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Winter course I > Advanced immunology > Flashcards

Advanced immunology Flashcards

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1
Q

what are the 9 functions of Fc receptors?

A
  1. clearance of immune complexes
  2. phagocytosis (antigen presentation) (FcyRI)
  3. production of cytokines
  4. antibody dependent cellular cytotoxicity (ADCC)
  5. modulation of cellular activation
  6. mast cell degranulation (FcE, food allergies)
  7. generation of high affinity antibodies
  8. prevents autoimmunity by forming a late auto-immune checkpoint (FcyRIIb, peripheral tolerance)
  9. transportation/recycling of Ig (IgG; FcRn and plgR; IgA and IgM)
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2
Q

what is ITAM and ITIM?

A

immune receptor tyrosine based activating/inhibitory motif, signalling of Fcy receptors depends on it

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3
Q

name the 3 factors that influence FcR mediated signal output

A
  1. glycosylation
  2. polymorphisms and copy number variation
  3. expression level
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4
Q

what is the function of FcaR of IgA?

A

mediate phagocytosis, endocytosis, ADCC and respiratory burst and is expressed by myeloid cells

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5
Q

what treatment is used to target FcR in autoimmune diseases?

A

Intravenous immunoglobulins (IVIg)

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6
Q

what is the definition of epigenetics?

A

heritable changes in gene function that cannot be explained by changes in DNA sequence

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7
Q

name the 2 key players of regulating gene expression

A
  1. transcription factors
  2. gene regulatory elements
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8
Q

name the 4 epigenetic mechanisms

A
  1. DNA methylation
  2. nucleosome positioning
  3. histone modification
  4. 3D genome folding
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9
Q

name the 4 reasons where gene regulation and epigenetics is essential for

A
  1. immune system diversity
  2. immunological memory
  3. efficient clearing of chronic viral infections and cancer
  4. pathogens to propagate and persist
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10
Q

what are the 3 functions of transcription factors?

A

transduce signals to the chromatin, control immune cell diversification and immune cell development

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11
Q

what is genomic imprinting?

A
  • DNA methylation; add methyl-group to cytosine to reduce binding of transcription factors to result in inactivating gene and low gene expression
  • imprinted genes are involved in embryonic growth
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12
Q

name the 5 outcomes of epigenetic mechanisms

A
  1. differentiation
  2. activation
  3. proliferation
  4. apoptosis
  5. transformation
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13
Q

what is 3D genome folding?

A

it shapes effective adaptive immunity, misfolding causes developmental syndromes

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14
Q

true or false? chromatin dictates DNA accessibility

A

true

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15
Q

what is the function of epigenetics?

A

creates cellular diversity from identical DNA by shaping gene expression patterns in response to external and internal signals

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16
Q

what is signal transduction?

A

any process by which a cell converts one kind of signal or stimulus into another, involving ordered sequences of biochemical reactions inside the cell

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17
Q

how do signalling proteins interact with eachother and with lipid signalling molecules?

A

via modular protein domains

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18
Q

how does signal transduction occur?

A

through a kinase cascade or second messengers

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19
Q

what are the 3 outcomes when a signal reaches its target?

A
  1. gene transcription
  2. cytoskeleton
  3. metabolism
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20
Q

how do signalling proteins recruit to the plasma membrane?

A
  1. by binding to phosphorylated sites on a membrane-associated protein
  2. recognition of activated small G proteins
  3. by binding to membrane lipids
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21
Q

what are the 3 stages of signal transduction?

A
  1. signal perception
  2. intracellular signal transduction
  3. cellular response
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22
Q

name 3 chemical messengers

A
  1. enzymes
  2. second messengers
  3. linkers
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23
Q

name the dual role of phosphorylation

Study These Flashcards
A
  1. activation by phosphorylation
  2. activation by dephosphorylation
24
Q

how is a signal amplified and how is it terminated?

Study These Flashcards
A

signal amplification by kinase cascades and termination of signal by dephosphorylation

25
name the 2 characteristics of a ligand binding receptor
1. on plasma membrane 2. intracellular, in endosomes (TLR3/7/9)
26
explain the BCR and TCR signal transduction pathway
they use the signal transducers Iga/b and CD3 complex, activation leads to formation of Slp76/65 scaffold
27
name the 3 pathways that Syk tyrosine kinase is involved in
FcEr, integrin and BCR signalling
28
name the 3 pathways IL-4 expression is regulated by
1. IFNy 2. TCR through NF-kB 3. TCR through ERL/JNK and NFAT
29
which diseases can be a result of signalling defects?
1. immune deficiencies 2. cancer 3. BTK defects
30
which BTK defects could occur and what is the result?
1. no BTK --> XLA 2. BTK always activated --> CLL 3. BTK protein increased --> autoimmune phenotype
31
how does targetting BTK in disease work ?
CXCR4 signalling is inhibited, CLL cells enter the circulation and die
32
describe the 3 signal model of T cell activation
1. antigen-specific; TCR activation 2. co-stimulation (antigen-independent) --> proliferation and survival 3. cytokines --> T cell differentiation
33
which signals are required for T cell activation?
signal 1 and 2
34
which receptor is the most important one for signal 2 activation?
CD28
35
what are the 2 options of T cell differentiation?
1. CD8+ T cells --> killer T cells 2. CD4+ T cells --> helper T cells
36
name 4 different costimulatory receptors
positive costimulatory receptors: 1. CD28 2. ICOS negative costimulatory receptors: 3. CTLA-4 4. PD-1
37
name the 3 characteristics of CD28
1. involved in initial activation events for naive T cells 2. enhances TCR-induced proliferation (IL-2) and survival (Bcl-xL) (production of memory and effector T cells) 3. binds to CD80/86 expressed by activated APCs
38
name the 3 characteristics of ICOS
1. help to maintain activity of already differentiated cells 2. binds ICOS-ligand on activated APCs 3. expressed on memory and effector T cells
39
when does clonal anergy occur?
when only signal 1 is received, the cell is rendered nonresponsive anergy, this provides peripheral tolerance against self-reactive T cells
40
name the 3 characteristics of CTLA-4
1. shut down signaling pathways 2. binds to CD80/86 with higher affinity than CD28 pathways 3. acts via phosphates
41
name the 3 characteristics of PD-1
1. helps mediate T cell tolerance 2. binds to PD-L1/2 on APC and tumor cells 3. acts via phosphates and receptor competition
42
how, when and why does T cell exhaustion occur?
chronic TCR stimulation during chronic viral infections, tumors, autoimmunity to dampen immunopathology and preventing autoimmunity
43
describe the 3 signal model in CTL exhaustion
1. persistent antigen 2. negative co-stimulation 3. chronic inflammation
44
name the 7 characteristics of T cell exhaustion
1. functional defects 2. inhibitory receptor 3. proliferative defects 4. survival defects 5. transcription factor changes 6. epigenetic changes 7. RNA transcriptome changes
45
name 2 checkpoint inhibitors
1. anti-CTLA-4 2. anti-PD-1
46
name 5 problems with immunotherapy
1. only a minority of patients respond 2. not all tumors respond 3. responses may not be long lasting 4. emergence of resistance in patients that previously respond 5. adverse events
47
when does cell migration of lymphocytes occur and why and how is it regulated?
- during development, homeostasis and immunity - homing to organs/tissues/compartments, cell-cell interactions and exit from compartments/organs --> inherently motile cells - role for adhesion between 2 cells, cell-extracellular matrix --> sitting still - regulated by chemokines and adhesion by integrins
48
what is the function of inflammatory chemokines?
induced expression (CXCL8 = IL-8), attract activated lymphocytes
49
what is the function of homeostatic chemokines?
constitutive expression in lymphoid organs (CCL21), attract naïve T/B/DC
50
name the 3 mechanisms of attraction
1. leukocyte chemotaxis; soluble gradient 2. leukocyte haptotaxis; bound gradient 3. leukocyte chemokinesis/haptokinesis; migration without gradient
51
how does adhesion happen?
adhesion through intergrins binding to extracellular and counter ligands
52
53
what is extravasation?
lymphocytes enter the lymph nodes at high endothelial venule (HEV) found in T zones of lymph nodes and Peyer's patch
54
what happens in a resting lymph node?
constitutive extravasation of naïve T and B lymphocytes
55
explain the different steps of lymphocyte extravasation
56
describe the mechanism of an activated T cell extravasation from blood
activated T cells acquire specific tissue homing capacities and are controlled by vitamin metabolites and instructed by DC-derived signals, integrins and chemokine receptors collaborate for effector cell homing for specificity and efficiency

Winter course I (15 decks)

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