L07 Biology of T lymphocytes

Question 1

The Thymus is where T cells are

Answer 1

“Educated”
-T cell acquires TCR (antigen specificity)
-learns tolerance of self
-learns HLA- restriction (only able to interact with HLA and peptides)

DiGeorge’s Syndrome - no thymus or very small thymus, difficulty making T cells
-Thymic involution occurs post-puberty

Question 2

T cell ontogeny is roughly characterized by

Answer 2

Anatomical Compartment
Cell surface molecules expressed

Question 3

What organs are included in the anatomical compartment?

Answer 3

Bone marrow
Thymus (cortex, medulla)
Periphery (blood, lymph nodes, spleen)

Question 4

Positive Selection

Answer 4

CD4+ and CD8+ immature thymocytes must bind HLA class I and HLA class II on THYMIC epithelial cells with “just the right” affinity.
-If not, they under apoptosis and die
-Learns self HLA restrictions

Question 5

Negative Selection

Answer 5

Cells that remain from positive selection and respond to self HLA presenting self peptide on interdigitating dendritic cells undergo apoptosis and die or become anergic (tolerance)

Question 6

Central T Lymphocyte Tolerance

Answer 6

• Involves immature “double positive” T cells
  -strong recognition to antigens results in apoptosis
  -remember antigens present in the thymus are almost always self antigens

Question 7

Tolerance learned during ontogeny is called

Answer 7

Central tolerance

Question 8

Result of Positive and Negative Selection

Answer 8

Most thymocytes (>90%) are killed during the rigorous requirements for surviving the positive and negative selection process
- Remember that a small population of T cells process the y/s TCR, they leave the thymus for epithelial sites without undergoing positive and negative selection

Question 9

The resulting cells leaving the thymus are:

Answer 9

-a/b TCR+, CD3+, CD4+ or a/b TCR+, CD3+, CD8+
- Self-HLA restricted (aka- self MHC restricted)
-Self tolerant
-Respond to foreign antigens (in context of self MHC)

Question 10

Stem cells migrating to the thymus express these molecules on their surface

Answer 10

Chemokine Receptors

Question 11

Circulation of Mature naive T Cells

Answer 11

• after leaving the thymus, mature T cells enter the blood and lymphatic vessels and eventually home to secondary lymphoid tissue
• Lymphocytes constantly recirculate- approx. 2% of the total pool every hour
• about 10^4 lymphocytes enter a given lymph node every second
• Recirculation increases the chance that a lymphocyte will encounter its antigen

Question 12

Specific receptor-ligand interactions between lymphocytes and endothelial cells occur ___________________.

If, while filtering through a lymph node, a T cell encounters an APC expressing HLA + foreign peptide __________________

Answer 12

• that mediate recirculating and homing of lymphocytes
• it may respond or not (exhibit tolerance)
  Responses = activation
  Tolerance = no activation

Question 13

The clonal selection theory is … and what 2 types of cells does this theory consist of

Answer 13

it is the first exposure to antigen that finds the matching epitope and begins to replicate
The clonal selection theory consist of Effector cells and Memory cells

Question 14

Each succeeding round of antigen exposure produces ….

Answer 14

New effector cells and memory cells

Question 15

Activation of T lymphocytes

Answer 15

B cells tend to deal with extracellular antigens
T cells respond to intracellular or cell-associated antigens

Upon encountering an antigen, T cells become activated
- CD4+ T helper cells produce cytokines
-CD8+ cytotoxin T cells expressing foreign antigen (cytotoxicity)

Question 16

Most exogenous antigens are processed by dendritic cells and presented to …

Answer 16

CD4+ T helper cells

Question 17

Recognition of foreign antigens by T cells:

Answer 17

Processing of exogenous antigen and processing of endogenous antigens

Question 18

The T cell antigen receptor (TCR) complex consist of

Answer 18

TCR, CD3 and Zeta chains (CD247)

Question 19

TCR characteristics

Answer 19

-member of the Ig supergene family
- composed of a and b chains
-has conserved (C) and variable (V) domains
-recognizes Ag+ HLA on APC

Question 20

CD3 characteristics

Answer 20

• composed of y,s and e chains
• complex is found on all mature T lymphocytes
  -chaperone for TCR
  -critical signaling molecule

Question 21

Zeta chains (CD247) characteristics

Answer 21

• signaling molecules

Question 22

Co-receptors for T cell activation

Answer 22

• CD4 facilities binding of HLA class II molecules to the TCR
  -CD8 facilities binding of HLA class I molecules to the TCR
  -CD4 and CD8 are mutually exclusive on mature T cells
• They are adhesion molecules and signal transducers

Question 23

Positive co-stimulatory interactions

Answer 23

• B7 (CD80): CD28
• CD40: CD40L (CD154)

Question 24

Negative co-stimulatory interactions

Answer 24

-PD-L1:PD-1
-B7 (CD80): CTLA-4

Question 25

Immunological Synapse

Answer 25

CTLA-4, T cells, APC, signaling

Question 26

Peripheral T cell Tolerance (Anergy)

Answer 26

• functional inactivation of T cells
• occurs when the primary signal (MHC/peptide-TCR binding) happens without secondary signal (ex. B7-CD28 binding)
• secondary signal needed to stabilizes IL-2 mRNA

Question 27

Peripheral T cell Tolerance (Activation-induced cell death)

Answer 27

-Activated T lymphocytes will die by apoptosis if repeatedly stimulated with antigen
- Induces expression of Fas and Fas ligand resulting in apoptosis
-Expression of pro-apoptotic proteins resulting in apoptosis

Question 28

Peripheral T cell Tolerance (Regulatory T cells)

Answer 28

-CD4+, CD25+ and FoxP3+
- Suppress or inhibit the activation of other T cells
- most likely due to the production of inhibitory cytokines