Lecture 13; Immune cell receptors Flashcards
What can immune cell receptors be divided into?
MYELOID CELLS (innate)
LYMPHOID CELLS
What are the myeloid cell receptors?
- Fc Receptors
- TLR (Toll Like Receptors)
- Other innate receptors such as mannose receptors
What are the lymphoid cell receptors?
- B cells – Immunoglobulin M
- T cells – T cell Receptors
- NK cells – NK inhibitory and activating receptors
Describe the Fc receptor
- Many forms but all have Ig-domains
- Binds to the effector (Fc) region of IgA, G, D, M or E.
- Low affinity. Only binds immune complexes (multiple AB with antigen, avidity reaction).
What are some examples of Fc receptors;
- FcγRI, II, III bind IgG subtypes.
- FcεR binds IgE on mast cells. Atopic allergy.
- FcαR binds IgA (gut)
What are ALL Fc receptors linked to?
• Linked to adaptor proteins that contain ITAM motifs.
What are Fc receptors essential for?
• Essential for Ig mediated phagocytosis.
Describe B Cell receptor;
- IgM expressed on all naive B cells from the bone marrow.
- Has a transmembrane domain.
- Associates with Igα and Igβ molecules possessing ITAM motifs.
What does the activation of the BCR require?
- Activation requires cross-linking of BCR by multivalent antigen.
Binds Syk kinase. Initiates a phosphorylation cascade.
• BCR is also associated in larger complex of CD19, TAPA and
CD21 (CR2) essential to signalling.
Write some notes on the Ta/b variant receptor;
- α/β TcR must develop in the thymus.
- α/β cells are either CD4 or CD8 and found in blood and lymphoid organs
- β -chain gene rearrangement dependent on γ gene silencer. All α/β T cells start off as γ/δ T cells
- α/β knockout mice still have some protection
Write some notes on the Td/g variant receptor;
- γ/δ T cells can develop independently of thymus.
- γ/δ T cells found in sites around the body such as skin IEL.
- γ chain gene rearranges before β-chain gene. Suggests it is a more primordial receptor.
- γ/δ knockout mice are susceptible to mycobacterial infections
Whats an ITAM?
Immunoreceptor-based Tyrosine Activation Motif Found on cytoplasmic domains of TcR/BcR/FcR Binds Src family kinases
Only on the Z chain, and the length of time spent p/ph them (total p/ph) determines the strength of reaction with self and what happens to the developing T cells
What happens after ITAM activation?
PLC-γ
PIP2 -> DAG and IP3
What does DAG do?
DAG activates PKC-θ
PKC-θ activates NFkB
What does IP3 do?
- IP3 increases Ca2+
• Ca2+ binds Calmodulin
• Activates Calcineurin phosphatase
• Calcineurin de-phosphorylates NF-ATc
NFAT is primary driver of T cell response (Cyclosporin inhibits this)
What does GEF do?
Guanine exchange factors (GEF) activate Ras
• Ras activates MAP kinase cascade
• MAP kinase activates c- Fos component of AP-1
What do the three arms of activation in the T cells do?
Nuclear translocation of NF-AT,NF-κB and AP-1 to induce specific gene transcription, proliferation and differentiation
What do NK receptors recognise?
NK cells are a population of potent lymphoid cells with receptors that recognise non- classical MHC (HLA-C, HLA-G and HLA-E) among others
Most NK cell receptors are termed INHIBITORY receptors.
What do NK receptors do?
Most NK cell receptors are termed INHIBITORY receptors.
They actively PREVENT cytolytic killing when triggered by their ligand such as HLA-E.
In the absence of MHC on the target, no inhibition and killing.
What are the NK receptors coupled wiht?
Inhibitory receptors are coupled to adaptor molecules with ITIM motifs.
Some NK receptors are activating. They recognise specific ligands associated with cell stress or infection.
NK cells can express both inhibitory and activation receptors on the same cell.
The default response is inhibition.
This must be overridden by activation signal Role is surveillance of cells lacking classical MHC.
How do NK cells compete for activation?
NK inhibitory receptors (KIR) mediate SHP1 mediated dephosphorylation that directly competes with the TcR driven phosphorylation.
Summerise the TCR a/b variant;
- Classical MHC class I and class I
- CD4 or CD8
- Part of the CD3 complex
- Peptide antigens
- CD3 associated
- ITAMs on ζ-chain
- Lck and Zap70 kinases
Summerise the TCR g/d variant;
- CD1 ligand
- CD4 or CD8 or not
- Part of the CD3 complex
- Non-peptide antigens e.g. LAM
- Limited peripheral repertoire
Summerise the NK receptors;
- C-type or Ig like
- Non-classical MHC HLA-G, E
- Many different types
- Inhibitory and activating
- Non-polymorphic
- ITIM motifs – inhibitory signal
- SHP-1 phosphatase
Summerise the BCR;
• Membrane IgM • BCR complex CD19, CD21, TAPA1 • Recognises soluble antigen – cross-linking • ITAMs on Igα and Igβ • Syk, Fyn,Blk, Lyn kinases
Summerise the FcR;
- Bind Fc domains of Ig
- Multiple receptors for each class
- No consistent binding mode
- Cross-linking by immune complex
- ITAM receptors
