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Onc Boards > Important Facts > Flashcards

Important Facts Flashcards

1
Q

Serine/threonine kinases

A

Raf kinase / BRAF
Akt/PKB (known as Akt)
CDKs

MEK - technically dual specificity - serine/threonine and tyrosine

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2
Q

Receptor tyrosine kinases

A

c-Kit
Insulin receptor
EGFR
PDGFR

MEK - technically dual specificity - serine/threonine and tyrosine
ABL

**JAKs are non-receptor tyrosine kinases
**FAK is a non-receptor tyrosine kinase

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3
Q

JAKs include receptors for

A

Interferon (IFN)
Erythropoietin (EPO)
Thrombopoietin (TPO)

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4
Q

Tumor suppress genes/proteins

A

Retinoblastoma protein
p53
PTEN
CDKN2A
NF1
APC
KEAP1

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5
Q

Growth inhibitory factors

A

TGF-beta (to normal cells, but can foster tumor progression by activating EMT)

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6
Q

3 different DNA tumor virus oncoproteins

A

EIA (from human adenovirus type 5)
Large T antigen (from SV40 virus)
E7 oncoprotein (from HPV)

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7
Q

Transcription factors

A

E2Fs

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8
Q

Pro apoptotic proteins

A

Bax and Bak

Fas ligand (CD95 or FasL) and its interaction with the Fas receptor

tumor necrosis factor (TNF) and its receptor interaction

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9
Q

Anti-apoptotic

A

Bcl-2, Bcl-XL, and Mcl1

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10
Q

Mitogenic growth factors

A

Hepatocyte growth factor (HGF)
Transforming growth factor-alpha (TGF-alpha)
Platelet derived growth factor (PDGF)

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11
Q

Trophic factors

A

IGF-1
IGF-2

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12
Q

Anti-angiogenic factors

A

Thrombospondin-1 (Tsp-1)

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13
Q

Pro-angiogenic factors

A

VEGF (with HIF-1alpha transcription factor and VHL tumor suppressor)
TGF-alpha
TGF-beta
TNF-alpha
G-CSF
PDGF-Beta and PDGFR
IL-8
HGF
Angiopoietin 1 and 2 (and their receptors Tie-1 and Tie-2)

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14
Q

Monoclonal antibodies and targets

A

bevacizumab (Avastin) = VEGF-A

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15
Q

IHCs

A

Vimentin - mesenchymal cells
Cytokeratin - epithelial cells
CD204 - histiocytic sarcoma

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16
Q

Jak2/STAT5 is usually responsive to what interleukins

A

IL-2
IL-3
IL-6

17
Q

Death receptors

A

Fas receptors
TNF receptors

18
Q

Type 1 small molecule inhibitors

A

Toceranib

19
Q

Type 2 small molecule inhibitors

A
20
Q

Type III small molecule inhibitors

A
21
Q

Covalent inhibitors (small molecule inhibitors)

A

ibrutinib, afatinib

**irreversible

22
Q

Palladia targets what TKRs

A

Kit
PDGFR
VEGF
FLT3
CSF1R

23
Q

Pro-inflammatory cytokines

A

TNF-alpha - mediator of acute inflammatory response to bacteria; produced by macs and DCs; 2 forms (type I and type II)

IL-1 - acute inflammation; produced by activated mononuclear phagocytes, neuts, epithelial cells, endothelial cells; 2 forms (alpha and beta); binds to cell receptors leading to activation of NF-kB and AP1

IL-6 - acute inflammation; produced by phagocytes, vascular endothelium, fibroblasts; made in response to PAMPs, IL-1, TNF

IL-12 - secreted by DCs and macs; produced in response to TLRs; stimulants IFNgamma by NK cells and T cells; host resistance against intracellular

IL-18 - enhances NK cells

IL-15 - growth stimulating and survival of NK and T cells

IL-25

IL-33

24
Q

Functions of immunoglobulins

A

IgG – longest serum half life; functions – opsonization, complement activation, ADCC, feedback inhibition for B cells

IgE – defense against helminths, immediate hypersensitivity

IgD – naïve B cell antigen receptor

IgM – naïve B cell antigen receptor, complement activation

IgA – mucosal immunity

25
Q

Classes of dendritic cells

A

Classical – CD11 b (drives CD4 response) and CD8 (in lymphoid tissues) or CD103 (peripheral tissues) which is involved in cross-presentation

Plasmacytoid DCs – primarily function in viral infections, when they secrete type I IFN and play role in Ag presentation

26
Q

Cytoplasmic tyrosine containing motifs on signaling proteins of immune receptors

A

ITAMs - involved in cell activation

ITIMs - inhibit cellular response

27
Q

Co-receptors for T vs B cells

A

T cells - CD4 and CD8

B cells CR2/CD21

28
Q

Inhibitory receptors for T vs B cells

A

T cells - CTLA-4, PD-1

B cells - CD22, FcyRIIB (contains an ITIM motif)

29
Q

Co-stimulatory signals for T cells

A

CD28 on the T cell - binds CD80/86 (aka B7-1/2) expressed on activated APCs

CD80/86 expression is induced by TLRs and IFNgamma

CD4 ehnances expression of CD80/86 by CD40-dependent pathway

Tregs are dependent on CD80/86:CD28 mediated co-stimulation

CD28 signaling amplifies signals induced downstream of the TCR and amplifies the NF-kB pathway

PI3K is recruited to the CD28 tail —> activates Akt and Itk as well as PLCy

Net result of CD28:B7 costim is increased expression of anti-apoptosis Bcl-2 and Bcl-XL promoting T cell survival, IL-2 production

OTHER COSTIM:

CD40L on T cells and CD40 on APCs (B cells, macs, DCs)

CD40L activates APCs to make them more potent by enhancing B7 expression and IL-12 secretion (IL-12 promotes T cell differentiation)

30
Q

Ligation of the TCR by MHC-peptide ligands causes

A

Phosphorylation of ITAMs linked to CD3 or delta chains

31
Q

Transcription factors activated by TCR signaling

A

NFAT - required for expression of genes encoding IL-2, IL-4, TNF; activated by calcium-calmodulin

AP-1 - transcription factor composed of FOS and Jun

NF-kB - TF activated in response to cytokine synthesis; important for TLR and cytokines

Also miRNAs - small non-coding RNAs that are transcribed from DNA but not translated – inhibit expression of genes (Argonaute proteins assoc w miRNA to form RISC)

32
Q

Cytokines

A

IL-2 = growth, survival, and differentiation cytokines for T cells (promotes proliferation and differentiation of CD8 T cells into CTLs); activates JAK/STAT, induces anti-apop Bcl-2, stims cell cycle progression through degradation of p27

IL-17 = most important cytokines for maintenance of memory CD4 and CD8 T cells (CD127 is IL-17 receptor on Tmem cells)

IL-15 = also important for CD8 memory/survival of memory cells; produced by many cell types including DCs

IL-12 = causes differentiation of Th0 cells to Th1 cells; produced by DC pop during innate immune response

IL-4 = causes differentiation of Th0 cells to Th2 cells; involved in allergic rxns and response to helminths

IL-5 = involved in allergic rxns and response to helminths

IL-13 = involved in allergic rxns and response to helminths

IL-1 = promotes differentiation of Th0 cells to Th17 cells

IL-17 = produced by Th17 cells, interacts with macrophages

IL-22 = interacts with macrophages

IL-6 = promotes differentiation of Th0 cells to Th17 cells

TGF-beta = promotes differentiation of Th0 cells to Th17 cells

IFNgamma = secreted by CD8 T cells and Th1 cells; activates macrophages, tells B cells to switch to IgG, stims expression of proteins that enhance MHC Ag presentation

Type I IFN - stimulates differentiation to cytotoxic T cells; produced by CD pop during innate immune response

IL-21 = plays a role in induction of CD8 memory and prevention of exhaustion; produced by activated CD4 cells; contributes to generation of plasma cells, facilitates B cell selection events and B cell differentiation

33
Q

B cell activation is facilitated by

A

CR2/CD21 receptor on B cells

C3d complement fragment is recognized by CR2 —> enhances strength of BCR signaling

34
Q

What stimulates B cell proliferation

A

NF-kB and AP-1 (activated by CD40:CD40L signaling cascade)

35
Q

Heavy chain isotope (class) switching

A

Regulated by cytokines produced by T helper cells
• IFNy —> B cells switch to IgG
• IL-4 —> B cell switches to IgE
• TGF-beta, BAFF, and APRIL —> B cell switches to IgA at mucosal sites

CD40 signals work w cytokines to induce switch

Onc Boards (4 decks)

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