Immuno: Phagocytosis, Inflammation Flashcards
1
Q
describe PAMPs (pathogen associated molecular patterns)
A
- essential to microbial survival and metabolism which makes them relatively invariant and evolutionary stable
- examples:
- peptidoglycan found in bacterial cell walls
- flagellin, a protein found in bacterial flagella
- LPS from the outer membrane of gram-negative bacteria
- lipopeptides, molecules expressed by most bacteria
- nucleic acids such as viral ds RNA
2
Q
which toll like receptors (TLRs) are associated with viruses?
A
TLR 3, 7, 8, 9
3
Q
describe opsonization
A
- addition of an opsonin, to ensure cell is readily identified, and more efficiently taken by phagocytes (enhance phagocytosis)
- phagocytes have specific receptors for this mechanism:
- CR1 - complement receptor for C3b fragment (complement cascade)
- Fc receptors for Fc region of immunoglobulins (antibodies)
4
Q
describe the opsonins
A
- antibodies: opsonize the antigen
- Fc region of antibody binds to phagocytic cell receptors
- phagocytic cells do not have Fc receptors for IgM but IgM activates complement to do the opsonization
- main opsonin: IgG
- complement molecules: opsonize the antigen
- opsonized antigen binds to CR1 receptor on the phagocyte
- main opsonins: C3b, C4b and C1q
- circulating proteins (secreted pattern recognition receptors): pentraxins, ficolins, collectins (Mannose-binding lectin, MBL)
5
Q
describe the mechanism of phagocytic recognition, engulfment and killing
A
- chemotaxis and ingestion: phagocytes migrate and recognize PAMPs that drive initiation and perpetuation of the inflammatory response
- phagolysosome formation: lysosome fused with phagosome (death ~30 min)
-
destruction and elimination:
- oxygen-dependent system (respiratory burst)
- liberation of lactic acid, lysozyme and nitric oxide
6
Q
describe oxygen-independent phagocytic killing
A
- lysozyme: split peptidoglycan
- lactoferrin and reactive nitrogen intermediates: deprive pathogens of iron
- proteolytic enzymes: degrade dead microbes
- defensins, cathepsin G and cationic proteins: damage microbial membrane
7
Q
describe oxygen-dependent degradation (oxidative burst)
A
- NADPH oxidase produces superoxide which recombines with other molecules to produce reactive free radicals
- the superoxide reacts with NO forming peroxynitrate
- myeloperoxidase uses the derived H2O2 to produce hypochlorite (antimicrobial)
- to combat infxns, immune cells use NADPH oxidase
- absence of NADPH oxidase will prevent the formation of ROS and resulti n chronic granulomatous disease (CGD)
8
Q
describe lab tests for CGD
A
- the nitroblue-tetrazolium (NBT) test
- the higher the blue socre, the better the cell is at producing ROS
- in CGD, the test will be negative
9
Q
describe Chediak-Higashi syndrome
A
- autosomal recessive disorder that arises from a mutation of a lysosomal trafficking regulator protein
- the disease is characterized by large lysosome vesicles in phagocytes with poor killing action leading to:
- susceptibility to infxns
- abnormalities in nuclear structure of leukocyte
- anemias
- hepatomegaly
- Dohle bodies (cytoplasmic inclusions in neutrophils)
- clinical presentation: albinism, neutropenia, periodontal disease, recurrent infxns
10
Q
describe the steps of the inflammatory response
A
- injury/immediate rxns:
- injury/damage causes release of chemical mediators, cytokines, histamine
- attracts leukocytes to the site of injury
- vascular reactions:
- histamine causes vasodilation, increased vessel permeability (redness and heat)
- delivers leukocytes, fluid and clotting factors to the site of injury
- edema and pus formation:
- edema (swelling) helps contain the infxns and attract neutrophils
- debris and WBCs form pus
- bradykinin stimulates pain receptors
11
Q
summarize the mediators of acute inflammation
A
12
Q
describe the cell adhesion molecules (CAMs)
A
-
selectins
- glycoproteins
- bind to carbohydrates
- expressed on leukocytes and endothelial cells
-
mucins
- proteins
- present CHO ligands to selectins
- present on endothelial cells and neutrophils
-
integrins
- proteins; heterodimers
- expressed on leukocytes
- bind to Ig superfamily molecules
-
ICAMs
- Ig CAMs
- expressed on endothelial cells
- bind to integrins
13
Q
describe the 4 steps of leukocyte extravasation
A
- rolling
- mediated by binding of selectins (endothelium) to mucin-like CAMs (leukocyte)
- activation
- chemokine binding induces conformational change in integrins (leukocyte)
- arrest/adhesion
- integrins now capable of binding Ig-superfamily CAMS (endothelium)
- transendothelial migration
- migration through tight junctions of inflamed endothelium
14
Q
describe leukocyte adhesion defect (LAD)
A
- patients with LAD1 have an inherited defect that causes a deficiency of the B-2 integrin subunit (CD18)
- this subunit is involved in the formation fo the B-2 integrins by dimerization with different CD11 subunits
- the main function of these proteins is to allow neutrophiles to make their way out of the blood stream by adhering to the different ligand ICAM-1
- in LAD1 patients, neutrophils cannot extravasate and fight against bacteria in tissues
15
Q
describe the Kinin system (mediator of inflammation)
A
- Hagman factor (XII) activation leads to bradykinin formation
- increased vasodilation, permeability, pain and smooth muscle contraction
