Adaptive immunity part 2 Flashcards
Immunoglobulin genes
-Immunoglobulin genes have repeated sequences
What do the repeated regions in immunoglobulins contain?
- The repeated sequences code for the variable region and this allowed scientists to determine how you can make several different variable regions from one gene. —The repeated sequences were also found in regions called diversity and joining regions.
- A process called gene rearrangement allows one of the duplicated sequences in each region to be used to make the protein.
How does DJ recombination (gene rearrangement) work?
- The recombination reaction creates a loop in the immunoglobulin gene that leaves one of the repeat sequences in place.
- The others are contained within the loop which is removed by RAG proteins.
- The first gene rearrangements (DJ recombination) select diversity and joining regions. The constant region (Fc) is constant.
Second gene rearrangement
- A second rearrangement selects the variable region. The constant region (Fc) is constant.
- Here the loop is made in the cluster of variable sequences.
- Next VDJ’ recombination brings one of the remaining variable sequences next to the DJ combination.
What do rearranged Ig genes encode?
-Rearranged Ig genes encode mRNA to make antibody protein
What does VDJ recombination provide?
-VDJ recombination provides antibody and T-cell diversity
T-cell receptor genes also rearrange to create diversity
- T-cell mediated immunity is very important for B-cell help and in anti viral immunity.
- T-cell receptors are not a class of immunoglobulin, they resemble immunoglobulin but are made by different genes that rearrange but are only expressed in T-Cells.
Adaptive or acquired immunity
- Gene rearrangement is the key feature of adaptive immunity.
- Gene rearrangement only takes place in B and T-cells
- This allows you to acquire an immune response
- This allows your immune system to adapt.
How do you select the right T and B cells?
- T and B cells rearrange genes at random (10 million each day)
- Each cell can only rearrange genes once
- Cells that have rearranged the right gene segments bind antigen. Antigen binding triggers cell division. (This is clonal expansion)
- Clonal expansion generates large numbers of cells making the same receptor. The other cells die.
What do T-cells recognise?
- T-cells do not recognise antigens directly. They recognise infected cells.
- Antigens are broken down in cells and small parts of them are sent to the plasma membrane on a conveyor belt. This is called antigen presentation.
What is the role of dendritic cells and macrophages?
-Dendritic cells and macrophages present antigens to T helper cells
HOW DO B-CELLS PERSUADE T-CELLS TO PROVIDE HELP?
- If B-cells and T-cells are to agree on an antigen, the B-cell has to be able to present the antigen it recognises to T-cells, otherwise the T-cell cannot see it.
- To do this the B-cell becomes an antigen presenting cell, the early antibodies remain attached to the surface of the B-cell. This allows the B-cell to capture the antigen and present it to the T-cell.
What does the membrane anchor do?
- The membrane anchor allows the B-cell to phagocytose the antigen
- The membrane bound immunoglobulin can take the antigen into the cell where it is degraded
- Parts of the antigen can be loaded onto the antigen presentation conveyor belt
What does the antigen conveyor belt do?
- The conveyor belt presents small bits of antigen to the T-cell receptor
- If the T-cell and B-cell agree on the antigen the T-cell is activated by the T-cell receptor: antigen interaction
What is co-stimulation?
- After antigen interaction, the T-cells then express CD40 ligand which can bind CD40 on B cells.
- CD40 ligand delivers more signals to the T-cell (Co-stimulatory signals)
What does co-stimulation do?
- Co-stimulation induces cytokine secretion from the T-cell.
- Cytokines cause the B-cell to proliferate
Plasma cells and memory cells
- Memory B cells retain the membrane bound receptor and can keep communicating with T-cells
- Plasma B cells remove the membrane anchor and secrete immunoglobulin
- Plasma B cells proliferate to make antibodies secreted into the blood. The memory B-cells keep the antibody attached to the plasma membrane so they can respond to new infections and keep communicating with T-cells.
Cytokines from the helper T-cell determine the fate of the B-cell
- IL4 drives memory cells
- IL10 drives plasma cells
Antibody class switching
- Once the VDJ recombination is complete the B-cell can get signals to undergo a second recombination called antibody class switching.
- The 3 prime end of the immunoglobulin gene has sequences coding for the different constant regions used by different antibody types. These have Greek letters that correspond to the M, G, A and E used to describe different antibody types for example immunoglobulin G (IgG), will have the gamma sequence form the constant region.
- The VDJ recombination generates an antibody that has a membrane anchor that holds it in the plasma membrane to act as a B-cell receptor. Signals from the B-cell receptor and cytokines can trigger the first switching rearrangement which removes the membrane anchor and add a region
What happens in VDJ recombination and antibody class switching?
-The coding sequence for different FC domains lies in the same immunoglobulin gene
What happens to the constant region during recombination?
-The constant domains can be switched during recombination to generate isotypes using the same variable region
What do cytokines determine?
-Cytokines from the T helper cells determine the antibody type made by the B cell
