Immuno (Innate) Flashcards
What are sentinel cells?
-pro inflammatory chemokines, lipid mediators, cytokines & antimicrobial
-dendritic cells, mast cells, macrophages
What are the inflammatory mediators? (Chemokines & cytokines)
-IL-1B, IL-6, TNF-a
-from macrophages
-leukocyte & endothelial activation = systemic reaction
What are the inflammatory mediators? (Plasma proteins)
-C3a = mast cell degranulation, smooth muscle contraction
-C5a = same as C3a + leukocyte chemotaxis, vascular permeability
-from complement activation
What are the inflammatory mediators? (Vasoactive amines)
-histamine & serotonin
-from mast cell degranulation
-vascular permeability & smooth muscle contraction
Describe mast cells role in inflammation.
-histamine & serotonin
-vasoactive (vasodilation) = vascular permeability increase
-> more leukocytes
Describe physiological effects of inflammation.
-hypothalamus = fever, anorexia, sleepiness, depression
-liver = increased acute phase proteins (iron sequestration)
-bone marrow = increased white cell production
-IL1, IL6, TNF-a, HMGB1
Describe pathological effects of inflammation.
-fever, acidosis, hypotension, complement activation, intravascular coagulation, endothelial damage
-multiple organ system failure
-death
-SIRS
-IL1, IL6, CCL8, TNF-a, NO
Describe leukocyte extravasation.
-macrophages & dendritic cells = cytokines
-activate endothelial cells = express selectins & ligands for integrins -> secrete chemokines
>selectins = rolling
>integrins = adhesion
>chemokines = migration
Describe leukocyte kinetics during inflammation.
Days -> weeks
1. Neutrophils dominate during acute inflammation
2. Monocytes/macrophages dominate later
3. Lymphocytes present once adaptive immune system is
Describe phagocytosis.
-neutrophils & macrophages
-cytokine production
-present antigens
What are the steps of phagocytosis.
- Recognition of microbe
- Endocytosis
- Phagosome maturation
- Fusion of phagosome & lysosome
- Killing of bacteria inside phagolysosome
Describe intracellular killing mechanisms (oxidative).
-oxygen & glucose
-ROS & RNS
-toxic
Describe intracellular killing mechanisms (non-oxidative).
-cationic proteins = damage bacteria cell wall
-lysozyme = damage mucopeptides in bacterial cell wall
-lactoferrin = sequestrates iron & inhibit bacterial growth
-proteolytic & hydrolytic enzymes = digest killed bacteria
Describe extracellular killing by NETs.
-neutrophil extracellular traps
-increase inflammatory stimulus
-extrude strands of nuclear DNA & proteins into ECF
-traps & kills microbes
Describe the alternative pathway.
-complement proteins activated on microbial surfaces (present on host cells, not microbes)
Describe the lectin pathway.
-activated when carbohydrate-binding plasma protein, mannose-binding lectin (MBL) binds to terminal mannose residues on surface of glycoproteins
Describe the classical pathway.
-activated by antibodies that bind to microbes/antigens
Describe the membrane attack complex (MAC).
-breaches cell membrane of microbe = allows water to rush into cell
-destruction by osmotic lysis
-C5b67 -> C8 unfolds hydrophobic region -> C9 creates cylindrical pore -> MAC -> osmotic lysis
Describe Type I interferons.
-produced by virus infected cells
-nonspecific response to viral infection
-IFN-a & IFN-B = inhibit viral replication (protein synthesis, RNA, gene expression, & virion assembly) & induce antiviral state
Describe NK cells.
A. Kill cells that are infected
-healthy host cells express MHC which are recognized by inhibitory receptors (engaged = NK inactive)
B. Secrete IFN-Y = activates macrophages (kills phagocytosed microbes)
-NK cells activated by infected or mutated cells where ligand for activating receptors are expressed & class I MHC expression is reduced/inhibited (not engaged = NK active)