T-Cell Receptors and MHC Complex - Diebel Flashcards
What do T-Cells require in order to be activated?
Cell-to-cell contact with antigen presenting molecules on the surface of other cells
Th1 CD4+ T-Cells are polarized by:
IL-12
IL-18
IFN-gamma
Th1 CD4+ T-Cells effector cytokines produced:
IGN-gamma (pro-inflammatory & chemotactic for monocytes/macrophages)
TNF
What types of cell-surface molecules/receptors do APC have?
PRR = Pathogen Recognition Receptor (PAMPs)
CD80 (B7-1) binds to T-cell CD28
CD86 (B7-2) binds to T-cell CD28
MHC II
What types of cell-surface molecules/receptors do T-cells have?
CD28 binds to CD80/86
CD4 binds to MHCII
CD3/TCR binds to MHC II
What master transcription factor generates cytokines in Th1 T-cells?
T-Bet
How are M1 (angry) macrophages activated and what cytokines do they secrete?
Activated by IFN-gamma secreting Th1 T-cells
TNF-alpha and IL-1
Th17 CD4+ T-Cells are polarized by:
TGF-Beta
IL-1
IL-6
IL-23
Th17 CD4+ T-Cells effector cytokines produced:
IL-17
IL-22
What master transcription factor generates cytokines in Th17 T-cells?
ROR-gamma-t
What is the main function of Th17 T-cells?
Cause Inflammation; more powerful that Th1; cause severe autoimmunity through IL-17
What is the main function of Th1 T-cells?
Recognize antigen and make lymphokines to attract M1 macrophages to attack a serious infection
Where do Th17 T-cells play their biggest role?
Maintaining the integrity of mucosal surfaces
Th2 CD4+ T-Cells are polarized by:
IL-4
Th2 CD4+ T-Cells effector cytokines produced:
IL-4
IL-5
IL-13
What master transcription factor generates cytokines in Th2 T-cells?
GATA3
What is the main function of Th2 T-cells?
Alternatively Activates M2 Macrophages to wall-off parasites/pathogens and promote healing; IL-4 attracts eosinophils
Follicular Helper Tfh CD4+ T-Cells are polarized by:
IL-6
IL-21
Follicular Helper Tfh CD4+ T-Cells effector cytokines produced:
IL-4
IL-21
What master transcription factor generates cytokines in follicular helper Tfh T-cells?
Bcl-6
What is the main function of the follicular helper Tfh T-cells?
Stimulated by antigen to migrate from T-cell areas of lymph nodes into the B-cell follicles, where B-cells are activated and undergo class switching
Treg CD4+ T-Cells are polarized by:
IL-2
TGF-Beta
Treg CD4+ T-Cells effector cytokines produced:
IL-10
TGF-Beta
What master transcription factor generates cytokines in Treg T-cells?
FOXP3
What is the main function of the Treg T-cells?
Suppress activation and function of all other T-cells; known as antihelpers
Describe IPEX.
Regulatory T-cells are not working properly to turn off the immune response
How is the kiss of death or lethal hit initiated y Cytotoxic Killer CD8+ T-cells?
Through the Fas (CD95) - Fas (CD95L) ligand interaction, the target cell has been given the signal to undergo apoptosis through DNA fragmentation and nuclear collapse.
How are Cytotoxic T-Cells activated?
Contact in the lymph node with antigen-presenting dendritic cell and IL-2 from Th1 T-cells
What markers on the cell surface of B-cells are used to fluorescently identify them?
CD19
CD20
What markers on the cell surface of T-cells are used to fluorescently identify them?
CD3
CD4
CD8
How are T-cells restricted?
Only recognize specific antigen on cells that are genetically identical to themselves (MHC)
What do APC Dendritic Cells express?
High levels MHCII
B7 (co-stimulatory molecule)
How must APC macrophages be activated?
Phagocytosis to express MHCII
Co-stimulatory molecules
What do B-cells express and how must they be activated?
MHC II
Antigen binding to antibody prior to co-stimulatory molecules
How are TCR activated for signal transduction?
CD3 and DC cytokines
LFA-1 (leukocyte functional antigen)
ICAM-1 (intercellular adhesion molecule
CD2 bind to?
LFA-3
Somatic Mutation in T-Cells
Addition of 0-6 nucleotides by TdT can be added between the V-D or D-J domains
How are T-cells selected?
1) Cannot recognize “self”
2) Not recognize free antigen
3) Recognize antigen peptide plus self MHC
What is positive selection of T-cells?
T-cells must recognize MHC Class I or MHC Class II molecules (self-restriction)
What is negative selection of T-cells?
T-cells that recognize self-antigens bound to MHC II are killed (T-cells need to be tolerant to self-antigens)
What cytokines can be released by CD8+ T-cells?
TNF, Perforin, and Granzymes
What are the three “classical” MHC Class I gene loci?
HLA-A
HLA-B
HLA-C
MHC Class I Structure
1 transmembrane domain
3 alpha domains
1 B2 Microglobulin (cell surface)
What are the MHC II gene loci that encode 2 peptides (alpha subunit and beta subunit)?
DP encodes DP aB
DQ encodes DQ aB
DR encodes DR aB
What does MHC III produce?
Complement Proteins
TNF-alpha and TNF-Beta
Lymphotoxin Beta
HLA-B27
Ankylosing spondylitis
Psoriasis
IBD
Reiter’s Syndrome
HLA-DR2
Narcolepsy
MS
Hay Fever
Lupus
HLA-A3/B14
Hemochromatosis
HLA-DQ2/GQ8
Celiac Disease
HLA-DR3
DM Type 1
Grave’s Disease
HLA-DR4
DM Type 1
RA
HLA-B53
Malarial Resistance
How many different Class I MHC molecules could each cell express?
6
How many different Class II MHC molecules could each cell express?
12 (DP, DQ, DR)