Exam III and IV Flashcards
1
Q
Pro B cell stages
A
Heavy Chain rearrangement
2
Q
Pre B cell
A
First checkpoint –> light chain rearrangement –> Second checkpoint
3
Q
Immature B cell
A
Makes functional IgM
4
Q
Survival of pro-B cell depends first on the productive rearrangement of the
A
heavy chain
5
Q
Immature B cell can either be
A
u:k or u:l
6
Q
how many successive attempts can be made of the kappa chain
A
5 successive attempts can be made of the kappa chain.
7
Q
Immature B cell first undergoes
A
negative selection in the BM
8
Q
receptor editing allows
A
the immature B cell more chances to make a nonreactive BCR (only editing in light chain)
9
Q
B cell undergoes receptor editing
A
to make IgM with different specificities and not till the receptor is NOT self reactive, the B cell leaves the BM.
10
Q
Maturation of B cells
A
immature B cells leave BM and enter circulation and secondary lymphoid organs.
11
Q
Interaction with _ provides the required maturation and survival signals _
A
FDC; Positive selection
(competition with other B cell is the limiting factor for space in folice
12
Q
enigmatic follicular dendritic cell
A
storage vessel for antigens ready for B cell stimulation.
CR1 and CR2 bind to intact virus particles and retain them at the cell surface
13
Q
capture and display of intact antigens by CR2 expressed on
A
FDC and macrophages
14
Q
How do B cells become activated?
A
When their receptors are cross linked by antigens
15
Q
Much like T cell activation, B cell activation requires
A
Cross linking (clustering) and association with signaling adapters
16
Q
B cell signaling cascade initiated from
A
ITAM domains in IgA and IgB
17
Q
BCR triggering is greatly ENHANCED by
A
B cell coreceptor:
CD19/CR2/CD81
increase BCR signal intensity by 10,000 fold.
Work best with complement labeled antigens
18
Q
CR2
A
binds to the antigen/microbe and initiates B cell activation
19
Q
Binding of CR1 to C3b
A
bound to a pathogen facilitates its cleavage by Factor I to iC3b and C3d.
20
Q
The CR2 component binds to
A
C3d
21
Q
Two types of antigens activate B cells
A
T dependent: Require T cell help for production of antibodies (protein antigens)
T independent:
22
Q
T dependent B cell activation
A
CD40/CD40Ligand interaction with T cells
Essential for T cell help
Required for isotype switching, affinity maturation
23
Q
CD40:CD40L
A
B cells need two signals for activation by T cell dependent antigens.
To obtains T cell help, B cell must take up antigen through BCR, process and present peptide via MHC class II
24
Q
T independent antigens
A
T1 and T2
25
TI1 (T independent antigens)
combination of BCR and TLR signals activate B cell
Require contribution from TLR signaling.
26
TI2
repetitive carbohydrate antigens present at high density on a pathogen surface, leads to extensive BCR cross linking
27
TI1
TLR
28
TI2
crosslinking
29
plasma cells
migrate to medullary cords or BM
- have no cell surface immunoglobulin or MHC class II, no further division, specialized for antibody secretion
30
primary expansion of antigen activated B cells
medullary cords --> primary follicle --> creates the germinal center
31
cell entire devoted to antibody production
plasma cell
32
germinal centers
sites where somatic hyper mutation, affinity maturation and isotype switching occurs
33
memory B cells
maintained and circulate through body ready to rapidly respond upon pre-exposure to pathogen.
34
somatic hypermutation
Changes affinity for antibody
35
Resting B cell
Surface Ig: Yes
MHC class II: yes
High rate Ig Secretion: no
Growth : yes
Somatic hyper M.: yes
Isotype switch: yes
36
plasma cell properties
Surface Ig: no
MHC class II; no
High rate Ig Secretion ; yes
Growth ; no
Somatic hyper M.; no
Isotype switch: ; no
37
T cells, development and selection
Thymus
38
B cell location and development
BM
39
Function of T cell
kill or make cytokines
40
Function of B cell
make antibodies
41
Like B cells, T cells generate receptors through
somatic recombination
42
T cells are more _ than B cells
diverse
43
two classes of T cell receptors
alpha/beta and gamma/delta
44
majority of conventional T cells
alpha beta
45
T cell receptor class with high degree of receptor diversity
alpha beta
46
alpha/beta recognize
MHC/peptides
47
where are alpha/beta abundant
all secondary lymphoid tissues
48
gamma/delta abundant in
gut mucosa
49
types of alpha/beta T cells
CD4 and CD8
50
CD4+ T helper cells
Produce cytokines to help clear infections
recognize MHC II
Antigens tend to be from extracellular sources
51
CD8 + Cytolytic T cells
Killer cell
MHC I though CD8
Cytoplasmic sources
52
CD4 consists of
D1-4
53
CD8 consists of
alpha and beta chain
54
TCR complex needs help from
CD3 to transmit signals.
Also required for Cell surface expression
55
preTCR
Beta + pTalpha
56
steps in T cell receptor formation
1. beta, gamma and delta chains attempt to rearranged simultaneously
- if beta is successful, then it's tested with preTCR
If gamma and delta are both successful, then rearrangement is complete and cell becomes a gamma/delta
2. alpha, gamma and delta attempt rearrangement.
57
double positive
when CD4 and CD8 are both expressed. after cell has rearranged beta chain successfully
58
Pre TCR purpose
tests the ability of a rearranged beta chain to form complex with the preTalpha.
Stops rearrangement at the other beta locus - allelic exclusion
59
which chain in T cell receptors have more attempts at functional rearrangement?
alpha
60
implication for AB vs. GD TCR rearrangement
Delta gene is situated within alpha gene locus. Rearrangement of the alpha chain results in the deletion of delta loci, so no chance to make a gamma/delta.
61
timing of rearrangement of the beta and alpha chains
RAG expression
62
when T cells begin rearrangement, they are
double negative.
Neither CD4 or CD8 expressed
63
when PreTCR is tested and proven to be successful,
CD4 and CD8 will be unregulated (double positive)
64
after selection is complete,
T cells enter the periphery, only CD4 or CD8 will be expressed.
65
thymic involution
as we get older, our thymus produces less and less T cells
66
Cortex contains
cortical epithelial cells
thymocytes
medullary epithelial cells
67
Medulla contains
dendritic cell
macrophage
68
Positive selection of T cells occur in
cortex of thymus
69
Positive selection of T cells occur
first, then negative
gets rid off poor binders
70
what cells do positive selection in T cells
thymic epithelial cells
71
negative selection of T cells occur in
Cortico-meduallry region
72
Negative selection cells
dendritic cells.
Overly strong binders eliminated
73
Positive selection determines whether a T cell will
commit to the CD4 or CD8 phenotype.
74
Positive selection determines whether a T cell will
commit to the CD4 or CD8 phenotype.
75
Lack of CD8 Case study
Patient had a deficiency in TAP which is needed for MHC class I, and with our CD8, there is no + selection for CD8 T cells in the thymus
76
Pneumocytosis carinii
lacking CD4 T cells
77
MHC class II deficiency seems from
B cells not expressing HLA-DQ or HLA-DR
78
CD3 chains
EY
ED
79
What cells activate T cells?
Dendritic cells, in the sites of infection, take up pathogen derived antigens. When triggered by PAMPs and inflammation at sites of infection, DC migrate to draining lymph nodes. They undergo maturation, enhancing their ability to present antigen and activate T cells.
80
Naive T cells
Prior to recognition of antigen and activation.
Need several signals (MHC and co-stimulation) to become activated.
81
Effector T cell
Activated cell, antigen experienced.
Need ONE signal, short lived
82
Memory T cell
antigen experienced, easily activated state indefinitely.
REQUIRE ONE signal
83
Two signals needed for naive T cells
MHC peptide
Costimulaiton through B7-1 or B7-2.
84
B7-1 and B7-2 are
co-stimulatory molecules that are uniquely expressed by DC, Macrophages, B cells.
85
B7 binds to CD28 on
naive T cell
86
What happens when T cells recognize their cognate antigen?
- TCR initiates signaling through CD3 and CD4/CD8
- immune synapse forms at site of T cell-APC interaction
- T cell and APC remind in sustained interaction for up to 24hrs
- T cell disengages divides and emigrates from lymph node to seek out infected cell in periphery
87
ITAM
immunoreceptor tyrosine based activation motifs
these are not phosphorylated in resting T cell.
Binding of MHC ligand to T cell receptor leads to phosphorylation of ITAMs
88
PLC-y -->
CA2+, NFkB, AP1, NFAT
change the pattern of gene expression, cell division, proliferation and differentiation to effector T cells.
89
Immunological synapse
structure that forms along the interface of T cell and APC during sustained interaction of T cell activation
90
P-SMAC
peripheral,
adhesion molecules
91
C-SMAC
TCR, co-stimulatory molecules and lots of signaling molecules
92
MOST important cytokine for T cell proliferation
IL2!!!!!!!!!!
93
T cell gets signal 1 and 2
activated T cell
94
T cells get signal 1, not 2
T cell becomes anergic
95
T cell gets signal 2, not signal 1
no effect on T cell
96
cytotoxins
perforin
granzymes
granulysin
97
cytokines
IFNy
LT
98
Th2 cell
IL4, IL13, IL 5
99
Th2 effect
barrier immunity on
eosinophils
basophils
mast cells
macrophages
100
Treg cells
IL10, TGF-beta
101
Treg effect
inhibition of other T cell types
Dendritic cells
102
Th17 cells
IL17
Neutrophils
103
Th17 effect
acute inflammation - neutrophils
104
Th1 cells secrete
IFN-y
105
Th1 effect
systemic immunity
macrophages
NK cells
CD8 T cells
106
3 signal hypothesis
MHC/peptide
Costimualtion CD80/86
Cytokines IL12
107
Signal 3 (cytokines, IL12)
instructs T cell differentiation
108
Th1 driven responses
intracellular pathogens and tumors
109
Th1 product
IFN-y
110
IFNy effect
increased MHC class I and II
Th1 cells development
Isotype switching
Macrophage activation
111
activated macrophage results in
Increased expression of costimulators - B7 molecules
Killing of phagocytosed microbes
Secretion of cytokines (TNF, IL1, IL12)
Increased expression of MHC molecules
112
Th2 responses provide protection against
multicellular parasites and mediate hypersensitivity responses
113
Th2 provide proliferative signals to
B cells, and drive isotype switching between IgG1 and E
Often associated with allergy
114
Th2, signature cytokine product
IL4
115
Th2 --> IL4/13
activation of eptithelial cells and smooth muscle cells
116
Th2 --> IL5
eosinophil and B cells
117
Th2 --> IL3/IL9
basophils and mast cells
118
Actions of IL4
Iso-type switching to IgE
Inhibition of macrophage activation
Development and expansion of Th2 cells
119
Th17 protects against
extracellular bacteria, by recruiting neutrophils.
120
Th17 often associated with
immune disorders
121
Major product of Th17
IL 17 (IL23 is important for maintenance of Th17 phenotype)
Th17, appear early in infection - before Th1 and Th2
122
how does CD4 become a Th17 cell?
must be exposed to TGF beta and IL6
123
Th17 --> IL17 -->
activate endothelial cells which recruit neutrophils via IL6
124
IL22
induces keratinocytes and epithelial cells to express antimicrobial peptides
125
Treg cells main function
suppress immune responses
126
TF for Tregs
FoxP3
127
Tregs suppress T cells expressing
CD4 and CD25
128
Tregs secrete
IL10 and TGF-beta
129
IL 10 function
Reduces IL12 and TNFalpha, reduces expression of MHC costimulatory molecules
130
TGF-beta function
blocks cytokine production, proliferation of T and B cells and cytolytic activity
131
How Tregs can have a negative effect
tumors secrete TGF-beta, which induces Tregs at the tumor site to suppress anti tumor responses
132
Tfh Cells secrete
IL21
Provide B cells with help to class switch and high affinity antibody production
