T cells Flashcards
(135 cards)
1
Q
what are the 3 signals do naive cells require
A
Activation, survival and differentiation
2
Q
What are the activation signals
A
CD4 and MHC/ TCR
3
Q
what are the survival signals
A
CD80/86 and CD28
4
Q
Draw interaction of DC and APCs
A
5
Q
What is the signal for T cell differentiation
A
IL-12
6
Q
what are co-inhibitors of T cells
A
CTLA-4 to CD80/86
PD-1 - PDL
7
Q
What are the co-stimulators of T cells
A
CD28-CD80/86
ICOS-ICOSL
8
Q
what are main APCs
A
mature DCs, macrophages and B cells
9
Q
what ligation signal is optimal for t cell clonal expanssion
A
CD28-CD80/86
10
Q
CD28-CD80/86 what does it induce
A
IL-2 and IL-2r
11
Q
what does il-2 receptor consist of
A
alpha, beta and gamma
12
Q
what does the removal of il-2 on activated t cells cause
A
cell death
13
Q
what does il2 and il2r initiate
A
t cells to enter cell cycle, inducing t cell proliferation
14
Q
what is icos expressed by
A
activated CD4+ T cells
15
Q
what is icos induced by
A
T cell receptor and CD28 signals.
16
Q
What does icos regulate
A
growth, proliferation, survival and induce cytokine production by CD4 t cells
17
Q
ICOS expression on TFH cells
A
help B cell responses such as isotype switching through IL-4/IFN-g.
18
Q
CD40L on T-cells binds to
A
CD40 on activated APC
19
Q
whats induced on DC after CD40L stimulation
A
OX40/OX40L
20
Q
OX40 signalling important for
A
T cell survival and homeostasis
supports the generation of memory T cells.
21
Q
OX40 deficient mice
A
exhibit reduced CD4 T-cell proliferation in response to viral infection.
22
Q
What role do B cells play in T cell activation?
A
resent soluble antigens, including toxins and viruses.
23
Q
What role do B cells play in T cell activation?
A
intracellular or extracellular pathogens
24
Q
Role of Dendritic Cells in T Cell Activation
A
through peptides and viral antigens, including allergens - deliver all three signals necessary for naïve T cell activation
25
anergy
lack of co-stimulatory signals
26
27
CTLs kill target cells through two primary pathways
Perforin-Granzyme Pathway, Fas-FasL Pathway
28
Perforin-Granzyme Pathway
CTLs release perforin, which forms pores in the target cell membrane, and granzymes, which enter through these pores and induce apoptosis
29
Fas-FasL Pathway
CTLs express Fas ligand (FasL), which binds to Fas on the target cell, triggering apoptosis through activation of caspases
30
Regulatory mechanisms- CLTs
PD-1 and CTLA-4, which can downregulate CTL activity
31
CTL - Therapeutic strategies
checkpoint inhibitors, aim to enhance CTL responses against tumors by blocking inhibitory signal
32
Vaccines CTL
stimulate robust CTL responses are also a goal in the fight against chronic viral infections, such as HIV and HBV
33
CTL
Cytotoxic T lymphocytes
34
what are the 2 signals needed for CTL
TCR and MHC 1 and co-stimulatory signal: CD28 on the T cell and CD80/86 (B7 molecules) on the APC
35
CD8+ T cells priming lead to
Clonal expansion, differentiation to kill target cells
36
what do CTL express
IL-2 receptor=
37
what chemokines guide ctls to site of inflammation
CXCR3, CCR5
38
PD-1/PD-L Pathway inhibts CTL by
inhibition of the PI3K/Akt pathway, which is essential for cell survival = cell death, promote the development
39
PD-1 - tumour microenviroment
high levels of PD-L1 expression on tumor cells can engage PD-1 on T cells= tumor to escape immune surveillance.
40
clta-4 vs cd80/86
has higher affinity and restricts IL-2 production
41
autoimmune disorders linked to dysregulated PD-1 &/or CTLA-4
Type 1 diabetes, RA
42
immunological synapse
t cell and APC interaction
43
T cell and APC interaction triggers the formation of immune synapse leading to what changes
1. Accumulation and segregation of surface molecules
2. cytoskeletal polarization
3. polarised exocytosis
44
cytoskeletal polarization
Actin filaments and microtubules align towards the APC
45
Polarized Exocytosis
polarized towards the AP- secretory vesicles directed to IS
46
c-SMAC
Enriched with TCR/CD3
47
p-SMAC
Contains integrins such as LFA-1, which forms a ring around the c-SMAC, providing structural support.
48
d-SMAC
adhesion molecules like CD4, which stabilize the interaction between the T cell and APC.
49
what's the SMACs
central, peripheral, distal
50
CD45
Interfere with TCR signaling due to its size and phosphatase activity- so only in d-smac and excluded from c-smac
51
CD45 whats the point
dephosphorylating certain proteins, ensuring TCR signaling is neither too weak nor too strong- preventing inappropriate t cell activation
52
smac
supramolecular activation molecules
53
what signals are required for th1
IL-12 and IL-18
54
what do th1 produce
IFN-γ, TNF-α, and IL-2
55
th1 combat
intracellular infections, such as bacteria and viruses
56
how do th1 help combat(4)
activating macrophages, aiding CD8+ T cell function, enhancing antigen presentation, and influencing B cell antibody class switching
57
IL-18 and IL-12 drive what activation
NK cells
58
TLR4 ligand
LPS, on gram negative bacteria and DAMPs
59
TLR 4 function
activation of NF-kB, and release of pro-inflammatory(TNF-a, IL-1, IL-6), upregulates co-stim molecules on APCs
60
TLR4 in vaccines and therapeutics
upreg could boost the immune response against infections and cancer, downreg could dampen harmful inflammation in diseases like sepsis and autoimmunity. - induce inflam response to vaccine
61
what disease needs upreg of tlr4
sepsis
62
il-12/il-12r
activates the STAT4 (Th1)
63
IL-18 binds to the IL-18 receptor
activation of NF-κB- contributes thfa and ifny production
64
IFNγ/ IFNγr
STAT1 (Th1)
65
STAT4/1
promotes Tbet expression
66
tbet
transcription factor for th1
67
th1 positive feedback loops
IFNy induce its own production, upregulating IL12 - cell more responsive to IL-12 and il-18
68
what does th1 upreg
IgG2 (extracellular bacteria) class switching, granuloma formation, macrophage phagocytosis
69
GM-CSF - released by th1
activates macrophages
70
th1 and RA
activating macrophages - increase inflammation in RA also IBD
71
Th2 involved in what responses
Allergen responses (Helminths)
72
what cells do TH2 activate
eosinophils, basophils, and B cells (IgE)
73
why cant TH1 see TH2 infections
they (Helminths) dont have LPS
74
how do they differentiate into th2 and not th1
express lower levels of peptide-MHC (pMHC) and co-stimulatory molecules
75
what cytokines lead to th2
IL-4,IL-2, IL-33 and TSLP
76
What do TH2 produce
IL-4, IL-5, and IL-13 (inducing IgE class switching)
77
what does IgE do
bind to mast cells and basophils= release histamines
78
ILC2 Activation
activated by IL-25 and thymic stromal lymphopoietin (TSLP)- amplifying Th2
79
il-5 function in th2
recruits eosinophils, which release cytotoxic proteins that can damage or kill parasites.
80
IL-13 th2
increases mucus production, which can help to trap and expel helminths and their eggs from the gut.
81
IL-4 and IL-13 (TH2)
promote tissue repair/ remodelling and wound healing through the activation of M2 macrophages
82
Necrotic (damaged or dead) epithelial cells release
IL-25/ TSLP (alarmins) and IL-33
83
examples of helminths
roundworms, tapeworms
84
Fibrosis
chronic activation of Th2 responses, excessive formation of connective tissue
85
FcεR1
high-affinity receptor for the Fc region of IgE antibodies
86
cross-link IgE
cause degranulation of mast cells and basophils= release histamines and inflammatory ctokines
87
symptoms when IgE bound to mast cells
smooth muscle constriction, increased vascular permeability, edema, and secretion of mucus
88
examples of tissue remodelling by il-13 and il-4
asthma, chronic allergens
89
fc region
on igE antibodies
90
fc binds to
FcεR1
91
cross-linking
two IgE antibodies bound to the same cell recognize the same allergen- as allergen has multiple identical epitopes
92
Histamine
Causes vasodilation and increases the permeability of blood vessels
93
cytokines released by mast cells and basophils
IL-4 and IL-13, TNF alpha (promotes inflammation and recruitment)
94
another granular content like histamine
Prostaglandins
95
eosinophils releasein th2 response
release MBP, ECP and EPO (damage paracitic membrane)
96
Th9 Cells
related to Th2 cells, induced by TGFβ, produce il-9
97
Th3 Cells
produced by TGFβ, they contribute to mucosal immunity and tolerance and induce IgA production
98
Th22 Cells
relate to Th17, they produce IL-22 involved in skin homeostatic and inflammation (can be promoted by AH receptor - found in smoke)
99
Ex-Th17 Cells
former Th17
100
Tr1 Cells
T cells produce IL-10 and can suppress immune responses. They may produce IFNy-promote immune cells
101
STAT 6 inhibition
activated by IL-4 inhibits IFNγ production to prevent Th1 differentiation
102
STAT1 and STAT4 inhibit
(promoted by IFNγ) inhibit Th2 differentiation by suppressing IL-4 production.
103
wht cells do th2 interact with
ILCs, basophils, eosinophils, mast cells,
macrophages and DCs
104
what cells do th1 interact with
CD8+ Tcells, NK cells, macrophages and DCs
105
Th17 produce
IL-17A, IL-17F, TNF (tumor necrosis factor), IL-21, and IL-22
106
IL-17A and IL-17F
attract neutrophils and other immune cells to the site of infection or inflammation.
107
Th17 function
fungal pathogens - candidia albicans
108
IL-21 produced by Th17 cells
supports differentiation of tfh
109
dysreg of th17 response
leads to RA and MS
110
what CD defines T cells
CD3
111
T helper cells (aka CD4 T cells) CDs
CD3+CD4+
112
CTLs, cytotoxic T lymphocytes (aka CD8 T cells) CDS
CD3+ CD8+
113
= NKT cells (CD161 is aka NK1.1) CDs
CD3+ CD161+
114
gamma/delta T cells
innate like - small population of t cells
115
SCID
severe combined immunodeficiency (too little T cell activity)
116
Example of SCID
Genes that affect IL-2 (IL-2 fuels TH cell proliferation)
The genes that re-arrange the TCR and BCR
117
treatment of SCID
1. Avoid infection
2. Passive transfer of antibodies
4. Bone-marrow transplantation
5. Gene-therapy to replace defective gene
3. Continual antibiotics
118
what does HIV-1 infect
CD4+ T cells (leads to depletion and death)
119
HIV-1
Human Immunodeficiency virus 1
120
what structures is the thymus made from
cortex, medulla, cortico-medullary junction
121
thymus cortex
largest part of thymus mostly composed of epithelial cells
122
thymus medulla
contains epithelial cells, macrophages, DC
123
why do so many cells in thymus die
selection
124
what are the several key stages of t cell development in thymus
DN, DP, SP
125
Bone marrow chimeras
allowed identification of CD4 and CD8
126
TCRαβ^lo
as T cells begin to test their receptors against self-peptides presented by MHC (rearrangement in DP phase)
127
TCRαβ^+
denote T cells that have successfully undergone the positive selection ( (SP phase CD4^+ or CD8^+)
128
what are the thymic APC
cTEC, mTEC and mDC
129
APECED
mutations within AIRE
130
Sympathetic ophthalmia
to presentation of self-Ag and the immune system attacks the undamaged eye
131
Mumps/Measles orchitis
Both the mumps and measles viruses can cause inflammation of the testis
132
Some antigens are (usually) never ‘seen’ by the immune system
eyes and testis
133
cell-intrinsics
Quiescence (returning to resting state), programmed cell death, memory
134
cell-extrinsic
Regulatory cells, immune supressive cytokines and drugs
135
innate regulatory cells
Myeloid derived suppressor cell
