1.8 Immunology of Shock
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What is septicemia?
- Life threatening bacterial infection of the blood stream
- Gr+ or Gr- bacteria
What is sepsis?
- Presence of pathogenic organisms or their toxins in the blood or other tissues
- Characterized by a systemic inflammatory response which can progress to circulatory system dysfunction, multiple organ failure, and death
What is septic shock?
Severe sepsis with hypotension despite adequate fluid resuscitation
What is toxic shock?
Subset of septic shock produced by organisms which produce super-antigens
What is anaphylatic shock?
- Type 1 hypersensitivity
- Circulatory collapse
- Respiratory difficulties
- IgE mediated
What is the microorganism most likely involved in the initiation of septic shock?
- Gr(-) endotoxin - LPS
- Gr(+) exotoxin - superantigen
- Virus - influenza, varicella
- Fungi - Candida spp
- E. Coli
- Pseudomonas aeruginosa
- Staph Aureus
- Strep pyogens and agalactiae
- And others
What is the mechanism by which endotoxins can result in the pathophysiology of shock?
- Gr- Bacteria
- Binds to CD14 and TLR
- Activates Macrophages and NK cells
- Induce synthesis of TNF-a and IL-1B
- Responsible for Septic Shock
What is the mechanism by which superantigens can result in the pathophysiology of shock?
- Gr+ Bacteria
- Bind to HLA II and TCR
- Activate macrophages and CD4+ T cells
- Induce synthesis of TNF-a, IL-1B, IL-2, and IFN-y
- Responsible for Toxic Shock Syndrome
What is the pathophysiology of anaphylactic shock, including sensitization, mast cell activation, and degranulation, and mediator activities?
- Allergen cross-links IgE on mast cells through Fce receptors
- (Cross linking causes degranulation, breakdown of Arachidonic Acid, Synthesis and secretion of cytokines)
- Mediators released
- Bronchoconstirction, mucus secretion, diminished cardiac contractility, increased vascular permeability, vasoconstriction of arteries
What do endotoxins bind to?
CD14 and TLR
What does Endotoxins (LPS) activate?
Macrophages and NK cells
What does Endotoxin (LPS) induce synthesis of?
TNF-a and IL-1B
What is Endotoxin (LPS) responsible of causing?
What type of bacteria produces Endotoxin (LPS)?
Gr (-) Bacteria
What type of bacteria produces Superantigen (Exotoxin)?
Gr (+) Bacteria
What does Superantigens bind to and is it at the antigen binding site?
What does Superantigens (Exotoxin) activate?
Macrophages and CD4+ T Cells
What does Superantigen (Exotoxin) induce synthesis of?
TNF-a, IL-1B, IL-2, and IFN-y
What is Superantigen (Exotoxin) responsible of causing?
Toxic Shock Syndrome
What diseases are Superantigens implicated in?
- Food Poisoning
- Erythematous skin reaction
- Toxic Shock Syndrome
What does Superantigens cross link with?
MHC II and TCR V-B regions
Are superantigens processed by APC?
What do activated APC and T cells release and what do they affect?
- Release inflammatory cytokines and other mediators
- Affects endothelial cells
Who are most susceptible to sepsis?
- Individuals w/ compromised immune response
- Organ transplant recipients
- Patients w/ long term vascular access
What does Nitric Oxide do?
What does Leukotrienes and Prostaglandins do?
What does Bradykinin do?
Increase capillary permeability
What does disseminated intravascular coagulation do?
Formation of clots
Where are Cardiac Mast Cells found and what receptors do they possess and what binds to them?
- Present in and around cardiac vessels
- Has Fce receptors which bind IgE
What can degranulate Cardiac Mast Cells?
- Antigen and other stimuli
- C3a and C5a, substance P, eosinophilic cationic proteins
- Muscle relaxants, contrast media
What do histamine bind to on vascular smooth muscle and what is the effect?
- H1 Receptors
- Rapid decrease in mean aortic pressure
- Increase in coronary blood flow
What do histamine bind to on cardiac tissue and what is the effect?
- H2 Receptors
- Induces arrhythmias and AV conduction blocks
- Induces tissue factor which activates factor X leading to formation of thrombi
What does histamine induce release of and what are the effects?
What are CV effects of eicosanoids (Leukotrienes, Prosteoglycans)?
- Induce increased coronary vascular resistance
- Decreases contractile function
What are CV effects of platelet activation factor (PAF)?
- Decreases coronary blood flow
- Depresses myocardial contractility
- Recruits neutrophils and eosinophils
- Activates platelets
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