Immunology 5

Question 1

What is immunological tolerance?

Answer 1

mmune toleranceis the state of unresponsiveness of theimmunesystem to substances or tissues that have the potential to induce animmuneresponse.

Question 2

how are intracellular antigens obtained?

Answer 2

Intracellular proteins are broken down using a proteasome. This is then transported to the ER and golgi, through a protein carrier, where they are bound to MHC Class I. The MHC Class I is then transported to the membrane where is is embedded within the membrane and can be recognised by CD8 + cells.

Question 3

How are extracellular antigens obtained?

Answer 3

The pathogen enters the cell by phagocytosis. The pathogen is then digested and the proteins broken down into fragments by a proteasome. The fragments are then transported to the ER and golgi, through a protein carrier, where they are bound to MHC Class II. The MHC Class II is then transported to the membrane where is is embedded within the membrane and can be recognised by CD4 + cells.

Question 4

What are the co-stimulatory molecules in the two types of T cells?

Answer 4

CD8 + and 4-1BB interacts with MHC Class I and 4-1BBL respectively.

CD4 and CD28 interact with MHC Class II and CD80/CD86 respectively.

Question 5

Where does Haematopoiesis occur?

Answer 5

The bone marrow

Question 6

What is positive selection?

Answer 6

Only those lymphocytes that recognise antigens presented on MHC are selected for.

Question 7

What is negative selection?

Answer 7

Only those cells that ignore autologous (self) antigens are selected for in the prevention of autoimmune diseases.

Question 8

How does T cell maturation/Selection occur?

Answer 8

1. In the cortex of the thymus, the immature T cells proliferate and express both CD4 and CD8 receptors.
2. The cells then enter the medulla and here can recognise an antigen presented via MHC is positively selected for.
3. The surviving T cells lose either CD4 or CD8 and so become either a Th or Tc. If the cell recognised a peptide presented via MHC class I it keeps the CD8 co-stimulator and if the peptide recognised was presented by MHC class II the cell keeps CD4 for future cell activation.
4. The T cells migrate deeper into the medulla. In the medulla, thymus cells express self antigens from around the body. Cells that recognise self cells are negatively selected for.

Question 9

What percentage of T cells reach maturation?

Answer 9

5% - around 2 million cells (out of approximately 60 million produced by the thymus).

Question 10

What gene enables medulla thymus epithelial cells to express antigens from around the body?

Answer 10

Aire gene - Auto-immune regulator gene.

AIREis a transcription factor expressed in the medulla (inner part) of the thymus. It is part of the mechanism which eliminates self-reactive T cells that would cause autoimmune disease.

Question 11

What is the role of the Air gene?

Answer 11

n the centre of the medulla, the self-peptides are presented by the medullary thymic epithelial cells. This process is controlled by the auto-immune regulatory gene, which causes the expression and subsequently the breakdown & presentation of organ specific proteins that are normally not expressed in the thymus. So these thymic cells produce, breakdown and present proteins specific for the lung, heart, kidney, brain and anything else. This way self recognition by mature T cells outside of the thymus is prevented.

Question 12

What cells enable positive selection in the thymus?

Answer 12

Dendritic cells, macrophages, cortical epithelial thymic cells. These cells present non-self antigens to immature lymphocytes.

Question 13

What is acquired tolerance? Give an example.

Answer 13

Acquired tolerance develops instantaneously.

For example, in the Eutherian fetoembryonic defence system. An embryo is not attacked by the mothers immune system as neither the egg, sperm nor embryo expresses MHC. As a result no antigens are presented. In addition to this, the membrane of the zygote contains many glycoproteins and so even if antigen presentation occurs, the lymphocyte activation is suppressed as the antigen cannot be reached.

Question 14

How does tolerance come about?

Answer 14

Tolerance is built up overtime due to the presence of growing concentrations of environmental antigens (food, air, drugs) that increasingly get presented by the antigen presenting cells during the negative selection, and then therefore get ignored. Lymphocytes learn not to respond to a continuous gradient of antigens; in the thymus there is also exposure to antigens that are selected for and so do not respond to. If there tolerance fails we get allergies formed - e.g. milk allergy.

Question 15

How are there 5 variations of the same B cell receptor?

Answer 15

The Fc region of the antibody can be swapped. As a result the same B cell receptor can produce IgD, IgM, IgG, IgE and IgA, all with the same Fab.

Question 16

What is class-switching?

Answer 16

Initally, IgM is produced from the B cell. IgM has low affinity for the antigen. B cells can now switch the Ig classes depending mainly on the location where the antibodies need to be present. So the different immunoglobulins have different functions. IgG e.g can cross the placenta and thus protects the foetus. IgE is the main cause of your allergies because it triggers histamine release from the mast cells, and IgA is preferably found in mucosa, tears, saliva and breast milk. Therefore class-switching is driven by swapping the constant region (and so the Fc region).

Question 17

How is the variable region of antibodies produced?

Answer 17

Through gene recombination. The gene for the variable region is made up of a variable gene, diversity gene and the joining gene (there is also a constant gene but this is not apart of the variable region). Diversity is produced by recombination fo gene segments.

Question 18

What is the difference between the heavy chain and the light chain?

Answer 18

The light chain is shorter. The gene encoding the light chain does not have a diversity segment and so diversity is reduced. There are fewer options for the constant gene - there is only kappa and lambda.

Question 19

What happens to the genes not picked?

Answer 19

The gene-segments that we did not pick have been deleted from the genome of the cell. Thus, every next receptor that is made in this cell will be identical to the one we just made.

Question 20

What is a polyclonal antibody?

Answer 20

It is possible that several B cells get activated because their antigen receptors happen to recognise parts of the same pathogen. There will thus be a mixture of B cell clones leading to the production of a mixture of antibodies. This antibody mixture is called polyclonal. These thus target the same pathogen but not necessarily via the same antigen.

Question 21

What is somatic hypermutation? What is the ratio?

Answer 21

In normal cells, the mutation rate is 1 in a billion. In V, D and J segments, the mutation rate is 1 in 1000. This very high mutation rate is known as somatic hypermutation.

Question 22

What is the importance of somatic hypermutation?

Answer 22

The cells with the higher affinity will get further positively selected while the non binding or badly binding cells will not get the co-activation signal from the antigen presenting cells and thus die via apoptosis.
As a result it can produce plasma cells that produce cells with a higher affinity.

Question 23

When does somatic hypermutation occur?

Answer 23

After the B cell has been activated in the lymph node. Since mature B cells continuously need to be activated in order to proliferate there will be a positive selection of the B cells with a higher receptor affinity for the pathogen. It therefore means later on in the infection, when class-switching occurs, the activated b calls can produce antibodies with higher affinity.

Question 24

What happens if co-stimulation fails?

Answer 24

Anergy.

Question 25

What happens if negative T cells selection fails?

Answer 25

There is a chance that co-stimulation fails leading to anergy.

Self-recognising CD8+ T cells start attacking cells.

Self-recognising CD4+ T cell could cause positive selection of a maturing B cell in the lymph node
Maturing B cell makes self-recognising antibodies.

               An auto-immune disease is born

Question 26

What is antigenic drift?

Answer 26

The mechanism for variation in viruses that involves the accumulation of mutations within the genes that code for antibody-binding sites.

Question 27

What is antigenic shift?

Answer 27

The process by which two or more different strains of a virus, or strain of two or more different viruses, combine to form a new subtype having a mixture of the surface antigens of the two or more original strains.