Question

Leukotrienes are released by macrophages that release prostaglandins.

Histamine is released by platelets and mast cells when exposed to complement proteind C3a or C35.  

8. For each of signs, suggest a factor that might be mediating that response during inflammation:

a. hot to the touch

b. redness

Fever is an innate immune response like inflammation, however it may cause malaise, body aches and tiredness. First understand something about how the brain regulates body temperature. So be able to diagram how hypothalamus processes information from the body to keep the core body temperature at a given set point, usually around 37 degrees centigrade. Chemicals called pyrogens released by phagocytes cause the hypothalamus to use prostaglandins to raise the body temperature set point. The hypothalamus then employs the skin to help raise the body temperature by increasing metabolism through goosebumpsand shivering which require repeated muscule contractions, inhbition of sweating and constriction of blood flow to the skin to conserve heat to the core of the body. Once the pyrogens are no longer detected by the hypothalamus, the setpoint temperature returns to normal by lowering the metabolic rate and dilating blood vessels in the skin to release heat.

9. What are the advantages of fever in fighting infection? How specific is the fever response? What happens when the fever spikes?

Another important component of innate immunity are cells that perform certain functions.

a. Eosinophils can phagocytize and also have non-phagocytic means of killing foregin cells. Eosinophils may secrete antimicrobial chemicals against pathogens too large to ingest, for exmaple parasitic worms. LPS from Gram negative bacteria stimulate eosinophils to eject mitochondrial DNA which combines with proteins to form a trap that binds and kills bacteria.

b. Natural Killer cells use perforin and granzyme to kill virally infected cells and neoplasms. NK cells use cell surface markers to distinguish between healthy cellls and infected or tumor cells. There are programmed to kill other cellls unless they detect an inhibitory signal.

c. Neutrophils may use phagocytosis, or several other modes of killing to destroy foreign cells. 1. enzymes in Neutrophils cell membrane add electrons to oxygen to create superoxide radicals, or hydrogen peroxide or hypocholrite which are all antimicrobial compounds. 2. Neutrophils may synthesize NO which induces inflammation. 3. Neutrophils may use the nuclear basket to create NETS to trap microbe which are then subject to antimicrobial chemicals. Neutrophils disintergrate in the process of forming NETs.

10. In Type III Hypersensitivity circulating antibodies may bind to antigen and the Ag-Ab complexes may lodge on the epithelial surface of the inside of arteries. Complement is activated by the Classical pathway, Ag-Ab complexes. The activation of complement leads to inflammation and attracts neutrophils. H.w do neutrophils contribute to the destruction of functional tissue under these conditions? p528-529

Answer 1

Type III hypersensitivity reactions are immune-complex mediated reactions with tissue damage caused by Ag-Ab complex deposition. During these reactions, Ag binds to Ab to form immune complex which get deposited in tissues particulary epithelial surfaces of blood vessels. This deposition initiates complement cascade resulting in C3b, C5a formation.

C5a act as a chemoattractant which brings in neutrphils. C3b as an Opsonin tiggers Neutrphil to release lysosomal enzymes. Activation of complement thus helps in efficient removal of immune complexes for circulating blood.

As long as immune complexes are present in circulating blood, they are not harmful to functional cells of tissue. As immune complexes get deposited in tissue, it activates variety of mediators of inflammation, causing neutrophils and phagocytes to enter at the site of deposition. As phagocytes try to engulf immune complexes from tissue, they release toxic products, proteases and some lytic enzymes which cause damage and death of functional cells of tissue.