Adaptive immunity 1 Flashcards
What is the adaptive immune system?
the specific and acquired branch of the immune system which provides immunological memory
How are both the innate and adaptive immune system further divided?
Into cellular (e.g. B and T cells) and humoral aspects (proteins, antibodies, soluble mediators)
How does adaptive immunity provide immunological memory?
B and T cells are primed to respond to specific pathogens
Which cells mediate the adaptive immune system?
B and T cells (but still requires innate immune cell involvement e.g. APCs)
What are the 3 receptors of the adaptive immune system?
T cell receptor, B cell receptor, Major Histocompatibility Complex
What is the difference between innate receptors and adaptive immunity receptors?
Innate receptors are highly conserved (same amongst individuals and species) whereas adaptive receptors have variable structures to recognise specific pathogens
How do adaptive immune receptors (TCRs, BCRs, MHC) change structure?
genes encoding the receptors can be rearranged to form a diverse range of receptors with wide specificity.
Where do T cells originate?
From haemopoietic stem cells in bone marrow
What happens to immature T cells (thymocytes) after they have differentiated in bone marrow?
They travel to the thymus to mature and be educated
Term to describe immature T cells
thymocytes
After maturation in the thymus, where do T cells travel?
circulate in the lymph and stored in lymph nodes
Function of T cells
drive cellular immunity and recognise peptides (e.g. on antigen presenting cells)
Name of receptor used by T cells to recognise antigens
T cell receptor (TCR)
How are T cells able to respond to any antigen?
TCRs are very diverse as their genes can be rearranged
When does TCR diversity arise?
during thymic education
Which processes ensure T cells only respond to foreign antigens and not ‘self peptides’?
Negative and positive selection during thymic education
What are the 2 main types of T cells?
CD4+ helper T cells and CD8+ cytotoxic T cells
How many subsets of CD4+ T helper cells exist?
5 subsets
When are T cells negative for both CD4 and CD8?
When they are thymocytes (immature T cells) entering the thymus
What are CD4 and CD8?
proteins and coreceptors for the T cell receptor (TCR)
Which coreceptor do cytotoxic T cells express?
CD8
Which coreceptor are T helper cells positive for?
CD4+
Which MHC does CD4 bind to?
MHCII (only present on APCs)
Which MHC do CD8 bind to?
MHCI (present on all nucleated cells)
What is the main type of T cell receptor?
alpha-beta chain receptors (consist of constant and variable region)
What are the 2 components of T cell receptors (TCRs)?
Constant region and variable region (can change to bind to any antigen)
What is the variable region of the TCRs also known as?
antigen binding site
How to T cells bind to antigens?
The variable region of the T cell receptors binds to antigen via MHC (on APC/nucleated cell)
Which genes are responsible for the transcription and translation of the variable region of the TCR?
V (variable), D (diversity), and J (joining) genes
What is VDJ rearrangement?
the process by which T cell receptors have different antigen binding sites / variable regions.
What are the 2 terms used to describe the rearrangement of the VDJ genes to change the antigen binding site of the TCR?
VDJ rearrangement / somatic recombination
How does VDJ rearrangement / somatic recombination give rise to extreme variable region diversity?
Each gene segment (V, D, J) has multiple parts that can be transcribed. E.g. V segment has >45 different parts, D segment has 2 parts and J segment has 50 parts for alpha chains. Therefore selecting just one part of each gene segment gives rise to 10^15 (45x2x50) combinations for the alpha chain.
What happens once T cells have expressed their receptors (VDJ rearrangement)?
T cells undergo thymic education
What are the 2 processes that occur during thymic education?
Positive and negative selection
Which cells present self-antigens to the T cells via MHC during thymic education?
thymic epithelial cells
What are the 2 types of thymic epithelial cells?
Cortical and medullary epithelia
What is the first stage of thymic education?
Positive selection
What is the purpose of positive selection?
To ensure that all the TCRs of the T cells that leave the thymus can recognise and interact with the MHC (which presents antigens to the T cell). If TCRs cannot interact with MHC the T cell is useless.
What happens during positive selection of thymic education?
The thymic epithelial cell presents a self peptide to the TCR via a MHC. If there is moderate binding to the MHC, this means there are TCR-MHC interactions so the T cell is positively selected.
What happens if there is no binding during positive selection?
The T cell will undergo apoptosis and is phagocytosed by a macrophage (TCR does not interact with MHC)
Function of negative selection during thymic education
Ensures no self-reacting T cells leave the thymus and starts recognising/attacking self peptides/antigens.
How do self-reactive T cells arise?
By chance, VDJ rearrangement has produced a variable region on the TCR that recognises self antigens
What happens during negative selection of thymic education?
A thymic epithelial cell presents a self peptide to the TCR via MHC. If there is strong binding of the TCR to the self peptide this means the T cell is self-reactive and is negatively selected by undergoing apoptosis.
What happens is self-reactive T cells leave the thymus?
can lead to autoimmune diseases
Where do T cells go after thymic education?
leave the thymus and migrate to lymph nodes and spleen
What are the T cells that leave the thymus known as?
naive T cells (even though they have been educated they haven’t yet encountered antigens/microbes)
What process drives T cell activation?
Antigen presentation via MHCI or MHCII
Which cells can undergo antigen presentation?
all nucleated cells (not just special APCs)
Function of MHCI receptors
presents endogenous proteins (viral, tumour cells)
Where are MHCI receptors found?
all nucleated cells
Function of MHCII receptors
present exogenous proteins (post-phagocytosis therefore only on phagocytes/special APCs)
Which T cells are activated by antigen presentation via MHCI receptors (on all nucleated cells)?
CD8+ T cells
Which T cells are activated by antigens presented by MHCII receptors (on phagocytes)?
CD4+ T cells
How does antigen presentation occur?
APCs (e.g. DCs) phagocytose pathogens at epithelial barrier. DCs migrate to the lymph nodes and mature en route by increasing their costimulatory activity. This allows the APC to activate CD4+ T cells. (CD4+ due to MHCII on APC)
What happens as the APC is maturing on the way to the lymph node after phagocytosis?
APC upregulates its costimulatory receptors/proteins which will allow it to interact with the costimulatory receptors on the CD4+ T cell during T cell activation.
Examples of the costimulatory molecules on APCs
CD40 and CD80/CD86
What is T cell activation also known as?
T cell priming
Where does T cell activation/priming occur?
in the lymph nodes (after APC arrives)
Function of T cell priming/activation
To select the CD4+ T cell with the complementary TCR to the antigen and initiate its division and differentiation into T helper cell subsets
What are the 3 signals that drive T cell activation/priming?
- MHCII-TCR interaction (DC presenting antigen to CD4+ T cell via MHCII)
- Co-stimulatory receptors on CD4+ T cells and APC interact
- Secretion of cytokines by APCs
What is the effect on the CD4+ T cell when cytokines are released from the APC in the final stage of T cell activation/priming?
The cytokine binds to the specific cytokine receptor on the CD4+ T cell which stimulates differentiation into a CD4+ T helper cell subset.
Which T cells are activated by nucleate cells presenting the endogenous protein via MHCI?
CD8+ cytotoxic T cells
How does CD8+ cytotoxic T cell activation/priming occur?
- MHCI-TCR interaction as the nucleated cell presents the endogenous peptide
- Co-stimulatory receptors on both the nucleated cell and CD8+ cytotoxic T cell interact
- Cytokines are released by the nucleated cell which instructs the T cell to degranulate, releasing enzymes for apoptosis of the infected nucleated cell.
Which type of T cell has subsets?
Only CD4+ T helper cells (CD8+ cytotoxic cells don’t have subsets)
What is responsible for inducing CD4+ T cells to differentiate into a specific subset?
The type of cytokine released by the APC determines which subset the T helper cell differentiates into e.g. IL-4 triggers differentiation into T helper 2 cell
What are the subsets of CD4+ T helper cells?
Helper or regulatory - T regulator cells, T follicular helper cells, T helper 17, 1, 2 cells
What are the different functions of the T helper cell subsets?
initiate phagocytosis by macrophages, stimulate antibody production by B cells, immune suppression by interfering with MHC-TCR, barrier and mucosal immunity.
Functions of cytotoxic CD8+ T cells
produce different pro-inflammatory mediators (cytokines), degranulation, induce apoptosis of host cells
What is clonal expansion?
the specific T cell (that targets the specific antigen) increases in number
Where does clonal expansion occur?
Secondary lymphoid organs (lymph nodes, spleen, tonsils)
Difference between effector and memory T cells
Effector T cells (majority) exert a particular function whereas memory T cells (minority) circulate and provide immunological memory
