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MICRO
Bacterial Interaxns w/ Macrophages
| Question | Answer |
|---|---|
| What is the first line of defense in innate immunity? | Macrophages |
| Where are macrophages derived? | From peripheral blood monocytes which leave vasculature and differentiate into tissue macrophages |
| How are macrophages activated? | - Upon ingestion of bact./bact. products - By cytokines or chemokines |
| What are the names of macrophages in various tissues? 1. lung 2. CT 3. liver 4. kidney 5. brain 6. bone | 1. alveolar 2. histiocytes 3. Kupffer cells 4. mesangial cells 5. microglial cells 6. osteoclasts |
| What are the 5 functions of macrophages? | 1. detect microbial invasion 2. restrict microbial spread 3. recruit immune cells 4. act as accessory cells in lymphocyte activation 5. act as effector cells in cell-mediated immunity |
| What are the 5 steps of phagocyotosis? | 1. recognition 2. uptake 3. maturation 4. killing 5. Ag presentation |
| Describe the bact. recognition step 1 of phagocytosis. | Bact. can be recognized by multiple host receptors and involves common Ag-receptor interaxns b/w bact. and macrophage |
| What are the surface structures of GRAM + bact. that influence recognition? | capsule, PG layer, surface proteins (change Ag presentation in Borrelia recurrentis), flagellum |
| What are the surface structures of GRAM - bact. that influence recognition? | outer membrane, capsule (masks epitopes), pili (phase variation in E. Coli pap), PG layer, flagellum (regulated expression) |
| What are other macrophage-bact. interaxns? | - use PRR's, LPS in Gram - and Gram +, plasma derived, membrane-derived, receptors generate diff host responses, multiple macrophage surface receptors may recognize molecules on single bact., EC pathogens avoid recognition capsules |
| What are 4 types of common membrane-derived receptors? | 1. C-type lectins (eg. macrophage mannose receptor) 2. leu-rich proteins (eg. CD14) 3. scavenger receptors (eg. scavenger receptor A type 1) 4. integrins (eg. CR3) |
| Describe the bact. uptake step 2 of phagocytosis. | - Recognition b/w ag and receptor starts a transmembrane activation cascade-signal transduction. The surface structure is remodeled by depolymerizing and repolymerizing actin. Bact. is internalized w/i a phagosome. |
| How does bact. enter non-phagocytic cells when bact. internalization is not passive and is active? | 1. trigger mech 2. zipper mech |
| Describe the Trigger Mech. - What induces? - Cytoskeleton remodeling? - What promotes? - An eg. | - pathogen-induced - involves major cytoskeleton remodeling - promoted by effector proteins - Salmonella typhimurium |
| Describe the Zipper Mech. - What induces? - Cytoskeleton remodeling - How? - An eg. | - receptor-mediated - minimal cytoskeleton remodeling - bact. slide into cell - Listeria monocytogenes |
| What is a phagosome? | A membrane-bound compartment in which bact. is internalized, usu. passive. |
| Describe the bact. maturation step 3 of phagocytosis. | - Phagosome acidifies and fuses w/ endocytic vesicles to form "early" or "late" endosomes, depending on the proteins present on the vesicle surface. |
| What allows the maturation of the phagosome from the periphery to perinuclear region? | Microtubules |
| What do "early" endosomes display? | - Rab5 - Transferrin receptor (Tfr) - other fluid phase markers (FPM) |
| What do "late" endosomes display? | - Rab7 - EEA1 - M6PR - LAMP-1 and -2 - H+-ATPase - other FPM |
| What do phagolysosomes display? | - Cathepsin D - LAP - H+-ATPase |
| What can block or alter steps in maturation process of the phagosome? | IC bact. |
| What are 4 mechanisms and eg. of each that alter phagosome trafficking? | 1. bact. survive and replicate in phagolysosome 2. bact. escape and replicate in cytosol 3. modulate endocytic pathway 4. alternative membrane trafficking |
| Describe mech 1. | - Phagosome completely matures and fuses with endocytic organelles, accelerating maturation into phagolysosome where it replicates in high numbers. - Has mechs to resist low pH and other antimicrobial products generated |
| Describe mech 2. | - Initially ingested in phagosome, but expresses enzymes to degrade phagosomal compartment and avoids fusion with lysosome. The cytosol is nutrient-rich for replication. - Cell-to-cell spread |
| Describe mech 3. | - Phagosomes are arrested at an early stage. Bact. have proteins that subvert the normal maturation process. - Occurs only w/ live bact. and unactivated macrophages. - Mycobacterium has no acidification. - Salmonella survives acid and forms vacuole. |
| Describe mech 4. | - The phagocytic compartment isn't accessible to endocytic network so no lysosome fusion events. There is a close interaxn w/ ER and Golgi. - May be related to entry mechs where novel receptors and/or processes are used for internalization. |
| Describe the bact. killing step 4 of phagocytosis. | - The phagocytic compartment isn't accessible to endocytic network so no lysosome fusion events. There is a close interaxn w/ ER and Golgi. - May be related to entry mechs where novel receptors and/or processes are used for internalization. |
| Describe the bact. Ag-recognition step 5 of phagocytosis. | Ag are degrated into oligopeptides of 13-18 aa then they bind to Class II MHC and are presented by nearby APC. The Ag presentation on cell surface stimulates T-cells. |
| What do activated macrophages secrete? | - IL-1 - TNF alpha - IL-6 - IL-8 - IL-12 |
| What are the local and systemic effects of IL-1 secretion? What are the local and systemic effects of IL-1 secretion? | - Local: activates vascular endothelium, activates lymphocytes, local tissue destruction, increases access of effector cells - Systemic: fever, production of IL-6 |
| What are the local and systemic effects of TNF-alpha secretion | - Local: activates vascular endothelium and increases vascular permeability which leads to increased entry of IgG, completment and cells to tissues and increased fluid drainage to lymph nodes - Systemic: fever, mobilization of metabolites, shock |
| What are the local and systemic effects of IL-6 secretion? | - Local: lymphocyte activation, increased Ab production - Systemic: fever, induces acute-phase protein production |
| What are the local and systemic effects of IL-8 secretion? | - Local: chemotactic factor recruits neutrophils, basophils, and T cells to site of infxn |
| What are the local and systemic effects of IL-12 secretion? | - Local: activates NK cells, induces the differentiation of CD4 into TH1 |
| What are consequences of bacteria internalization? | - Beneficial when released in moderation - Lymphocyte recruitment and activation - Cross-activation of other immune cells - Increased vascular permeability |
| How can a macrophage response damage the host? | - if continuously stim., can cause tissue dz - ROI, RNI, hydrolytic enzymes damage tissue - TNF-alpha and IL-1 can cause fever, wasting, and septic shock - chronic inflammation - phagocytes contribute to autoimmune dz - can disseminate pathogens |
| An eg. of organism that survive and replicate in phagolysosome. | Coxiella |
| An eg. of organism that escapes and replicates in cytosol. | Rickettsia, Shigella, E. Coli, Listeria |
| An eg, of organism that modulates endocytic pathway. | Myobacterium, Salmonell |
| An eg. of organism that alternates membrane trafficking. | Legionella, Brucella, Chlamydia |
Created by:
kelgsny
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