PAPER 4 : APPLIED PHYSIOLOGY
Transplantation Immunology &
Autoimmune Diseases
Transplantation Immunology
● Transplantation - Process of moving cells, tissues, or organs, from one site to
another, either within the same person or between a donor and a recipient.
● Graft - A portion of body tissue that is surgically removed from the donor, and
then implanted or transplanted, usually to replace damaged tissue in the
recipient’s body.
Types of
transplantation
1. Autograft
2. Allograft
3. Isograft
4. Xenograft
Basis of graft rejection
Human Leukocyte Antigen (HLA) complex - Group of genes
that encode the proteins responsible for identifying foreign
agents to the immune system.
Distinguishing between self and non-self:
● The major histocompatibility complex
markers - MHC I and MHC II ➡ play role
in rejection
Histocompatibility : The degree of similarity
between the HLA genes of the donor and
recipient
1. Dendritic cells - Recognize HLAs (non-self molecules) of transplanted tissue ➡
Process and present the foreign HLAs to the helper T cells and cytotoxic T cells
2. Cytotoxic T cells - Target and kill the grafted cells
3. Helper T cells - Release cytokines that activate macrophages to kill graft cells
Clinical manifestation of graft rejection
1. Hyperacute : Immediate (minutes to hours)
2. Acute : Weeks to months
3. Chronic : Months to years
Immunosuppressive
therapy
● Immunosuppressive drug therapy
can help train your body to accept
new organs and tissues from
transplants.
● Immunosuppressant drugs also are
known as anti-rejection
medications.
Immunosuppressive drugs
● Biologics such as adalimumab (Humira®) and infliximab (Remicade®).
● Calcineurin inhibitors such as tacrolimus (Envarsus XR® or Protopic) and cyclosporine (Gengraf®, Neoral® or
Sandimmune®).
● Corticosteroids (prednisone).
● Inosine monophosphate dehydrogenase (IMDH) inhibitors such as mycophenolate mofetil (CellCept®).
● Janus kinase inhibitors such as tofacitinib (Xeljanz®).
● Mechanistic target of rapamycin (mTOR) inhibitors such as sirolimus (Rapamune®).
● Monoclonal antibodies such as basiliximab (Simulect®).
Clinical transplantation
Corneal graft
Donor - dead
Skin graft
Donor - living/ dead
● Orthotopic : Tissue or organ
grafts transplanted to their
normal situation in the recipient
Kidney transplant
Donor - living/ dead
● Heterotopic : Tissue or organ
grafts transplanted to an
abnormal situation in the
recipient
Liver transplant
Donor - living/ dead
● Auxiliary/ accessory : Extra
organ graft
Heart transplant
Donor - dead
The heart must be donated by
someone who is brain-dead but is still
on life support.
Mechanical ventilation and
medications keeps their heart beating
and blood flowing to their organs.
Uterus transplant
Donor - living/ dead
● Means of enabling pregnancy in
MRKH (Mayer- Rokitansky-
Küster- Hauser syndrome)
Autoimmune disease
Autoimmune disease
1. Systemic autoimmune diseases
● Rheumatoid arthritis
● Systemic lupus erythematosus
● Scleroderma
● Dermatomyositis
2. Organ-specific autoimmune diseases
● Graves disease ➡ Thyroid gland
● Type 1 diabetes ➡ Beta cells of endocrine pancreas
● Vitiligo ➡ Skin
Systemic Lupus
Erythematosus (SLE)
● SLE patients produce autoantibodies to a
number of self-antigens, such as DNA, histones,
RBCs, platelets, leucocytes, and clotting factors.
Symptoms
● fatigue
● fever
● hair loss
● sunlight-sensitive “butterfly” rash
● skin lesion
● joint pain
● decreased kidney function
Rheumatoid Arthritis
(RA)
Symptoms:
● Joint inflammation
● Pain in joints
● Permanent joint deformities ➡ crippling
Immunodeficiency diseases
Immunodeficiency disorders prevent your body from fighting infections and
diseases.
1. A congenital, or primary, disorder is one you were born with.
2. Acquired, or secondary, disorders you get later in life.
Immunodeficiency diseases
1. Primary immunodeficiency
Caused by mutations
● X-linked agammaglobulinemia (XLA)
● Common variable immunodeficiency (CVID)
● Severe combined immunodeficiency (SCID), which is known as alymphocytosis
Immunodeficiency diseases
2. Secondary immunodeficiency
Caused by Prolonged (chronic) and/or serious disorders such as diabetes or cancer,
drugs and rarely, radiation therapy
● AIDS
● cancers of the immune system, like leukemia
● immune-complex diseases, like viral hepatitis
● multiple myeloma (cancer of the plasma cells, which produce antibodies)
References
● https://www.immunology.org/
● https://www.mainehealth.org/
● https://my.clevelandclinic.org/
● https://courses.lumenlearning.com/
● https://www.researchgate.net/
● https://www.britannica.com/
● https://www.healthxchange.sg/
● https://pathology.jhu.edu/
● https://www.healthline.com/
● Choli Hartono, Thangamani Muthukumar, and Manikkam Suthanthiran.
Immunosuppressive Drug Therapy.
Thank you
