Properties and functions of effector T cells

Question 1

What is the only cell type that can stop inflammatory actions of Th17?

Answer 1

Treg

Question 2

Activation/priming of naive CD8+ T cells on encounter with antigen

Answer 2

1. antigen specific signal
2. co stimulatory signal
3. cytokine signal

Question 3

The 3rd signal for Tc cell activation comes from _____ in the form of ___

Answer 3

APC; IL-12

- IL-12 directs immune responses toward CD8 Tc cell responses (adaptive cellular immune responses)

Question 4

Proteins in granules of cytotoxic T cells

Answer 4

Perforin, granzymes, granulysin

Question 5

Perforin

Answer 5

Aids in delivering contents of granules into the cytoplasm of target cell

Question 6

Granzymes

Answer 6

Serine proteases, which activate apoptosis once in the cytoplasm of the target cell

Question 7

Granulysin

Answer 7

Has antimicrobial actions and can induce apoptosis

Question 8

Cytokines

Answer 8

IFN-gamma, LT- alpha, TNF-alpha

Question 9

Cytotoxic effector molecules

Answer 9

Fas ligand

Question 10

Delivery of cytotoxins is aimed ___

Answer 10

Directly at the target cell, upon specific antigen recognition by cytotoxic T cell

Question 11

Cytotoxic recognition process

Answer 11

Collision and nonspecific adhesion –> specific recognition redistributes cytoskeleton and cytoplasmic components of T cell –> release of lytic granules at site of contact

Question 12

Life cycle of a Tc cell

Answer 12

Antigen recognition –> activation –> clonal expansion –> differentiation into memory CD8+ T cell or effector CD8+ T cell = killing of infected target cells or macrophage activation
*differentiation occurs in the peripheral tissues, while everything else occurs in lymphoid organs

Question 13

Cytotoxic T cells are _____ and _____ of target cells

Answer 13

Selective; serial killers
- CTL recognizes virus-infected cell –> CTL programs target cell to die –> CTL moves to another target cell –> first target cell dies

Question 14

Cytotoxic T cells kill their targets by ___

Answer 14

Inducing apoptosis

- apoptotic products will be taken up by macrophages or DC

Question 15

Thymus regulatory tolerance

Answer 15

T cell specific for self antigen recognized in thymus becomes a natural regulatory T cell (aka central Tregs)

Question 16

Peripheral regulatory tolerance

Answer 16

T cell specific for self or commensal microbiota antigen recognized in persence of TGF-beta becomes an induced regulatory T cell (aka peripheral Tregs)

Question 17

Cytokines produced by Treg cells

Answer 17

IL-10 and TGF-beta

- inhibit other self-reactive T cells (located in the periphery)

Question 18

What part of thymic selection eliminates autoreactive T cells?

Answer 18

• negative selection

- T regs get rid of T cells that escape thymic elimination

Question 19

General properties of regulatory T cells

Answer 19

FOXP3+CD4+CD25+Tregs
Suppress the proliferation and IL-2 production of naive cells
- both CD4+ and CD8+ cells could be suppressed

Question 20

Effector mechanisms of regulatory T cells

Answer 20

• Surface molecules: constitutive expression of CTLA-4 (CD152)
• Cytokines: IL-10, TGF-beta (release of cytokines suppresses activation of all cells)
• Cytotoxins, perforin, gransyme A, Fas-FasL

Question 21

CTLA-4

Answer 21

Molecule that inhibits activation

Question 22

Anything that ____ or _____ has a stronger binding effect

Answer 22

Regulates; inhibits

Question 23

Foxp3

Answer 23

Max transcriptional factor that directs development of T regs

Question 24

Regulatory T cells suppression mechanisms

Answer 24

Cell to cell contact dependent and soluble factor (IL-10 or TGF-beta) dependent suppression

Question 25

CTLA-4 binds to _____, sending dendritic cell into apoptosis, or an inactive state

Answer 25

CD80/86

Question 26

IL-10

Answer 26

- potent immunomodulatory cytokine - *anti inflammatory* - down regulates production of Th-1 type cytokines - * decreases expression of MHC 2 and co stimulatory molecules on DCs (tolerogenic state) - regulates activation/function of mast cells - regulates cytokine production by eosinophils - directly suppresses T cell proliferation

Question 27

Migration of DCs

Answer 27

- Steady state: migrate everyday, contributes to homeostasis | - Pathogen induced: only happens during infection

Question 28

Triadic function of TGF-beta

Answer 28

- Sword: paralyzes cell activation/differentiation to suppress immune response - Wand: converts naive T cells into iTregs and Th17 to aid in their combat against inflammation and infection - Shield: protect and maintain Tregs against apoptosis and destabilization when surrounded by inflammation and consistent stimulation

Question 29

Cytotoxins

Answer 29

Perforin, Gransyme A

Question 30

Th17 cells

Answer 30

- physiologic role in immunity by conferring protective function against microbial pathogens - represent pro-inflammatory subset, which in excess contributes to autoimmunity and tissue damage - various subsets of Th17 cells with distinct function and pathogenic capacity

Question 31

Non pathogenic subset

Answer 31

Incapable of promoting autoimmune inflammation and might act anti-inflammatory

Question 32

Highly pathogenic Th17

Answer 32

From naive precursor cells that occur independently of TGF-beta signaling in the presence of IL-23, IL-6 and IL-1B

Question 33

Tregs vs Th17

Answer 33

- both pathways are reciprocally interconnected, requiring a balance between both cell types = influence over outcome of immune response - shared requirement of TGF-B provides phenotypic and functional plasticity in both populations = differentiated cells to "re" differentiate - Th17 = pro-inflammatory, which can turn into autoimmune when in excess, while Tregs have antagonistic effect, that when in failure also leads to autoimmune diseases

Question 34

TH17/Treg balance provides a basis for understanding the immunological mechanisms that ______ and _______

Answer 34

Induce/regulate autoimmunity; chronic inflammation

Question 35

Therapeutic approaches

Answer 35

Targeting molecules influencing the Th17/Tregs axis

Question 36

Mechanisms that contribute to immunological self-tolerance

Answer 36

- negative selection in the bone marrow and thymus - expression of tissue-specific proteins in the thymus - no lymphocyte access to some tissues - suppression of autoimmune responses by regulatory T cells - induction of anergy in autoreactive B and T cells

Question 37

Anergy

Answer 37

Absence of co stimulatory signal, naive T cells that have received the first signal become anergic and die by apoptosis

Question 38

Immunological tolerance

Answer 38

Non responsiveness of the lymphocyte population to the specific antigen self (self tolerance) or non-self

Question 39

Peripheral tolerance

Answer 39

Antigen recognition in the absence of the co stimulatory signal

Question 40

Co stimulatory signal and specific signal

Answer 40

Activates T cell

Question 41

Specific signal alone

Answer 41

T cell becomes anergic

Question 42

Co stimulatory signal

Answer 42

No effect on T cell

Question 43

Immunologically privileged sites

Answer 43

- brain - eye - testis - uterus (fetus) - hamster cheek pouch

Question 44

Tolerogen

Answer 44

When an antigen induces tolerance

Question 45

The most important form of tolerance is ____

Answer 45

Non reactivity to self antigens

Question 46

Mechanisms of central tolerance

Answer 46

- negative selection in the thymus | - autoimmune regulator (AIRE)

Question 47

Mechanisms of peripheral tolerance

Answer 47

- absence of co stimulatory signal - immunologically privileged sites (immunological ignorance) - regulatory T cells