Question

1. Infections of various organ systems (urinary tract, skin, central nervous system, pulmonary system) may lead to the development of sepsis. The infections can be caused by both gram-positive and gram-negative bacteria. The sepsis is associated with the endotoxin from gram-negative bacteria and the superantigen toxins produced by gram-positive bacteria.

1. Explain how release of the endotoxin leads to development of sepsis.

2. Explain how superantigen toxins lead to development of sepsis.

3. Explain how the sepsis, if severe enough, could result in septic shock.

Answer 1

a. Sepsis is a medical condition occurs when our body shows overwhelm immune response to bacteria (bacterial infections).

Endotoxins are outer components of some gram-negative bacteria. For example lipopolysaccharide or LPS is an endotoxin. It is not soluble and has deleterious effect on the host.

LPS is a Pathogen-Associated Molecular Patterns—PAMPs which is recognized by Pattern Recognition Receptors (PRRs) present on host cells. Binding of LPS to PRRs triggers the signalling cascade and upregulates TNF-α, IL-1 and IL-6, complement and coagulation pathways. And thus lead to inflammation and other effects.

Levels of endotoxin correlate directly with severity of inflammatory mediator secretion and other cytokines and chemokines secretion. High endotoxin lead to overwhelmed immune response, causing damage to many organs.

b. Superantigens are molecules that are potent T lymphocyte mitogens and simultaneously bind to class II MHC molecules. They are secreted proteins (exotoxins) that exhibit highly potent lymphocyte-transforming (mitogenic) activity directed towards T lymphocytes. They are often associated with staphylococcal products and are involved in enterotoxemias and toxic shock syndrome in humans. Superantigens are capable of activating up to 20% of the body’s T-cells, compared to normal antigen induced T-cell response where 0.001-0.0001% of the body’s T-cells are activated. This causes a massive immune response that is not specific to any particular epitope on the superantigens. And this massive immune response lead to sepsis as described above.

c. Septic Shock is a dangerous medical condition in a patient with sepsis which could lead to death due to organ damage, metabolic abnormalities and dangerously low blood pressure. At high level of endotoxins, higher amount of cytokines, chemokines and proinflammatory mediators are produced. This cytokines triggers vasodilation and thus low blood pressure, reduced heart contraction, endothelial damage, and alveolar capillary damage, leukocytes adhesion and activation of coagulation system. All these could lead to serious physiological impairedness and dysfunction of organs.

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