Effector T Cells and Cell-mediated Cytotoxicity

Question 1

Cell mediated immunity

Answer 1

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

Question 2

Effector T cells

Answer 2

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

Question 3

CD2 in effector T cells

Answer 3

Higher levels than in naive cells

Question 4

LFA-1 in effector T cells

Answer 4

Higher levels than in naive cells

Question 5

CD44 in effector T cells

Answer 5

Up regulated following TCR signaling

Question 6

CD62L in effector T cells

Answer 6

Low levels

Question 7

CCR7 in effector T cells

Answer 7

Not present

Prevents recirculation to secondary lymphoid tissue

Question 8

Effector CD4+ T cells

Answer 8

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

Question 9

Lymphotoxin

Answer 9

Membrane bound effector molecule of Th1 cell

Promotes macrophage activation by Th1 (along with IFNgamma)

Question 10

CD40 ligand

Answer 10

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

Question 11

IL17 + IL22 secreted by Th17

Answer 11

Promotes inflammation

Question 12

IL10 + TGF-beta secreted by Treg

Answer 12

Down regulate cellular immune responses and inflammation

Question 13

Effector molecules of CD8+ cells

Answer 13

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

Question 14

CTL-mediated immune responses

Answer 14

Activation phase and effector phase

Question 15

Activation phase of CTL mediated immune response

Answer 15

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

Question 16

Effector phase of CTL mediated immune response

Answer 16

Differentiated CTL engage and kill target cells

Differentiate into Tc1 or Tc2 cells

Question 17

Licensing of antigen-presenting dendritic cells

Answer 17

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

Question 18

Costimulation of CTL-Ps

Answer 18

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

Question 19

Activated CTL-P

Answer 19

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

Question 20

Memory CTL-P

Answer 20

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

Question 21

IL2 in CTL responses

Answer 21

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

Question 22

Tc1 cells

Answer 22

Differentiated CTL
Secrete IFNgamma
Kill by perforin and Fas ligand

Question 23

Tc2 cells

Answer 23

Secrete IL4
Only small amount of IFNganna
Kill by perforin

Question 24

CTL mediated destruction of target cells

Answer 24

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

Question 25

Conjugate formation

Answer 25

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

Question 26

Membrane attack

Answer 26

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

Question 27

Perforin

Answer 27

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

Question 28

Granzyme B

Answer 28

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

Question 29

Fas pathway

Answer 29

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

Question 30

Caspases

Answer 30

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

Question 31

Serpins

Answer 31

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

Question 32

NK cells

Answer 32

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

Question 33

NK cells in effector function

Answer 33

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

Question 34

Opposing signals model

Answer 34

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

Question 35

C-type lectins

Answer 35

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

Question 36

Inhibitory receptors

Answer 36

Lectin-like inhibitory receptors, killer cell inhibitory receptors

Question 37

Antibody dependent cell-mediated cytotoxicity (ADCC)

Answer 37

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

Question 38

CD16

Answer 38

Important activating receptor for NK cells | Activates ADCC

Question 39

NKT cells

Answer 39

``` 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 ```

Question 40

CD1d

Answer 40

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