Week 2: Diebel's master doc Flashcards
What polarizes Th1 cells?
IL-12, IL-18, IFN-gamma
What do Th1 cells secrete?
IFN-gamma, TNF
What cells are responsible for contact hypersensitivity?
Th1 cells
What polarizes Th2 cells?
IL-4
What do Th2 cells secrete?
IL-4, IL-5, IL-13
What are Th17 cells polarized by?
TGF-beta, IL-1, IL-6 and IL-23
What do Th17 cells secrete?
IL-17 and IL-22
What polarizes Tfh cells?
IL-6 and IL-21
What do Tfh cells secrete?
IL-4 and IL-21
What polarizes Treg cells?
IL-2 and TGF-beta
What do Treg cells secrete?
IL-10, IL-35, TGF-beta
What does the allele HLA-B27 cause?
ankylosing spondylitis
What does the allele HLA-DR2 cause?
10x more likely to develop narcolepsy, also linked to MS, hay fever and SLE
What does the allele HLA-A3/B14 cause?
90x more likely to develop hemochromatosis
What does the allele HLA-DQ2/GQ8 cause?
celiac disease
What does the allele HLA-DR3 cause?
T1DM and Grave’s disease
What does the allele HLA-DR4 cause?
RA and T1DM
What does the allele HLA-B53 cause?
protection from childhood malaria
Describe the molecular interactions that occur between CD4+ T cell and an APC?
1) LFA-1 and ICAM-1 bind to make synapse
2) MHC II interacts with TCR/CD3 and CD4 to recognize
3) CD28 and B7 (CD80/86) provides co-stimulatory signals
How many different MHC-I molecules can be expressed?
6
How many different MHC-II molecules can be expressed?
12
What are the antigen presenting cells?
Macrophage, Dendritic cell, B cell
How do macrophages, DC and B cells uptake antigens?
Macrophages: phagocytosis
DC: phagocytosis and endocytosis
B cells: receptor-mediated endocytosis
Which antigen presenting cells have both constitutively active MHC-II expression with further activation?
DC and B cells
What do TAP1/TAP2 proteins do?
transporter associated with antigen processing. These take peptides from proteasomes to take them to RER membranes
What does ERAAP do?
helps trim peptide to better fit into MHC1 molecule
What does calnexin do?
chaperone protein that ensures proper folding of MHC-1 molecules
What does the invariant chain do?
helps to hold MHC alpha and beta chains together before antigen binding
What does CLIP do?
Class II associated invariant chain peptide. Holds MHCII in place and keeps binding site open for antigen to bind
What does HLA-DO and HLA-DM do?
Removes the CLIP protein from the MHCII molecule and helps to add antigen into MHC molecule
What is the normal CD4+:CD8+ ratio?
2:1
What does MHC-I deficiency result it?
Low CD8+ cells presenting at ~3-4 years old. Problems with fighting viral infections
What does MHC-II deficiency result it?
worse outcome than MHC-I cause Th1 cells are involved in B and T cell activation. Will have a low CD4+:CD8+ ratio
What do Th2 cells secrete to differentiate and proliferate B cells?
IL-2, IL-4, IL-5
What are the cellular interactions between Th2 and B cells in T-dependent B cell proliferation?
CD28–CD80/86, CD40L–CD40, TCR/CD4–MHCII
When is C-kit found on T cells
Stem cell to DN2
When is CD44 found on T cells?
DN1 –> DN2
When is CD25 found on stem cells
DN2–> DN3
When is CD3 found on stem cells?
DN3–>Mature T cells
What are the cytokines that drive Th0 into Th1 and Th2, respectively?
IL-12 to Th1, IL-4 to Th2
What are the polarizing signal of Treg cells?
IL-2, TGF-beta
What are the polarizing signals of Th17?
IL-1, IL-6, IL-23, TGF-beta
What is the polarizing signals of Th2 cells?
IL-4
What is the polarizing signals of Tfh cells?
IL-6, IL-21
What is the polarizing signals of Th1?
IL-12, IFN-gamma, IL-18
What are the killing mechanisms of Tc and NK cells?
perforin and granzyme, Fas ligand, TNF-alpha release kills through caspase signaling
What does the lectin-like receptors of NK cells do?
Looks to see if cells have abnormal HLA-E molecules
What do KIR receptors of NK cells do?
Looks for abnormal MHC-I molecules
Are most Lectin-like receptors activating or inhibiting?
activating
Are most KIR receptors activating or inhibiting?
inhibitory
What cells are able to do antibody-dependent cell-mediated cytotoxicity (ADCC)?
NK cells, macrophages, monocytes, neutrophils, eosinophils
What are the four types of Treg effector mechanisms they use to control T cell proliferation
1) CTLA-4 interacts with CD80/86 of DC to turn off DC
2) Treg secrete IL-10, Il-35 and TGF-beta to cause cell cycle arrest
3) Tregs contain CD25 5o soak up IL-2 in environment
4) Tregs can secrete granzymes to kill any T cells
Generally describe IPEX?
Down-regulation of Foxp3 transcription factor leading to decreased Treg cells leading to autoimmunity
What are treatments for IPEX?
IVIG treatment, bone marrow transplant
Generally describe APECED
Problem with negative selection in thymus resulting in increased T cell proliferation that can be self-reactive.