For example, TLR3 (on the inner surface of vesicles formed by endocytosis) binds to double-stranded RNA, a form of nucleic acid characteristic of certain viruses. Similarly, TLR4 (located on immune cell plasma membranes) recognizes lipopolysaccharide [LPS], a type of molecule found on the surface of many bacteria As in invertebrates, detection of invading pathogens in mammals triggers phagocytosis and destruction Activation of TLRs triggers a signaling cascade Production of cytokines and type I interferons (IFNs) Clicker question #1: Pseudomonas aeruginosa is a pathogen. It is a Gram negative, motile, bacterium. Toll-like receptors and the structure they recognize are listed
below, which one is not involved in recognition of a Pseudomonas infection? A. TLR3: double-stranded RNA B. TLR4: LPS C. TLR5: Flagellin D. All of the above are involved E. None of the above are involved A. NO double stranded because double stranded RNA is not present in bacteria****** ^ not true.. see figure B. LPS is present- because the Pseudomonas aeruginosa pathogen is gram negative C. It is MOTILE so it would have a flagellum Inflammatory response (=inflammation) Triggered by infection Cytokines = signaling molecules (extracellular) of the immune response Histamine (produced by mast cells) triggers dilation of blood vessels: permeability increases Symptoms of inflammation Increased blood flow: reddening -erythema Outpouring of fluids: swelling -edema Pus = fluid rich in white blood cells, dead pathogens, cell debris Heat: fever Systemic inflammatory response Systemic =throughout the body Fever is a systemic response, triggered by pyrogens (=molecules released by macrophages, cause elevation in body temperature)
Septic shock (life-threatening condition) caused by an overwhelming inflammatory response Types of phagocytes Macrophages are found throughout the body (in organs and tissues) -First responders Neutrophils circulate in the blood (can quickly go to site of infection) o Neutrophils are attracted by signals (cytokines and complement molecules) from infected tissues Which type of phagocyte is already present at the site of infection and which type gets recruited there? Macrophages- already present Neutrophils get recruited by cytokines Phagocytosis Phagolysosome = phagosome + lysosome : contains lysozyme, proteases, phosphatases, nucleases, lipases, oxidases Killing of microbes by oxidation within the phagolysosome Increased O 2 uptake = respiratory burst Toxic oxygen species : -Hydrogen peroxide (H 2 O 2 ) -Nitric oxide (NO)
Evasion from innate immunity Two examples of bacterial persistence after phagocytosis 1. Listeria monocytogenes (listeriosis) 2. Mycobacterium tuberculosis (tuberculosis) Trypanosomes: Frequent changes in the surface protein prevent the host from developing immunity. Listeria monocytogenes has life cycle inside host cells Immune evasion by lysis of phagosome LLO (l isteriol ysin O) = pore-forming protein expressed by Listeria
Symptoms of TB Necrosis of the lungs : X-rays reveal destroyed lung tissue Two stages of TB: Stage I: Exposure, mild disease Granuloma formation Stage II: Reactivation Only occurs in 10% of infected ppl What type of response is activated after phagocytosis?
- Spring '14
- Biology, cells, Cytotoxic T cells