infused
