Exam 4 Immunology: CH 7 & 8

Where is the development of T lymphocytes?

Thymus

What do the stages of gene rearrangement of T-cell development lead to?

The 1 degree repertoire of T-cell receptors (TCRs)

What kind of selection is there of the T cell repertoire?

Positive and negative

What do the processes of negative and positive selection acting on the primary repertoire of TCRs lead to?

The production of the circulating population of mature Naive T-cells

What are similarities in the production of B and T cells?

1. They derive from bone marrow stem cells

2. They undergo gene rearrangement

How does gene rearrangement vary between B and T cells?

T-cells: Precursors of T-cells leave the bone marrow and move to the thymus

B-cells: Rearrangement occurs in the bone marrow

What are the 2 main distinct T cell lineages?

a:B receptors and y:o receptors

What is the difference between a:B and y:o receptors?

a:B: 1-2% of the primary repertoire leave the thymus

y:o : Not as stringent selection

What is the major function of the thymus with regard to T-cells?

To ensure that mature T-cells that leave the thymus are restricted to the particular MHC class expressed by an individual person (self MHC)

What does positive selection lead to?

The death of immature T-cells having receptors that do not interact with any self-MHC 1 and 2

What does negative selection lead to?

The death of immature T-cells that are autoreactive (receptors bind too strongly to a self-MHC molecule)

Mature T cells leaving the thymus and circulating in secondary lymphoid organs are?

1. Rendered tolerant of self-antigens

2. Responsive to foreign antigens

3. Ready to fight infection

aB and yo are what to each other?

2 lineages that develop in parallel from common precursors

T cells also express what while developing in the thymus?

Other cell surface proteins related to their eventual functions (CD4 and CD8 glycoproteins)

How do T-cells reach the thymus from bone marrow stem cells and the thymus?

Through blood

What does NOT occur in the thymus?

activation and no lymphatic connection

Where do T cells travel to from the thymus?

Secondary lymphoid tissues like the spleen or lymph nodes

If T cells are not activated, what happens?

They recirculate between blood, secondary lymphoid tissues, lymph and GALT

Where is the thymus located?

Upper anterior thorax (above heart)

What are immature T cells called?

Thymocytes

Where are immature T cells (thymocytes) imbedded?

Thymic stroma

What is the thymic stroma?

Epithelial cell network

The thymus is a primary lymphoid organ. T or F?

True

What is the thymus involved in?

1. Development of T cells

2. NOT lymphocyte recirculation (via lymph)

3. Blood is the only way for T cells to enter/exit

Once a Thymocyte matures, where does it go?

progressively moves from outer subcapsular region to the inner cortex and the medulla

What is rudimentary thynus called?

Thymic anlage

During development, where is the thymus cortex?

Outer

During development, where is the thymus medulla?

Inner

What is the thymic anlage colonized by?

cells from bone marrow

What populates the medulla?

Progenitor cells ——> thymocytes and dendritic cells ——> medulla; and bone marrow derived macrophages

Developing thymocytes which are spherical occupy?

interstices of an extensive network of epithelial cells

What is the cortex made up of?

Macrophages, cortical epithelial cells, and immature thymocytes

What is the medulla made up of?

Mature thymocytes, medullary epithelial cells, dendritic cells and macrophages

What do macrophages do for both the cortex and medulla?

Remove thymocytes that fail to mature properly

What are Hassall’s corpuscles?

Feature of the medulla and sites of cell destruction

Hassall’s corpuscles stain what color?

Pink/red

Medulla stains what color?

Pink/Red

Cortex stains what color?

Dark/purple

The thymus stains what color?

Dark/purple

What is the thymus stained with for microscope observation?

Eosin and hematoxylin

The thymus is multi-lobal. T or F

True

What is DiGeorge’s Syndrome?

A deletion on chromosome 22 where the thymus fails to develop and therefore, T cells are absent

What does DiGeorge’s syndrome essentially lead to?

Susceptibility to a wide range of opportunistic infections

What is DiGeorge’s syndrome similar to?

SCID (Severe Combined Immunodeficiency Disease)

What happens to the thymus with age?

Atrophies

The thymus is developed before birth and is most active in young people. T or F

True

What is it called when the thymus begins to shrink and fat takes over areas once packed with thymocytes?

Involution

Reduced production of new T cells does not impair ADULT immunity. T or F

True

Does a thymectomy (removal of thymus) impair adult immunity?

No

Once established, the repertoire of mature peripheral T cells is?

Long lived / self renewing

How do mature T cells differ from mature B cells?

T cells: Long lived and self renewing

B cells: short living and replenished by bone marrow

How are subpopulations of thymocytes identified?

By the changes in cell surface proteins expressed at each stage of thymocyte maturation

There are distinct steps of thymocyte maturation. T or F

True

What are the steps of thymocyte maturation?

1. Thymocytes are marked by changes in the status of TCR genes

2. Expression of the TCR protein

3. Production of other T cell surface glycoproteins (CD4, CD8, CD3 complex)

Progenitor T cells that enter the thymus lack _____ but have ____

Mature T cell glycoproteins (CD4, CD8 and CD3); CD34 (stem cell surface glycoproteins)

TCR genes are in what configuration?

Germline

What happens to progenitor T cells upon interaction with thymic stromal cells?

They proliferate and differentiate

If there is no CD4 or CD8, what is the thymocyte called?

“Double negative” Thymocyte

Approximately 1 week after progenitor T cells proliferate, they express what?

T cell specific adhesion molecule: CD2 and CD5

What is NOT present while progenitor T cells have adhesion molecules being expressed?

TCR complexes

What is the IL-7 receptor on T cells essential for?

Binding IL7 secreted by thymic stromal cells

What does the IL7 secreted by thymic stromal cells tell the T cell to do?

The next step in maturation

What occurs at Notch 1?

All stages of maturation in the thymus signals are sent through this receptor

Where does Notch 1 receptor drive T cells?

Into differentiation

What does Notch 1 do in regard to pathways?

Keeps T cells on T cell path and not allowing BCR genes to be opened up for rearrangement

B, y and o chains genes rearrange at the same time. T or F

True

Is there a set order for B cell Ig genes to rearrange?

Yes

What happens if a productive y:o chain rearrangement is made prior to productive B rearrangement?

It leads to y:o receptor which signals cell to stop rearrangement of B chain

More frequently the B chain productively rearranges before the y and o. T or F

True

B chain assembles with?

a surrogate a chain

What does the surrogate a chain (pta- pre-T cell receptor) do?

Signals the cell to halt rearrangement B, y and o and being proliferate

What happens after the expression of pre-TCR?

The recombination machinery is reactivated and targeted towards the a chain loci (and y:o loci)

What is the yo lineage?

A minority of cells that have successful recombination of the y and o gene rearrangement that occurs before the a chain rearranges

What is the aB lineage?

A majority of cells that have productive rearrangement of the a chain 1st

Where is the o chain located?

In the a chain locus

What does a rearrangement of the a chain locus result in?

Deletion of the complete o chain locus from the chromosome

Cells committed to one lineage can contain productive rearrangements for?

The TCR genes of the other lineage

What chain is the exception to containing productive rearrangements for other lineages?

a chain

What does failure to have productive rearrangement lead to?

Cell death by apoptosis

What is the fate of 98% of thymocytes?

Cell death by apoptosis

What do macrophages in the thymus continually do?

Remove dead cells

What color dye is used for cells marked for apoptosis?

Red

Apoptotic cells are ___ in the cortex and ___ in the medulla

Scattered; Rare

What color are macrophages dyed?

Purple

Red dye is higher?

Magnification

Apoptotic cells are visible in macrophages. T or F?

True

aB receptor MUST be abundant on T cells. T or F

True

TCR B chain locus include?

Variable (V), Diversity (D) and Joining (J)

TCR a chain locus includes?

V and J

Which is rearranged first a or B?

B (Similar to Ig heavy chain)

a is the equivalent of what in Igs?

Light chain

What does production of a functional B chain lead to?

B chain translation and assembly with surrogate a chain (preTa), CD3 proteins and zeta (z) chain to form a pre-T cell receptor (pre- TCR)

What happens after the formation of pre-TCR

Moves to the cell surface

What are the two roles of a pre-TCR?

1. Triggers thymocyte proliferation and halts B chain gene rearrangement

2. Ensures that only 1 type of T cell receptor B chain is expressed by the T cell

Unproductive rearrangement at 1 B chain locus can lead to rearrangement of the B chain on?

The homologous chromosome and at the same locus

Which chain genes does the unproductive rearrangement NOT apply to?

Ig H

Why is Ig H chains the exception to unproductive rearrangements?

2 sets of DB, JB, and CB gene segments that are tandemly associated with VB gene segments

How many potential rearrangements per cell?

4

How many of T cells make successful rearrangement of the B chain gene?

80%

What is the success rate of for productive H chain gene rearrangement by B cells

55%