T lymphocytes and Antigen Recognition Flashcards
What is a T lymphocyte?
-detects and combats intracellular pathogens -sees foreign antigen via a receptor on its cell surface (T cell receptor: TCR) -antigen seen is a small peptide fragment of the pathogen; peptide presented by MHC molecule on the surface of a host infected cell (ie self MHC+foreign peptide)
Name the two major populations of T-cells?
use CD4 co-receptor use CD8 co-receptor
What type of co-receptor sees a peptide on MHC class 2- “class 2 restricted”?
CD4 co-receptor
What type of co-receptor sees a peptide on MHC class 1- “class 1 restricted”?
CD8 co-receptor
What part of the appropriate type of MHC molecule does a co-recpetor bind to?
Invariant (non-polymorphic) part of the appropriate type of MHC molecule.
How do co-receptors effect T cell-target cell interaction?
increase the avidity( the overall strength of binding between an antibody and an antigen) of T-cell target cell interaction
How does a T cell see antigen?
2 major populations of T cells Use CD4 co-receptor, see peptide on MHC class II - “class II restricted” Use CD8 co-receptor, see peptide on MHC class I - “class I restricted” Co-receptor molecules bind to the relevant MHC (conserved part, not the antigenic peptide), increase the avidity of T cell-target cell interaction and are important in signalling
What are CD8 T cells also known as?
Cytotoxic T lymphocytes,CTL or Tc
What are CD4 T cells also known as?
T helper cells ot Th
How do CD8 T cells destroy their target?
they are cytotoxic and kill target cells; They also secrete cytokines e.g. interferon-gamma Induce apoptosis in the target cell
How do CD4 T cells destroy their target?
Secrete cytokines which may recruit cells of innate immunity Help activate macrophages amplify and help CTL and B cell responses
Where do T lymphocytes Develop?
Thymus
What do T cells develop from?
Bone-marrow derived precursors
Where do T cells move to as they develop?
Thymus outer cortex to the Thymus inner medulla
At the initial stage of T-cell development what receptors do they express?
They do not express TCR or CD4 or CD8 (known as the double negative stage)
The first stage is the formation of TCR, using ……?
Gene segment recombination similar in principle to antibody gene rearrangement( although different gene segments are used)
What do cells that express TCR do in the THYMUS and what is this stage known as?
Cells which express TCR go on to express both CD4 and CD8 Double positive stage
what happens to the cells after the double positive stage ?
The cells undergo selection for those which express a useful TCR
What is positive selection?
Allows the survival of cells whose TCR recognises self MHC
What is negative selection?
removes cells whose TCR recognises self MHC very strongly?
What happens to a developing T cell that can’t bind to MHC?
Destroyed
What happens to a developing T cell that binds to the MHC strongly?
Destroyed
What happens to a Developing T cell that binds to the MHC weakly?
Survive
In thymus selection 1 at the pre TCR checkpiont , what happens if the new beta chain is functional and what happens if it is not functional?
Functional- survuve and development to CD4+CD8+TCR Not functional- death by apoptosis
Are MHC molecules molecules continuously present peptides, even in the absence of infection?
Yes
What do MHC molecules indicate and what are they markers of?
MHC molecules are markers of “self”, and indicate the “health” of cells
MHC molecules do not display a sample of the internal contents of cells at the cell surface for possible immune cell recognition. Is this statement true or false?
False
What class of MHC are the classical transplantation antigen?
MHC class 1
What is the function of MHC class 2?
MHC class 2 are regulatory, controlling the ability to mount immune responses.
What type of cells are MHC class 2 expressed?
“professional” antigen presenting cells e.g. Dendritic cells, macrophages and B lymphocytes
What type of cells express MHC class 1?
Nearly all cells
What is the major histocompatibility complex?
the MHC is a group of tightly linked genes important in specific immune responses found in all vertebrates MHC molecules present antigens to T lymphocytes
Recall the outline structure of MHC class 1?
The peptide binding region is made out of - Alpha 1 and Alpha 2 The immunoglobulin like region is made up of Alpha 3 and Beta 2- microglobulin
Recall the outline structure of MHC class 2?
The peptide binding region is made out of- Alpha 1 and Beta 1 The immunoglobulin like region is made up of Alpha 2 and Beta 2
MHC markers are essentially markers of self? true or false
True
What do cells do to indicate they are healthy?
They continuously display a processed sample of the internal contents of cells at the cell surface as an indicator of the health of cells
What is the human MHC known as?
HLA region: Human Leukocyte Region
Is the expression of the MHC dominant, recessive or co-dominant?
Co-dominant
Is the MHC polygenic?
Yes there are several class 1 and class 2 loci
Human MHC genes are Highly polymorphic. What does this mean?
large number of alternative different versions of the same gene within the population Different people have different immune responsiveness
A group of MHC alleles linked on one chromosome is termed as …
MHC haplotype Because humans are diploid we have 2 MHC haplotypes
Does diversity in MHC molecules exist at an population level?
Yes
Does diversity in T cell receptors exist in a population level?
NO- Within an individual
List an example of Antigen presenting cells (APC)?
Dendritic Cells B Lymphocytes Macrophages(activated)
What are APC’s?
Antigen presenting cells are cells that can present processed antigen (peptides) to T lymphocytes to initiate an acquired (adaptive) immune response
Where are dendritic cells located?
Widely spread e.g. skin & mucosal tissue
Where are B cells located?
Lymphoid tissue
Where are activated Macrophages Located?
Lymphiod Tissue
Why are there two pathways of antigen presentation?
antigens in different locations require different responses different pathways present antigen from different locations to different T cell subsets
Where are Exogenous antigens located and what type of T cell are they presented to? What type of MHC is used to express this type of antigen?
Exogenous antigens - captured from the external environment Exogenous antigens are presented by MHC class 2 to CD4 T cells.
Where are Endogenous antigens located and what type of T cell are they presented to? What type of MHC is used to express this type of antigen?
Endogenous antigen - synthesised in the cytoplasm Endogenous antigens (external to the cell) are presented by MHC class 1 to CD8 t cells
State the significance of polymorphism in MHCs
greater MHC diversity permits greater diversity of antigen presentation.
MHC polymorphism in the population allows for variability and a diverse range of different peptides derived from antigens to be recognised in individuals. Thus, at least a proportion if the population should be able to mount an adaptive immune response against any pathogen. The clinical significance is that MHC genes are responsible for organ rejection, so patients must be closely matched to the donor. Also, similar traits are seen in those of the same race.
