Immunology 2 - lectures 6-9 Flashcards
(44 cards)
What are the 5 most important cytokines secreted by activated macrophages and what does each do?
1) IL-6; lymphocyte activation (inflammatory cytokine)
2) TNF-alpha; most potent immune cell / endothelium activator
3) IL-1B; most potent immune cell / endothelium activator (product of inflammasome)
4) CXCL8; PMN recruiter (chemokine)
5) IL-12; T-cell / NK cell recruiter.
What are most potent cytokines made by an activated macrophage and what is their general method of action?
TNF-alpha and IL-1beta; induce expression of ICAM-1 and selectins, promote vascular permeability.
How do IL-1beta/ IL-6 / TNF-alpha affect the following organs during sepsis?
1) liver
2) bone marrow endothelium
3) hypothalamus
4) fat, muscle
5) dendritic cells
1) promotes release of acute-phase proteins (C-reactive protein, mannose-binding lectin), leading to activation of complement opsonization.
2) neutrophil mobilization to increase phagocytosis
3) increase body temp to decrease viral and bacterial replication
4) protein and energy mobilization to increase body temp.
5) TNF-alpha causes migration to lymph nodes and maturation to initiate adaptive immune response.
What does IL-6 do on liver?
causes production of C-reactive protein, fibrinogen, mannose-binding lectin, hepcidin (CRP opsonizes bacteria, routinely measured clinically).
How do IL family signal?
via JAK-STAT pathway
How do TNF family signal?
via NF-kB (inflammatory gene expression) and caspase pathways (programed cell death).
What signals allow dendritic cells and naive T cells to ‘find’ the T cell zone of the lymph node?
Both express CCR7 (chemokine receptor) which ‘follow’ CCL19 and CCL21 chemokines produced in T cell zone.
What signals allow naive B cells to ‘find’ the B cell zone of the lymph node?
naive B cells express CXCR 5 (chemokine receptor) which ‘follow’ CXCL13 chemokine produced in B cell zone.
What proteins get upregulated in activated DCs?
1) CCR7 - navigates to lymph node.
2) B7.1 and B7.2 (also called CD80 and CD86) - co-stimulator for naive T cells.
What proteins facilitate DC / T cell binding?
T cell expresses LFA-1, DC expresses ICAM-1. low-affinity binding becomes high-affinity via ‘inside-out signal’ in T-cell if TCRs recognize MHC-presented peptide.
When naive T cells recognize antigen via TCR-DC connection, what signal cascade leads to proliferation?
CD3 via tail ITAM (immunoreceptor tyrosine activation motifs), proteins adjacent to TCR which recruit a tyrosine kinase (ZAP-70 in T-cells) which activates NF-kB via phospholipase 3 cascade (DAG/IP3) . Also need B7.1/7.2 on DC to bind CD28 on T-cell for full co-stimulation.
How are CD4 T-cell subsets defined?
By cytokines and other factors secreted by DCs during T-cell education. Specifically:
TGF-beta -> Treg cells.
IL-12 -> Th1 cells
IL-6 -> T-fh cells
Th1 cells
1) How are they activated
2) what is the primary cytokine they secrete
3) what is the effect of the secretion?
1) IL-12
2) IFN-gamma
3) activation of infected macrophage.
Th2 cells
1) How are they activated
2) what is the primary cytokine they secrete
3) what is the effect of the secretion?
1) IL-4
2) IL-4
3) activate eosinophils, plasma cells and mast cells to target helminths (cells too large to phagocytose), eventually tamps down its own production.
Th17
1) How are they activated
2) what is the primary cytokine they secrete
3) what is the effect of the secretion?
1) TGF-beta and IL-6
2) IL-17
3) activate neutrophils, particularly in the gut.
Tregs
1) How are they activated
2) what is the primary cytokine they secrete
3) what is the effect of the secretion?
1) TGF-beta
2) TGF-beta and IL-10
3) surpress immune response
Where do B-cells develop and mature?
develop in the bone marrow, mature in the lymph nodes and spleen.
How does the B-cell produce unique BCR?
1) production of heavy chain via DJ and VDJ rearrangements (using RAGs and TdT, gives 1/9 chance of successful rearrangement per chromosome).
2) viable heavy chain traffics to cell-surface, pairs with surrogate light chain
3) tonic signaling causes cell to stop HC rearrangement, proliferate and begin LC rearrangement.
What protein is down regulated to insure allelic exclusion during B-cell development?
tonic signalling at pre-BCR and BCR stages reduce expression of RAG genes and target RAG-2 for proteosomal degradation. HC locus access is also reduced.
Where do the following 3 processes occur in the lymph node?
1) B cell activation
2) B cell proliferation
3) B cell differentiation into memory and plasma cells and class switching.
1) T-cell zone (via activated T helper cell)
2) Germinal center dark zone (via somatic hypermutation)
3) Germinal center light zone
In what part of the antibody gene does somatic hypermutation occur and what is the critical enzyme?
In V(D)J regions of HC and LC, critical enzyme = activation-induced deaminase (AID).
What process is responsible for class switching?
IgM to IgD due to RNA processing
IgM to IgG/IgA/IgE due to DNA rearrangement.
Activation-induced deaminase is the critical enzyme for rearrangements.
What are the three mechanisms by which NK cells decide to kill host cells?
1) foreign proteins in cell membrane
2) MICA, MICB (cell surface distress proteins, MHC1-homologs without antigen)
3) Loss of MHCI expression
What cytokines do CD8 cytotoxic T cells secrete?
IFN-gamma (activate macrophages)
TNF-alpha
