Immunology of transplantation and malignancy.ppt

Edu

1. Click to add text
Immunology of Transplantation
and Malignancy

2. Transplant
Transplant/ Graft: Tissue or organ transplanted
Donor: Individual from whom the transplant is obtained
Recipient: Individual to whom it is applied

3. Classification of transplants
Based on organ or tissue transplant
Based on anatomical site of origin of the transplant and its
site of placement:
Orthotopic : anatomical normal sites eg: skin grafts
Heterotopic: placed in anatomically abnormal sites

4. Living or dead materials:
Vital grafts eg: kidney or heart
Structural grafts eg: bone or artery
Based on genetic relationship between the donor and the
recipient

5. Types of graft
Autograft
(on him/herself)
Isograft
Same genetic
constitution
Allograft
Genetically non-identical
members of same species
Xenograft
Members of different
species

7. Allograft reaction
First set of response :
T lymphocytes
Humoral antibodies also produced
Detection by hemagglutination, lymphocytotoxicity,
complement fixation test and immunofluorescence
Second set response:
Antibodies formed more rapidly
CMI also involved

8. Hyperacute rejection:
Specific antibodies in high titres
Graft remains plae
Rejected within hours without attempt at vascularisation
Eg: kidney transplants

9. Histocompatibility antigens
Presence of antigens in grafted tissue that are absent in the
recipient –recognised foreign
Parent
AA
Parent
BB
F1 Hybrid
AB

10. Eichwald –Silmser effect:
Unilateral sex –linked histoincompatibility
Male to female –rejection (Y chromosome)
Female to male –no rejection
Antigens that participate in graft rejection –histocompatibility
antigens

11. Histocompatibility testing
Blood grouping –ABO blood group typing
HLA compatibility –HLA typing

12. HLA typing
Microcytotoxicity test
Molecular methods
Tissue matching

13. Microcyto-toxicity test
Lymphocyte suspensions are added to microwells
Microwells containing HLA typing sera
Incubated with complement
Cells containing corresponding antigen –killed by
complement mediated membrane damage

14. Detected by addition of eosin or trypan blue
Staines only dead cells
Antisera obtained from multigravidae, placental fluid and
from multiple blood transfusion recipients.

16. Molecular methods
RFLP with Southern blotting
PCR

17. Tissue matching
Mixed lymphocyte reaction
T lymphocytes
Exposed to HLA incompatible
antigens
Blast transformation

19. Priviledged sites
Sites where allografts are permitted to survive
Placenta –immunological barrier
MHC antigens –low density on trophoblastic cells
Incomplete mucopolysaccharide barrier around the
trophoblastic cells
Alpha fetaprotein in fetal blood –immunosuppressive
Other sites are : brain, hamster cheek pouch, testes

20. Graft versus host reaction
Graft mounts an immune response to antigens of the host
Occurs when
Graft contains immunocompetent T cells
Recipient possess antigens that are absent in graft
Recipient must not reject the graft

21. Immunology of Malignancy
Cell undergoes malignant transformation –acquires new
surface antigens
Tumour makes cell antigenically different from the normal
tissues of the host
Considered as allograft
Expected to induce immune response

22. Clinical evidence
Spontaneous regression
Chemotherapy cures
Overcome defense mechanisms
Cellular response
Immunodeficiency states

23. Tumor antigens
Tumor specific antigens:
Present in malignant cells
Induce an immune response
Tumor associated antigens:
Antigen found in some tumours and in few normal cells
Oncofetal antigens and fetalantigens
CEA
Differentiation antigen

24. Immunological Surveillance
Primary function of CMI –seek and destroy malignant cells
Inefficiency of surveillance mechanisms –increased
incidence of cancer

25. Immunotherapy of cancer
Passive immunotherapy -antisera
Specific active
Unprofitable
Tumour cell vaccines
Nonspecific active:
BCG
Non-living Corynebacterium parvum
Specific adoptive chemotherapy
Lymphocytes
Transfer factor
Immune RNA

26. Thank you