T cell, autoimmune, hypersensitivity Flashcards
T cells
CD8 cytotoxic
class I
Cd4 T helper
class II
TCR
no somatic hypermutation as can lose ability to recognise MHC otherwise
monovalent
membrane bound
antigen recognition
more variable than BCR
TCR diversity
2 chains Beta and alpha
VDJ rearrangement
Beta chain first
Dj then VJ
CD4, CD8 double negative expressed
Then alpha chain rearranged
CD4, CD8 double positive expressed
RAG 1/2 P and N nucleotide addition
As no somatic hypermutation needs more diversity as fixed
T cell selection
successful TCRβ chain rearrangement
Positive selection
double positive TCR against self peptide/MHC on cortical epithelial cells
Only cells with no affinity die as no positive survival signals
Depending on the MHC T cell becomes single positive
NEgative selection
Remove T cells with high affinity for self peptide/MHC by apoptosis
Thymus
cortical epithelial cells for positive selection
(dendritic cells and macrophages to trigger negative selection
Macrophages are important for removing
thymocytes that fail to mature
TCR signalling
TCR can only be expressed with CD3
Once bound to MHC Lck binds CD8/4
CD3 phosphorylated by Lck
recruits ZAP-70
ZAP-70 phoshporylates LAT
LAT gets PLCgamma and GRB2
GRB2 gets SOS, activates RAS and MAPK pathways RAF,MEK,ERK
Activates transcription factors including IL-2
Cytotoxic T cell
CD8 T cell recognise MHC class I
Proliferate with IL-2 and also make perforin and granzyme
Release IFN gamma to increases expression of MHC
Il-2
Master T cell regulator
Cause T cell survival and proliferation
Co stimulation
T cells need 2 signals
signal 1
TCR and MHC
with CD4/8
signal 2
CD28 with B7 on APC for signal and
CD40L with CD40 on APC to activate APC
Thymus dependent antigens
APC, dendrite takes up antigen and presents on MHC
Presents to T cell
MHC class II-TCR and CD4
B7-CD28
CD40-CD40L
T cell activates B cell
CD40L-CD40
CD28-B7
TCR,CD4-MHC
B cell can take up antigen and present on MHC, when T cell binds it recognises to help activate
CD28-B7
CD40L-CD40
signals needed for survial and proliferation-CD40
Germinal centres
follicular
dendritic cells hold antigens for a long time on immune complexes
Somatic hypermutation occurs so only B cell with highest affinity after muations survive
Thymus independent antigens
TI antigens are microbial products
composed of repetitive elements (polysaccharides and lipopolysaccharides) which crosslink membrane Ig and induce B cell proliferation.
T helper 1
Made by IL-12 and IFN-γ
Make IFN-γ, inflammation
activate phagocytes
T-BET
ILC1
Th2 cells
Made by IL-14
Make IL-4, IL-5 and IL-13
Help against parasites
Parasite too big for phagocytosis, mostly antibodies made
GATA3
ILC2
Th17 cells
Made by IL-6 and TGF-β
Make IL-17 and IL-22
extracellular bacteria and fungi
RORγT
ILC3
Follicular helper T (Tfh) cells
MAde by IL-6
MAke IL-21
promtoe antibody response
small amount so B cells compete and only highest affinity survive
Treg
made by TGF-β
supress the activity of other T cells
FOXP3.
Innate lymphocytes
Similar to T helper cells
act before T helper cells
Memoery cells
Some T/B cells develop long lived cells that cause a secondary response that is faster and greater in magnitude than the first
Tolerance
aquired
recognise infectious non-self
need adjuvant, PAMPs and DAMPS as well as antigen
Central tolerance
First make T cell receptors
positively selecting those clones with some
affinity for self MHC and negatively selecting clones that bind too strongly to self MHC
plus peptide
timing, dose of antigen,
amount of costimulation and location are important
A mouse A with bone marrow from B at borth accept a skin graft from B but not from C
How can all relevant self antigens be expressed in the thymus?
transcription factor called AIRE
Turns on pheripheral genes in the thymus so T cell see all genes
Without AIRE
Autoimmune Polyglandular Syndrome Type
1 (APS-1)
or APECED