12 Cooperation leads to effective immune responses Flashcards
T cells can only recognise antigen presented by antigen presenting cells.
B cells can recognise antigens on surface of pathogen, or free antigen
Nevertheless, T cells need to “help” B cells to fully activate.
How do they do this?
Subsets of T helper cells help activate B cells
CD4 T helper cells can also activate CD8 T cells, and macrophages making them more effective at phagocytosis
What is role of antibodies?
Block toxins
Opsonise microbe - Fc portion binds to Fc receptor on phagocyte, to increase phagocytosis
Activate complement - Fc receptor activates C3b. Causes opsonisation/ chemotaxis/ increased vascular permeability. This shows innate and adaptive working together
IgE bind mast cells - cause degranulation and release of histamine causing chemotaxis and increased vascular permeability
Once T cell mature, it enters circulation, expressing T-cell receptor (TCR) which recognises antigens presented by MHC
Which cells can presents MHC to t-cell to activate it?
Antigen presenting cells -
- dendritic cells most common, as can present large amounts of MHC. Usuaully present in lymphoid tissues
- macrophages + B cells - although lower expression of MHC and other co-stimulatory molecules
What is life cycle of dendritic cell?
Bone marrow
Immature dendritic cell in blood
Update antigen in blood
Move in lymph to lymhoid tissue
Becomes mature dendritic cell in lymhpoid tissue
Presents MHC to naive T cell - thereby activating it
Which MHC molecules to CD4 and CD8 T cells respond to?
CD4 T - recognise antigens presented by MHC class II molecules derived from degradation from phagocytosed organisms
CD T - recognise peptides derived from antigens in cytoplasm presented by MHC class I molecules
How do antigens end up as part of MHC class II?
Once organism phagocytosed or antigen endocytosed from outside, then lysosomes breaks down peptides.
Then fuses with MHC class II, which then moves to cell surface
How do antigens end up as part of MHC class I?
Antigen must be in cytoplasm of cell
Proteasome degrades this
Transported to endoplasmic reticulum, where it is bound to MHC I
Moves through golgi region and via exocytic vesicles to present on cell surface
CD4/ CD8 T cell recognises MHC complex on surface of antigen presenting cell. But still needs second signal to become activated
How is this achieved?
CD28 molecule on T cell binds to B7 molecule on APC
CD40 molecule on T cell binds to CD40L molecule on APC
This binding occurs in what is known as the immunological synapse
This leads to activation of CD3, which triggers a chain of reactions which result in T cell activation and cytokine release from APC
Some super-antigens such as staphylococcal enterotoxin B stimulate extensive T-cell activation and a cytokine storm
Each T cell/ B cell expresses its own antigen receptor, either a TCR or Ig molecule
Cloncal expansion allows large increase in numbers of antigen-specific T/ B cells
Which interleukins are required for clonal expansion?
What can lymphocytes sub-roles can they eventually differentiate into?
IL2 and IL7
B-cell antibody synthesis T-cell help T-cell regulation T-cell cytotoxicity Cytokine release Memory B cells
When B cells start clonal expansion to plasma cells, some mutation will occur, which will mean daughter cells may not be as effective at producing correct immunoglobulin
How is this process regulated?
B cells with disadvantageous mutations undergo apoptosis
Those which show correct immunoglobulin, are selected to continue dividing
They then encounter dendritic cell which is presenting antigen. With help of CD4 T helper cells, B cells then differentiate into plasma cells or memory B cells
Whole process aided by follicular T helper cells (Tfh) - these are significantly damaged in HIV infection
Similarly to T-cell superantigens, sometime B cells can be activated directly without T-cell help.
Antibody response not optimal, and not very good at creating memory response
What can activate them?
Lipopolysacharride on bacteria cell wall
Bacterial DNA
Once body has dealt with infection, adaptive immune system keeps some antigen-specific cells in standby as memory T and memory B cells.
Memory cells are much easier/ quicker to activate than naive cells, so generate faster immune response when re-stimulated.
How is immune response different during repeat infection?
Antibody response will mainly be IgG and IgA which will be of higher affinities to those usually produced during initial response
Where do these lymphocytes live -
- central memory T cells
- effector memory T cells
- memory B cells
- central memory T cells - peripheral lymphoid circulation
- effector memory T cells - migrate to sight of inflammation
- memory B cells - spleen/ lymph nodes
How do lymphocytes provide acquired immunity
B cells - humoral immunity - produce antibodies
T cells - cell-mediated immunity - destroy intracellular organisms
What is role of these interleukins?
IL-2
IL-7
IL-12
IL-2 - T-cell proliferation
IL-7 - B/T cell proliferation
IL-12 - induction of Th1 cells (CD4 cells)
Once infection resolves, IL-2 and IL-7 production drops, so cell division of lymphocytes slows.
