T cells Flashcards
Innate vs Adaptive immune response?
Innate - non-specific, no memory created, fast response
Adaptive - specific, memory created, slower response
Humoral response vs cell mediated response?
Humoral response leads to antibody production.
Cell mediated response involves activation of phagocytes, T-cells and B-cells.
What are T cells?
A lymphocyte that can recognise specific antigens and can activate or deactivate other immune cells.
Unlike B cells, T cells are unable to recognise pathogens w/out assistance
Where are T cells formed? Where do they mature?
Formed- bone marrow from multi-potent haematopoietic stem cells
mature- thymus
What are the 3 types of T cell? What are their functions?
Helper T cell:
- Express CD4 on their surface.
- involved in antigen presentation & help other cells.
- Involved in the activation of macrophages
-binds to antigen presented by B cell
if they match, t cell releases CD4 ligand- causing the release of cytokines causing b cells to duplicate
-activate class switching too
Cytotoxic T cell:
- Present CD8 on their surface.
- recognise & kill infected or cancerous cell due to antigen presentation
- release perforin which destroy cell
- key part of cell-mediated response
T regulatory cell:
- Supresses autoimmune response
- After T helper and cytotoxic cells have killed a pathogen, T regulatory cells kill those T cells by apoptosis.
Describe the structure & function of T cell receptors?
2 peptide chains (α and β chains)
Constant region- defines the T-cell type
Variable region- recognises specific antigens on pathogens.
Antigen-binding site
Disulphide bonds
Transmembrane region
Intracellular domain
Function- recognise antigens presented on MHCs class II of APCs that use to display which proteins are inside of them
NOTE- look at diagram on notes!
How do T cells work?
- An antigen-presenting cell e.g. macrophage detects, engulfs & digests pathogens into hundreds or thousands of antigen fragments.
- Antigen presentation occurs on Major Histocompatibility Complexes class II
- T cells become activated towards a certain antigen once they encounter it displayed on an MHC II
NOTE- After a pathogen enters a cell, it can no longer be detected by the humoral immune response (immunoglobulins). Instead, the cellular immune response must take over (T and B cells).
Explain the steps for T cell maturation
Occurs in thymus
- Immature T-lymphocyte in the thymus develop functional T-cell receptors (TCRs).
- Positive selection of t- lymphocytes that will interact correctly w/ MHC molecules
- Negative selection to remove self-reacting thymocytes by apoptosis- prevents self-reacting T cells causing autoimmune disease.
- Peripheral tolerance - some self-reactive T-cells escape the thymus so Regulatory T-cells are involved in peripheral tolerance.
- The mature naïve T cells exit the thymus & migrate through the bloodstream or lymphatic system to the lymph nodes, spleen & tonsils where they await activation.
What is MHC? Explain the role of MHC in immune tolerance
Major histocompatibility complex
MHC proteins present antigens of pathogen to the rest of immune system to trigger response & destroy the pathogen quickly.
MHC/HLA are a cluster of genes that define self & so they are unique to every individual.
- Self-peptides are presented by MHC proteins so the t-cell canrecognisethe MHC as self.
- Stops our immune cells attacking us = immune tolerance.
NOTE: a donor organ displays foreignantigens,which the T-cells don’trecogniseas self. They are classified asnon selfand can lead to T cell attack.
Definition of immune intolerance?
The state of unresponsiveness of the immune system to substances or tissues that have the potential to induce an immune response
Define autoimmunity
When the immune system attacks its own cells and tissues and can lead to an autoimmune disease.
Explain the role of MHC?
MHC proteins present antigens from the pathogen to the rest of immune system in order to trigger a response and destroy the pathogen quickly.
MHC/HLA are a cluster of genes that define ‘self’ - so they are unique to every individual.
Self-peptides are presented by MHC proteins so the t-cell can recognise the MHC as self.
Stops our immune cells attacking us = immune tolerance.
NOTE: a donor organ displays foreign antigens, which the T-cells don’t recognise as self. They are classified as non self & can lead to T cell attack
how does immune tolerance relate to autoimmunity?
Cells in the thymus use MHC markers (class I & class II) to present peptides, allowing immature T cells to bind.
If TCRs are incapable of binding, the T cell will undergo apoptosis.
If a T cell’s TCR successfully binds to the MHC complexes on the thymic cells, enter lymph node where T cell receives survival signals & is thus positively selected- no chance of autoimmunity
This positive selection process also determines if a T cell will become a CD8+ T cell or a CD4+ T cell.
- If a TCR complex binds strongly to MHC class II, the complex will send intracellular signals to induce the expression of a protein. Leads to cells become CD4+.
- If a developing T cell does not bind strongly to MHC class II, T cell differentiates into a CD8+ cell.
In sum, the process of positive selection leads to the survival of mature CD8+ and CD4+ T cells capable of recognising MHC complexes.
What is negative selection?
Occurs in the Thymus
Makes sure that T cells don’t recognise self cells as foreign & attack- leads to an autoimmune response
When TCRs bind too strongly to the MHC complexes in the thymus, the intracellular signalling is strong- leads to cell death, thereby eradicating immature T cell that have a high likelihood of being self-reactive & attacking our own cells
How are T helper cells activated? What do they differentiate into?
- APCspresent processedforeign antigensbound toMHC II.
- Clonal selection - TCRsrecognise the antigen w/in the MHC IIantigen-binding cleft. -1st signal CD4 interacts w/ a region of the MHC II molecule separate from the antigen-binding cleft.
- Recognises the self-protein. - Co-stimulation - the signalling protein B7 on the APC binds to the CD28 protein receptor on the helper T cell- 2nd signal
- The activated helper T cell proliferates, dividing by mitosis (clonal expansion) to produce clonal naive helper T cells.
- Naive helper T cells differentiate into subtypes w/ different functions.
- TH1 - secrete cytokines that are involved in stimulating other cells e.g. Macrophages, Neutrophils, Cytotoxic T-cells, NK cells. Interferon-𝛄 recruits macrophages.
- TH2 - secrete cytokines that activate B cells to start differentiation. Other cytokines from TH2 cause antibody class switching. TH2 cells recruit eosinophils & cause B-lymphocytes to produce IgE
