W05 - IMM.: Transplantation; Immunotherapy

Question 1

Define auto/ iso/ allo and xenografting.

Answer 1

AUTO = tissue returning to same individual after period outside the body

ISO = An isograft is the transplant of tissue from a genetically identical twin donor to the recipient

ALLO = genetically nonidentical members of same species

XENO = between members of different species

Question 2

Describe major antigenic differences between donor and recipient in humans.

Answer 2

• ABO compatibility
• recipient must not have anti-donor HLA antibodies
• donor selected with as close of a possible HLa match to recipient
• organ variation

Question 3

Define the concept of privileged sites.

Answer 3

a

Question 4

Illustrate complications of transplantation.

Answer 4

GRAFT REJECTION
afferent phase: donor mhc recognised by recipient CD4+ T = allorecognition

effector phase: recruitment of macrophages, CD8+ T cells, NK cells, B lymph. = tiss dmg or rejection

Question 5

Describe measures taken to prevent graft rejection.

Answer 5

• pre-testing screening, typing.
• Irradiation of red blood cells and whole blood results in reduced post transfusion red cell recovery and increases the rate of efflux of intracellular potassium.

Question 6

Describe mechanisms of graft rejection involved in hyperacute, acute and chronic
rejection.

Answer 6

HYPERACUTE: within hours, preformed ab to ABO or HLA I ag
* type II reaction = vascular thrombosis = graft destruction
> cross-matching to ensure compatibility

ACUTE = days/weeks of transpl. | HLA incompatibility
* type IV delayed = allogenic reponse in LN and T => graft
* potnetially also ab-mediated rejection

> ensure HLA matching but shortages lead to common mismatch

CHRONIC: mos/years after transplant
* allogenic reaction mediated by T = repeated acute rejection
* pre-existing AuImm disease

Question 7

Define and explain Graft Versus Host Disease.

Answer 7

GVHD: T cells respond to allogeneic recipient ag. dt mismathces

= widespread, 4w post SCT. skin, gut, liver lung involvement, HIGH MORT. RISK

=> chronic GVHD affecting skin and liver

> Imm suppr: CORTICOSTEROIDS

Question 8

Illustrate the current clinical spectrum of transplantation.

Answer 8

SC Transplantation

AUTOLOGOUS: minimal risk

ALLOGENIC: mortality rate 20% even with well-matched
- only in hematologic malign.
- SCID
- Reduced/abn myeloid cell production

Question 9

Define the principles of treatment of hypersensitivity, autoimmune and immune
deficiency disorders.

Answer 9

IMM SUPRR.
> corticosteroids
> T-cell signalling blockade: cyclosporine, tacrolimus
!infective and ca. risk; NEPHROTOXIC

> IL-2 Blockade via MAbs
- Rapamycin
! hypercholesterol., HT, anemia,

> Antiproliferatives via AZATHIOPRINE, mthxr.: prevent lymph. proliferation but not specific and can cause myelotox.

Question 10

Illustrate broadly measures for prevention and treatment of graft rejection.

Answer 10

conditioning prior to transplanting

may include chemotherapy, monoclonal antibody therapy, and radiation to the entire body. It helps make room in the patient’s bone marrow for new blood stem cells to grow, helps prevent the patient’s body from rejecting the transplanted cells, and helps kill any cancer cells that are in the body

Question 11

Criteria for transplantation

Answer 11

good evidence dmg irreversible

alternative tx not applicable

disease must not recur

Question 12

Tissue Typing Techniques

Answer 12

HLa Typing

ABO Typing

Question 13

Describe potential therapeutic uses of monoclonal antibodies and cytokines/ cytokine antagonists.

Answer 13

T CELL INHIBITION via
- anti-IL2£
- anti-TCR

MONOCLONAL Ab via
- RITUXIMAB: 1st line for NH lymphoma = CD20 specific on b cells = facilitates cytotox. and lysis, followed by phagocytosis

• INFLIXIMAB: AuImm disease such as RhArth., anky spondy, CD, UC
• blocks function of TNFa

-HERCEPTIN: HER2 breast ca., binds HER2 protein on cancer cells

Question 14

Explain the clinical uses of immunoglobulin therapy.

Answer 14

HUMAN NORMAL IMMUNOGLOBULIN (HNIG)
hep A
measles
polio
rubella
or specific Ig for: Hep B, rabies, tetanus, varicella-zoster

*use for primary or secondary immune deficiencies
- CVID
- IDIOPATHIC THROMBOCYTOPENIC PURPURA
- Kawasaki
- GBSyndrome
- WAS

> IV Ig = imm. defs. and AuImm disorders
Polyclonal IgG

Question 15

Understand the use of checkpoint inhibitors in cancer therapy

Answer 15

Faciliate adaptive immunity and promote anti-tum responses, high risk for adverse effects though.

• utilises PD-1 signalling to activate T cells via antibody blockade (it is suppressed by tumours)

Question 16

Understand adoptive cell therapy

Answer 16

utilises resected melanoma speciment to acquire fragments grown in IL-2. Lymphocytes develped from this is then infused back into the patients.

• utilises tumour-infiltrating lymphocytes

Question 17

Example of Adaptive Immunity

Answer 17

ACTIVE ADAPTIVE
1) infection or exposure
2) immunisation, vaccines

*memory granted

Question 18

Examples of Innate Immunity

Answer 18

PASSIVE INNATE
1) placental transfer of IgG, colostral IgA
2) Immunoglobulin therapy or immune cells

Question 19

Direct Vs Indirect ImmunoTherapies

Answer 19

DIRECT: targest specific elements
- MAbs
- chimeric antigen receptors (CARs)
- Bi-specific abs

INDIRECT: promotes activity of the whole immune system
- tumour vaccines
- adoptive cell transfers
- cytokine therapies
- CHECKPOINT INHIBITOR THERAPIES
- stimulatory antibodies

Question 20

Polyclonal Vs Monoclonal antibodies

Answer 20

POLYCLONAL = immunisation w/ ag lead to different B cell clones generating abs specific for the ag; multiple epitopes and variable regions

MONOCLONAL made via = immunisation of known ag or mix of ag with myeloma cell line = HYBRIDOMAs.