0: resting stage, 1: ligand binding, 2: conformational change, 3: GTP bound Ga dissociates, 4: Ga as a GTPase converts Ga-GTP to Ga-GDP, 5: reassembly of heterotrimeric G protein
2
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GPCR on vs off
GTP bound to G protein is active (on), GDP bound to G protein is inactive (off)
3
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RTK components
extracellular domain w ligand binding site, hydrophobic transmembrane alpha helix, cytosolic segment w domain w protein kinase activity, C-terminal w tyrosine residues that the receptor's own kinase phosphorylates
4
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RTK activation
activated by extracellular growth, differentiation factors, or metabolic regulators
5
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SH2 domains
~100 amino acids, conserved binding pocket that accommodates a phosphorylated tyrosine residue. mediate a large number of phosphorylation-dependent protein-protein interactions
6
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JAK-STAT signaling
Janus kinase (JAK) signal transducer, activator of transcription (STAT) pathway, regulated by post-translational modifications
7
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IFNγ signaling
IFNγ: cytokine produced by immune cells, signals through its receptor which activates JAK-STAT1 pathway to induce expression of classical interferon-stimulated genes
8
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Rapamycin
binds a prolyl-isomerase (FKBP12) to form complex that broadly inhibits cell growth and proliferation, targets mTOR kinase in mammals
9
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FK505/tacrolimus
binds to FK binding proteins, inhibits calcineurin - t cells express low levels so they are sensitive
10
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Caspase
protease enzymes essential in programmed cell death - cysteine in active site cleaves target protein after Asp residue - produced as a zymogen
11
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inflammasome activation
multimeric protein complexes, assemble in the cytosol after sensing PAMPs or DAMPs
promote maturation of IL1B and IL18 cytokines and induce pyroptosis (lytic cell death)
14
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inflammasome structure
consist of sensor PRRs, an adaptor ASC, and an effector pro-caspase-1
15
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central tolerance
developing lymphocytes encounter self-antigens in generative/central lymphoid organs
16
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peripheral tolerance
mature lymphocytes encounter self-antigens in peripheral/secondary lymphoid organs/tissues
17
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T cell anergy
when T cells recognize antigens without co-stimulation and lose their ability to transmit activating signals, or after recognition of self antigens when inhibitor receptors of the CD28 family are used
18
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inhibitory receptors of the CD28 family
CTLA-4 or PD-1
19
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CTLA-4
CD152, inhibitory for T cell activation, controlled by regulation of its surface expression, binds to same ligans as CD28
20
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PD-1
programmed death-1, higher affinity for B7 than CD28,
21
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multiple sclerosis
demyelination of neurons due to CNS antigen T cells activated in periphery reencountering antigen in brain (when unknown inflammation trigger causes blood-brain barrier to become locally permeable to leukocytes)
increases in cytosolic/organellar Ca2+ concentrations in lymphocytes control functions such as metabolism, proliferation, differentation, antibody/cytokine secretion, and cytotoxicity
25
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second messengers
small non-protein molecules that pass along a signal initated by the binding of a ligand (first messenger) to its receptor
immunoreceptor tyrosine-based activation motifs - cytoplasmic region of the T cell receptor - signalling is activated by tyrosine phosphorylation of the ITAM
29
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apoptosis morphologic characteristics
cell is shrunken w condensed cytoplasm, membrane blebbing, apoptotic bodies (cell disassembly into membrane-enclosed vesicles)
30
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intrinsic apoptosis pathway
mitochondria mediated - mitochondrial outer membrane permeabilization, cytochrome C released from mitochrondria, apoptosome assembly, procaspase 9 cleaved into caspase 9, procaspase 3 cleaved into caspase 3
31
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extrinisc apoptosis pathway
death receptor mediated - activated by extracellular ligands binding to cell-surface death receptors
32
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autophagic cell death
large scale autophagic vacuolization of the cytoplasm, induced/inhibited by autophagy inhibitors/inducers (tat-beclin 1 - a cell penetrating autophagy-inducing peptide)
33
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necrosis
cell death as a consequence of extreme physicochemical stress - heath, osmotic shock, mechanical stress, freeze-thawing
34
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necrotic cell death pathways
necroptosis, ferroptosis, pyroptosis
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necroptosis
Necroptosis-inducing complex (necrosome); RIPk1, RIPk3, MLKL phosphorylated, MLKL forms channels that induces influx of ions and causes cell to burst
36
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ferroptosis
increased levels of intracellular reactive oxygen species
37
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pyroptosis
activation of inflammatory caspases, release of IL1B or IL18
38
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kinase
mediate transfer of phosphate onto a protein
39
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phosphatase
remove phosphate group from a protein or target
40
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adaptor proteins
membrane-anchored or cytoplasmic proteins with several signaling modules that serve to link two proteins together
41
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Co-receptors
CD4 and CD8, engagement with the T cell receptor enhances phosphorylation of ITAMs
42
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Src family PTKs
Eg Lck and Fyn, close proximity to ITAMs?
43
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the CRAC channel
calcium release-activated channel
44
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CD28
used by naive T cells as a co-stimulatory receptor - enhances antigen receptor signals that induce transcription factor activation and PI3K activation (therefore ensuring T cell activation)
45
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CD40
used by naive B cells as a co-stimulatory receptor - enhances antigen receptor signals that induce transcription factor activation and PI3K activation (therefore ensuring B cell activation)
46
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B7 family
expressed mainly on specialized APC such as dendritic cells
47
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MAPK cascade
made up of Raf, MEK, and ERK - mitogen-activated protein kinase - turned on by activated PTKs - MAPKs phosphorylate and activate transcription factors that induce new gene expression
48
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DISC
death-induced signaling complex - formed by the extrinisc apoptosis pathway
49
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Bcl2 family
regulates mitochondrial outer membrane integrity in the intrinisic apoptosis pathway - have one or more Bcl2 homology (BH) regions
50
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Autoimmunity
the immune response to self as a result of the breakdown in self-tolerance. presence of antibodies (by B cells) and T cells directed against normal components of a person
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molecular mimicry
cross reacting antigens - similar structures shared by molecules from dissimilar genes or protein products - eg a foreign antigen that resembles a self antigen. Eg: streptococcal M protein and heart muscles
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Treg in self-tolerance
can suppress self-reactive lymphocytes that recognize antigens different from those that the Treg cell recognizes - aka regulatory tolerance
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True or false: Autoimmunity is the immune response to self, which is a result of a breakdown in immune tolerance (self-tolerance).
true
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True or false: Autoantibodies are produced by autoreactive T cells.
false
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True or false: Autoreactive or self-reactive lymphocytes are generated by our own immune system
true
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True or false: Since autoreactive lymphocytes will be eliminated by central tolerance mechanisms, there are no autoreactive lymphocytes that enter peripheral tissues.
false
57
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True or false: Apoptosis is an uncontrolled cell death process
false
58
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True or false: Apoptosis is associated with the release of DAMPs
false
59
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True or false: Apoptosis is caspase-dependent programmed cell death
true
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True or false: Necrosis is caspase-independent cell death
false
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True or false: Pyroptosis is a form of cell death that is associated with the release of pro-inflammatory cytokines upon cell rupture due to caspase 1 activation
true
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True or false: NLRP3 signaling leads to NFkB-independent generation of pro-inflammatory cytokines and cell death through formation of a multi-protein complex known as the inflammasome.
"What tissues, organs, or body systems can be affected by autoimmune diseases? (A) Skin (B) Joints (C) Thyroid (D) All of the above"
(D) All of the above
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Which of the following is correct regarding where B and T cells mature just prior to traveling to lymph nodes? (A) B cells mature in the thymus; T cells mature in the thyroid gland (B) B cells mature in the bone marrow; T cells mature in the thymus (C) B cells mature in the thyroid gland; T cells mature in the pancreas (D) B cells mature in the pancreas; T cells mature in the bone marrow
(B) B cells mature in the bone marrow; T cells mature in the thymus
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"Which of the following transcription factor is specific for Treg cells: (A) T-bet (B) RORrt (C) GATA-3 (D) FoxP3"
(D) FoxP3
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Choose the correct sequence of events for G-protein coupled receptor (GPCR) activation: I. GTP-bound Gα dissociates from the ligand-bind GPCR, releasing Gα-GTP and Gβγ to trigger their respective effector proteins II. The intrinsic GTPase activity of Gα converts Gα-GTP to Gα-GDP III. A conformational change of the GPCR induced by ligand binding, which creates a binding pocket for Gα IV. Reassembly of heterotrimeric G protein
(A) IV - III - II - I (B) III - II - I - IV (C) III - I - II - IV (D) I - II - IV - III "