L2 Cells of Innate Immunity Flashcards
what are the cells involved in innate immunity?
- phagocytes
- mast cells and basophils
- eosinophils
- NK cells
What cells types make up phagocytes?
- neutrophils
- macrophages
what are the macrophages called in the brain?
microglial cells
what are the macrophages called in the lung?
alveolar macrophages
what are the macrophages called in the liver?
Kupffer cells
what are the macrophages called in the spleen?
macrophages
what are the macrophages called in the kidney
mesangial phagocytes
what are the macrophages called in the joint?
synovial A cells (synoviocytes)
when do monocytes become macrophages?
once they enter the cell
what type of macrophages are found in the lymph node?
resident and recirculating macrophages (monocytes?)
how is a phagolysosome formed?
PAMPs on bacterium binds to PRRs on macrophage
macrophage engulfs bacterium by phagocytosis and a lysosome joins the phagosome= phagolysosome
how is direct recognition carried out?
PAMPs (pattern activation molecule patterns) on pathogen binds to PRR (pattern recognition receptors) on phagocyte
what is the role of TLRs?
a group of membrane bound receptors that exists on cytosolic vesicles and external cell membranes
there are about 10 different ones - each recognize different molecular patterns and signaling leads to different signaling cascades
How are opsonins produced?
- B cells secreting IgG antibodies
- macrophages generate IL-6 – target hepatocytes to secrete CRP
- Complement release C3b
define opsonins
molecules that have attached to the pathogen
an interaction of any of the 3 pathogen-bound opsonins triggers what?
phagocytosis
how are receptors on the phagocyte and opsonins paired?
on phagocyte —- on pathogen
FcYR — FcY (IgG)
CRP-BP —- CRP
CR-1 —– C3b
*These are not PRR (pattern recognition receptors), they are specific receptors
what are the armamentariums contained within the phagosome?
- Lysosomes (4)
- NADPH oxidase (ROIs, ROSs) (4)
- iNOS - inducible nitric oxide synthase (NO and other RNI)
define phagosome?
recognition and binding of pathogen is followed by ingestion of a portion of the plasma membrane which extends outward and surrounds the microbe forming a phagocytic vacuole.
vesicle that contains the engulfed pathogen
when the lysosomes fuses with the phagosome, what are the 4 lysosomal products that are released?
- defensins
- lysozyme
- lactoferrin
- myeloperoxidase
*cytotoxic to microorganisms
what is the role of lactoferrin?
binds to iron - removes an essential ingredient for microbial growth
what is the role of lysozyme?
destroys muramic acid in bacterial cell walls
what is the role of defensins?
permeabilize bacterial and fungal membranes
what is the role of myeloperoxidase?
released from lysosomal granules
enzyme requires to generate hypochlorite
what is the role of hypoclorite?
potent antimicrobial agent that mediates its function by halogenating bacteria` cell walls.
what is required for the function of the NADPH oxidation complex?
glucose - from pentose phosphate pathway
what activates NADPH oxidase?
the respiratory burst from phagocytosis
NADPH uses oxygen in the presence of cytosolic NADPH to generate?
superoxide anion
what is a superoxide anion?
reactive oxygen species (ROS) aka reactive oxygen intermediate (ROI)
what is the initiating step for the other ROSs/ROIs?
the generation of the superoxide anion
what are the products that result from the activation of NADPH oxidase?
- superoxide
- hydroxyl radical
- hydroxyl ion
- hydrogen peroxide
* hypochlorite is formed when myeloperoxidase is available - it is a catalyst
what enhances the activation of NADPH oxidase?
interferon gamma and tumor necrosis factor (IFNY and TNF)
what is formed when nitric oxide reactions with ROI?
reactive nitrogen intermediates (RNIs)
why are Nitric oxide and other RNIs important?
elimination of intracellular organisms that are resistance to ROIs and lysosomal enzymes in phagolysosomes
what are the molecular targets of NO?
iron sulfur proteins in the ETC – inhibit respiratory cycle
what does the synthesis of NO require?
nitric oxide synthase
what is nitric oxide synthase?
L-arginine + oxygen —-[iNOS]—> L-citruiline +NO
what cytokines activate iNOS
TNF
IFNY
what cytokines do the down regulation of iNOS?
IL-4
TGF Beta (transforming growth factor) - most effective
IL-10
what are the cytokines secreted by activated macrophages?
IL-1 IL-6 IL-12 IL-18 TNF IL-15
which cytokines play a role in inflammation?
TNF
IL-1
what are the chemokines secreted by activated macrophages?
IL-8 (CXCL8)
MCP-1 (CCL2)
describe the role of TLR 2 and TLR 4 in generation of pro IL-1
signaling of TLR 2 and 4 –> activation of NFkB (transcription factor required for transcription of pro-IL-1) = inflammatory cytokine secrete by activated macrophages
how is caspase 1 generates from procapase 1?
the NALP3 inflammasome complex converts proenzyme to its active form – then that activates IL-1 and IL-18
how do PAMPs and DAMPs activate the inflammasome
PAMPs and DAMPs are responsible for binding the damaged molecules of microbial products
once those are bound = inflammasome!
what are 5 examples of DAMPs
- MSU - monosodium urate monohydrate -uric acid crystal - gout
- cholesterol crystals
- skin irritants - sunburn!
- glucose derived ROS - Type II DM
- free fatty acids
- asbestos
what are the receptors on macrophages that play a role in immune response
- for cytokines
- for chemokines
- for PRRs
- for FcyR
- for CRP-R
- for CR-1
identify the tissue distribution of CD200R
cells of myeloid lineage
what is the role of CD200?
suppresses immunity activity
expression on tumor cells suppresses anti-tumor cytotoxic immune responses
what cells is CD 200 expressed on
T cells
B cells
dendritic cells
