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immuno > season 2 episode 1 > Flashcards

season 2 episode 1 Flashcards

1
Q

IgE receptor

A

FceRI
Crosslinking of the FcεRI via IgE-antigen complexes leads to degranulation of mast cells or basophils and release of inflammatory mediators.

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2
Q

Fc receptor

A
  • inhibitory receptor FcyRIIB
    - B cells and myeloid cells
  • activating receptor Fc3RI
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3
Q

ITAM

A
  • immunoreceptor tyrosine-based activating motif

- in the cytosolic domain of Fc

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4
Q

CD8

A
  • 25 aa cytosolic domain
  • composed of 1 alpa &1 Beta
  • interacts with class I MHC and also beta 2 microglobulin
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5
Q

what is the match?

B7-1,2

A

CD28 (CD4 lymphocyte)

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6
Q

What cell expresses B7?

A

class II MHC APC

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7
Q

what is the match?

ICAM-1

A

LFA-1

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8
Q

What cell expresses LFA-1?

A

CD4 helper T cell

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9
Q

How is ITAM activated?

A

phosphorylation leads to the docking of other signalling molecules

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10
Q

what are two potential precursors of NFkB

A

IKK, IkB,

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11
Q

what are cytokines involved in Jak-Stat type 1 signalling?

A

IL-2-7,9,11-13,15,21,23,

GM-CSF, G-CSF

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12
Q

What are the pro-inflammatory cytokines?

A

IL-1,6,8,11,12,15,18

TNF-alpha

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13
Q

What are the anti-inflammatory cytokines?

A

IL-10, TGF-beta

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14
Q

what are the MAJOR pro-inflammatory cytokines

A

TNF, IL-1, IL-6

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15
Q

Local effects of TNF/IL-1 on vascular endothelium

A

increase:
procoagulant
express leukocyte adhesion molecules
production of IL-1 chemokines

decrease: anticoagulant

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16
Q

local effects of TNF/IL-1 on leukocytes

A

activation and production of cytokines

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17
Q

local effects of TNF/IL-1 on fibroblasts

A

proliferation and increase collagen synthesis

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18
Q

Which cells produce TNF-alpha?

A

macrophages and monocytes

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19
Q

Which cells produce TNF-beta?

A

T lymphocytes

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20
Q

Which cells produce TNF?

A

macrophages, monocytes, T lymphocytes, neutrophils, NK cells

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21
Q

What is the most potent inducer of TNF?

A

Endotoxin (LPS)

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22
Q

What does LPS do?

A

interacts with endothelium to induce ICAM1, VCAM1 and E-selectin to permit egress of granulocytes into inflammatory loci

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23
Q

What is the primary mediator of septic shock?

A

TNF

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24
Q

What is the activator of neutrophil? What does is cause the neutrophil to do?

A

TNF causes them to adhere, chemotaxis, degranulation, and respiratory burst

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25
Q

What are the TNF receptors?

A

TNFR p75: TNF receptor 1

TNFR p55: TNF receptor 2

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26
Q

Where is IL-1 primarily produced?

Secondarily?

A

primarily: macrophages and monocytes
secondarily: neutrophil, endothelium, keratinocytes, and others

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27
Q

what are the effects of IL-1 on the CNS?

A

fever, lethargy, sleep, and anorexia (with TNF=loss of apetite)

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28
Q

What is second in line to cause ICAM-1, VCAM1 and E-selectin stimulation by endothelial cells?

A

IL-1

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29
Q

What cytokine does IL-1 exclusively induce production of? How does IL-1 do this?

A

IL-2

by causing proliferation of CD4 T cells

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30
Q

What is the “second in line” in production of acute-phase proteins?

A

IL-1

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31
Q

How is IL-1 neutralized?

A

IL1-ra (receptor antagonist)

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32
Q

What produced IL-6?

A

primary: mononuclear phagocytic cells
secondary: T, B cells, fibroblasts, endothelial cells, keratinocytes, hepatocytes, bone marrow

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33
Q

What is the “first in line” in synthesis of acute phase proteins?

A

IL-6

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34
Q

What are the roles of IL-6?

A

acute phase protein,
pyrexia,
stimulate plasma cell differentiation
TH17 immune regulation (primary role)

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35
Q

What cells PRIMARILY produce IL-8?

A

macrophages

Mast cells release it from granules

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36
Q

What are the roles of IL-8?

A

Activate and Chemotaxis of neutrophils

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37
Q

IL-12 is from:

A

from DC and macrophages (primary)

B cells, PMNs, and mast cells

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38
Q

IL-12 effect on T cells

A

activate Th1, IFN gamma production

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39
Q

IL-12 effect on NK cells

A

IFN-gamma production

proliferation, cytoxicity, and cytokine production

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40
Q

What is a synergetic cytokine with IL-12? What does it do?

A

IL-18 is the IFN-gamm-inducing factor stimulates IFN-gamma release

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41
Q

IL-15 source

A

primary: mononuclear phagocytic cells
other: epithelial, fibroblasts

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42
Q

IL-15 effects

A

activate NK cells
T-cell growth factor (like IL-2)
chemotaxis for T cells
survival of CD8 memory T cells

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43
Q

most important role of IL-15

A

activation of NK cells

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44
Q

IFN-gamma source

A

Th1 and NKs

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45
Q

What does IFN-gamma stimulate?

A 
NK and neutrophil
expression of class I and II MHC
Ag presentation by APC
cytokine production by APC
expression of ICAM-1
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46
Q

what does IFN-gamma inhibit?

A

allergic responses by suppressing IL-4 mediated effects

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47
Q

What are antiviral interferons?

A

IFN-alpha and beta

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48
Q

What are the anti-inflammatory cytokines?

A

IL-10, 1ra, and TGF-beta

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49
Q

production of what molecules is inhibited by IL-10?

A

inhibits: production of
IFN, TNF (Th1),
IL-4, IL-5 (Th2),
IL-1beta,6,8,12

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50
Q

EXPRESSION of what molecules is inhibited by IL-10?

A

inhibits: expression of class II MHC, CD80, CD 86 (costimulators)

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51
Q

What does IL-10 do with allergens?

A

controls tolerance to them

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52
Q

What cells does TGF-beta act on?

A

inhibits B, T cells, macrophages, NK cells

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53
Q

What produces TGF-beta?

A

macrophages and regulatory T cells

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54
Q

What is the role of Th1 cells?

A

Intracellular microbe response
IFN-Y kill phagocytized microbes
stimulates IgG (phagocytosis)

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55
Q

what is the role of Th2 cells?

A

IL-4 (M2 macrophage)
IL-5 (eosinophil)
IgE: Helminths and allergic diseases

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56
Q

what is the role of Th17 cells?

A

IL-17A,17F, 22;

extracellular bacteria, fungi

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57
Q

What is T-bet

A

Th1 transcription factors

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58
Q

What is GATA-3

A

Th2 transcription factors

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59
Q

What is RORgammaT

A

Th17 transcription factors

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60
Q

What is FOXP3

A

T regulatory cell transcription factors

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61
Q

How does IL-2 control proliferation of T cells?

A

APC presents Ag; IL-2 produced to

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62
Q

CD40

A

CD40 is a costimulatory protein found on antigen presenting cells and is required for their activation. The binding of CD154 (CD40L) on TH cells to CD40 activates antigen presenting cells and induces a variety of downstream effects.

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63
Q

What is cRel and RelA (p65)?

A

in the NF-kB family (transcription factor)

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64
Q

What is CD28

A

costimulatory receptor (TCR)

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65
Q

What class of Ig can make up BCR complexes

A

IgM and IgD on b cells
IgG, A,or E on memory b cells
Think of Ig alpha and beta with ITAMs

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66
Q

What are downstream transcription factors targeted by BCR and TCR signalling?

A

NFAT, NFkB, AP-1

for cell growth, differentiation, survival

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67
Q

How is complement protein involved in BCR signalling?

A

C3d and an antigen are bound to a microbe
Ig binds to antigen, CR2 to C3d
both contribute to signal transduction

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68
Q

What is an inhibitory signal protein for lymphocytes in JAK-STAT? Is this always an inhibitory protein?

A

E3 ubiquitin ligase

In TLR/IL-1 it promotes transcription of inflammation

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69
Q

What are SOCS? What causes these to be expressed?

A

suppressors of cytokine signaling;

prolonged TLR signaling stimulates expression of SOCS

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70
Q

Describe the steps after ITIM phosphorylation

A

ITIM-phosphate binds to SH2 domain of tyrosine phosphatase which dephosphorylates substrates of the activation pathway

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71
Q

What are coreceptors of B cells?

A

CR2/CD21

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72
Q

What is an inhibitory receptor and analog of CD28?

A

CTLA-4

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73
Q

What are inhibitory receptors in B cells?

A

CD22 and FcgammaRIIB

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74
Q

What are cytokines involved in JAK-STAT type II signaling?

A

IFN-alpha/beta/gamma, IL-10,20,22

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75
Q

What attenuates JAK-STAT type II signal cascade?

A

E3 ligase

76
Q

State the order of the proteins involved in TNF receptor signaling pathway

A 
TNFR1 binds TNF
TRADD
TRAF to 2 different paths:
to inflammation and survival proteins by MAP kinase_>JNK->AP-1, 
and IkB->NFkB
OR 
death by Caspase 8->apoptosis,
77
Q

What are important intermediates in IL-1, 18, and TLR signal cascade?

A

Receptor
IRAK
TRAF6
transcription factors via E3 ubiquitin ligase

78
Q

What does MAP kinase activate in TLR/IL-1 signaling?

A

IFN transcription

79
Q

Where are the kappa chains of an Ig located in the genotype?

A

Chromosome 2

80
Q

Where are the lambda chains located in the genotype?

A

Chromosome 22

81
Q

Where are the heavy chains located in the genotype?

A

chromosome 14

82
Q

Where do B cells differentiate?

A

bone marrow

83
Q

where do T cells differentiate?

A

thymus

84
Q

What are “double-positive” T cells? Where are they found?

A

cortex of thymus
Both CD4 and CD8
TCR expression begins

85
Q

What are “single-positive” T cells? Where are they found?

A

Lose expression of either CD4 and CD8 so that they only express one;
Increase expression of TCR;
Found in medulla of thymus

86
Q

What is the general role of Th cells?

A

maturation of B cells into plasma cells and memory B cells,

and activation of cytotoxic T cells and macrophages.

87
Q

Where does somatic hypermutation occur?

A

germinal centers of lymphoid follicles on B cells

88
Q

What causes somatic hypermutation?

A

Cs are turned to Us and DNA repair often repairs it wrong

89
Q

Where are MHC genes in the genotype?

A

chromosome 6

90
Q

What are the class I MHC genes?

A

HLA-A, B, C

91
Q

What are the class II MHC genes?

A

HLA-DR, DQ, DP

92
Q

How much diversity can class I MHC have?

A 
one set of genes from each parent;
any cell can express six different class I molecules
93
Q

How much diversity can class II MHC have?

A

both chains are polymorphic so potential of 10-20 different molecules

94
Q

What are the damage signals?

A

HMGB1
Uric acid
HSP

95
Q

TGF-beta source and purpose

A

anti-inflammatory from M2 macrophage for tissue repair

96
Q

autografts

A

from another part of the body

97
Q

isografts

A

from genetically identical individual

98
Q

allogenic grafts

A

from same species

99
Q

xenogenic grafts

A

from different species

100
Q

what are the three alleles that are checked to predict the likelyhood of matching a transplant? (besides ABO blood typing)

A

HLA-A, B, and DR

101
Q

What is another name for B7?

A

CD80

102
Q

What affects recombination of V, D, and J Ig gene segments?

A

RAG-1 and RAG-2 recombinase enzymes are critically involved in the gene rearrangement process

103
Q

Which antibody class significantly crosses the placenta?

A

IgG

104
Q

What chromosome contains the TCR beta chain?

A

7

105
Q

What chromosome contains the TCR alpha chain?

A

14

106
Q

Which chromosome contains the heavy chain?

A

14

107
Q

What is the first two steps in B cell development?

A

rearrangement of the heavy chain then

RAG1 and RAG2 joins the DH and JH

108
Q

What is the second step in B cell diversification?

A

junctional diversity: addition of N nucleotides in the joints between gene segments via
TdT

109
Q

What causes the B cell to halt recombination of H chain and proliferate with that mew chain?

A

BCR binds to antigen and Igalpha and beta initiate signal transduction via ITAMs;
This halts reocomb and cloning occurs (large pre-B cell)

110
Q

What is a large pre-B cell?

A

a B cell that is undergoing recombination of the heavy chain then binds to an antigen (BCR), causing proliferation;
dividing cells are larger than resting cells

111
Q

What domains does the light chain have?

A

V and C

112
Q

What light chain develops first? last?

A

First: kappa
then if that fails:
Last: lambda

113
Q

When are the light and the heavy chains assembled?

A

Once a successful light chain, (kappa or lambda), is produced it is attached to the heavy chain (usually m) for either secretion or membrane insertion.

114
Q

IL-7 function

A

helps B cell determine lineage,
regulate Ig rearrangement
anti-apoptotic for T cells in lymph/spleen

115
Q

Describe the development of B cell

A 
Bone marrow: recombination, 
Ag in/dependent signaling
Negative selection
Spleen/Lymph node: 
Switch IgH to IgM/D expression,
T cell in/dependent activation
116
Q

What is negative selection of B cells?

A

If the BCR can bind strongly to self-antigen, then the B cell undergoes one of four fates: clonal deletion, receptor editing, anergy, or ignorance

117
Q

What is the fate of B cells that cannot produce a viable heavy chain arrangement on either homologous chromosome?

A

apoptosis in the bone marrow

118
Q

What is Bruton’styrosinekinase(Btk)

A

Bruton’sagammaglobulinemiatyrosinekinase(Btk)isacytoplasmictyrosinekinase importantinB‐lymphocytedevelopment,differentiation,andsignaling

119
Q

What characterizestheB‐1cellsthatdevelopprenatally?

A

UNIQUE innate B-1 cells with IgM and IgA
LackNnucleotides. PossessspecificityforbacterialpolysaccharideAg. Ariseearlyinembryonicdevelopmentprecedingthedevelopmentofthe majority subsetofBcells.
TheyhavelittleornoIgDonthecellsurface.

120
Q

What is receptor editing? What is the purpose?

A

Successiverearrangementatthelight‐chainlociwhen reactivitytoself‐antigenoccursduringB‐celldevelopment.
2nd chance mechanism after self-reactivity.
Potentially more efficient than starting a new B cell

121
Q

WhatisthefateofanimmatureBcellthathasspecificityforself‐antigen?

A

rearrangementof light‐chaingenes

122
Q

If the two kappa chain genes fail to produce a viable light chain then what occurs?

A

Lambda is up to bat

123
Q

What is the route of naive B-2 cells which don’t encounter an antigen?

A

bloodstream, HEV of lymphoid cortext, primary lymphoid follicle, efferent lymphatic vessel

124
Q

What is plasmablast?

A

early, short-lived B cell that is effective in the early antibody response.

125
Q

Where do plasma cells typically reside during standby?

A

reticular sinusoidal cells in the red pulp of the spleen and the medullary cords of the lymph nodes.

126
Q

What is the enzyme involved in recombination of the VDJ segments during recombination? What enzymes are needed to initiate this?

A

VDJ recombinase

RAG1, and RAG2

127
Q

What controls expression of IgM and IgD?

A

alternative mRNA splicing

128
Q

What receptor does IgE bind to on mast cells?

A

Fc epsilon RI

129
Q

What is immune exclusion in the intestinal lumen?

A

IgA promotes clearance and blockage of pathogens and Ags from epithelial receptors, trapping them in the mucus

130
Q

Which Ig forms dimers when secreted?

A

IgA

131
Q

What is artemis nuclease?

A

Involved in VDJ recombinase; binds to DNA and makes a single cut near the top of the hairpin.

132
Q

Describe the steps of the VDJ recombinase mechanism

A

RAG1 and 2 initiate recombination via ds breaks between the recombination signal sequence (RSS);
Artemis nuclease dous a ss cut near tip of hairpin;
DNA ligase repairs double strand breaks;
DNA dependent kinase and Ku repair DNA

133
Q

How many constant domains are on IgM and IgE?

How many constant domains on IgD,G, and A?

A

4 C on mu and epsilon;

3 on delta, gamma, and alpha

134
Q

What is passive immunity

A

It is adaptive or acquired, but it is donated from another organism

135
Q

What are the 3 ways to generate receptor diversity?

A

Somatic recombination
Junctional diversity
and Somatic hypermutation

136
Q

on which chromosome is the H chain gene located? How many V, D, and J segments are on this chromosome?

A 
chromosome 14;
V-100
D-27
J-1
C-9
137
Q

on which chromosome is the kappa chain gene located? How many V, D, and J segments are on this chromosome?

A 
2
V-35
D-0
J-1
C-2
138
Q

on which chromosome is the TCR beta chain gene located? How many V, D, and J segments are on this chromosome?

A 
7
V-67
D-2
J-2
C-2
139
Q

on which chromosome is the TCR alpha chain gene located? How many V, D, and J segments are on this chromosome?

A 
14
V-54
D-0
J-61
C-1
140
Q

Describe somatic recombination.

A 
heavy chain:
intervening gene segment deletion
transcription of recombined product
splicing of VDJ segment then 
translation
Light chains and TCRs are the same except V is directly combined with J
141
Q

What is the “address” signal sequence on the gene responsible for sending the heavy chains to the ER? Do the light chains need this?

A 
The L (leader) segment.
Light chains do not need this
142
Q

How many V, J, and C segments are on the kappa gene?

A

V:30-35
J:5
C:1

143
Q

What does RAG1 and RAG2 do?

A

Initiate V(D)J recombination by introducing double-strand breaks at the border between a recombination signal sequence (RSS) and a coding segment.

144
Q

What does the VDJ recombinase complex do?

A

it removes the DNA which is between the V,D, and J segments, thus abriding the DNA in prep for transcription, splicing, then translation

145
Q

How does TdT work?

A

During recombination the DNA has undergone dsDNA breaks. It needs to be rejoined via TdT polymerase.
This is error prone and adds N often (mutation)

146
Q

What are the two mechanisms for junctional diversity?

A

Removal of nucleotides from V, D, and J segments by exonucleases at recombination.
Also TdT replaces nucleotides with N

147
Q

What keeps a V segment to only combine with a J segment and no other combination?

A

the 12 bp and 23 bp on the RRS (recombination signal sequence)

148
Q

What is the hypervariable site called? Where is it located?

A

CDR3

It is in the Variable region and it is the most important site for antigen recognition

149
Q

What form does all BCRs take when on the cell membrane?

A

monomeric

150
Q

What are all the functions of IgG?

A

opsonization, complement activation, antibody-dependent cell mediated cytotoxicity, neonatal immunity feedback inhibition of B cells

151
Q

What are all the functions of IgM?

A

First secreted Ab upon infection, Naive B cell Ag receptor, complement activation

152
Q

What form does IgA take?

A

monomer in blood, but dimer when secreted into mucosa

153
Q

What is the mechanism of isotype switching?

A

DNA is deleted between S (switch) segments and recombination occurs in that region
(from delta and mu to gamma, alpha, and epsilon)

154
Q

Where is somatic hypermutation occuring?

A

germinal centers of lymphoid follicles

where memory cells wait for action by 2nd exposure

155
Q

What is the mechanism for affinity maturation?

A

random mutation on V regions of Ag over time (while on standby or activation)

156
Q

When does somatic hypermutation occur?

A

upon infection the cell undergoes somatic hyptermutation, then selection for the best Ab weeds out the less effective ones (apoptosis upon failure to bind)

157
Q

Where does affinity maturation occur in the chromosome?

A

CDR1-3 segments (part of V segments)

158
Q

What parts of the MHC molecules in individuals?

A 
alpha 1 and alpha2 domains of Class I
alpha 1 and beta 1 of class II
159
Q

What chromosome has the HLA genes?

A

chromosome 6

160
Q

What are the typical genes which are looked at when HLA typing for transplant?

A

HLA-A, HLA-B, and HLA-DR

161
Q

What is a haplotype?

A

MHC (HLA)
new genotype via recombination of chromosome of 1 parent
(why siblings are different and rarely match HLA)

162
Q

What are all the cytokine receptor families?

A

Type I, Type II, TNF, IL-1, and G protein 7TM

163
Q

What ligands does the 7TM, g proteins bind?

A

chemokines

164
Q

What is the main cytokine which links innate and adaptive immunity?

A

IL-12

165
Q

What are the cytokines which lead to proliferation of B cells?

A

IL-2, IL-4, and IL-5

166
Q

What are the cytokines with are synergistic in class switching to IgE?

A

IL-4 and IL-5

167
Q

What cytokine is an antagonist for IL-4?

What does it inhibit?

A 
INF-gamma;
blocks class switching to IgE
168
Q

Which cells and cytokines are correlated to chronic inflammation?

A

Th2 cells;
IL-4 and IL-5
Chronic because it is memory (adaptive)

169
Q

What mechanism Is used by both TCR and Ig to generate diversity?

A

Somatic recombination of V, D, and J segments

170
Q

Have progenitor T cells that enter the thymus from the bone marrow rearranged their TCR genes already?

A

No

171
Q

Is interaction with thymic non-lymphoid cells critical?

A

Yes

172
Q

Do T cells mature in the thymus via presence of foreign antigen?

A

No

173
Q

Are MHC class II molecules involved in positive selection of T cells?

A

No

174
Q

Are mature, fully differentiated T cells found in the cortex of the thymus?

A

No

175
Q

What chains transduce the signal in TCR signaling?

A

Lck on the CD3 co receptor

176
Q

Are T cells with fully rearranged alpha/beta chains found in the thymus?

A

No

177
Q

Where are gamma/delta T cells located?

A

mature in the thymus, live near epithelium

178
Q

Where does CD4, CD8 specifically bind?

A

invariant portion of MHC class II/class II molecules

179
Q

Do intracellular calcium levels rise following activation of CD4 cells?

A

Yes

180
Q

Does interaction of B7 and CD28 stabilize mRNA so effective IL-2 can occur?

A

yest

181
Q

What agents can activate CD4 cells?

A

MHC, superantigens, CD1 presentation, polyclonal activators

182
Q

What IL are involved with memory cell induction and isotype switching?

A

IL-4 or IL-5

183
Q

What is the function of LFA-1?

A

adhesion with ICAM

184
Q

What do you think when you hear complementarity-determining region on a TCR?

A

hypervariable regions
CDR (complementarity determining region)
there are 3 of them

185
Q

What cytokines does Th2 cells produce?

A

IL-4, 5, 10, 13
(antibody response/
inhibitor of phagocytes)

186
Q

What cytokines does Th1 cells produce?

A

IFN-gamma, IL-2, TNF-beta

cytotoxic

immuno (3 decks)

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