Organ transplants/MS Flashcards
6 laws of tissue transplantation
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
Syngeneic donors
Between genetically identical individuals
Usually the same individual, identical twins, or isogenic strains
Allogeneic donors
From one individual to another of the same species
Xenogeneic
Between individuals of different species
4 types of organ rejection
Hyperacute
Accelerated
Acute
Chronic
Hyperacute organ rejection
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
Accelerated organ rejection
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
Acute organ rejection
Occurs within days/ months
Mainly involves cellular immunity
Can be reversed by immunosuppressive drugs
T cell mediated response against foreign MHC
Chronic organ rejection
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
Muromonab-CD3 (OKT3)
Blocks killing by cytotoxic human T cells
Along with steroids, proved to be more effective at reversing acute rejection than did conventional steroid treatment
Antithymocyte globulin
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
Basiliximab
Binds to the IL2 receptor on activated lymphocytes
Acts as an IL2 antagonist
Blocks IL2 from binding to activated lymphocytes
Same as Daclizumab
Environmental factors causing MS
More common in people who live farther from the equator
From decreased vitamin D production and intake
What is MS?
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
Pathological hallmarks of MS
White matter lesions (usually optic nerves, brainstem, cerebellum, and spinal cord)
They contain perivascular inflammation and demyelination
How does the autoimmune-mediated demyelination work?
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
4 subtypes of MS
Benign
Relapsing-remitting
Primary progressive
Secondary chronic progressive (usually after EE type)
Signs and symptoms of MS
Vision impairment Tingling and numbness of the skin and limbs Difficulty walking Weakness and exhaustion Memory loss Depression Urinary and bowel problems
What would you use to treat MS exacerbations?
Synthetic adrenal glucocorticoids like prednisone
Want to dampen down the immune system and reduce IL 2
Inhibit the expression of pro-inflammatory genes
Interferon-Beta
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
Glatiramer acetate
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
Mitoxantrone
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
Tysabryi (Natalizumab)
Monoclonal antibody against alpha4 integrin
Interferes with the ability of immune cells to attach to endothelial cells and cross the BBB
Fampridine-SP
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
Fingolimod
Sphingosine 1-phosphate receptor modulator
Sequesters lymphocytes in lymph nodes, preventing them from contributing to an autoimmune reaction
Dimethyl Fumarate
Activates Nrf-2 increasing the expression of mitochondrial and anti-oxidant genes that reduce inflammation and protect oligodendrocytes and neurons
3 contributers to why organ transplants fail
CD8+ cells
Antibodies
Cytokines
