Lecture 4 - Adaptive immunity Flashcards
How long after the first encounter with a microorganism does the adaptive immune response take to become effective?
2-4 days
What does a vaccination do to the immune system?
- Initiates a primary immune response, generating memory cells without making the person ill
- Later, if some similar pathogens invade the body, specific memory cells already exist
- The memory cells recognise the agent and produce massive numbers of lymphocytes and immunoglobulin that overwhelm invaders
What did Edward Jenner develop in 1798?
The jennerian vaccination for smallpox.
He observed that injecting fluid from cowpox pustules into the skin of children led to the acquisition of immunity to smallpox
Which lineage of cells is the adaptive immune response mediated by?
Lymphocytes of the lymphoid lineage
What is the role of T lymphocytes?
Kill virus infected and cancerous cells (CD8+/ cytotoxic t cells)
Activate other cells of the immune system (CD4+ helper T cells)
What is the role of B lymphocytes?
Secrete immunoglobulins (antibodies)
What is the role of Natural Killer (NK) cells?
Cells that are considered part of the innate immune system as they don’t require prior activation.
They lack antigen specific receptors and are capable of killing virus infected cells immediately, without clonal expansion.
How are NK cells activated?
Binding of an activating receptor to surface molecules produced by cell damage, e.g. cancer, or that are encoded buy infecting viruses
What is the definition off an antigen?
A molecule or parts of molecules recognised by the variable antigen receptors of lymphocytes
What is the definition of a naive lymphocyte?
Mature Lymphocytes that have not yet encountered an antigen
Once naive lymphocytes come into contact with an antigen, what do they differentiate into?
Effector cells
What is the process prior to differentiation into effector cells that involves vigorous proliferation that selectively expands the numbers of lymphocytes with receptors for specific antigens known as?
Clonal selection
Where does interaction between activated DCs and lymphocytes occur?
Lymphoid tissues, which they enter through the bloodstream
How do T lymphocytes recognise antigens?
T cell receptors generated during their differentiation, interact with APCs via complementary ligands
Are CD4+ t cells helper or cytotoxic?
Helper
Are CD8+ t cells helper or cytotoxic?
Cytotoxic
Does CD4 bind MHCI or II?
MHCI
Does CD8 bind MHCI or II?
MHCII
Where’re dendritic cells especially numerous?
Epithelia and mucosal surfaces
What are Langerhans cells?
A subset of DCs that reside in the keratinised epidermis for several months
What are dermal or interstitial DCs?
Skin resident DCs found in the dermal layer
What are mucosal gut DCs and what are their roles?
Dos that are concentrated at specialised sites of antigen collection that overlie lymphoid tissues.
Some have specialised surface properties that enable them to extend their long dendritic processes between the cells of the epithelium and into the lumen to sample antigens
These cells are directly exposed to ingested antigens and to commensal bacteria as well as invading pathogens
These cells have a specialised role in preventing inflammatory responses to harmless gut residents
What are M cells?
Specialised cells that deliver antigen from the lumen of the gut to the underlying tissue, where dendritic cells cluster
What is the process of adaptive immune system activation? (7 points)
- Dendritic cell engulfs pathogen
- migration to lymph
- Here the DC comes into contact with naive T cells, to which it presents its antigen and the T cell docks with the DC
- T cells activate and proliferate thorough clonal expansion
- These proliferated T cells differentiate into effector T cells
- These effector T cells come into contact with macrophages or B cells and activate them
- Active B cells will produce antibodies specific to the pathogen
Whats the process of DC migration and activation of T cells? (5 steps)
- DCs are generated from progenitors in the bone marrow. Here they lie and wait for pathogens entering the body through sites of injury for example.
- DCs express PRRs which bind to and phagocytose these pathogens
- Once bound they mature and migrate to the lymphatics, changing their behaviour to stop phagocytosing, starting to express immune stimulatory molecules
- Here the T cells inspect the DCs for antigen
- If they find one they recognise, T cells activate and proliferate differentiating into effector cells.
What is the name of the process that allows T cells to alter their receptors in order to achieve a perfect fit with the antigen displayed on DC for example?
Somatic hypermutation
How do T cells know which immune cells to interact with?
They recognise MHC surface proteins on DCs which display peptides for recognition. They then differentiate into effector cells, which are capable of killing cells or activating those displaying the same complex of MHC and antigen.
What did Peter Medwar establish in 1944?
Established that the timing and vigor of rejection is
related to differences between histocompatibility antigens of donor and recipient.
Rejection within the first week = Major histocompatibility complex
Slower rejection process = Minor histocompatibilty complex
What are the two internal compartments of cells that need to be monitored for pathogens?
The cytoplasm
Vesicles of the endosomal/ lysosomal pathway
What class of MHC molecules monitor the cytoplasm?
MHCI
What class go MHC molecules monitor vesicular compartments?
MHC II
Which cell types express MHC class I?
Virtually all body cells
Which type of molecules does MHCI bind?
Peptides generated by cytoplasmic proteases from cytoplasmic proteins
Which cell types recognise molecules displayed on MHCI?
Cytotoxic T cells (CD8+)
Which cell types express MHC class II?
Cells of the immune system, particularly B cells, macrophages and DCs
Which cell types recognise molecules displayed on MHCII?
Naive helper T cells (CD4+)
Which type of molecules does MHCII bind?
Peptides generated from internalised antigen in the
endosomal compartments of cells
Upon activation, what do CD8 T cells produce?
Perfroins and Granzyme
What are perforins?
Proteins that form pores in the membrane of target cells
What are granzymes?
Proteases that induce programmed cell death on entry into target cells
How do granzymes mediate cell death?
- Granzymes target proteins that regulate apoptosis such as BID and pro caspase 3
- Granzymes cleave bid which in its truncated form cause cytochrome c to release from miochondria into cytosol
- Simultaneously granzyme b activates pro caspase 3 which in turn cleaves icad
- CAD migrates into nucleus where it degrades dna ensuring death of cell
What are the steps in the process of antigen-MHCII complex recognition on macrophages by T helper cells? (2 steps)
1. Helper T cells recognise fragments of a pathogen that has been internalised by macrophages and are carried to the cell surface by MHC class II molecules.
- The helper cell is then stimulated to activate the macrophage to destroy the internalised pathogen.
What are the steps in the process of antigen-MHCII complex recognition on B cells by T helper cells? (5 steps)
- B cells internalise antigens bound to their surface immunoglobulin and deliver them to the endosomal
compartments of the cell - Here they are digested into fragments.
- The antigen fragments then bind to MHC class II molecules which carry them to the cell surface
- Here they are recognised by helper T cells
- Helper T cells activate
the B cell to proliferate and
differentiate into an antibody-
secreting plasma cell
The CD4 cell subset, Th1, are produced in order to stimulate which immune cell?
Macrophages
The CD4 cell subset, Th2, are produced in order to stimulate which immune cell?
B cells and the production of antibodies
What is the costimulatory pair for MHCII found on the T cell?
TCR with CD4 coreceptor
What is the costimulatory pair for B7 (CD80/86) found on the T cell?
CD28 CTLA-4
What is the costimulatory pair for CD40 found on the T cell?
CD40L
