How to destroy a microorganism Flashcards
Why can phagocytic cells digest bacteria?
Because of their large relative size compared to bacteria
What is the neutrophils main role?
phagocytosis mediated intracellularly however they can kill intracellularly. Recognition occurs through PRRs
How can phagocytosis be more readily facilitated?
If the bacterial cell is opsonised through complement or antibodies.
What is the function of eosinophils?
Intracellular phagocytosis for small pathogens however these innate cells are implicated more so in the immunity against parasitic worms, which are too large to be engulfed. A worm is coated with antibody, eosinophils bind to immune complexes through the Fc receptor which causes an extracellular release of granules (exocytosis) which are toxic to the parasite. This is an example of ADCC
Macrophage function?
Endocytosis of microorganisms, opsonisation increases efficiency of endocytosis. They have MHC-II on their surface, facilitating antigen presentation to helper T cell. MHC-II required for antigen presentation to T helper cells via the TCR.
What does infection cause a phagocytic cell to do?
To adhere to the blood vessel endothelium and is chemotactically attracted to the site of infection and sequester through the endothelial tissue to enter tissues. Macrophages are cells of the mononuclear phagocyte lineage depsite migratory capability to infection site. There are also fixed tissue macrophages; microglia in the brain, Kupffer cells in liver for example. Epithelioid and giant cells are activated in chronic long-term inflammation.
What is the process of phagocytosis?
1)Chemotaxis through a concentration gradient of cytokines
2) adherence to phagocyte through PAMP recognition by PRRs
3) Cell activation via PRR-PAMP binding; ingestion phase activated by actin-myosin contractile system.
4) initiation of phagocytosis; endosome forming around pathogen; endocytosis begins; pseudopodia formation via actin-myosin contractile system
5) phagosome formation mediated via psuedopodia fusion
6) lysosomes of phagocytic cell fuse with phagosome and discharge their microbicidal granules (lysozyme) onto the phagosome-containing microorganism
7) release of degradation products (pinocytosis)
TB has evolved to avoid phagocytosis
Describe the process of oxygen dependent killing mechanisms
After the pathogen has been phagocytoses, in the cytosol there is an increase in hexose monophosphate activity (a respiratory burst) generating NADP (reduced) from NADPH. The electrons pass from NADPH to the plasma membrane of cytochrome b558 which reduces molecular oxygen to superoxide anion. Superoxide anion is converted to hydrogen peroxide by superoxide dimutase. Hydrogen peroxide then has two possible reactions; i) addition of Fe2+ resulting in -OH (hydroxyl radical which is one of the most potent free radicals) and ii) addition of Cl- and myeloperoxidase (MPO) generating HOCL, a chloramine and a potent halogenating system capable of killing both bacteria and viruses.
A separate killing mechanism is by nitric oxide formed by inducible nitric oxide synthase (iNO).
Describe oxygen independent killing mechanisms.
Defensins; cationic peptides, high concentrations in phagosomes, act as disinfectants against bacteria, fungi and enveloped viruses.
Bacterial membrane damage through neutral proteinase (cathepsin G), lysozyme (tears, saliva, splits mucopeptide in bacterial cell wall) and lactoferrin which chelates iron, an essential nutrient for bacteria. Killed organisms are digested by hydrolytic enzymes and the degradation products released into the exterior.
What is chronic granulomatous disease?
A genetic immunodeficiency disease in which individuals cannot produce ROS intermediates in a respiratory burst due to mutations in the phagocyte NAPH oxidase enzyme (PHOX) (X linked, recessive). Results in defective killing engulfed microorganisms, individuals more prone to infections, fatal if not treated; recurrent infections.
Describe the process of opsonisation
Antibody and complement aid phagocytosis through opsonization. The Fab part of antibody binds to pathogen’s antigen. The Fc part of the antibody is then recognised by FcR on phagocytes, so that phagocytosis can be more readily performed as pathogen is more easily recognised. Immune complexes also activate complement which increase opsonisation which has a chemotactic effect and also increases vascular permeability. Opsonisation increases Fc receptors becoming cross-linked for phagocytosis to be initirated= a high avidity multiple bond. Low affinity single bonds (small number of Fc binding to FcR) does not trigger phagocytosis.
Describe the characteristics of immature dendritic cells
non motile, MHC-low, highly phagocytic, B7 low, quiescent in tissues, awaiting infection.
Describe the charactersitcs of mature dendritic cells
motile; move from infected tissue to lymph nodes, MHC high, poorly phagocytic, B7 high, stimulate T cells.
What is B7?
A costimulatory molecule essential for the full activation of T lymphocytes.
How does differentiation from immature to mature DCs oocur?
Via IL-1, TNF, PAMP recognition. Dedifferentiation is not possible.
