Test 4: DTH and Transplant

Question 1

What is contact dermatitis caused by?

Answer 1

CD4+ TH1 cell-mediated hypersensitivity

Question 2

When is contact dermatitis elicited?

Answer 2

Second skin exposure to allergen (first sensitized–>TH1 differentiation)

Question 3

What are some common dental allergens?

Answer 3

• liquid monomer acrylic
• proteins in latex
• accelerators in rubber latex

Question 4

Are all contact allergens natural proteins?

Answer 4

No, some are artificial chemicals and not all proteins

Question 5

How to contact allergens become immunogenic?

Answer 5

-act as haptens attaching to carrier self-protein which is then taken up by Langerhans cells on skin and recognized as foreign particle

Question 6

What are some characteristics of the inflammatory response from DTH?

Answer 6

• post capillary venules surrounded by lymphocytes
• blistering and necrosis of epidermal cells
• pruritic
• edema
• infiltrated by basophils and eosinophils

Question 7

How is the immunological diagnosis determined?

Answer 7

Patch Test

Question 8

How is contact dermatitis treated?

Answer 8

Systemic Corticosteroids

Question 9

What is the major stimulus to transplant rejection?

Answer 9

Incompatability of MHC molecules (proteins from MHCs)

Question 10

What is the difference between Autografts, syngenic grafts, allografts, and xenogenic grafts?

Answer 10

• Auto: from the same person
• syngenic: from identical twin
• Allograft: From different person
• Xenograft: from different species

Question 11

How many T cells can directly recognize and foreign MHC molecule?

Answer 11

2%

Question 12

When the allogenic MHC molecules are DIRECTLY presented by graft APCs, what cells are stimulated?

Answer 12

CD4 and CD8 (nucleated allogenic graft cells have MHC I)

Question 13

How are allogenic MHC molecules INDIRECTLY presented?

Answer 13

Recipient APCs phagocytose remnants of allogenic MHC molecules and present them to CD4 cells

Question 14

What type of graft rejection is characterized by hemorrhage and thrombotic occlusion, mediated by pre-exisiting Abs in host, and begins within minutes/hours?

Answer 14

Hyperacute rejection

Question 15

What is the major obstacle of xenografts?

Answer 15

Natural antibodies to other species’ cells

Question 16

What two things are tested before transplants?

Answer 16

ABO incompatability and Abs against allogenic MHCs

Question 17

Which T cell is more important in Acute rejection and why?

Answer 17

CD8+, epithelial cells from vascularized grafts present MHC I molecules–>vascular and parenchymal injury and necrosis

Question 18

What is the major cause of graft rejection?

Answer 18

Chronic rejection , months to years later (used to be acute, but immunosuppressant drugs helped)

Question 19

In chronic rejection, what causes the arteriosclerosis in graft tissue?

Answer 19

Proliferation of intimal smooth muscle cells

Question 20

What causes the Smooth muscle cell growth?

Answer 20

lymphocytes activate macrophages (IFN-gamma) which secrete smooth muscle cell growth factor

Question 21

What causes fibrosis of the graft in chronic rejection?

Answer 21

Macrophages secrete mesenchymal cell growth factors–>fibroblasts and collagen

Question 22

Which MHC loci are important for transplant matching?

Answer 22

HLA-A and HLA-B, HLA-DR most important

Question 23

What is the highest number of molecule matches that still predict poor survival?

Answer 23

4

Question 24

In two-way mixed lymphocyte reaction (MLR), what is the indicator that the lymphocytes are incompatible?

Answer 24

radio-labeled DNA used for clonal expansion–>DNA synthesis by both

Question 25

How is One-way MLR different from Two-way?

Answer 25

One set of leukocytes is blocked from synthesizing DNA

Question 26

What is used for the low resolution Lymphocytotoxicity test?

Answer 26

Anti-sera from a woman that has many pregnancies (expresses many different Abs) that will kill cells if they have the same HLA specificity

Question 27

What does Molecular HLA typing detect?

Answer 27

polymorphic nucleotide sequences

Question 28

What is the most important immunosuppressive drug and what is its major action?

Answer 28

Cyclosporin: inhibits transcription of genes for cytokines (IL-2 which causes proliferation of T cells)

Question 29

What does TGF-beta do?

Answer 29

-generalized immunosuppressive cytokine

Question 30

What is the major drawback of cyclosporin?

Answer 30

Renal toxicity (also gingival hyperplasia)

Question 31

What can be used as a substitute for Cyclosporin?

Answer 31

FK506=Tacrolimus; less renal toxicity

Question 32

What drug has a synergistic effect with cyclosporin?

Answer 32

Rapamycin/Sirolimus (inhibits a kinase involved in IL-2 signalling)

Question 33

What makes Mycophenolate Mofetil lymphocyte specific?

Answer 33

It blocks de novo synthesis of purines: lymphocytes rely on this more than other cells

Question 34

Immunological effects of corticosteroids

Answer 34

- reduced number of MHC II molecules - inhibit T cell activation - inhibit T cell migration and release of IFN-gamma (macrophage activation)

Question 35

How do corticosteroids affect inflammation?

Answer 35

- stops cytokine and NO - reduces emigration of lymphocytes - induces apoptosis of lymphocytes and eosinophils

Question 36

What are two commonlyused corticosteroids?

Answer 36

Prednisone and methyl-prednisone

Question 37

What is the most commonly transplanted tissue? Organ?

Answer 37

Tissue=cornea | Organ=kidney

Question 38

How long do recipients of kidney transplants have to be on immunosupressive therapy?

Answer 38

Their whole lives

Question 39

Why is immunosuppressive therapy needed even with an identical twin donor?

Answer 39

subtle differences in minor histocompatability immunogens

Question 40

When would you need a bone marrow transplant?

Answer 40

SCID, Aplastic anemia, Leukemia and anemia

Question 41

Where do the donor stem cells come from?

Answer 41

- iliac crest | - peripheral stem cells

Question 42

What does the recipient need to have done before receiving a bone marrow transplant?

Answer 42

ablation of all lymphocytes

Question 43

How can you tell that a bone marrow transplant was successful?

Answer 43

peripheral leukocytes and mature PMNs in a few weeks

Question 44

What happens in Graft Vs Host Disease (GVHD)?

Answer 44

Graft cells recognize the recipient cells as foreign (can be good with leukemia--will attack those cells)

Question 45

Where can GVHD be manifested?

Answer 45

Skin and mucous membranes Liver Small intestinal epithelia