Immune System 3 Flashcards
Describe the development of B lymphocytes.
- Generation of B-cell receptors in the bone marrow
- Negative selection in the bone marrow
- Migration of B cells through the circulatory system to lymphoid organs and B-cell activation
- Antibody secretion and memory cells in bone marrow and lymphoid tissue
Describe the activation of B cells leading to antibody production.
- Mature B cells enter a secondary lymphoid tissue
- In absence of its specific antigen B cell leaves the lymph node and recirculate
- Naive B cells encounter an antigen in a secondary lymphoid tissue
- Antigen-specific B cells are further activated by helper T cells
- Some proliferate in the primary follicle and differentiate into plasma cells which secrete IgM antibody and fight infection (primary response)
- Others migrate in a secondary lymphoid follicle where they mature slowly - once completely differentiated they turn into plasma cells secreting high affinity antibodies
- As primary response subsides B cells in the secondary lymphoid follicle also develop into memory B cells
- At a second encounter with the same antigen these memory B cells will rapidly activate and develop a secondary quicker and stronger antibody response
Describe the structure of T cell receptor
- Made of 2 polypeptide chains - alpha and beta
- Each chain have a variable and constant region
- Each V chain contains 3 CDRs
State the difference between T cell receptors and antibodies.
- T cell receptors always stick on the surface of T cells unlike antibodies
- T cell receptors act in a complex
- TCR can only detect antigens that are located on the surface of MHC molecules (located on our cells)
Describe MHC class 1
- Expressed on all nucleated cells
- Binds TCR of CD8+ T cells
Describe MHC class 2
- Mainly expressed on APC
- Binds TCR of CD4 T helper cells
Describe the process of endogenous antigen presentation to CD8+ T cells.
- Proteins from pathogens are made in the cytoplasm are presented by MHC class 1 molecules
- Proteins must be processed to peptides before binding
- All nucleated cells have MHC class 1 molecules so any cell infected by virus can be killed by cytotoxic CD8 T cells
Describe the process of exogenous antigen presentation to CD4 T helper cells.
- Exogenous antigens are internalised and presented by MHC class 2
- Proteins processed to peptides before binding
- APCs activate helper CD4 T cells
Describe the similarities between B cell development and T cell development.
- originate from bone marrow stem cells
- rearrange receptor genes
- express pre-T receptor
- elimination of self-reactive T cells (negative selection)
State the differences between T cell development and B cell development.
- T cells undergo development in thymus
- alternative lineages: CD4+ OR CD8+ must be able to interact with self MHC
- Positive selection (elimination of non-functioning cells)
Describe the development of T cells.
- T cell progenitors develop in the bone marrow and migrate to the thymus
- Positive and negative selection in the thymus
- Mature T cells migrate to the peripheral lymphoid organs
- Activated T cells migrate to sites of infection
What can an immature T cell recognise when they leave the bone marrow and migrate into the thymus?
- can recognise self MHC and respond to a foreign peptide (defence)
- Recognise and respond to self MHC plus SELF peptide (danger); eliminated by negative selection
- No recognition of self-MHC (useless); eliminated by positive selection
Describe positive selection of T cells.
- select T cells with a TCR that is able to bind to MHC + self peptide
- Occurs when the TCR of double-positive (CD4+ CD8+) T cells recognise MHC molecules expressed on cortical epithelial cells
- These then move to medulla and mature to single positive cells
Describe negative selection.
- Removes cells with a TCR binding tightly to self peptides
- Occurs when the TCR of CD4 or CD8 T cells recognise MHC molecules expressed on dendritic cells/macrophages with high affinity
- T cells with moderate binding to MHC-self peptides complexes are allowed to survive
How do activated T cells acquire effector functions in the secondary lymphoid tissue?
Must encounter an antigen presented by dendritic cells and interact with co-stimulatory molecules
Describe the function of activated T cells.
- CD8+ T cells acquire cytotoxic activity - kill cells bearing the MHC 1 - peptide complex
- CD4+ T cells mainly function by secreting cytokines - help other cell types
Once TCR has acquired effector functions what happens?
- no longer require co-stimulation
- change of location; no longer enter lymph nodes instead enter tissues via activated endothelial at sites of infection and inflammation
Describe the two ways to activate CD8 T cells.
1) CD8+ responses can be directly activated from infected cells presenting MHC 1/peptide complexes
2) Require help from CD4+ T cell to get activated
Describe the mechanisms of killing by cytotoxic CD8+ T cells.
1) secretion of cytotoxic granules - perforin, polymerises in membrane and granzymes (proteases) enter cell
2) fas ligand on T cell interacts with fas on target
3) Can also secrete cytokines - secrete gama IFN which inhibits viral replication, up regulates MHC class 1 expression and antigen presentation and increases macrophage phagocytosis of dead cells.
State the 4 types of specific CD4+ T helper cells and their functions.
TH1 - active against intracellular bacteria + help macrophages
TH2 - active against extracellular bacteria + help the B cells
TH17 - active against extracellular pathogens + help the neutrophils with phagocytosis
TFH - supporting B cells maturation
Treg - regulatory cells e.g. inhibit antigen presentation to T cells to reduce autoimmunity
