German Induced immunity Flashcards
What are the resident macrophages in the Brain bone liver skin
Brain: microglia
Bone: osteoclasts
Liver: Kupffer cells
Skin: Langerhans cells
What do diacyl lipopeptides recognize?
TLR-2 and TLR-6
What do triacyl lipopeptides recognize?
TLR-2 and TLR-1
What does flagellin recognize?
TLR-5
What does LPS recognize?
TLR-4 and MD-2
What does dsRNA bind?
TLR-3
In the endosome
What does ssRNA bind?
TLR-7
In the endosome
What does CpG DNA bind?
TLR-9
In the endosome
Which cells are responsible for controlling the immune responses to parasites
Basophils
What are some macrophage receptors?
Mannose receptor CD206
Complement receptors 3 and 4 (Mac1, CD11b/CD18)
Dectin-1
Macrophage receptor with collagenous structure (MARCO)
Scavenger receptor A (SR-A)
SR-B (CD36)
LPS receptor (CD14)
What is the pathway for LPS Cytokine production?
TLR4, MD2, CD14 and LPS form at the macrophage surface. MyD88 binds TLR4 and activates IRAK4 to phosphorylate TRAF6, which leads to a cascade that phosphorylates IKK. IKK phosphorylates IkB, leading to its degradation and releasing NFkB, which enters the nucleus, transcribes inflammatory cytokines which are released all around.
What is NOD and what does it do?
Nucleotide-binding Oligomerization Domain. Recognizes bits of chopped up bacteria in macrophage cytoplasm, dimerizes, and phosphorylates TAK1 to phosphorylate IKK and then make cytokines
How do Inflammasomes work?
IL-1B binds to receptors for it, MyD88 pathway is turned on and pro- IL1B is turned on. Caspase 1 cleaves it and IL-1B is released.
How does Caspase get turned on?
NLRP3 oligermizes and cleaves procaspase1 into caspase 1 (this is a checkpoint that prevents an inflammatory response if it it turned off)
What are the 6 families of cytokines?
Class I Class II IL1 IL17 TNF Chemokines
Cytokines use what kind of signaling?
JAK-STAT
What 5 inflammatory cytokines to macrophages release?
IL-1B TNF-a IL-6 CXCL8 IL-12
What does IL1B do?
Activates endothelium, activates lymphocytes destroys tissue Increases access of effector cells Fever Production of IL6
What does TNFa do?
increases endothelial permeability, allows increased entry of IgG and complement and cells and increased drainage to lymph nodes. Fever, Mobilization of metabolites, shock
What does IL6 do?
Activates lymphocytes, increases antibody production, fever, induces acute-phase protein production
What does CXCL8 do?
Chemotaxis, recruits neutrophils, basophils, and Tcells
What does IL12 do?
Activates NK cells, induces differentiation of CD4 T cells in to Th1 cells.
What are acute phase proteins?
C-reactive protein, mannose-binding lectin. Found in liver, activate complement. IL-6 turns on liver production
How is adaptive immune response turned on?
TNFa stimulates migration to lymph nodes and maturation
What does C-reactive protein do other than complement?
Binds to phosphocholine on bacterial surfaces, acting as an opsonin
What causes septic shock syndrome?
Systemic infection with gram-negative bacteria. Macrophages make TNFa, which lets lymph and cells leak out everywhere. Vessels collapse, coagulation, wasting, organ failure, death.
What are the four kinds of chemokine?
CL, CCL, CXCL, CX3CL
What do adhesion molecules do?
Tether leukocytes
What do proteases do?
Open basement membranes (MMPs and Elastase)
What are the 4 steps of diapedesis?
Rolling (selectin-mediated adhesion) Rolling adhesion (CXCL8 Receptor binds.) Tight binding (LFA-1 and ICAM-1) Diapedesis Migration
What is the primary innate killer?
Neutrophils
What are the four neutrophil granule types?
Azurophil granules (myeloperoxidase, defense's, Cathepsin G) Specific granules (lactoferrin, collagenase, lysozyme) Gelatins granules (gelatinase, lysozyme) Secretory granules (CR1, CR3, CD14, CD16)
What are the three steps in Oxidative burst?
- Make a superoxide using NADPH
- Dismutase the superoxide to make H2O2
- Catalase to make water and oxygen out of H2O2
What are the 3 kinds of Neutrophil extracellular traps?
- Non-lytic, DNA
- Non-lytic, mitochondrial DNA
- Lytic
What cells initiate adaptive immunity?
Dendritic cells
What are dendritic cells derived from?
Monocytes
What causes the interferon response?
Viral infections
What causes synthesis of Interferons?
IRF3 in cells, made by TRAF6
What are two things that bind viral RNA to make interferons?
RLR-retinoic acid inducible gene-I like receptor
MAV- mitochondrial antiviral signaling protein
Type I vs Type II interferons
INFa and INFB= Type I
IFNg=Type II
What releases interferons?
Diseased or stressed cells, leukocytes
What activates NK cells?
Interferons. Proliferation, differentiation into cytotoxic effector cells. Then effector NK cells induce apoptosis in virally infected cells
What regulates the transition from innate to adaptive immune response?
NK cells
What keeps NK cells from killing healthy cells?
MHC I receptors
How does a macrophage turn on a NK cell?
IL12 and IL15
When turned on by kissing a macrophage, what does a NK cell make?
IFN-g, which turns on the macrophage to increase phagocytosis and secrete inflammatory cytokines
What happens when there are mor NK cells than dendritic? Vis versa?
When too many NK cells, they kill dendritic cells. When few NK cells, they drive dendritic cells to mature and start adaptive immunity
What are the inflammatory cytokines?
IL-1B TNF-a IL-6 CXCL-8 IL-12