L94: Adaptive Immunity I Flashcards
What are the two components of adaptive immunity?
- Cell-mediated response;
2. Humoral (antibody) response.
Which cells carry out the responses of adaptive immunity?
T and B cells
What is the role of T cells in adaptive immunity?
T-cells drive cell-mediated immunity, this includes activation of macrophages, natural killer cells (NK) and antigen-specific cytotoxic T-lymphoctyes.
What is the role of B cells in adaptive immunity?
B-cells drive the humoral response through the production of antibodies.
What is the main difference between innate and adaptive immunity?
In adaptive immunity, there is an immunological memory.
What is immunological memory?
Where each pathogen is ‘remembered’ by a specific T-cell receptor and/or B-cell receptor.
Describe the kinetics of adaptive immunity:
- ‘Establishment of infection’ occurs as a microorganism has entered and reaches the antigen threshold level to initiate an adaptive immune response (innate immune response happens here too);
- Once threshold has been reached, ‘induction of adaptive response’. At this point the level of microorganism continues to increase;
- Once the ‘adaptive immune response’ has been initiated, the level of microorganism begins to clear;
(area under the graph from 1-3: duration of infection)
- After clearance, ‘immunological memory’ is achieved. (up to 20 years).
With regards to genetics, what is the difference between innate and adaptive immunity?
Innate immunity is regulated by one gene, adaptive is regulated by multiple genes leading to many signature patterns for immunity.
What are the three main molecules involved in recognition of foreign antigens? (adaptive)
- T-cell Receptor (TCR);
- B-cell Receptor (immunoglobulins [Ig]);
- Major histocompatibility complex (MHC proteins).
What are the two classes of T-cells?
- CD4+ (helper);
- CD8+ (cytotoxic).
What does CD stand for?
Cluster of differentiation (cell surface markers involved in signalling)
What does MHC stand for?
Major histocompatability complex (cell surface markers involved in signalling)
Which MHCs do CD4+ cells interact with?
MHC Class II
Which MHCs do CD8+ cells interact with?
MHC Class I
What is CD3?
A co-receptor involved in the binding and activation of both CD4 and CD8 (also co-receptors) to MHCs
Describe the structures of T-cell receptors (TCR):
- Two classes of TCRs: ab chains and gd chains (antigen binding sites);
- Majority are ab;
- Each chain, a and b (or g and d) have a variable and a constant region;
- For an a-chain, two gene segments encode the variable region of the chain;
- V (variable) and J (joining);
- For b-chains, three gene segments encode for the variable region of the chain;
- V (variable), D (diversity) and J (joining);
- This leads to millions of T-cells, each specific to one antigen.
What process (genetic) leads to variation within TCRs?
Somatic recombination (mutation)
Which part of the TCR is specific to different antigens?
The antigen binding site
In the body, where are B and T cells produced?
The bone marrow
In the bone marrow, lymphocytes are…
Undifferentiated
Where are B-cells processed (differentiated)?
The bone marrow
After differentiation of lymphocytes to B-cells, where are B-cells transported to?
The blood stream and lymphatic organs
Give two examples of lymphatic organs
- Lymph nodes;
- Lymphatic ducts;
- Spleen
Where are T-cells processed (differentiated)?
The thymus gland
What is the name of the process given to differentiation of lymphocytes to T-cells?
Thymic Education
Explain the process of Thymic Education:
- Lymphocytes (from bone marrow) transferred to thymus;
- Low expression of CD4+, CD8+ and TCRs;
- As cells mature, they move to the cortex region and adhere to epithelial cells;
- Positive selection as to whether they bind to MHC I or II and therefore CD8+ and CD4+, respectively;
- From this point they will express either CD4+ or CD8+;
- If no binding, apoptosis;
- Negative selection to determine whether T-cells bind to self-antigens;
- If they bind to self antigens, apoptosis;
- If no binding, ‘fully educated’;
- Released as naive T-cells.
What is meant by naive T-cells?
After thymic education, T-cells are described as naive until they have been exposed to a foreign antigen
After differentiation of lymphocytes to T-cells, where are T-cells transported to?
The blood stream and lymph nodes
Why are lymph nodes (secondary lymphatic organs) important sites for the adaptive immune response?
They contain numerous B and T cells, and also dendritic cells
What are the three signals required for CD4+ T-cells to become activated and differentiate?
- Signal 1: APC presents antigen on MHCII, binding of CD4+ with this MHC;
- Signal 2: CD28 interacts with CD80/86 expressed on mature dendritic cells;
(if signal 1 but no signal 2, anergy)
- Signal 3: Cytokines direct differentiation.
What is the major role of TH1 cells?
Heighten ongoing immune response by supporting macrophage function
What is the major role of TH17 cells?
Expression of IL-17 to dictate innate immune response
What is the major role of TH2 cells?
Support humoral (B-cell) response, mainly in adaptive immunity. Lead to production of lots of anti-inflammatory cells (mast cells and eosinophils).
What is the major role of Tfh cells?
Largely reside in lymph nodes and promote B-cell activation
What is the major role of Treg cells?
To regulate immune response, turn cells ON and OFF and also programme cells to undergo apoptosis
What is involved for the activation of CD8+ cells?
- APC presents antigen on the MHC I to TCR;
- CD8 acts as a co-receptor;
- This directs differentiation to CD8+ and memory cells.
What is an alternative name for CD8+ cells?
Cytotoxic T-cells
How do viruses infect cells?
They require genetic machinery for replication
How are viruses removed from infected cells?
CD8+ cells induce the host cells to undergo apoptosis
What is apoptosis?
- Programmed cell death;
- Requires energy (ATP);
- Contents remain inside of cell;
- No unwanted bi-response (i.e. no inflammation).
What is necrosis?
- Cell death;
- No energy required;
- Spilling out of contents;
- Bi-response, inflammation.
What do granules contain?
- Granzyme: Proteases that induce apoptosis*;
- Perforin: Pore-forming protein to direct granzyme into target (infected) cell.
- Which apoptic signalling pathways do granzymes target?
- Caspase-3;
- Disrupts mitochondrial membrane releasing cytochrome c.
