Immunosuppressants (All slides) Flashcards
What role do immunosuppressants play?
Organ transplants (acute and chronic rejection)
Bone marrow transplants
Autoimmune diseases
What are the major cells involved in innate/natural immunity?
Complement, granulocytes, macrophages, natural killer cells, mast cells, and basophiles
What are the characteristics of innate/natural immunity?
Primitive
Does not require priming
Low affinity
Broadly reactive
What are the major cells involved in adaptive/learned immunity?
B lymphocytes (make antibodies) T lymphocytes (make helper, cytolytic, and regulatory - suppressor - cells)
T cells that are activated differentiate and divide and release cytokines and lymphokines
What are the charactertistics of adaptive/learned immunity?
Antigen specific
Antigen exposure and priming occurs
Very high affinity
Immune cels are derived from ________ in _______ that produce __________
Pluripotent stem cells; bone marrow; lymphoid stem cells
What is responsible for autoimmune diseases?
Humoral immunity
How do B lymphocytes work?
They mature in the lymphoid tissue, encounter antigens (specific structural confirmations) and mature into plasma cells that produce specific antibodies.
This is humoral immunity
Describe humoral immunity
Slow developing to first exposure
Second exposure much more dramatic
Responsible for autoimmune diseases
To decrease action, must suppress bone marrow
How do T lymphocytes work?
T lymphocytes pass through the thymus gland, require antigen presenting cells to recognize specific antigen (antigen presented as peptide fragment); requires cell to cell contact
Describe cellular immunity
Initial response very quick
Main target in transplantation
What do we target in transplantation?
Cellular immunity
Describe T cells
All T cells are CD3+ T cells have 2 types: Helper and cytotoxic Helper T cells are CD3+ and CD4+, have MHC class 2 Cytotoxic T cells are CD3+ and CD8+, have MHC class 1
Describe the dif kinds of t helper cells
Th1 - IL2, IL12, IFNY, TNF-alpha
Th2 - IL4, IL5, IL6, IL10, IL13
What are the antigen presenting cells? What role do they play?
Dendritic cells, Macrophages, B cells
All pick up antigens and present to t-cells, stimulating immune response
What information is gathered in a patient workup for transplants?
History and physical exam Extensive lab work, Chest x-ray, and EEG testing for hepatitis and AIDs Cardiac evaluation if over 45 or diabetic Flex sigmoidoscopy if over 50 Hemoccults to check for blood in stool Mammogram if female over 40 Pap smear and pelvic exam for females Mantoux test for tuberculosis Blood and tissue type testing
What things play a role in Histocompatibility?
ABO blood type (Donor and recipient must be ABO compatible; endothelial cells have A and B antigens) Major histocompatibility complex (MHC) Panel reactive antibodies Cross-matching
What are MHC Class 1? Where are they found?
HLA A, B, and C; found on all nucleated cells, inherit 2 class 1 antigens from each parent
(CD8 cytotoxic T cells!)
What are MHC Class 2? Where are they found?
HLA DP, DQ, DR - found on B cells, APC, macrophages, monocytes. Inherit 1 class 2 antigen from each parent
CD4 cells helper T cells
What are PRA’s?
Panel reactive antibodies
Antibodies (of the recipient) to HLA molecules
The more PRA’s you have, the more sensitized the recipient is
Increased PRA = Increased risk for rejection
What things can increase PRA count?
Pregnancy
Blood transfusions
Prior transplant
How does cross-matching occur?
Look for cross-matching of B and T-cells
Donor lymphocytes are incubated against recipient serum
Determines if recipient has circulating antibodies against the MHC antigens of the donor
Virtually eliminates hyperacute rejections!
What are post surgical complications of transplants?
Rejection - greatest risk within first 3 months
Infection (Pneumocystis jerovicii (carnii) is common; virus)
Acute tubular necrosis (Delayed graft function)
Hypertension
Cancer
What types of rejection are there?
Hyperacute
Accelerated acute rejection
Acute rejection
Chronic rejection
Describe hyperacute rejection
Occurs within minutes; irreversible
Results of preformed circulating antibodies
Activation of complement –> thrombosis –> vascular injury —> ischemia —> graft loss
Rare if cross match is negative!
Describe accelerated acute rejection
Occurs within 1-4 days
Prior sensitization to donor antigens (transfusions, prior transplant)
Mediated by both cellular and humoral immunity
Difficult to treat
Describe acute rejection
90% T cell mediated; 5-10% humoral mediated, which is more difficult to treat
Tubulitits, vasculitis, and perivascular infiltration occurs
Symptoms are due to cytokine release (TNF, IL-1, and IL-2)
Which type of rejection can occur throughout life? When?
Bouts of acute rejection can occur throughout life, ie when you get sick
Describe chronic rejection
Occurs gradually over months to years
Etiology is unknown -
Immune and non-immune mechanisms, drug toxicity, chronic ischemia, repeated bouts of acute rejection
