Organ transplants/MS

Question 1

6 laws of tissue transplantation

Answer 1

Transplanting to a different species fails
Transplants in unrelated species members fail
Autografts succeed
First allograft is initially accepted, but is rejected later
Second allograft is rejected rapidly
Close relationships between the donor and the recipient aids the acceptance of the graft

Question 2

Syngeneic donors

Answer 2

Between genetically identical individuals

Usually the same individual, identical twins, or isogenic strains

Question 3

Allogeneic donors

Answer 3

From one individual to another of the same species

Question 4

Xenogeneic

Answer 4

Between individuals of different species

Question 5

4 types of organ rejection

Answer 5

Hyperacute
Accelerated
Acute
Chronic

Question 6

Hyperacute organ rejection

Answer 6

Due to preformed antibodies against the donor organ
Occurs within hours
Cannot be stopped by immunosuppressive drugs
Preformed antibodies directed against foreign tissue
Ex: anti-blood group antibodies

Question 7

Accelerated organ rejection

Answer 7

Mediated by antibodies and T cells
Variation of hyperacute
Occurs when the recipient has been exposed previously to low levels of donor tissue antigens and makes a rapid memory response when the donor organ is transplanted
Cannot be stopped by immunosuppressive drugs

Question 8

Acute organ rejection

Answer 8

Occurs within days/ months
Mainly involves cellular immunity
Can be reversed by immunosuppressive drugs
T cell mediated response against foreign MHC

Question 9

Chronic organ rejection

Answer 9

Occurs within months/years after transplant
Characterized by thickening and fibrosis of the vasculature of transplanted organ, involving both cellular and humoral immunity
Treated with immunosuppressive drugs
T cell mediated where the foreign MHC looks like a self MHC loaded with an antigen

Question 10

Muromonab-CD3 (OKT3)

Answer 10

Blocks killing by cytotoxic human T cells

Along with steroids, proved to be more effective at reversing acute rejection than did conventional steroid treatment

Question 11

Antithymocyte globulin

Answer 11

Antiserum from immunization of sheep/horses with human lymphoid cells
Antilymphocytes act on the small peripheral lymphocytes
With continued administration, thymus dependent lymphocytes are also depleted

Question 12

Basiliximab

Answer 12

Binds to the IL2 receptor on activated lymphocytes
Acts as an IL2 antagonist
Blocks IL2 from binding to activated lymphocytes
Same as Daclizumab

Question 13

Environmental factors causing MS

Answer 13

More common in people who live farther from the equator

From decreased vitamin D production and intake

Question 14

What is MS?

Answer 14

An autoimmune disease
Immune system attacks and destroys the myelin basic protein
Causes degeneration of the CNS resulting in a progressive decline or motor and cognitive functions

Question 15

Pathological hallmarks of MS

Answer 15

White matter lesions (usually optic nerves, brainstem, cerebellum, and spinal cord)
They contain perivascular inflammation and demyelination

Question 16

How does the autoimmune-mediated demyelination work?

Answer 16

Acute inflammatory response of auto-reactive T cells and macrophages produce demyelination
By releasing pro-inflammatory factors that damage oligodendrocytes and axons
Antibodies can also bind and signal for destruction
In short: T cells and macrophages release pro-inflammatory factors that damage oligodentrocytes and axons

Question 17

4 subtypes of MS

Answer 17

Benign
Relapsing-remitting
Primary progressive
Secondary chronic progressive (usually after EE type)

Question 18

Signs and symptoms of MS

Answer 18

Vision impairment
Tingling and numbness of the skin and limbs
Difficulty walking
Weakness and exhaustion
Memory loss
Depression
Urinary and bowel problems

Question 19

What would you use to treat MS exacerbations?

Answer 19

Synthetic adrenal glucocorticoids like prednisone
Want to dampen down the immune system and reduce IL 2
Inhibit the expression of pro-inflammatory genes

Question 20

Interferon-Beta

Answer 20

Slows the advance of the affliction and reduces the frequency of attacks
Subcutaneous injection
Reduces inflammation, maybe by promoting apoptosis of autoreactive immune cells
Side effects: flu like symptoms

Question 21

Glatiramer acetate

Answer 21

Random polymer composed of 4 amino acids that are found in myelin basic protein and may work as a decoy
Shifts the population of T cells from pro-inflammatory TH1 to regulatory TH2
Doesn’t extend the time between relapses

Question 22

Mitoxantrone

Answer 22

Type 2 topoisomerase inhibitor
Disrupts DNA synthesis and DNA repair in healthy and cancer cells
Suppresses the proliferation of T cells, B cells, and macrophages
Impairs antigen presentation and decreases pro inflammatory cytokines

Question 23

Tysabryi (Natalizumab)

Answer 23

Monoclonal antibody against alpha4 integrin

Interferes with the ability of immune cells to attach to endothelial cells and cross the BBB

Question 24

Fampridine-SP

Answer 24

Selective neuronal K+ channel blocker
By closing the exposed K channels in damaged fibers, the axon can transmit nerve impulses again
Improves walking and coordination
Does not alter disease progression

Question 25

Fingolimod

Answer 25

Sphingosine 1-phosphate receptor modulator

Sequesters lymphocytes in lymph nodes, preventing them from contributing to an autoimmune reaction

Question 26

Dimethyl Fumarate

Answer 26

Activates Nrf-2 increasing the expression of mitochondrial and anti-oxidant genes that reduce inflammation and protect oligodendrocytes and neurons

Question 27

3 contributers to why organ transplants fail

Answer 27

CD8+ cells
Antibodies
Cytokines