Exam 2 Lecture 9: Effector T Cell Function

Question 1

How do effector T cells enter sites of infection

Answer 1

Expression of VLA-4 allows the, to bind VCAM on activated endothelial cells

Question 2

How do the requirements for activation change between naive and effector T cells regarding signal 1 and 2

Answer 2

Naive: require both signal 1 and 2
Effector: only require signal 1

Question 3

Types of effector lymphpcytes

Answer 3

CD8 T cell
B cell
Regulatory T cell
CD4 T cell

Question 4

What are the 5 major subsets of CD4+ T cells

Answer 4

Th1
Th2
Th17
Tfh
Treg

Question 5

Th1 (helper)

Answer 5

Inducing cytokine: IFNγ, IL-12
Defining Transcription Factor: T-bet
Function: bacteria & viruses ( intracellular)
activate macrophages

Question 6

Th2

Answer 6

Inducing cytokine: IL-4
Defining TF: Gata-3
Function: parasites (extracellular)
mast cells, eosinophils, basophils
mucus secretion
smooth muscle contraction
(can also be cause of allergy loop)

Question 7

Th17

Answer 7

Inducing cytokine: IGF-β, IL-6, IL-23
Defining TF: RORγt
Function: bacteria, fungus (extracellular)
macrophage and neutrophils
inflammation
phagocytosis
antimicrobial peptides
barrier function of epithelial cells
(can cause autoimmune diseases)

Question 8

Tfh (follicular helper)

Answer 8

Inducing cytokine: CD40, IL-21??
Defining TF: Bcl-6
Function: migrate to B cell area to help provide signals to B cells (linked recognition)

Question 9

Linked Recognition

Answer 9

Cooperation of B and T cells recognizing different epitopes on the same antigen that are taken up and processed by B cells

Question 10

Treg

Answer 10

Inducing cytokine: TGF-β
Defining TF: Foxp3
Function: block effector T cells-DC interaction
upregulate CD25 and become IL-2 hogs
secrete immunosuppressive or anti-inflammatory cytokines: TGF-β, IL-10

Question 11

CD8+ T cells

Answer 11

aka cytotoxic or cytolytic
most effective against intracellular pathogens

Question 12

`How do CD8+ T cells kill target cells

Answer 12

CD8+ cells become polarized, redistributing contents of cytoplasm t align lytic granules closest to target cells
Lytic granules contain perforin and granzyme B which are released at target cell synapse
induce apoptosis
aka kiss of death

Question 13

What happens to T cells after an infection is over

Answer 13

Contraction of all effector (CD4+ & CD8+) T cells
Leave behind memory T cells

Question 14

When does memory formation become dysfunctional? What happens to those cells and how can they be rescued?

Answer 14

Chronic infections, the antigen is not cleared
T cells exhausted, unable to do normal functions, express exhaustion markers, lose normal functions
Cancer can block exhaustion markers (immune checkpoint inhibitors) which can be. used for immunotherapy

Question 15

What happened during anti-CD28 TGN1412 clinical trial? What lessons were learned?

Answer 15

pre-clinical animal studies showed no toxic effects, intended to treat leukemia and rheumatoid arthritis
8 healthy volunteers, 6 received antibodies
All 6 patients had major cytokine storm, experienced multi-organ failure
Lessons: interpretation of preclinical (primate) studies, use of human in vitro studies, starting dose, interval between patients, preparation of adverse affects