Test 2 Flashcards
RIG-1-like receptors
recognizes viral RNA, not DNA; RNA helicase domain and 2 CARD domains; binds to Mitochondrial Antiviral Signaling Protein
Mitochondrial Antiviral Signaling Protein
what RIG-1 binds to; causes helicase-like domain to dimerize
IRF3
phosphorylated once RNA helicase-like domain dimerized; transcripture factor for IFN-B genes
NFkB
factors for cytokines activated once RNA helicase-like domain dimerizes
Effects of IFN-B
autocrine and paracrine signaling
oligoadenylate synthetase
triggers endoribonuclease to viral genome
protein-kinase R
inhibits initiation factor for translation of IEF-2
IFN-a
actvates NK cells
lymphocytes
T-cells, B-cells, NK cells
Difference between NK cells and T-cells
don’t have to grow before proliferation; NK cells expresses CD56 and lacks CD3
NK cells: CD56 dim
better killers; found more in blood
NK cells: CD56 bright
found more in tissues
IL-12
binds to IL12RB-1 and 2 and activates NK cell
IL-15
doesn’t leave macrophage surface and activates NK cell
How does an NK cell assist in macrophage phagocytosis?
assists in respiratory burst by using IFN-gamma to mediate
NK cell secretes cytotoxic granules
induces cells to commit apoptosis
Major Histone Compatability molecules
“self” molecules because all cells can produce
dendritic cells
prime goal is to internalize pathogens to present the antigen to actvate adaptive immune system; NO RESPIRATORY BURST
When NK cells are abundant?
kill dendritic cells
When dendritic cells are abundant?
activates adaptive immune system
T-cell receptor
made up of alpha and beta chains; variable, constant, stalk segments, transmembrane region, and cytoplasmic tail
Alpha variable domains
70-80 possibilities
Beta variable domains
52 possibilities
somatic recombination
making of a T-cell receptor
recombination signal sequences
conserved 7-sequence, then nonconserved spacer region (12 or 23), then conserved 9-sequnce
cominbatorial diversity
different combos of V, D, and J
Recombination Process 1
Rag-1 or 2 binds then recruits the other; 12 and 23 sections bind; then the section between V and J is cleaved
Recombination Process: Ku Complex
Ku70 and Ku80; forms a ring around the sections trying to join
Recombination Process: DNA-PK
binds to Ku complex
Recombination Process: Artemis
has endonuclease activity and opens hairpin
Recombination Process: Tdt
terminal deoxynucleotidyl transferase processes DNA ends
Junctional Diversity: P-nucleotides
palindromic
Junctional Diversity: N-nucleotides
Tdt adds random nucleotides and stops after a strong binding results; DNA Polymerase fills in what is left; DNA Ligase checks bonds
How does the gamma and delta chains compensate for less V segments?
allows two D segments to be incorporated
CD34
stem cell marker
IL-7 receptor
FIRST STAGES ONLY; thymic stromal cells secret IL-7; pulls the cells into the thymus
Notch 1
ENTIRE MATURATION; receptor on thymocytes interacts with ligand on thymic stromal cells; intracellular domain cleaved and becomes a transcription factor
DN1
expresses KIT and CD44; NO CD25
DN2
expresses KIT, CD44, CD25 and starts B-chain rearrangement; Db and Jb combined
DN3
NO KIT OR CD44; expresses CD25, continues B-chain rearrangement; Vb and DJb combined
DN4
PROLIFERATION; important for adding diversity; B-chain rearrangement shutoff by inhibiting RAG1 and RAG2
How a B-chain is considered productive?
it needs to form a functional mock pre-T cell receptor
rescuing a non-productive B-chain
a max of 4 tries to get a productive B-chain to form
T-cell a-chain
does not have a max number of tries; both a-chains can be rearranged at the same time
thymic cortical epithelial cells
surround the thymocytes while maturing
How many thymocytes make it through selection?
10-30%; variety of MHC makes it difficult
CD4 T-cell
must interact with MHC Class II
CD8 T-cell
must interact with MHC Class I
Positive Selection: weak or no binding
cell dies
Positive Selection: moderate or strong binding
cell lives
Negative Selection: moderate binding
cell lives
Negative Selection: tight binding
cell dies
Negative Selection cells
macrophages and dendritic cells
Positive Selection cells
thymic cortical epithelial cells
autoimmune regulator transcription factor
allows the cells to present self peptides found in all different tissues
Which T-cells go through postive and negative selection?
a and B T-cells; not delta and gamma
Region: Proliferation and Differentiation
sub-capsular region
Region: Positive Selection
cortex
Region: Negative Selection
cortico-medullary junction
Found where: MHC Class I
all nucleated cells
Found where: MHC Class II
macrophages, dendritic, and B-cells
MHC Class I molecule
a1 and a2 form peptide-binding cleft; a3 transmembrane; B2-microglobulin covalently attached
What domain do a3 and B2-m mimic?
immunoglobulin-like fold domain
MHC Class II molecule
a and B transmembrane; B1 and a1 peptide-binding cleft; B2 and a2 makeup immuno-globulin fold domain
What forms the elongated shape on CD8 T-cells?
glycosylated regions
MHC Class I Peptides
8-10 a.a.; amino and carboxyl ENDS embed in a-helices to stabilize; PEPTIDE ANCHORS, also
peptide anchors
pockets madeup within MHC for peptides’ sidechains to insert
MHC Class II Peptides
13-17 a.a.; gets stability only from PEPTIDE ANCHORS
HLA Complex
human leukocyte antigen genes
B2-microglobulin
not polymorphic
Role of MHC
binds peptide fragments from pathogens and displays on surface
MHC Polygenic
contians several different Class I and II genes
MHC Polymorphic
each gene has a lot of variation; MOST POLYMORPHIC GENE
MHC Gene
found on chromosome 6; 4 million b.p.; 200 genes
