L: T cells and B cells (MCH)

incomplete

What are T cells derived from?

Bone marrow stem cells

Where do T cell precursor cells arrive?

The thymus

How long do T cell precursor cells spend in the thymus?

7-21 days

What do T cell precursors undergo in the thymus?

Differentiation and proliferation into a mature but antigen naive phenotype

What is a thymocyte?

Immature T cells

How many thymocytes does the thymus contain in mice?

10⁸

How many cells are made in the thymus every day?

5×10⁷

What percentage of thymocytes actually leave the thymus?

2-4%

What happens to the thymocytes that don’t leave the thymus?

They die in the thymus

what is one location that mature T cells populate after leaving the thymus?

Lymph nodes

What does MCH stand for?

Major Histocompatibility Complex

What are CD4 and CD8?

Small double positive thymocytes

What receptor do T cells use to recognise antigens?

TcRs

Why do thymocytes die from a lack of “positive selection”?

They don’t recognise the body’s own MCH molecules

What happens to the cells that do recognise the body’s own MCH molecules?

They mature and express high levels of TcR, CD4 or CD8 to become single positive cells

What occurs during “negative selection" of thymocytes?

T cells with high affinity for the body’s own MCH are eliminated as they could become autoreactive T cells

What is the selection of thymocytes into T cells called?

T cell education

What selection occurs in the cortex?

Positive selection

What selection occurs in the medulla?

negative selection

What cell mediates positive selection?

Cortical epithelial cells

What cell mediates negative selection?

Dendritic cell

What is the structure of T cell receptor (TcR)?

two polypeptide chains, membrane bound, each with a V and C domain

What is a T cell receptor almost like but not quite?

An immunoglobin

What is the TcR binding site similar to?

An antibody

What type of rearrangement do TcR undergo and what is this similar to?

chromosomal rearrangement and this is similar to antibody genes

What is the difference between TcR and Antibodies when binding to antigens?

Antibodies bind the antigen they are raised against on its own, while TcR only recognises an intern when it is bound by an MCH molecule

How can the TcR recognition of antigens be described?

MCH restricted

What is antigen processing?

Antigens are broken down into peptide fragments within antigen presenting cells

What are examples of antigen presenting cells?

Dendritic cells, macrophages and B cells

What happens to the peptide fragments after antigen processing?

They are bound to MCH molecules and transported to the cell surface for T cell recognition

How many types of MCH molecules are there?

2

What is the structure of MCH class 1?

Two chains - heavy chain and small beta2- microglobulin

What is found on the upper surface of MCH class 1 molecules?

A groove into which small 8-10 amino acid peptides sit

Which cells express MCH class 1?

Almost every cell in the body (low levels in CNS)

Where are there low levels of MCH class 1?

CNS

What is the structure of MCH class 2?

Two chains - alpha and beta (both membrane bound)

What can be found on the upper surface of MCH class 2 molecules?

A groove into which longer peptides, over 20 amino acids sit

Which class of MCH have longer peptides in their upper surface groove?

MCH class 2

Which cells express MCH class 2?

More limited to specialised antigen presenting cells and immune cells (macrophages, dendritic cells, B and T cells)

Which type of T cells recognise MCH class 1?

CD8 T cells

Which type of T cells recognise MCH class 2?

CD4 T cells

What are the peptides picked up by MCH class 1 derived from?

Internal contents of cells such as the cytoplasm and nucleus

Where does MCH class 1 meet peptides?

In the endoplasmic reticulum

What are the peptides picked up by MCH class 2 derived from?

External sources outwith cells

Where do MCH class 2 molecules meet peptides?

In endosomes

What does polymorphic mean?

Occurring in several different forms

Are all MCH molecules the same or do they differ and what word could describe this?

Polymorphic (highly)

Where are polymorphisms of MCH molecules located?

In the peptide binding groove

What does polymorphism mean for different MCH molecules?

They present different peptides to the immune system

What are many MCH molecules associated with?

Autoimmune diseases