The Immune System & Cancer Flashcards

1
Q

Describe cancer cells.

A

-mutations triggered by chemicals, radiation, viruses, inherited defects in regulatory genes
-cells proliferating uncontrollably by growing clone of cells that develop into tumor/neoplasm
-mechanisms of tumor suppression: DNA repair, cellular senescence, apoptosis etc

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2
Q

Describe the different types of tumor neoantigens.

A
  1. Mutated proteins
    -altered versions of normal proteins
    -melanoma associated antigen recognized by T cells (MART1)
    -encoded by mutated genes & not found on normal cells
    -single tumor can express many neoantigens
  2. Differentiation antigens
    -expression of antigens not normally found in adults (fetal only)
    -oncofetal antigens
    -carcinoembryonic antigen (CEA/CD66e) in GI tumors
  3. Overexpressed cellular proteins
    -expression for longer times or at diff locations
    -abnormal high levels of expression (PSA in prostate cancer)
  4. Oncogenic viruses antigens
    -response against tumor
    -FOCMA in FeLV cats/Mareks disease in chickens
  5. Cancer/testis antigens
    -tumor antigens expressed in testes & various tumors
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3
Q

Describe immune surveillance.

A

-1909 Paul Erlich
>host defense prevent neoplastic cells from developing into tumors
-1953 Gross & Foley
>tumor stimulated IR
-1950s MacFarlene Burnet
>tumor cell neoantigens induce IR against cancer
>immune surveillance theory

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4
Q

Describe cancer immunoediting.

A

2002 Dunn & Schreiber
1. Elimination phase
-tumor cells killed by NK, CD4 & CD8 T cells
2. Equilibrium phase
-IS unable to destroy tumor
3. Escape phase
-detectable tumors

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5
Q

Describe the immune surveillance elimination via the innate IS.

A
  1. Neutrophils
    -make TAIL (TNF related apoptosis inducing ligand)
    -stim apoptosis in tumor cells
  2. NK cells
    -failure to express MHCI
    -express non classical molecules (MICA/MICB)
    -express NKG2D = bind MICA/MICB on tumor cells
  3. Macrophages
    -classically activated M1 macrophage kill tumor cells
    -recognize DAMPs from dying tumor cells thru macrophage TLRs
    -activate macrophage by IFNy made by tumor specific T cells
    -make NO
    *M2 macrophages = promote tumor growth thru secretion of vascular endothelial growth factor (VEGF) & TGF-B
    >can gen anti inflammatory environment within tumor
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6
Q

Describe the immune surveillance elimination via the adaptive IS.

A
  1. CD8 T cells
    -specific for tumor peptides presented on MHCI
    -directly lyse tumor cells using perforins & granzymes
  2. CD4 T cells
    -activated by APCs presenting tumor antigens leading to direct/indirect destruction of tumor
  3. NKT cells
    -recognize Ag presented by non classical MHC I on tumor cells
    *tumor bearing hosts make Ab against tumor antigens
    >Ab kill tumor cells by activating complement or by antibody-dependent cell-mediated cytotoxicity
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7
Q

Describe equilibrium.

A

-tumor cells remain but dont progress
>not completely eliminated/dont proliferate

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8
Q

Describe immunological escape mechanisms.

A

-similar to self
-no PAMPS
-not all cells express same neoantigens
-switch off T cell response
-tumor derived IL4, IL6, IL10, TGFB, PGE2, IDO
-T cell checkpoint molecules
>CTLA4, PDL1
>anergy

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9
Q

Describe tumor escape: immunosuppression.

A
  1. TGFB
    -induce tumor cell prolif & angiogenesis
    -suppress element of host anti tumor IR
  2. Indoleamine 2,3 dioxygenase (IDO)
    -suppress T cell prolif
  3. Galectin 1
    -stim angiogenesis
  4. PDL1
    -slow down IR
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10
Q

Describe transformed cells.

A
  1. Downreg molecules that can facilitate T cell or NK mediated attack
    -ex. Loss of MHC, Tc epitopes, ICAM1
  2. Upreg/secrete molecules that can kill lymphocytes
    -ex. FasL
  3. Anergize T cells that infiltrate tumor
    -ex. PDL1, PDL2, IL10, IDO
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11
Q

Describe tumor immunotherapy via nonspecific immune stimulation.

A

-cytokine therapy (interferons, TNFa, IL2, IL4)
-T-LAK cells
>gen by taking peripheral blood lymphocytes & activating them w IL2 & returning them IV
-microbial products
-checkpoint inhibitors

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12
Q

Describe the principles of immune checkpoint therapy.

A
  1. CTLA4
    -inhibitory receptor expressed on T cells
    -ligand = B7 expressed on cancer cells
    -blocking of CTLA4 by antibodies = cytotoxic T cells against tumor cells
  2. PD1
    -blocks tumor cell apoptosis by binding to ligand PDL1
    >allows cytotoxicity & apoptosis
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13
Q

Describe passive VS active immunization.

A
  1. Passive
    -monoclonal Ab against tumoral Ag
  2. Active
    -chemically modified tumor cells
    -vaccine against oncogenic viruses
    EX: FeLV, Mareks disease
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