Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
63 Cards in this Set
- Front
- Back
Positive TCR Selection |
Found in cortex thymus. Double negative thymocytes (CD3-,CD4-,CD8-). Progenitor cells develop into positive selection. Self MHCI and self MHCII binding with moderate affinity gets survival. Differentiate into CD8 or CD4 |
|
Negative TCR Selection |
Found in cortico-medullary thymus. T cells dialogue with dendritic cells. High affinity self peptides and MHCI/MHCII destroyed. Remove self reactive T cells. |
|
Location of TCR development |
Thymus |
|
Thymus Cortex |
Epithelial cells create thymic stroma composed of macrophages and thymocytes |
|
Thymus Medulla |
Epithelial cells. Dendritic cells self reactive screening. Macrophages remove dead lymphocytes and Hassall's corpuscle site of cell destruction. |
|
TCR structure and location |
Heterodimer of alpha and beta chain variable region. Membrane bound. CD3 [epsilon,delta][gamma,epsilon][zeta,zeta]
|
|
CD4 structure |
T cell co-receptor. Four domains D1,D2,D3,D4. Found on helper T cell. Contact MHCII at beta2 |
|
CD8 |
T cell co-receptor. Alpha and beta domain. Found on cytotoxic T cell. Contact MHCI at alpha3. |
|
Variable domain TCR response |
Multiple gene segment, somatic recombination, junctional diversity (P/N nucleotide division), RSS recombination. No class switching or hypermutaiton. |
|
Variable domain TCR |
Alpha chain on chromosome 14 (V+J) Beta chain on chromosome 7 (V+D) |
|
AIRE |
autoimmune regulator is a transcription factor turns on peripheral genes in thymus |
|
Naive T cell stimulation |
TCR signal and B7 co-stimulation from APC. Lack of stimulation lead to anergy
|
|
Naive T cell loaction |
Recirculating of T cell in SLT. Enter lymphatic drainage via HEV, requires homing.
|
|
Homing naive T cell |
Cell adhesion molecules and chemokines CCL19+CCL21 produced by stromal and dendritic cells. Glycan and selectin slows movement |
|
Naive T cell adhesion |
L selectin binds to GlyCAM slows lymphocyte rolling. Activated LFA binds to ICAM. Anchor T cell leads to diapedesis |
|
Naive T cell adhesion molecules |
link dendritic cell to t cell. ICAM-LFA, ICAM3-DC-Sign |
|
B7(CD80) |
secondary signal for activation by APC. Ligates with T cell CD28. Stimulates T cell differentiation and proliferation |
|
CTLA-4 |
Cytotoxic T lymphoctye Associated Antigen. Present on activated T cell that has high affinity for B7. Delivers inhibitory signal limits cell proliferation |
|
Anti-CTLV4/Ipilimumab |
Monoclonal antibody against CTLA4 blocks B7-CTLA4 ligation. T cell remain active enhance immune system |
|
Dendritic cell |
APC originating in bone marrow myeloid stem cell. Located in all peripheral tissues. Phagocytize antigen and migrate to lymph node.
|
|
Mature dendritic cell characterisitcs |
Stop phagocytosis, develop finger like extensions to increase surface area. Expression of MHC with co receptors |
|
Dendritic cell co-receptors and ligands |
Receptors (ligand): B7(CD28 Tcell), CCR7(CCL21 SLT), DC-SIGN(ICAM3 Tcell). ICAM1/2(LFA T cell) |
|
IL-2 function |
Stimulate T cell proliferation and differentiation to effector. Produced by activated T cell. Autocrine signalling. |
|
IL-2 receptor naive vs active t cell |
Naive t cell has gamma and beta chain for low affinity IL-2 and active has gamma, beta, and alpha chain for high affinity. |
|
Transcription Factor TH1 |
T-bet |
|
Cytokine Exposure TH1 |
IL-12 from DC/macrophages and INF-gamma from NK cells |
|
Cytokine Profile TH1 |
INF-gamma (positive feedback but inhibits TH2 and TH17) and CD40L. |
|
Immune Role of TH1 |
Activate macrophages and kill resident bacteria. Cell mediated IR |
|
Cytokine Exposure TH2 |
IL-4 from eosinophils, basophils, mast, or NK |
|
Transcription Factor TH2 |
GATA 3 |
|
Cytokine Profile TH2 |
IL-4 (positive feedback but inhibits TH17), IL-5, IL-13, CD40L, IL-10 and TGF-beta (both inhibit TH1 and macrophages) |
|
Immune Role TH2 |
IgE production, recruit eosiniphils, mast cells, basophils, protect mucosa parasites. Humoral immunity bias due to Ab dominated |
|
Cytokine Exposure TH17 |
IL-6, IL-23, TGF-beta (all from DC) |
|
Transcription Factor TH17 |
ROR-gammaT |
|
Cytokine Profile TH17 |
IL-17 |
|
Immune Role TH17 |
IL-17 triggers tissue to produce: IL-6 (Inflammation), CXCL8,12 (recruit neutrophil), G-CSF and GM-CSF (stimulate neutrophil release from bone marrow). Protects against extracellular bacteria and fungi. |
|
Cytokine Exposure TFH |
IL-6 |
|
Transcription Factor TFH |
Bcl-6 |
|
TFH's CXCR and ICOS |
CXCR ligates with CXCL13 produced by stromal cells in B cell follicle. Causes migration from T cell area to B cell area. ICOS binds to ICOSL of DC |
|
Cytokine Profile TFH |
IFN-gamma induces IgG1/IgG3, IL-4 induces IgE, and CD40L to signal CD40 on B cell |
|
Immune Role TFH |
Stimulate B cell for: somatic hypermutation, affinity maturation, class switching. Bias towards humoral immunity Ab dominated |
|
Origin Natural Treg |
immature thymocyte within thymus. High TCR affinity for self peptide but not enough to be deleted. 10-15% CD4 cells |
|
Transcription Factor Natural Treg |
FoxP3 |
|
Receptors on Natural Treg |
CD4, CD25, CD62L (L-selectin), CTLA4 (monopolizes APC B7 to lead to T cell anergy). |
|
Cytokine Profile Natural Treg |
IL-10 and TGF-beta inhibit T cell proliferation |
|
Immune Role Natural Treg |
Prevent autoimmune response and curtail normal protective immune response |
|
Origin Induced Treg |
Naive CD4 T cell in periphery in absence of infection. DC produce lots of TGF-beta. Some IL-6, IL-12, and IFN-gamma |
|
Transcription Factor Induced Treg |
FoxP3 |
|
Receptors on Induced Treg |
CD25 and CD4 |
|
Cytokine Profile Induced Treg |
IL-10 and TGF-beta inhibit cell proliferation. TGF-beta positive feedback. |
|
Immune Role Induced Treg |
suppress immune response, inflammation |
|
Why regulate macrophages |
Prevent local tissue damage, toxic microbiological agent releaced |
|
Cytokines that inhibit macrophages |
TGF-beta and IL-10. Treg and TH2 produces them |
|
Granuloma |
inflamed nodules made of macrophages. Form around non-degradable foreign bodies or around chronic intracellular infection. Central core giant macrophages. Outer ring is TH |
|
Naive B cell activation |
cross-linking of BCR to multiple antigen epitopes and co-receptors |
|
Thymus dependent antigens |
Require TFH and TH2 to activate B cell. Cognate interaction significant |
|
Cognate interaction of T/B cell |
B cell recognizes surface epitope and T cell recognizes intracellular protein |
|
Thymus independent antigen |
Activate naive B cell without T cell influence. High density of repetitive epitopes like polysaccharides. (capsule) Produces mostly IgM without class switching. Fetus to age 5. Found in peritoneum and pleural cavity |
|
Mitogens |
substance that cause differentiation of B cell regardless of specificity. Polyclonal activation. High dose of LPS via TLR-4 |
|
T cell synapse |
Contact point between T cell and DC |
|
Transcription factors activated during T-DC synapse |
NFAT:nuclear factor of activated T cell NFKB:nuclear factor kappa B AP-1:Fos/Jun protein |
|
Protein tyrosine kinase |
enzyme that phosphorylates tyrosine. FYN associated with CD3, Lck associated with CD4 and CD8, ZAP70 cytoplasmic protein |
|
ITAM |
immunoreceptor tyrosine based activation motif. Present in cytoplasmic tail of CD3 (gamma, delta, epsilon, zeta) binds ZAP70 |