Question

An inflammatory response is vital to eliminating an infectious agent. Fully describe inflammation, addressing each of the following in the description. (You may use diagrams) a. Complete description of the inflammatory response (be specific) b. Methods (more than one) of the initiation of inflammation c. At least 3 aspects of the immune response that are enhanced by inflammation and how they are enhanced.

Answer 1

A.  

The inflammatory response (inflammation) occurs when tissues are injured by bacteria, trauma, toxins, heat, or any other cause. The damaged cells release chemicals including histamine, bradykinin, and prostaglandins. These chemicals cause blood vessels to leak fluid into the tissues, causing swelling. This helps isolate the foreign substance from further contact with body tissues.

The chemicals also attract white blood cells called phagocytes that eat germs and dead or damaged cells. This process is called phagocytosis. Phagocytes eventually die. Pus is formed from a collection of dead tissue, dead bacteria, and live and dead phagocytes.

B. Activation of

• Cell surface pattern receptors recognize detrimental stimuli;
• Inflammatory pathways are activated;
• Inflammatory markers are released;
• Inflammatory cells are recruited. pathways

Inflammatory pathways impact the pathogenesis of a number of chronic diseases, and involve common inflammatory mediators and regulatory pathways. Inflammatory stimuli activate intracellular signaling pathways that then activate production of inflammatory mediators. Primary inflammatory stimuli, including microbial products and cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), mediate inflammation through interaction with the TLRs, IL-1 receptor (IL-1R), IL-6 receptor (IL-6R), and the TNF receptor (TNFR). Receptor activation triggers important intracellular signaling pathways, including the mitogen-activated protein kinase (MAPK), nuclear factor kappa-B (NF-κB), and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways.

NF-κB pathway

The NF-κB transcription factor plays important roles in inflammatory, immune response, survival, and apoptosis processes. The NF-κB family includes five related transcription factors: P50, p52, RelA (p65), RelB, and c-Rel. NF-κB activity is induced by a range of stimuli, including pathogen-derived substances, intercellular inflammatory cytokines, and many enzymes. Under physiological conditions, IκB proteins present in the cytoplasm inhibit NF-κB. PRRs use similar signal transduction mechanisms to activate IκB kinase (IKK), which is composed of two kinase subunits, IKKα and IKKβ, and a regulatory subunit, such as IKKγ. IKK regulates NF-κB pathway activation through IκB phosphorylation. IκB phosphorylation results in its degradation by the proteasome and the subsequent release of NF-κB for nuclear translocation and gene transcription activation. This pathway regulates pro-inflammatory cytokine production and inflammatory cell recruitment, which contribute to the inflammatory response.

C.

• The production of eosinophils from the bone marrow and their survival in peripheral tissues are enhanced by the cytokine IL-5, making them prominent cells in most allergic responses.
• Eosinophils are readily recognized by their prominent cytoplasmic granules that contain toxic molecules and enzymes that are particularly active against helminths and other parasites. The production of eosinophils from the bone marrow and their survival in peripheral tissues are enhanced by the cytokine IL-5, making them prominent cells in most allergic responses. Basophils and mast cells are morphologically similar cells that represent distinct lineages. By virtue of the cell surface expression of high affinity receptors for IgE (FcεRI), they are key initiators of immediate hypersensitivity responses and the host response to helminthic parasites, releasing histamine and other preformed mediators from their granules and producing important quantities of lipid mediators that stimulate tissue inflammation, edema, and smooth muscle contraction. Recent studies have demonstrated that in addition to their role in immediate hypersensitivity responses, mast cells play prominent roles in the host response to bacterial infection as well. Importantly, mast cells and, more prominently, basophils can release substantial amounts of IL-4, suggesting that they can play important roles in the induction of allergic immune responses.
• Phagocytic cells of the monocyte/ macrophage lineage also play key roles in the adaptive immune response by taking up microbial antigens, processing them by proteolysis to peptide fragments, and presenting them in forms that can activate T responses. Additional cells in this lineage include Langerhans cells in the epidermis, Kupffer cells in the liver, and microglial cells in the central nervous system. The most potent types of APC are the broad class of dendritic cells that are present in most tissues of the body and concentrated in the secondary lymphoid tissues. All of these cells express both class I and class II major histocompatibility complex (MHC) molecules that are used to permit recognition of processed antigen by the TCR on T cells. All MHC bearing cells appear to have the potential to express APC function if stimulated appropriately. In addition to the conventional dendritic cells described above, which have been thought to be derived from myeloid precursor cells, a second type of dendritic cell is recognized. These cells are designated plasmacytoid dendritic cells because of their histological morphology. They can produce very high levels of type I interferon and are thought to play special roles in antiviral host defense and autoimmunity. Recent studies of dendritic cell differentiation indicate that both myeloid stem cells and common lymphoid progenitors can give rise to both conventional dendritic cells and plasmacytoid dendritic cells, most likely through a dendritic cell precursor that is defined by its expression of the fms-like tyrosine kinase receptor-3 (Flt3).