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Innate Immunity > T cells > Flashcards

T cells Flashcards

1
Q

what are the 3 signals do naive cells require

A

Activation, survival and differentiation

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2
Q

What are the activation signals

A

CD4 and MHC/ TCR

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3
Q

what are the survival signals

A

CD80/86 and CD28

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4
Q

Draw interaction of DC and APCs

A
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5
Q

What is the signal for T cell differentiation

A

IL-12

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6
Q

what are co-inhibitors of T cells

A

CTLA-4 to CD80/86
PD-1 - PDL

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7
Q

What are the co-stimulators of T cells

A

CD28-CD80/86
ICOS-ICOSL

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8
Q

what are main APCs

A

mature DCs, macrophages and B cells

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9
Q

what ligation signal is optimal for t cell clonal expanssion

A

CD28-CD80/86

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10
Q

CD28-CD80/86 what does it induce

A

IL-2 and IL-2r

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11
Q

what does il-2 receptor consist of

A

alpha, beta and gamma

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12
Q

what does the removal of il-2 on activated t cells cause

A

cell death

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13
Q

what does il2 and il2r initiate

A

t cells to enter cell cycle, inducing t cell proliferation

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14
Q

what is icos expressed by

A

activated CD4+ T cells

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15
Q

what is icos induced by

A

T cell receptor and CD28 signals.

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16
Q

What does icos regulate

A

growth, proliferation, survival and induce cytokine production by CD4 t cells

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17
Q

ICOS expression on TFH cells

A

help B cell responses such as isotype switching through IL-4/IFN-g.

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18
Q

CD40L on T-cells binds to

A

CD40 on activated APC

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19
Q

whats induced on DC after CD40L stimulation

A

OX40/OX40L

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20
Q

OX40 signalling important for

A

T cell survival and homeostasis
supports the generation of memory T cells.

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21
Q

OX40 deficient mice

A

exhibit reduced CD4 T-cell proliferation in response to viral infection.

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22
Q

What role do B cells play in T cell activation?

A

resent soluble antigens, including toxins and viruses.

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23
Q

What role do B cells play in T cell activation?

A

intracellular or extracellular pathogens

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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

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25
Q

anergy

A

lack of co-stimulatory signals

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26
Q
A
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27
Q

CTLs kill target cells through two primary pathways

A

Perforin-Granzyme Pathway, Fas-FasL Pathway

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28
Q

Perforin-Granzyme Pathway

A

CTLs release perforin, which forms pores in the target cell membrane, and granzymes, which enter through these pores and induce apoptosis

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29
Q

Fas-FasL Pathway

A

CTLs express Fas ligand (FasL), which binds to Fas on the target cell, triggering apoptosis through activation of caspases

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30
Q

Regulatory mechanisms- CLTs

A

PD-1 and CTLA-4, which can downregulate CTL activity

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31
Q

CTL - Therapeutic strategies

A

checkpoint inhibitors, aim to enhance CTL responses against tumors by blocking inhibitory signal

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32
Q

Vaccines CTL

A

stimulate robust CTL responses are also a goal in the fight against chronic viral infections, such as HIV and HBV

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33
Q

CTL

A

Cytotoxic T lymphocytes

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34
Q

what are the 2 signals needed for CTL

A

TCR and MHC 1 and co-stimulatory signal: CD28 on the T cell and CD80/86 (B7 molecules) on the APC

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35
Q

CD8+ T cells priming lead to

A

Clonal expansion, differentiation to kill target cells

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36
Q

what do CTL express

A

IL-2 receptor=

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37
Q

what chemokines guide ctls to site of inflammation

A

CXCR3, CCR5

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38
Q

PD-1/PD-L Pathway inhibts CTL by

A

inhibition of the PI3K/Akt pathway, which is essential for cell survival = cell death, promote the development

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39
Q

PD-1 - tumour microenviroment

A

high levels of PD-L1 expression on tumor cells can engage PD-1 on T cells= tumor to escape immune surveillance.

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40
Q

clta-4 vs cd80/86

A

has higher affinity and restricts IL-2 production

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41
Q

autoimmune disorders linked to dysregulated PD-1 &/or CTLA-4

A

Type 1 diabetes, RA

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42
Q

immunological synapse

A

t cell and APC interaction

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43
Q

T cell and APC interaction triggers the formation of immune synapse leading to what changes

A
  1. Accumulation and segregation of surface molecules
  2. cytoskeletal polarization
  3. polarised exocytosis
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44
Q

cytoskeletal polarization

A

Actin filaments and microtubules align towards the APC

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45
Q

Polarized Exocytosis

A

polarized towards the AP- secretory vesicles directed to IS

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46
Q

c-SMAC

A

Enriched with TCR/CD3

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47
Q

p-SMAC

A

Contains integrins such as LFA-1, which forms a ring around the c-SMAC, providing structural support.

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48
Q

d-SMAC

A

adhesion molecules like CD4, which stabilize the interaction between the T cell and APC.

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49
Q

what’s the SMACs

A

central, peripheral, distal

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50
Q

CD45

A

Interfere with TCR signaling due to its size and phosphatase activity- so only in d-smac and excluded from c-smac

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51
Q

CD45 whats the point

A

dephosphorylating certain proteins, ensuring TCR signaling is neither too weak nor too strong- preventing inappropriate t cell activation

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52
Q

smac

A

supramolecular activation molecules

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53
Q

what signals are required for th1

A

IL-12 and IL-18

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54
Q

what do th1 produce

A

IFN-γ, TNF-α, and IL-2

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55
Q

th1 combat

A

intracellular infections, such as bacteria and viruses

56
Q

how do th1 help combat(4)

A

activating macrophages, aiding CD8+ T cell function, enhancing antigen presentation, and influencing B cell antibody class switching

57
Q

IL-18 and IL-12 drive what activation

A

NK cells

58
Q

TLR4 ligand

A

LPS, on gram negative bacteria and DAMPs

59
Q

TLR 4 function

A

activation of NF-kB, and release of pro-inflammatory(TNF-a, IL-1, IL-6), upregulates co-stim molecules on APCs

60
Q

TLR4 in vaccines and therapeutics

A

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
Q

what disease needs upreg of tlr4

A

sepsis

62
Q

il-12/il-12r

A

activates the STAT4 (Th1)

63
Q

IL-18 binds to the IL-18 receptor

A

activation of NF-κB- contributes thfa and ifny production

64
Q

IFNγ/ IFNγr

A

STAT1 (Th1)

65
Q

STAT4/1

A

promotes Tbet expression

66
Q

tbet

A

transcription factor for th1

67
Q

th1 positive feedback loops

A

IFNy induce its own production, upregulating IL12 - cell more responsive to IL-12 and il-18

68
Q

what does th1 upreg

A

IgG2 (extracellular bacteria) class switching, granuloma formation, macrophage phagocytosis

69
Q

GM-CSF - released by th1

A

activates macrophages

70
Q

th1 and RA

A

activating macrophages - increase inflammation in RA also IBD

71
Q

Th2 involved in what responses

A

Allergen responses (Helminths)

72
Q

what cells do TH2 activate

A

eosinophils, basophils, and B cells (IgE)

73
Q

why cant TH1 see TH2 infections

A

they (Helminths) dont have LPS

74
Q

how do they differentiate into th2 and not th1

A

express lower levels of peptide-MHC (pMHC) and co-stimulatory molecules

75
Q

what cytokines lead to th2

A

IL-4,IL-2, IL-33 and TSLP

76
Q

What do TH2 produce

A

IL-4, IL-5, and IL-13 (inducing IgE class switching)

77
Q

what does IgE do

A

bind to mast cells and basophils= release histamines

78
Q

ILC2 Activation

A

activated by IL-25 and thymic stromal lymphopoietin (TSLP)- amplifying Th2

79
Q

il-5 function in th2

A

recruits eosinophils, which release cytotoxic proteins that can damage or kill parasites.

80
Q

IL-13 th2

A

increases mucus production, which can help to trap and expel helminths and their eggs from the gut.

81
Q

IL-4 and IL-13 (TH2)

A

promote tissue repair/ remodelling and wound healing through the activation of M2 macrophages

82
Q

Necrotic (damaged or dead) epithelial cells release

A

IL-25/ TSLP (alarmins) and IL-33

83
Q

examples of helminths

A

roundworms, tapeworms

84
Q

Fibrosis

A

chronic activation of Th2 responses, excessive formation of connective tissue

85
Q

FcεR1

A

high-affinity receptor for the Fc region of IgE antibodies

86
Q

cross-link IgE

A

cause degranulation of mast cells and basophils= release histamines and inflammatory ctokines

87
Q

symptoms when IgE bound to mast cells

A

smooth muscle constriction, increased vascular permeability, edema, and secretion of mucus

88
Q

examples of tissue remodelling by il-13 and il-4

A

asthma, chronic allergens

89
Q

fc region

A

on igE antibodies

90
Q

fc binds to

A

FcεR1

91
Q

cross-linking

A

two IgE antibodies bound to the same cell recognize the same allergen- as allergen has multiple identical epitopes

92
Q

Histamine

A

Causes vasodilation and increases the permeability of blood vessels

93
Q

cytokines released by mast cells and basophils

A

IL-4 and IL-13, TNF alpha (promotes inflammation and recruitment)

94
Q

another granular content like histamine

A

Prostaglandins

95
Q

eosinophils releasein th2 response

A

release MBP, ECP and EPO (damage paracitic membrane)

96
Q

Th9 Cells

A

related to Th2 cells, induced by TGFβ, produce il-9

97
Q

Th3 Cells

A

produced by TGFβ, they contribute to mucosal immunity and tolerance and induce IgA production

98
Q

Th22 Cells

A

relate to Th17, they produce IL-22 involved in skin homeostatic and inflammation (can be promoted by AH receptor - found in smoke)

99
Q

Ex-Th17 Cells

A

former Th17

100
Q

Tr1 Cells

A

T cells produce IL-10 and can suppress immune responses. They may produce IFNy-promote immune cells

101
Q

STAT 6 inhibition

A

activated by IL-4 inhibits IFNγ production to prevent Th1 differentiation

102
Q

STAT1 and STAT4 inhibit

A

(promoted by IFNγ) inhibit Th2 differentiation by suppressing IL-4 production.

103
Q

wht cells do th2 interact with

A

ILCs, basophils, eosinophils, mast cells,
macrophages and DCs

104
Q

what cells do th1 interact with

A

CD8+ Tcells, NK cells, macrophages and DCs

105
Q

Th17 produce

A

IL-17A, IL-17F, TNF (tumor necrosis factor), IL-21, and IL-22

106
Q

IL-17A and IL-17F

A

attract neutrophils and other immune cells to the site of infection or inflammation.

107
Q

Th17 function

A

fungal pathogens - candidia albicans

108
Q

IL-21 produced by Th17 cells

A

supports differentiation of tfh

109
Q

dysreg of th17 response

A

leads to RA and MS

110
Q

what CD defines T cells

A

CD3

111
Q

T helper cells (aka CD4 T cells) CDs

A

CD3+CD4+

112
Q

CTLs, cytotoxic T lymphocytes (aka CD8 T cells) CDS

A

CD3+ CD8+

113
Q

= NKT cells (CD161 is aka NK1.1) CDs

A

CD3+ CD161+

114
Q

gamma/delta T cells

A

innate like - small population of t cells

115
Q

SCID

A

severe combined immunodeficiency (too little T cell activity)

116
Q

Example of SCID

A

Genes that affect IL-2 (IL-2 fuels TH cell proliferation)
The genes that re-arrange the TCR and BCR

117
Q

treatment of SCID

A
  1. Avoid infection
  2. Passive transfer of antibodies
  3. Bone-marrow transplantation
  4. Gene-therapy to replace defective gene
  5. Continual antibiotics
118
Q

what does HIV-1 infect

A

CD4+ T cells (leads to depletion and death)

119
Q

HIV-1

A

Human Immunodeficiency virus 1

120
Q

what structures is the thymus made from

A

cortex, medulla, cortico-medullary junction

121
Q

thymus cortex

A

largest part of thymus mostly composed of epithelial cells

122
Q

thymus medulla

A

contains epithelial cells, macrophages, DC

123
Q

why do so many cells in thymus die

A

selection

124
Q

what are the several key stages of t cell development in thymus

A

DN, DP, SP

125
Q

Bone marrow chimeras

A

allowed identification of CD4 and CD8

126
Q

TCRαβ^lo

A

as T cells begin to test their receptors against self-peptides presented by MHC (rearrangement in DP phase)

127
Q

TCRαβ^+

A

denote T cells that have successfully undergone the positive selection ( (SP phase CD4^+ or CD8^+)

128
Q

what are the thymic APC

A

cTEC, mTEC and mDC

129
Q

APECED

A

mutations within AIRE

130
Q

Sympathetic ophthalmia

A

to presentation of self-Ag and the immune system attacks the undamaged eye

131
Q

Mumps/Measles orchitis

A

Both the mumps and measles viruses can cause inflammation of the testis

132
Q

Some antigens are (usually) never ‘seen’ by the immune system

A

eyes and testis

133
Q

cell-intrinsics

A

Quiescence (returning to resting state), programmed cell death, memory

134
Q

cell-extrinsic

A

Regulatory cells, immune supressive cytokines and drugs

135
Q

innate regulatory cells

A

Myeloid derived suppressor cell

Innate Immunity (9 decks)

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