Pathogen Challenge and Phagocyte Recruitment PDF

26.5 Pathogen Challenge and Phagocyte Recruitment Microbial invasion is the ability of a pathogen to _ enter host cells or tissues, multiply, spread, and cause disease. Invasion is the ability of a pathogen to enter host \ cells or tissues, multiply, spread, and cause...

26.5 Pathogen Challenge and Phagocyte Recruitment Microbial invasion is the ability of a pathogen to _ enter host cells or tissues, multiply, spread, and cause disease. Invasion is the ability of a pathogen to enter host \ cells or tissues, multiply, spread, and cause disease. Tissue damage triggers the recruitment of a ~ large number of phagocytes.  Tissue damage and chemokine release Resident ^ ^ leukocytes and ^ damaged cells release cytokines, ^ or chemical mediators, that allow communication between^ white ∝ blood cells. (Figure 26.5a) Figure 26.5a  26.5 Pathogen Challenge and Phagocyte Recruitment Cytokines: a soluble protein (~5–20 kDa, ~45-180 ~ AA) produced by a leukocyte or damaged body cell; ~ … modulates an immune response. ^ E.g., interferon (IFN), TGF-β, Interleukin (IL) ∞ Chemokines: an important subclass of cytokines ~ that have the specific role of recruiting immune ~ cells to sites of injury. Produced by macrophages, ~ which are found in all of the body’s organ systems and stimulated by the presence of invading pathogens to secrete chemokines that establish a gradient of chemoattractants to attract other ~ immune cells especially neutrophils and T cells. … E.g., CC and√√CXC chemokines  Release of cytokines and chemokines draws macrophages and neutrophils to the area as they leave circulation (extravasation). (Figure 26.5b) Figure 26.5b 26.6 Pathogen Recognition and Phagocyte How Signal Transduction immune celk find our the enemy ! Pathogen-associated - collectivetern for molecular patterns (PAMP) all pclal 「 holecnks ^ fhct frigyor imnane – Pathogens have structures and response. Q reqtor - molecules not found in or on host cells (e.g., peptiglycan, cellwallt flagellin, dsRNA). bactevid virus Pattern recognition receptors – Leukocytes have membrane ~ bound or soluble proteins that recognize PAMPs. (Figure 26.6)  Signal transduction in phagocytes – Upon encountering a pathogen associated molecular pattern, Toll-like receptors (TLR) will send a signal to the nucleus. (Figure 26.7) PANMexample ① - ② receptor O - patternvecagnition ③ signcins pathway ω72 ① r , h use to yehe, tor immune response – Upon activation of TLRs, a leukocyte will start a phosphorylation cascade to transmit the activation signal to the nucleus, activating transcription factors to turn on genes in response to the activation signal. – NFκB is a key transcription factor that is activated in many different pathways. (Figure 26.8) 26.7 Phagocytosis and Phagocyte Inhibition Phagocytosis and the phagolysosome – Phagocytes will engulf pathogens upon recognition of PAMPs by their TLRs. (Figure 26.9) Time-lapse phase-contrast micrographs of the phagocytosis and digestion of a chain of Bacillus megaterium cells by a Figure 26.9 human macrophage. The bacterial chain is about 20 μm long.  Phagocytosis and the phagolysosome – When engulfed, the bacteria will be held in a membrane bound vesicle called the phagosome. – The phagocytic host cell will fuse lysosomes, making a phagolysosome. – Phagocytes also produce toxic reactive oxygen intermediates to kill the bacteria within a phagolysosome. (Figure 26.10)  Pathogens inhibiting phagocytes Some pathogens can survive the phagolysosome. – Mycobacteria tuberculosis produces carotenoids to neutralize singlet oxygen and has a waxy cell wall that absorbs free radicals. This pathogen lives and divides within phagocytes. – Some pathogens, such as Streptococcus pyogenes produce leukocidins, which kill white blood cells. Dead white blood cells are found in pus. Lastly, some pathogens contain a capsule, which makes it difficult for the phagocyte to engulf them. Host antibodies can counteract this, which is why pneumococcal vaccines are effective in preventing pneumonias caused by Streptococcus pneumoniae. Realend L