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Immunology 3115 > Effector T Cells and Cell-mediated Cytotoxicity > Flashcards

Effector T Cells and Cell-mediated Cytotoxicity Flashcards

1
Q

Cell mediated immunity

A

Recognize and eliminate cells that have been infected by viruses or transformed into cancerous cells
Involves antigen-specific effector cells, non-specific effector cells, and cytokines

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2
Q

Effector T cells

A

CD4+ helper (Th1) cells and CD8+ cytotoxic lymphocytes
Do not require CD28 costimulation (unlike naive cells) but can be costimulated by LFA-1 binding ICAMs on target cells
Higher levels of CD2 and LFA-1 to allow more efficient binding to target cells
Express CD44 (upregulated following TCR signaling), low CD26L and no CCR7
Traffick to tertiary lymphoid tissues and sites of inflammation

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3
Q

CD2 in effector T cells

A

Higher levels than in naive cells

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4
Q

LFA-1 in effector T cells

A

Higher levels than in naive cells

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5
Q

CD44 in effector T cells

A

Up regulated following TCR signaling

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6
Q

CD62L in effector T cells

A

Low levels

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7
Q

CCR7 in effector T cells

A

Not present

Prevents recirculation to secondary lymphoid tissue

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8
Q

Effector CD4+ T cells

A

Differentiate when under influence of polarizing cytokines and they come in contact with antigen
(to Th1, Th2, Th17, Tfh, Treg)
Have membrane and soluble effector molecules

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9
Q

Lymphotoxin

A

Membrane bound effector molecule of Th1 cell

Promotes macrophage activation by Th1 (along with IFNgamma)

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10
Q

CD40 ligand

A

Membrane bound effector molecule of Th2 cell
Allergic inflammation
Promotes B cell activation along with IL-4 with Tfh and Th2

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11
Q

IL17 + IL22 secreted by Th17

A

Promotes inflammation

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12
Q

IL10 + TGF-beta secreted by Treg

A

Down regulate cellular immune responses and inflammation

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13
Q

Effector molecules of CD8+ cells

A

Membrane-bound Fas ligand
Secreted IFNgamma, TNF and cytotoxins
Perforin, granzymes and Fas ligand mediate target cell destruction
IFNgamma and TNF enhance cell mediated immunity

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14
Q

CTL-mediated immune responses

A

Activation phase and effector phase

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15
Q

Activation phase of CTL mediated immune response

A 
Stimulation of naive precursor CTL (CTL-P)
Activated by TCR by foreign antigen/class I MHC complexes
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16
Q

Effector phase of CTL mediated immune response

A

Differentiated CTL engage and kill target cells

Differentiate into Tc1 or Tc2 cells

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17
Q

Licensing of antigen-presenting dendritic cells

A
  1. By Th1 or Th17 via antigen-class II MHC-TCR and CD40-CD40 ligand interactions
  2. Activation of TLR on dendritic cells by microbial products
18
Q

Costimulation of CTL-Ps

A

By CD28-CD80/CD86 interactions
IL2 provided by CD4+ T cells
CD8+ T cells interacting with IL2 receptor

19
Q

Activated CTL-P

A

Express high affinity IL2 receptors
Secrete IL2 ( not enough for autocrine growth/differentiation)
CD4+ T cell help is essential for development of memory CD8+ T cells

20
Q

Memory CTL-P

A

When activated, may secrete sufficient IL2 for proliferation and differentiation into effector CTL

21
Q

IL2 in CTL responses

A

CTL and Th1 are highly dependent on IL2 for proliferation and differentiation
Required in CTL for expression of genes coding for cytotoxic effector molecules that are stored in cytoplasmic granules
In absence of IL2, Th1/CTL undergo apoptosis

22
Q

Tc1 cells

A

Differentiated CTL
Secrete IFNgamma
Kill by perforin and Fas ligand

23
Q

Tc2 cells

A

Secrete IL4
Only small amount of IFNganna
Kill by perforin

24
Q

CTL mediated destruction of target cells

A
  1. Conjugate formation
  2. Membrane attack
  3. CTL-target cell dissociation
  4. Target cell destruction
25
Q

Conjugate formation

A

Only takes minutes
TCR recognition of forgein peptide presented by class I MHC on target cell
Stabilized by CD8 and LFA-1
TCR signaling causes transient increase in avidity for LFA-1 for ICAMS on target cell

26
Q

Membrane attack

A

Golgi stacks and storage granules containing cytotoxins reorient in the cytoplasm and concentrate near the interface between CTL and target cell
CTL release storage contents in space between 2 cells
Perforin monomers insert into the target cell membrane and polymerize into pores that trigger endocytosis

27
Q

Perforin

A

Undergo conformational change in presence of Ca to insert themselves in target cell membrane
Trigger endocytosis

28
Q

Granzyme B

A

Binds mannose-6-phosphate receptors on the target cells
Complexes are internalized
Perforin allows granzyme B to be released from the vesicle into the cytoplasm
Cleaves substrates to initiate apoptosis

29
Q

Fas pathway

A

Las ligand on CTL interacts with Fas on target cells leading to apoptosis
Independent of Ca

30
Q

Caspases

A

Cysteine proteases that cleave proteins after an aspartic acid residue
Fas and perforin pathways result in activation of caspase 3, which causes activation of enconucleases that fragment nucleosomal DNA and proteases that disassemble cytoskeleton

31
Q

Serpins

A

Expressed by CTL to protect themselves from granzyme B and perforin
Inhibit granzyme B

32
Q

NK cells

A

Non-specific cytotoxic effector cells
Important in defending against viruses and cancer
Arise from same protenitor as T ells but do not develop exclusively in thymus
Express IL2Rbeta, CD2 and CD16
Not MHC restricted
Make IFNgamma
First line of defence
Activated by IL12 produced by dendritic cells

33
Q

NK cells in effector function

A

Constitutively active
Cytoplasmic granules containing perforin and granzymes, express FAS ligand
Inhibitory and activating receptors
Kill cells with too low levels of class I MHC

34
Q

Opposing signals model

A

Balance between activating and inhibitory signals determines whether or not an NK cell will ultimately kill the target cell
Inhibitory signals always override activation signals

35
Q

C-type lectins

A

Recognize altered carbohydrate structures on virus-infected cells or cancer cells
Important category of activating receptor

36
Q

Inhibitory receptors

A

Lectin-like inhibitory receptors, killer cell inhibitory receptors

37
Q

Antibody dependent cell-mediated cytotoxicity (ADCC)

A

NK cells, neutrophils, eosinophils, monocytes and macrophages have receptors for Fc region of IgG
All of them (except NK) are activated through Fc receptors and release lytic contents of their lysosomes
NK cells activated through CD16, and use perforin and Fas pathways

38
Q

CD16

A

Important activating receptor for NK cells

Activates ADCC

39
Q

NKT cells

A 
CD4+ and CD4- T cells that express NK cell markers and have an invariant alpha/beta TCR that interacts with CD1d on APC and epithelial cells
Bridge adaptive and innate immunity
Secrete IL4 and IFNgamma
Have FasL effector function
Help while adaptive response is forming
40
Q

CD1d

A

On APC and epithelial cells
Present to NKT
Present lipid and glycolipid antigens

Immunology 3115 (14 decks)

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