T lymphocytes

Question 1

TH1 Cells

Answer 1

Cytokines that induce differentiation: IL-12. IFN-y
Characteristic Cytokines: IL-12. IFN-y
Function: Activate Macrophages
-Help macrophages perform better, also induce CD8 cells
-Th1 signals IFNy and CD40 to activate macrophage
Activated macrophage: phagosomes fuse lysosomes more efficiently, increased CD40 expression, TNFa secretion, ROS/NO/proteases are produced

Question 2

TH17 Cells

Answer 2

Cytokines that induce differentiation: IL-6, IL-21, IL-23
Characteristic Cytokines: IL-17, IL-6
Function: Enhance neutrophil response
-Major role in autoimmunity
-Activate tissue cells/recruiting neutrophils
-Defense against extracellular bacteria

Question 3

TH2 Cells

Answer 3

Cytokines that induce differentiation: IL4
Characteristic Cytokines: IL4, IL5, IL13
Function: Activate cellular antibody response to parasites (only if they recognize same Ag)
-Activate B cell differentiation to plasma cells (IL-5 production)
-induce human IgG2 isotype antibodies (very good at opsonization/complement activation)
-Induce clonal expansion
by upregulating CD-40 ligand and producing IL-4 and IL-5

Question 4

Treg Cells

Answer 4

Cytokines that induce differentiation: TGF-B
Characteristic Cytokines: TGF-B IL10
Function: Suppress other effector T cells (needs to be responding to same Ag on same APC to have effect)
-Block DC function and suppress responses of other effector T cells

Question 5

TH9 Cells

Answer 5

Cytokines that induce differentiation: IL12. IFN-y
Characteristic Cytokines: IL9
Function: Augment other immune responses
-Enhance Ig production/increases immune cell activity in res[. tract
-Increases intestinal permeability/proinflammatory Th cell responses
-Increases cell infiltration and enhances leukocyte functions (potent antiparasitic activity)
-Augment antitumor immune activity

Question 6

TH22 Cells

Answer 6

Cytokines that induce differentiation: IL6, IL23, TNF-a
Characteristic Cytokines: IL12, IL22
Function: Keratinocyte proliferation & epidermal hyperplasia
-Remodel epidermis, reinforcement of barrier function (blister)

Question 7

Stem Cell

Answer 7

Undifferentiated thymic progenitor stem cells go from bone marrow -> thymus

Question 8

Pro-T Cell (double negative)

Answer 8

-Cell starts to rearrange B or g/d genes (if fails in g/d -> cell dies)
-Can become g/d or a/b
-Somatic rearrangement occurs by RAG 1/2: B genes by
arranges V regions and D segments, then J (joining) segments, then join C region
-B chain expressed w help of pseudo a chain (failure -> try 2nd allele, failure ->
Revert to g/d cell, failure -> cell death)

Question 9

Pre T cell

Answer 9

-a chain somatic rearrangement occurs
Somatic rearrangement occurs: Combines V, J and C genes
-A chain is tested (failure -> try 2nd allele, failure -> cell death *no reverting to g/d cell after 2nd allele)
-Pre-T cell induces proliferation/expression of CD4 and CD8

Question 10

Double Positive

Answer 10

• Both a and B chains are appropriately expressed
• Express CD4 and CD8
• TCR binds to class I or II receptor on epithelial cells in cortex of thymus
• If it binds class I first = downregulates CD4 receptors/ upregulates CD8 receptors
• Opposite occurs if cell binds class II first

Question 11

Single Positive (immature T Cell)

Answer 11

• TCR affinity to MHC test:
• Too low affinity/avidity recognition of MHC = cell neglect -> cell death
• Too high affinity = Negative selection -> apoptosis signal
• Just right low affinity = Positive Selection -> survival signal/can move on to medulla
• TCR affinity to self-antigens (via AIRE expression):
• High affinity and binds self-peptide-MHC complex = Negative selection -> apoptosis signal
• T cell binds self-peptide-MHC complex and then moves on = Positive Selection -> Survival/can exit to periphery

Question 12

Naive Mature T Cell: Periphery

Answer 12

• Express only 1 receptor type and pass both MHC binding and self-peptide binding tests
• In blood vessels

Question 13

AIRE

Answer 13

Transcription factor that induces expression of “self” genes found in other places in body (tend to be endocrine) in medullary thymic epithelial cells

Question 14

Central Tolerance

Answer 14

-Self Ag test for single positive immature T cells protects against future autoimmune disease

Question 15

Cell Adhesion Molecules (CAM)

Answer 15

• Cell surface receptors that enable cells to bind to each other (4 classes)
• For Lymphocyte homing = movement of naive T cells into secondary lymphoid tissues

Question 16

Selectins

Answer 16

-Bind carbohydrates, initiate leukocyte-endothelial interaction

Question 17

Mucin- like Vascular Addressins

Answer 17

-Bind to L-selectin, initiate leukocyte endothelial interaction

Question 18

Integrins

Answer 18

Bind to cell adhesion molecules/ECM, strong adhesion

Question 19

Immunogglobulin Superfamily Members

Answer 19

Various roles in cell adhesions, target for integrins

Question 20

Lymphocyte Homing molecules

Answer 20

CD34/GlyCAM-1: Vascular addressins on endothelial cell for T cell to roll
L-selectin: On Tcell CD34/GlyCAM-1 + L-selectin = T cell rolling
CCL21: Chemokine on endothelium
CCR7: Chemokine receptor on T cell
CCL21 + CCR7 = LFA activation
LFA-1: Integrin on T cell
ICAM-1: Immunoglobulin superfamily member on endothelial cell
LFA-1 + ICAM-1 = Diapedesis (cell migration from blood vessel into tissue)

Question 21

T Cell -APC Interaction Molecules

Answer 21

LFA-1: Integrin on T cell
ICAM-1/ICAM-2: Ig superfamily member on APC
LFA-1: Integrin on APC
ICAM-3: Ig superfamily on T cell
LFA-1 + ICAM-1/ICAM-2 and LFA-1 + ICAM-3 = Intitial transient binding of Tcell-APC
CD-2: On T cells
LFA-3: Integrin on APC
DC-SIGN: On T cell
CD-2 + LFA-3 and DC-SIGN + ICAM-3 = strong adhesion of Tcell-APC

Question 22

Activation Signal 1

Answer 22

• CD4/CD8 on T Cell + Ag peptide on MHC II/MHC I on APC

- Only signal 1 without signal 2 = T cell is anergic (can’t respond/differentiate)

Question 23

Activation Signal 2

Answer 23

• Co-stimulatory molecule interaction
• CD28 on T cell + CD80(B1.1) or CD86(B1.2) on APC
• Only signal 2 without signal 1 = no effect, cell moves on

Question 24

Activation Signal 3

Answer 24

• Induces differentiation from activated T cells to effector T cells
• Cytokines from APCs/other immune cells influences effector type of CD4+ T cells and induces CD8+ T cells to cytotoxic T lymhocytes

Question 25

IL-2

Answer 25

• Naive T cells have low/moderate affinity IL-2 receptors
• Activated T cells produce more iL2 and upregulate a chain part of IL2R -> high affinity IL2R
• IL2 binding induces proliferation
• IL2 acts as paracrine and autocrine signal

Question 26

CTLs

Answer 26

• Protect against viruses, intracellular bacteria, tumors
• Fas ligand (FasL) binds to Fas on target cell -> induces apoptosis
• Releases cytoxins: Perforin (pores in membrane), Granulysin (disrupt membrane integrity), Granzyme (protease enters pores and chops up protein) -> necrosis

Question 27

Factors that Th Cell effector function

Answer 27

• Cytokine milieu determined by innate immune response
• Type of APC
• Cytokines produced by APC
• Abundance of specific peptide, MHC complex on surface
• Affinity of peptide
• Signal 3 main influencer

Question 28

T Cell effector migration to infection

Answer 28

• Downregulate L-Selectin = Th Cells can leave lymphoid organ
• Upregulate specifc adhesion molecules (Integrin a4B1, VLA-4) = adhesion to endothelial cells
• Upregulate CD44 (HA receptor) = can remain in tissue with lots of HA