Initiation of Acquired Immune Responses Flashcards
Revision
What are the roles of T cells and cellular immunity?
T cells and cellular immunity have a key role in defense against intracellular pathogens.
CD4+T cells
Key regulators of the entire immune systm
CDB + T cells
Kill virall infected body cells
= Cellular immunity
Unlike B cells, T cells can only recognise peptide antigens.
A single T cell expresses thousands of copies of a single antigen receptor (TCR).
A hypervariable region formed by the tips of the alpha/beta TCR is involved in antigen binding and is unique to each individual T cell.
Thus, each T cell expresses a unique TCR that can bind to only one specific peptide antigen.
What do T cells require to recognise peptide antigens?
T cells require protein antigens to be processed and presented to their T cell antigen receptor (TCR) in complex with major Histocompatibility Complex (MHC) molecules.
Very different to how B cells see antigens - B cells do not require any involvement of MHC molecules in order to “see” antigen.
What is the role of Major Histocompatibilty Complex (MHC) molecules?
Displays peptide antigens to T cells.
Also referred to as HLA (Human Leucocyte Antigens).
- Encoded by highly polymorphic genes.
- First identified in early transplanted procedures.
- Able to present many different peptides.
What are the two classes of MHC molecules and the roles of each?
Class 1 MHC
- Expressed on all nucleated cells
- Present peptide antigens to CD8+T cells
Class II MHC
- Expressed only on professional antigen presenting cells (APCs)
- Dendritic cells
- Also Macrophages, B cells
- Present peptide antigen to CD4+ T cells
(also contain some very special cells from the thymus)
In infected, inflamed tissue, particles and antigens derived from pathogens are released by phagocytes. What is the process of this?
Dendritic Cells (DCs) are the bridge between the innate immune system and the acquired immune system. The main function of dendritic cells is to process and present antigens on their cell surface to T cells. They are present in large numbers in tissues that are in contact with the external environment e.g. the skin (where there are specialised dendritic cells known as Langerhans cells) and other epithelial tissues (respiratory tract, gut etc)
Dendritic cells phagocytose pathogen-derived particles and antigens.
Pro-inflammatory TNFalpha stimulates immature tissue-resident Dendritic cells to increase expression of co-stimulatory molecules. What is the process of both?
Dendritic cells are in an immature state in normal (non-inflamed tissues).
In infected/inflamed tissues:
Dendritic cells recognise and phagocytose antigen debris (they express PRRs on their cell surface which can bind to microbial PAMPs).
In the presence of pro-inflammatory mediators such as TNFalpha, these dendritic cells start to mature and increase expression of key co-stimulatory molecules on their surface.
Dendritic cells digest ingestested proteins and display small peptides derived from these on their cell surface in complex with MHC proteins. What is the process of this?
After phagocytosing the pathogenic antigens, the dendritic cells breaks these protein antigens down into short peptides (6-15 amino acids long) and loads them onto MHC class I and MHC class II molecules. These peptide-loaded MHC molecules are transported to the cell surface. At the same time, the maturing dendritic cell leaves the infected inflamed tissue and migrates via the afferent lymphatic vessels into draining lymph nodes.
Antigen-activated CD4+ cells regulate innate and adaptive immune responses. What is the process of this?
CD4+ T cells differentiate into several different types of effector helper T cells (Th) cells which either remain in 2o(0 is higher than 2 as if a degree symbol) lymphoid tissues or migrate to sites of infection to help B cells, CD8+ T cells or macrophages
TFH cells = T follicular helper cells
Antigen-activated CD4+ T cells start to secrete a T cell growth factor, Interleukin 2 (IL-2) and also express the IL-2 receptor -> autocrine-mediated cell proliferation.
These proliferating cells are sometimes known as TH0cells (H is subscript) and they induce autocrine-/paracrine mediated proliferation of CD4+ and CD8+ cells as hey produce large amounts of interleukin 2.
This interleukin 2 (IL-2) is used by BOTH antigen activated CD4+ T cells AND antigen activated CD8+ T cells in order for them to proliferate and differentiate.
Effector TH1 cells migrate out of secondary lymph nodes and enter sites of infection/ inflammation (via transendothelial migration).
They become re-activated by infected, tissue-resident macrophages (in n antigen-specific manner).
Infected macrophages express bacterial peptide antigens on their cell surface (in complex with MHC-II).
As a result, the reactivated TH1 cells secrete pro-inflammatory cytokines, which enhances macrophage-mediated killing of internal pathogens by stimulating production of reactive oxygen species (ROS).
Antigen-activated CD8+ cells proliferate and differentiate into killer cells. How does this process occur?
Cytotoxic T lymphocytes (CTLs or Tc cells)
These CTLs migrate out of the lymph node and enter sites of infection in order to kill infected host cells.
CD4+ T cells differentiate into different effector helper T cells (Th) cells that can provide Interleukin-2 to promote proliferation and differentiation of anigen-activated CD8+ T cells into effector cytotoxic T lymphocytes (CTLs).
These newly formed CTLs migrate out of secondary lymph nodes and enter sites of infection/ inflammation (via transendothelial migration) in order to kill virally infected host cells.
How do CTLs kill infected host cells?
CTL recognizes and binds to virus-infected cell.
CTL programs target for death, inducing DNA fragmentation.
CTL migrates to a new target.
Target cell dies by apoptosis.
Any nucleated cell expresses MHC-1 molecules on their surface.
MHC-I molecules are constanty sampling the peptide pool within the host cell and displaying them on the cell surface.
In a normal setting, these MHC-I molecules will display self-peptides (from host or self-antigens)
Normally, very few auto-reactive CD8+ T cells are present (so the display of self-peptides is generally not a problem for most individuals).
During a viral infection, MHC-I molecules on virally infected cells will now start to display viral-peptides.
- His flags to the effector TLs that the cell has been infected - if that CTL expresses a specific TCR that recognizes the viral peptide that is being displayed, it will kill that infected cell.
Do B cells require MHC or Dendritic cells in order to respond to antigens?
B cells do NOT require MHC or Dendritic cells in order to recognise and responds to antigens.
What signals do T cells require to respond to antigen and fully activate?
Like B cells, T cells require other signals to respond to antigen and fully activate.
Co-stimulatory molecules expressed by the dendritic cell provide this help (Signal 2 in the diagram); signal 1 is provided by the peptide antigen/MHC complex.
Once activated, these T cells clonally proliferate and differentiate into different types of effector cells.
What is the process by which long-lived memory B cells are formed?
- Protein antigen bound to BCR is internalised by the B cell. The antigen is degraded and peptides derived from it are presented on the B cell surface in complex with MHC-II molecules.
- Effector TFH(FH are subscript)cells move into B cell zone of the lymph node where they are re-stimulated by B cells in an antigen-specific manner.
- Re-activated effector TFH cells stimulate the B cells to clonally proliferate and differentiate into long-lived plasma cells that secrete high affinity-specific antibodies (in the Germinal Centre reaction).
- Re-activated effector TFH cells stimulate the B cell to clonally proliferate and differentiate into long-lived memory B cells (Bm cells).
