Acute Inflammatory Response

Acute Inflammation is the process taking place within normal tissues when they become invaded by pathogens. Since this is the hallmark of Innate Immune Activity, it follows that this process is Rapid, Non-Selective, and less efficient than B or T-mediated immunity. However, they're quite sufficient for the elimination of non-specific "common everyday" microbes.

Clinically, this process presents with Redness, Hotness, Swelling, Pain and Loss of function within the affected tissues.

Immunologically, the events leading up to this state are due to cellular elements and aCellular Soluble chemicals, as follows;

1. Cellular Element: Phagocytes. Microbe reaches the tissue, to encounter the macrophages, which are the first cells to encounter the microbe. The PAMPs hook to PRRs and TLRs, and phagocytosis occurs, with subsequent MHC-II expression ( for acquired Immunity) and release of;

• IL-8; Acting on vascular endothelium to increase the expression of Adhesion molecules, more specifically the Adressins that bind to L-Selectins on WBCs, bringing more PNLs into the affected tissues, which are the first cells to arrive at the scene of events.
  

• IL-1; VD. And increase in vascular permeability. ALSO, goes to hypothalamus, causing elevation of Basal Body Temperature, by accelerating metabolic processes sympathetically, thus FEVER.
  

• IL-12; Stimulation of NK-cells for their KARs and KIRs.
  

• IL-6; Causes elevation of Acute Phase Reactants of the liver, and minor role in Fever production.

2. Soluble Element: Complement. MEANWHILE, both soluble agents as Defensins and Integrins, along with Complement system become active. Complement becomes active via Alternative pathway, due to pre-activation of BradyKinin and Kallikrin of C3 into C3b. Also activation occurs via Mannan-Binding Lectin, where Mannose-containing Glycoproteins of the organisms become bound to the Mannan-Binding Lectin (MBL), and the complex in turn activates MBL-Activated Serine Protease (MASP). The MBL-MASP complex catalyses C4 into C4b --> C4b2b --> C4b2b3b --> C5b. Complement acts via the;

• Formation of Membrane Attack Complex. The C5b causes addition of C6, C7, C8 and multiple C9.s that form pores within the cell wall --> ion influx. BAD for the organism!
  

• C3b the Opsonin. Binding to C3b and C5b to the organism allows The Microbe-C3b complex to become attached to C3b receptors found on the Phagocytes, entitled Opsonisation, easing Phagocytosis. Opsonisation occurs also via Antibodies' Fc portions.
  

• Anaphylatoxins (C3a, C4a and C5a) that both cause chemotaxis via Adhesion molecules expression and Indirect Increase of vascular permeability through acting on Mast cells and Basophils to release PGs, LTs and Histamine.

3. Innate Immunity secondary to Adaptive Immunity activity. Once the TCR receives the messages from the Phagocytes, and in turn activates B-Cells into IgM-secreting Plasma Cells. The antibodies produced can then enhance activation of phagocytes via two distinct mechanisms;

• Ag.-Ab. Complex can bind through the Fc portion of the Antibody to Fc receptors on Phagocytes, enhancing opsonisation. This Process is actually the main mechanism by which the antibodies work. Opsonization hastens phagocytosis by x4000 folds.
  

• Again, the complex initiates the Classical Pathway of Complement activation, with Fc portion undergoing conformational changes to accommodate C1q on CH2 domain --> C1qr --> C1qrs that joins the same path of MBL by going C4 into C4b --> C4b2b --> C4b2b3b --> C5b.