Adaptive Immune Response - Focus On T Cells Flashcards
What does the lymphoid progenitor cell give rise to?
Lymphoid cell
What proportion of the peripheral white blood cells are lymphoid progenitor cells?
20-30%
Is the lymphoid progenitor cells nucleus big or small?
Big
What size are lymphoid progenitor cells?
6-10 microns
What are the two types of cell that lymphoid progenitor cells can become?
Effector or memory cells
Where do T cells mature?
Thymus
What happens to the thymus in childhood?
Enlarges
What happens to the thymus in puberty?
Atrophies (basically disappears)
What proportion of T cells are alpha beta T cells?
90%
What are the three subtypes of alpha beta T cells?
Helper T cells
Cytotoxic T cells
Regulatory T cells
Why are helper T cells activated?
To secrete cytokines to help immune response or to become memory cells
What CDs to helper T cells express?
CD4 and CD3
What are the three subgroups of helper T cells?
Th1, Th2 and Th17
What CDs do cytotoxic T cells express?
CD8 and CD3
Why are cytotoxic T cells activated?
To kill infected targets or to become memory cells
How do cytotoxic T cells kill?
Via the release of toxic contents of granules or through induction of apoptosis
What CDs do regulatory T cells produce?
Mainly CD4+ but some CD8
What can regulatory T cells do?
Affect immune responses by either supressing them or activating them through direct cell contact or the secretion of soluble factors (cytokines)
What are the two main types of regulatory T cells?
Natural or inducible
What do gamma delta T cells do?
Recognise lipid antigens through TCRs
What type of molecule is the T cell receptor?
Dimeric
How are the two molecules of the T cell receptor linked?
Covalently by a disulfide bond
What parts are a T cell receptor made up of?
A variable and a constant immunoglobulin- like domain
What are the antigen binding sites on T cell receptors associated with?
CD3
How are alpha beta T cells restricted?
Through MHC I or MHCII
What does the alpha chain in the alpha beta T cell receptors consist of?
Germline variable, joining and constant regions
What does the beta chain in the alpha beta T cell receptors consist of?
Germline variable, diversity, joining and constant regions
What is the total repertoire of possible alpha beta T cell receptors?
1017
What is the total repertoire of possible gamma delta T cell receptors?
1019
How much of the mucosal T cells are made up by gamma delta T cell receptors?
70%
What are some gamma delta T cells restricted through?
CD1c
What stress indicators do some gamma delta T cells recognise?
HSP and butyrophilin
What are multi-histocompatibility complexes?
Surface expressed molecule which bind peptides derived from antigen and present to T cells
What do MHCs encode for?
Human leukocyte antigens
Where are MHC Is expressed?
All uncleared cells
Where are MHC IIs expressed?
On professional antigen presenting cells
What domains are MHCIS made up of?
Alpha 1-3 and beta2-microglobulin
What domains are MHCIIS made up of?
Alpha 1 and 2
Beta 1 and 2
Give the 5 steps in the antigen processing and presentation to CD4 cells
1- Uptake of extracellular proteins into vesicular compartments of APC
2- processing of internalised proteins in endosomal/lysosomal vesicles
3- biosynthesis and transport of class ii MHC molecules to endosomes
4 - association of processed peptides with MHCII molecules in vesicle
5- expression of peptide MHCs complexes on the cell surface
Give the steps in the antigen processing and presentation to CD8 cells
1- production of proteins in teh cytosol
2- proteolytic degradation of proteins
3- transport of peptides from cytosol to the ER
4- assembly of peptide- class I complex’s in the ER
5- surface expression of peptide -class I complexes
Where are dendritic cells usually derived from?
Myeloid (but can be lymphoid as well)
What happens when the dendritic cell is immature?
They capture the antigen and migrate to the lymphoid tissues where they mature and effectively present or show antigen to the T cells
Give 4 subtypes of dendritic cells
Langerhans, interdigiting, plasmacytoid and follicular
What is the only antigen presenting cell that can present to naive T cells ?
Dendritic cells
Give the names of 5 tissue specific dendritic cells
Langerhans, interstitial, blood myeloid, plasmacytoid, blood monocytes
Where would you find langerhans cells?
Skin
Where would you find interstitial cells?
In the dermis
Give the 3 types of other antigen presenting cells (nto tissue specific)
Macrophages
B cells
Endothelial (sometimes)
What is the first signal in teh APC-Tcell interaction?
The T cell recognising the peptide using its Tcell receptor
What is the second signal in teh APC-Tcell interaction?
The CD28 on the T cell and the CD80/86 on the APC also recognise each other
What is the third signal in teh APC-Tcell interaction?
APC produces cytokines
When the T cell enters the thymus , what happens if there is a productive TCR rearrangement?
It will go to see if it recognises self MHCs
When the T cell enters the thymus , what happens if there is a non- productive TCR rearrangement?
Apoptosis
What happens if the T cell doesnt recognise self MHC?
Apoptosis
What happens if the T cell recognises self MHC?
It is positively selected for
What happens if the TCR recognises self antigens?
Apoptosis
If the TCR doesnt recognise self antigens what happens?
It moves into the cortico-medullary region and into the medulla
What do CD4 T cells recognise on a MHCII?
A peptide in the binding groove
What do T helper cells do?
Produce a cytokine profile which directs the immune response to a particular outcome
What coreceptor do CD4 +Th1 cells express?
CD4
What do CD4+Th1 help to do?
Activate the cellular immune response
What do CD4+Th1 cells produce?
Gamma interferon
What do CD4+Th1 cells activate?
Cytotoxic T cells
What pathogens is the Th1 response effective against?
Intracellular infections, bacteria, Protozoa and viruses
What do CD4+Th2 cells help to activate?
Humoral immune response
What interleukins do CD4+Th1 cells produce?
4, 5, 13
What immune cells do CD4+Th1 cells activate?
B cells to produce an antibody
What do CD4+Th17 cells help to protect?
The gut mucosa
What do CD4+Th17 cells recruit (and where to)?
Neutrophils to the site of infection
What infections are the CD4+Th17 cells effective against?
Extracellular bacteria and fungi
What response does CD4+Th17 cells promote?
Neutrophil mediated inflammation
What coreceptors do CD4+Treg cells express?
CD4, CD35 and FoxP3
What is the function of CD4+Treg cells?
Maintain immune tolerance and suppress immune responses
What do CD4+Treg cells produce?
Anti-inflammatory cytokines IL10 and TGFbeta
How do tregs affect the functions of CD4+ and CD8+ T cells?
Inhibit the effector functions
What does TGF stand for?
Transforming growth factor
What do CD8+ cytotoxic T cells do?
Eliminate intracellular infections
What do CD8+ cytotoxic T cells produce?
IL2, TNFalpha and gamma IFN
Which T cell has a role in anti tumour immunity and rejection of transplants?
CD8+ cytotoxic
How do CD8+ cytotoxic T cells kill (4)?
Contact delivers lethal hit
CCTL then detaches and targets another cell
Releases cytolytic molecules from intracellular stores
Triggers apoptosis in target cells
How does perforin work?
Forms pores in target cell membranes which allows the entry of granzymes
What are granzymes?
Serine-esterase proteases
What do granzymes do?
Induce apoptosis
What are the three types of granzymes?
A, B and C
What do CTL cytolytic proteins act as?
A specific synapse between the CTL and target
What do the CTL cytolytic proteins limit?
Any collateral damage
What do caspases lead to?
Apoptosis
Which granzyme can trigger an apoptotic pathway?
B
What molecules ligates the Fasreceptor
FasL
What do NKTcells express?
T cell markers and NK cell markers
Give an example of the glycolipids NKTcells respond to
Alpha galactocyl ceramide
What are NKTcells restricted through?
CD1d
