Lecture 9: Inflammation Flashcards
What three mediators of defense normally circulate in the blood?
- Leukocytes
- Antibodies
- Complement proteins
Name the 5 cardinal signs of inflammation
- Rubor (redness)
- Tumor (swelling)
- Calor (heat)
- Dolor (pain)
- Functio laesa (loss of function)
What are the major cell types for acute inflammation?
Leukocytes, particularly neutrophils
What are the major cell types for chronic inflammation?
Lymphocytes and macrophages
What are the three major components of acute inflammation, which have to do with blood vessels?
- Dilation of small blood vessels
- Increased permeability of small blood vessels
- Emigration of leukocytes from microcirculation
Compare transudate and exudate
Transudate has extravascular fluid with low protein and little if any cell debris; Exudate is extravascular fluid with high protein content and cellular debris
What are three major components of pus?
Exudate with…
- Neutrophils
- Dead cell debris
- Microbes
Is histamine a vasodilator or vasoconstrictor?
Vasodilator
What are the most important leukocytes, which are capable of phagocytosis and production of growth factors for repai?
Neutrophils and macrophages
What do chemokines do, in relation to inflammation?
They are cytokines with the function of leukocyte recruitment
What are cytokines?
They are “messenger molecules” of the immune system
What are the proteins called that slow leukocytes in the blood, so they can attach to areas of inflammation?
Selectins
When the leukocyte becomes firmly attached at the point of offense, what protein mediates this process?
Integrins
What are exogenous agents, which are important in chemotaxis?
Bacterial products
What are endogenous agents, which are important for chemotaxis?
Cytokines, and similar products (like arachidonic acid metabolites)
Between neutrophils and monocytes/macrophages, which occurs first (at what point after edema) and at what point does the second leukocyte replace it?
Neutrophils come first at 6-24 hours after initial edema, and then they are replaced by macrophages at 24-48 hours after initial inflammation
What increases the efficiency of phagocytosis of microbes?
Opsonization, which coats the microbes with receptors
What is alpha 1-antitrypsin deficiency?
Predisposition to emphysema and cirrhosis due to a deficiency in alpha 1 antitrypsin (which normally restricts lysosomal enzymes, which can cause tissue destruction during inflammation)
Prostaglandins are generated by the catabolism of what acid by what mediator?
They are generated by the cyclooxygenase-mediated catabolism of arachidonic acid; catabolizing this enzyme is the “blood thinning” part of aspirin
What three functions are prostaglandins important for?
- Vasodilation
- Pain
- Fever
How are leukotrienes generated?
By the lipoxygenase-mediate catabolism of arachidonic acid
What are the three functions of leukotrienes?
- Chemotaxis
- Vascular permeability
- Bronchospasm
How are lipoxins generated?
By the process of lipoxygenase-mediated catabolism of arachidonic acid
What is the main role of lipoxins?
To suppress inflammation by inhibiting leukocyte chemotaxis
Where is histamine stored?
In mast cell granules
What 3 interleukins have roles in acute inflammation?
IL-1, IL-6 and Il-17
What is a critical step in the complement system? (involves 3 components)
The proteolysis (cleavage) of C2 into C3a and C3b
What is the classical pathway of activation of the complement system?
Triggered by the fixation of C1 to antibody-antigen complex
What is the alternative pathway of activation of the complement system?
It is triggered by contact with microbial components
What is the lectin pathway of activation of the complement system?
It occurs when circulating mannose-binding lectin recognizes microbial sugars
What three important functions does C3 proteolysis lead to?
- Pro-inflammatory state (for chemotaxis, for example)
- Opsonization with C3b (leads to phagocytosis)
- Cell lysis (kills microbes with thin cell walls)
All acute inflammatory reactions will have 1 of 3 outcomes: what are they?
- Complete resolution
- Healing by CT replacement (scarring/fibrosis)
- Progression to chronic inflammation
What are the three causes of chronic inflammation?
- Persistent infection (TB)
- Prolonged exposure to toxic agents (i.e. atherosclerosis)
- Hypersensitivity disease (RA)
What does the classical macrophage pathway lead to, and what function does it lead to?
It leads to macrophages (M1) with microbicidal and pro-inflammatory effects
What does the alternative macrophage pathway lead to, including what function?
Leads to macrophages (M2) whose principle function is tissue repair
What is the major function of lymphocytes?
They are mediators of adaptive immunity
Cytokines, like IL-1, IL-6 and TNF may produce what characteristic clinical changes related to inflammation?
- Fever
- Acute-phase proteins
- Leukocytosis
What are labile tissues, with one example?
They are tissues that continuously divide, such oral mucosa
What are examples of tissues with minimal regeneration capability (i.e. stable tissues)?
Liver, kidney, pancreas
What type of macrophage is implicated in repairing tissue by connective tissue deposition?
M2
Name the three steps in scar formation
- Angiogenesis
- Formation of granulation tissue within the site of injury (TGF-Beta is an important cytokine)
- Remoderling of CT into dense fibrous scar
What 4 factors influence tissue repair?
- Infection
- Diabetes
- Nutritional status (such as Vitamin C deficiency)
- Glucocorticoids (steroids)
What will the strength of sutured wounds be compared to the normal skin?
70%
What will the strength of tissue be at time of suture removal compared to the normal skin
10% the strength of normal skin
At 3 months after a procedure, what is the strength of the site compared to the normal skin?
70-80%
