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Immunology > transplantation and tumors > Flashcards

transplantation and tumors Flashcards

1
Q

autograft

A

one person to the same person

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2
Q

allograft

A

one person to a genetically different person

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3
Q

syngraft

A

-one person to a genetically identical person

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4
Q

xenograft

A

-graft to a different species

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5
Q

two mechs by which grafts are recognized by host t cells

A
  • recipeient t cells recognize the peptides from donor MHC molecules which have been processed in host APC’s
  • recipient t cells recognize unprocessed donor MHC molecules directly on the graft presenting cell (unprocessed)
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6
Q

hyperacute graft rejection

A
  • minutes or hours
  • due to preformed antibodies in the recipient
  • compliment also binds to antibody
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7
Q

acute graft rejection

-mechanisms

A
  • 10 to 14 days
  • due mainly to cell mediated immunity but some injury is also antibody mediated
  • diret contact with CD8 (perforin/granzyme and FAS L)
  • locally released cytokines and chemokines (inflammation, macrophage activation, infiltration of phagocytic cells)
  • antibody against donor HLA (complement binding and ADCC by NK cells)
  • direct NK cell attack
  • direct NK cell attack
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8
Q

stem cell transplantation

  • how are they obtained
  • what problem can occur
A
  • can be obtained from peripheral blood if colony stimulation factor is given or from umbilical cord blood and bone marrow
  • the major problem with bone marrow transplant is that competent T cells from the donor may be transplanted giving rise to graft versus host disease
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9
Q

graft versus host disease

  • what is it
  • what must occur to get this disease
  • mechanism of cytokine storm
A
  • a reaction of donor t cells against recipient MHC
  • the graft must be contain live t cells (bone marrow/thymus)
  • the recipient must be immunosuppressed
  • the donor and recipeint must have different HLA types
  • CD4 T cells in the graft are activated by allogenic molecules and produce a cytokine storm that recruits other T cells, macrophages, and NK cells to create the severe inflammation associated with this disease
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10
Q

cyclosporin and FK506

A

block a T cell phosphatase called calcineurin and inhibit cytokine production

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11
Q

corticosteroid

A

-also inhibit cytokine production

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12
Q

anti-CD3

A

monoclonal antibody that inhibits the binding of the coreceptor CD3

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13
Q

anti-IL-2 receptor

A

antibody that blocks the function of IL2

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14
Q

what is the problem with all forms of immunosuppressive therapy

A

-increases the risk of infection bu suppressing the bodies response to pathogens

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15
Q

types of antigens on the surface of tumor cells

A
  • virally controlled antigens
  • oncofetal antigens: alpha-fetoprotein (primary hepatocellular carcinoma) and carcino-embryonic antigen (CEA) (colon carcinoma)
  • abnormal peptides made by tumor cells
  • mutant antigens (Her2/neu - if positive can give herceptin)
  • tissue specific differentiation antigens (PSA, B Cell and T Cell spec antigens)
  • may lose HLA
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16
Q

flow cytommetry findings of b cell lymphoma

A
  • normally a population of b lymphocytes will have some lambda and some kappa cells
  • in b cell lymphoma, the cells are either all one or the other (monoclonal)
17
Q

what happens if a tumor cell loses its HLA 1

A
  • it will no longer be recognized by CD8 cells

- however, they will be killed by NK cells that recognize that they are HLA 1 negative

18
Q

natural killer cells

  • appearance
  • function
  • receptors
  • how are they activated
  • what do they produce
A
  • large granular lymphocytes
  • destroy infected malignant cells with absent or defective MHC 1 (this may occur after viral infection or malignant transformation)
  • have Fc receptors that can bind IgG and give rise to ADCC
  • can be activated by cytokines such as IL2, 12, and IFN gamma
  • they produce a variety of cytokines
19
Q

immune mechanisms of tumor rejection

A
  • principal mechanism is by cytotoxic CD8 cells using granzyme and perforin, production of TNF, and expression of FasL on the CD cell
  • killing of the tumor cells also takes place by activated macrophages and NK cells
20
Q

how do tumors escape the immune system

A
  • they release immunosuppressive factors like IL-10 and TGF-beta
  • they release factors that activate TREG cells
  • they select antigen-negative variants
21
Q

cancer immunotherapy

A
  • stimulation of the innate immuno mechanism
  • checkpoint inhibitors: clock CTLA4 and PD-1/PDL-1 to remove the brakes from cytotoxic t cells
  • immunization against oncogenic viruses such as hepB and HPV
  • increase immunogenicity of tumors (B7, MHC2, cytokine genes)
  • monoclonal antibodies: magic bullets with immunotoxins (ricin or radioactive isotopes)
22
Q

ipilimumab

A
  • anti CTLA4 monoclonal antibodies for the treatment of malignant melanoma
  • AI disease and inflammation seen in 40% of patients treated with this

Immunology (15 decks)

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