Adaptive Immunity - T cells Flashcards
What does the adaptive immune response consist of?
Cell-mediated responses and antibody (humoral) responses - these are carried out by T and B cells
What do T cells drive in adaptive immunity?
Cell-mediated immunity - it involves the action of macrophages, NK cells and antigen-specific cytotoxic T-lymphocytes
What do B cells drive in adaptive immunity?
Drive humoral immunity and produce antibodies
What is a key feature of the adaptive immune system?
Immunological memory - whereby each pathogen is ‘remembered’ by a signature T cell receptor and/or B cell receptor
What are the 4 stages to adaptive immunity?
- Establishment of infection
- Induction of adaptive response
- Adaptive immune response
- Immunological memory
What are the 3 main receptors of active immunity?
3 main molecules that are involved in recognition of foreign antigen by adaptive immune response:
- T cell receptor
- B cell receptor
- Major histocompatibility complex
Multiple genes encoding each allows the development of a repertoire of receptors with specificity for wide range of antigens
- TLR - just has 1 gene
- B cell receptor -
- overtime multiple genes that encode 3 major constituents
- can pick and choose what genes it wants
What are the 2 classifications of T cells?
- CD4+ (helper cells)
- CD8+ (cytotoxic cells)
What is ‘cluster of differentiation’ in T cells?
Cell surface markers involved in signalling
What is major compatibility complex in T cells?
Cell surface markers involved in signalling - molecules flagged for presenting antigen
CD8+ is a co-receptor that binds to what?
MHC class 1
CD4+ is a co-receptor tat binds to what?
MHC class 2
What is used to help anchor the T-cell receptor so it can get a tight signalling complex with the antigen?
CD8+/CD4+ and CD3
CD3 is a co-receptor. What is it involved in the activation of?
CD4+ and CD8+ cells
What is the function of Gamma-delta T cells?
- Only 5% in humans
- Little known about functions
How many antigens does each T cell have specificity for?
only 1
T cell receptors contain alpha and beta chains - how many genes code for each of the 2 polypeptide chains?
Multiple genes
What 2 regions are each alpha and beta chain made up of in a T cell receptor?
- Constant region
- Varied region
To make an alpha chain there are 2 gene segments which encode the variable region of the chain. What are these?
- V (variable)
- J (joining)
To make a beta chain there are 3 gene segments which encode the variable region of the chain. What are these?
- V (variable)
- D (diversity)
- J (joining)
To generate diversity in alpha and beta chains of T cell receptors, how are genes re-arranged?
By somatic recombination (mutation)
- Has the ability to pick from lots of genes
- Making alpha chains - picks one V gene and one J gene
- Making beta chains - picks one V gene, one J gene and one D gene
- Can pick one gene from a variety of genes
- By picking and choosing different genes you can produce a unique protein
How many combinations are there for V(D)J in the variant region of the beta chain of a T cell receptor?
Approx. 3x10^11
The protein structure of a T cell receptor is different to accommodate specific antigens. How is the structure different?
Specific antigen binding sites
What is the process of thymic education?
- Pre-thymic T cells enter the thymus. Cells are CD8 and CD4 positive (low expression). TCR genes are also rearranged (low expression)
- As the cells mature, they move into the cortex where they adhere to cortical epithelial cells. TCR’s on their surface interact with the MHC molecules on the epithelial cells (positive selection)
- Cells that are not selected are subject to apoptosis and are phagocytosed by macrophages
- Thymocytes then migrate into cortex and expression of CD3, CD4/CD8 and TCR increases
- TCR’s with self-reactivity are deleted because of contact with autoantigens presented by dendritic cells and macrophages (negative selection)
- Cells that express CD4 or CD8 appear and migrate to the periphery
What is the simplified process of thymic education?
- Can they bind to MCH class 1 or 2 (not just what they bind to but how strongly they bind) - called positive selection (if can’t bind to 1 or 2 they are disposed of by apoptosis then phagocytosis)
- Have T-cell receptor that can bind to infinite number of antigens - what happens next is where dendritic cells show T cell lots of different self-antigens. If T cell binds to one of self-antigens T cell is processed for cell death - negative selection
- Then moved to medulla - fully educated T cells - most will go to lymph nodes and can spread around the body
Even when T cells leave the thymus after thymic education why is it still defined as a ‘naïve’ T cell?
As it has still not been exposed to a foreign antigen
Where can T cells be found?
- They circulate in the blood and lymphatics
- Some T cells find their way to lymph nodes (secondary lymphoid organs) and remain
- Even though they have been ‘educated’ they are still ‘naive’ cells
Lymph nodes are ‘garrisons’ of immune cells. What does this mean?
Lymph nodes store ‘troops’ (immune cells) in anticipation of an immune reaction
What cells do lymph nodes contain?
- T cells
- B cells
- Dendritic cells
How are T cells activated by dendritic cells?
- Immature dendritic cells take up and process antigen in the epidermis
- Once taken up the antigen they migrate to lymph nodes and differentiate along the way
- Mature dendritic cells have co-stimulatory activity and can prime naïve T cells
- They can also transfer antigen to other dendritic cells resident in the lymph node
What are dendritic cells?
Antigen presenting cells
What do dendritic cells do once they are activated?
- They leave tissue and during migration they differentiate. Stop processing antigen and the MHC: antigen migrates to cell surface
- Once they arrive at the lymph noted they express high levels of MHCII: antigen
What is ‘priming’ of a T cell?
The activation and differentiation of a naïve T cell
What are the 3 signals involved in the ‘priming’ of naïve CD4+ T cells?
- Signal 1 - Need T cell receptor that recognises antigen - Dendritic cell (APC) presents antigen on MHC class II to T cell receptor on naïve T cell (CD4 also binds to MCHII) this causes ACTIVATION
- Signal 2 - APC as its moving into lymph node will start expressing a lot of CD80/CD86 (needs further anchoring through this binding) By these binding to CD28 - Co-stimulatory molecules engage so CD28 binds to CD80/CD86 which is a signal for survival and clonal expansion of T cells (signal 1 but no signal 2 leads to ANERGY)
- Signal 3 - T cell is exposed to cytokines (determines what type T cell will become by which cytokine has been produced) - Want T cell to become right type of T cell for the pathogen that is present (DIFFERENTIATION INTO SUBSETS OF EFFECTOR T CELLS) - after this the T cell will start to divide to produce many copies of itself
What is the definition of anergy?
Absence of the normal immune response to a particular antigen or allergen
What will determine what types of Specialised cell a naïve T cell will become?
Cytokines released by antigen presenting cells
Once a naïve T cell encounters presented antigen it undergoes expansion. What is meant by expansion?
It produces lots more of itself (many copies)
What are memory T cells and what can the allow?
- T cells that become long lasting in the body (they have a life span of over 20 years)
- They allow a faster and larger immune response to a secondary exposure to an antigen
What are the roles of Th1 cells?
- Numerous roles in supporting cellular immunity
- Linked to innate immunity and heighten ongoing responses in tissues
- Key role in supporting macrophage function
- Good at going back to front line and supporting innate immunity
What are the roles of Th17 cells?
- Play a role in host defence against pathogens
- Multiple roles in dictating immune responses
- Support innate immunity
Why are Th17 cells called this?
Because they express IL-17
What are the roles of Th2 cells?
- Major role in supporting humoral (antibody) immunity
- Activates mast cells and eosinophils. Protect against parasitic infections but also major role in allergy and hypersensitivity reactions
- Little innate immunity involvement
Where are Thf cells found?
Found in secondary lymphoid organs in B cell zone (not T cell zone)
What are the functions of Thf cells?
- Helps support B cell responses
- Promotes B cell activation and the formation of antibody producing plasma cells
What are Treg cells?
Regulatory T cells
What are the functions of Treg cells?
- Immune suppression (provide balance)
- Key modes of action:
- Release inhibitory cytokines
- Induce active T cells to undergo apoptosis
- Inhibit dendritic cell maturation and function
How are cytotoxic CD8+ T cells activated?
By antigen presentation on MHC class I presented to TCR
What are CD8+ T cells also known as?
Cytotoxic T cells
What are the functions of cytotoxic T cells?
- Induce host cells to undergo apoptosis (programmed cell death)
- With apoptosis all contents of the cell are kept inside so there is no further unwanted signalling
- Cytotoxic T cells release contents of granules in direct fashion (granzyme/perforin)
- Perforin produces pore in cells
- Granzyme targets apoptotic signalling pathways
What is the function of perforin?
Directs contents through cell wall (unknown mechanism)
What is the function of granzyme?
Once in cell, granzyme targets apoptotic signalling pathways:
- Caspase- 3
- Disrupts mitochondrial membrane releasing cytochrome c
What are the functions of perforin and granzyme inducing apoptosis?
Perforin facilitates granzyme entry into infected cell. Once in cell granzyme induces apoptosis
