Chp 6-8—Exam 3 Flashcards
phases 1-3 of b cell development
- repertoire assembly
- negative selection
- positive selection
b cell phase in bone marrow
repertoire assembly
stages of b cell development within phase 1
early pro
late pro
large pre
small pre
immature
VDJ heavy chain rearrangement for b cells occurs in the…
late pro B
VDJ rearrangement must provide a functional protein in 3…
reading frames
B cell heavy chain chances
2 - one chance with each parent’s chromosome
__% late pro B cells fail
50
b cell phase where RAG and TdT come in
large pre B
expresses heavy chain IgM as pre-Bcell receptor
large pre B
first functional pre B heavy chain initiates…
allelic exclusion
B cell stage which begins light chain rearrangement
small preB
light chain chances vs heavy chain in B cell
light chains get multiple chances on same chromosome
___ light chain tested first, 2 tries, then ____
kappa
lambda
____% small pre B cells can make a successful light chain
85
on the surface of immature B cell
IgM
receptor editing and clonal deletion occur in ______ phase of B cells
phase 2, negative selection
clonal deletion
B cell is eliminated if none of the new light chains succeed
receptor editing function
“fixes” immature B cells with autoreactive IgM
only ______ intolerant B cells undergo receptor editing
centrally
peripheral - it’s too late
lupus arises from…
B cells reacting to intercellular antigens ie DNA
B cells undergo maturation in…
primary lymphoid follicle
matured but naive B cells express mostly
IgD
location where development into plasma cells occurs
medullary cords
centroblast –> centrocyte pathway occurs with…
B cells that enter germinal center of secondary lymphoid follicle
centrocytes undergo…
affinity maturation
centrocytes that remain in follicle become…
memory cells
memory cells express…
IgG
double positive
immature T cell has CD4 and CD8 proteins
___ chain of TCR is made first, then____
Beta first
alpha next
thymocyte
uncommitted lymphoid precursor embedded in thymus stroma
after 4 days in thymus, thymocyte expresses…
IL-7 receptor
thymocyte is double…
negative
thymocytes migrate toward _____ and mature
subcapsular epithelium
first “fork in the path” for thymocytes
δ:𝛄 receptor or 𝛼:β receptor
T cell first checkpoint
Beta chain
___ chances for T cell to make a Beta chain
4
Beta + pTa =
superdimer
_____ leads to CD3 and Zeta expression
superdimer
at the end of first checkpoint, T cell is a …
pre-T cell
T cell second checkpoint
Alpha chain
at the end of the second checkpoint, T cell is a…
with a…
double positive immature T cell with a good TCR
stain red
failed immature T cells that die
primitive thymus structure present in embryo
thymic anlage
positive selection for T cells involves thymic…
cortical epithelial cells
ensures survival of T cell in positive selection phase
binds to MHCI or MCHII
a T cell failing to bind MHC gets ____ days to make a new TCR before it dies
name
3-4 days
MHC restriction
Lck and TH-POK involved in…
CD4 T cells
negative selection eliminates T cells that bind…
too tightly
alternative to negative selection after T cell release into circulation
Tregs
TdT improves diversity of ___ chain for t cells
Alpha
2 ways naive T cells move around
Enter lymph tissue through venule from circulation (HEV)
From node to node through lymphatic vessels, entering through middle T-cell area
homing
naive T cells attracted to T cell area
dendritic cells enter lymph node only through…
afferent duct
empty MHC in dendritics before exposure marker
yellow-green
MHC on dendrite surface presenting antigen marker
green
vesicles containing digesting antigens marker
red
vesicles containing MHC + antigen in cell marker
yellow
micropinocytosis
phagocytosis of extracellular pathogens, digestion, and loading of antigens into MHCII
antigens presented to CD4 cell
macropinocytosis
sampling of larger volumes of extracellular fluid to try and capture pathogens, like a fishing net
endosomal system allows MHCII presentation
rare way for viral antigen to be loaded on MHCII
cytosolic system
viral infection
MHCI is assembled with viral antigens from immunoproteasome (transported to ER through TAP)
presentation is to CD8 cells
cross-presentation
loading of antigens normally on MHCII to MHCI instead
dendrite fusion
a dendritic cell that’s totally doomed will transfer antigens from its infection to an uninfected dendritic cell, to be presented on MHCI
if a T cell recognizes a dendritic’s antigen..
LFA-1 changes shape and binds tightly for days
matching T-cell + dendritic cell
cognate pair
synapse signal 1
T cell binding to dendritic
synapse signal 2
B7 (dendritic) binds CD28 (T cell)
immunosuppressive drugs interfere with…
IL-2 signalling
“survival sign” preventing anergy
IL-2
old concept Type 1 CD4:
favors cell response, macrophages
TH1
old concept Type 2 CD4:
favors B cell response
TFH
TH1
activate…
fight… infections
macrophages
intracellular
TH17
enhance…
acts in…
neutrophil response
peripheral tissues
TH2
activate…
promote…
cellular/antibody response to parasites (granulocytes, IgE)
healing
TFH
activate…
fight …infections
migrates to…
B cells
fight ALL infections
migrate to B cell area
2 types of Tregs
Natural regulatory cells - made all the time - provide tolerance to our own tissues
Induced regulatory cells - in case of infection - TGF-β induces them
requires priming
CD8
priming involves MHCI or MHCII?
both
T cell cytokines are made when?
upon TCR binding to antigen
naive T cells only recognize…
dendritics
B7/CD28 not required after…
stimulation to proliferation by IL-2
CD8 cytotoxins
granzymes
perforin
serglycan
granulysin
granzymes
5 serine proteases
can turn proteins in target cell into DNA proteases
granulysin
detergent that dissolves membranes
CD8 binding –> apoptosis takes ____
5 mins
slow, deliberate process
CD40 binding to macrophage
CD40 causes… changes in macrophage
phagolysosome fusion becomes more efficient - production of oxygen radicals, nitric oxide, proteases increases
linked recognition
many B-cells in vicinity will be presenting different antigens from the pathogen
all B-cells presenting different epitopes will be stimulated by soluble cytokines in vicinity
___ stimulates B cells to react to sugars, lipids from pathogen
TFH
Hep B pathogenesis
unusually high production of TGF-β and Treg activity (wild type; most people)
super-resisters fight hepatitis very effectively
absence of FoxP3…
tx?
leads to attack on gut, skin, endocrine glands
stem cell transplant in infancy is the only treatment
