Immunosuppressants (All slides)

Question 1

What role do immunosuppressants play?

Answer 1

Organ transplants (acute and chronic rejection)
Bone marrow transplants
Autoimmune diseases

Question 2

What are the major cells involved in innate/natural immunity?

Answer 2

Complement, granulocytes, macrophages, natural killer cells, mast cells, and basophiles

Question 3

What are the characteristics of innate/natural immunity?

Answer 3

Primitive
Does not require priming
Low affinity
Broadly reactive

Question 4

What are the major cells involved in adaptive/learned immunity?

Answer 4

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

Question 5

What are the charactertistics of adaptive/learned immunity?

Answer 5

Antigen specific
Antigen exposure and priming occurs
Very high affinity

Question 6

Immune cels are derived from ________ in _______ that produce __________

Answer 6

Pluripotent stem cells; bone marrow; lymphoid stem cells

Question 7

What is responsible for autoimmune diseases?

Answer 7

Humoral immunity

Question 8

How do B lymphocytes work?

Answer 8

They mature in the lymphoid tissue, encounter antigens (specific structural confirmations) and mature into plasma cells that produce specific antibodies.

This is humoral immunity

Question 9

Describe humoral immunity

Answer 9

Slow developing to first exposure
Second exposure much more dramatic
Responsible for autoimmune diseases
To decrease action, must suppress bone marrow

Question 10

How do T lymphocytes work?

Answer 10

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

Question 11

Describe cellular immunity

Answer 11

Initial response very quick

Main target in transplantation

Question 12

What do we target in transplantation?

Answer 12

Cellular immunity

Question 13

Describe T cells

Answer 13

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

Question 14

Describe the dif kinds of t helper cells

Answer 14

Th1 - IL2, IL12, IFNY, TNF-alpha

Th2 - IL4, IL5, IL6, IL10, IL13

Question 15

What are the antigen presenting cells? What role do they play?

Answer 15

Dendritic cells, Macrophages, B cells

All pick up antigens and present to t-cells, stimulating immune response

Question 16

What information is gathered in a patient workup for transplants?

Answer 16

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

Question 17

What things play a role in Histocompatibility?

Answer 17

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

Question 18

What are MHC Class 1? Where are they found?

Answer 18

HLA A, B, and C; found on all nucleated cells, inherit 2 class 1 antigens from each parent

(CD8 cytotoxic T cells!)

Question 19

What are MHC Class 2? Where are they found?

Answer 19

HLA DP, DQ, DR - found on B cells, APC, macrophages, monocytes.
Inherit 1 class 2 antigen from each parent

CD4 cells helper T cells

Question 20

What are PRA’s?

Answer 20

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

Question 21

What things can increase PRA count?

Answer 21

Pregnancy
Blood transfusions
Prior transplant

Question 22

How does cross-matching occur?

Answer 22

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!

Question 23

What are post surgical complications of transplants?

Answer 23

Rejection - greatest risk within first 3 months
Infection (Pneumocystis jerovicii (carnii) is common; virus)
Acute tubular necrosis (Delayed graft function)
Hypertension
Cancer

Question 24

What types of rejection are there?

Answer 24

Hyperacute
Accelerated acute rejection
Acute rejection
Chronic rejection

Question 25

Describe hyperacute rejection

Answer 25

Occurs within minutes; irreversible
Results of preformed circulating antibodies

Activation of complement –> thrombosis –> vascular injury —> ischemia —> graft loss

Rare if cross match is negative!

Question 26

Describe accelerated acute rejection

Answer 26

Occurs within 1-4 days
Prior sensitization to donor antigens (transfusions, prior transplant)
Mediated by both cellular and humoral immunity

Difficult to treat

Question 27

Describe acute rejection

Answer 27

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)

Question 28

Which type of rejection can occur throughout life? When?

Answer 28

Bouts of acute rejection can occur throughout life, ie when you get sick

Question 29

Describe chronic rejection

Answer 29

Occurs gradually over months to years
Etiology is unknown -
Immune and non-immune mechanisms, drug toxicity, chronic ischemia, repeated bouts of acute rejection