Inflammation Flashcards
When can inflammation start to cause a problem?
When the reaction is very strong, it is prolonged and it is inappropriate
What part of the immune system is inflammation a part of
Innate immune system
What is characteristic of acute inflammation
Fluid and plasma protein exudation, and neutrophilic leukocyte accumulation
What is characteristic of chronic inflammation
Influx of lymphocytes and macrophages, and associated vascular proliferation and fibrosis
Outline the 4 steps of initiating an inflammatory response
- Inflammatory stimuli
- PAMPs/DAMPs recognized by PRRs
- Activation of surveillance cells
- Release of mediators
Define exudation
Increased vascular dilation and permeability
Where does exudation happen in the vasculature
In capillaries and venules (NOT arterioles)
Define exudate
Extracellular fluid collection rich in proteins and/or cells
What are the events that lead to oedema in tissues
There is an altered balance in hydrostatic and osmotic pressure which causes an increase of fluid and plasma proteins in tissues - causing oedema
List 5 general features of inflammatory mediators
- Can be found inactive or active
- Some are newly synthesized
- Can act directly or indirectly
- Many give positive feedback
- Most have short half lives
What is a principle source of newly synthesized inflammation mediators
Leukocytes
Name 5 mediators of acute inflammation and if they’re preformed or not
Histamine (P)
Serotonin (P)
Cytokines (NS)
Leukotrienes (NS)
Prostaglandins (NS)
What are the two phases of changes in vascular dilation and what cells/molecules are responsible for both
Immediate - histamine, serotonin, complement and blood clotting factors
Delayed - kinins, prostaglandins and leukotrienes
Name the cytokine:
Key role in triggering inflammation, induces cardinal signs of inflammation, prolongs and amplifies inflammation
TNF-alpha
Name the cytokine:
Responsible (with TNF-alpha) for sickness behavior, causes fever, lethargy and lack of appetite
Interleukin-1
Name the cytokine:
Produced by innate immune cells after stimulation (e.g. by PAMPs), affects both inflammation and acquired immunity, and is major mediator of the acute-phase reaction of septic shock
Interleukin-6
Serous exudate
Watery, clear, cloudy and relatively low in protein
Fibrinous exudate
Abundant in fibrinogen, observed in more severe reactions of the lungs and connective tissues
Catarrhal exudate
Cloudy, thin mucinous, associated with inflammation of mucous membranes
Suppurative/purulent exudate
Associated with bacterial infection by pyogenic organisms, characterized by large amounts of pus, usually causes an abscess but sometime diffuses and causes cellulitis
Hemorrhagic exudate
Usually in organs with a rich vascular supply
Necrotizing exudate
May be the result of ischemia, thrombosis of vasculature or acute venous congestion, often caused by the presence of necrotizing toxins produced by bacteria
What are 4 functions of exudate
- Dilute toxins
- Distribute mediators/clotting factors
- Neutralize toxins
- Drainage to lymphatics
What is the term used to describe inflammation of the lymphatic vessels
Lymphangitis
What is the term used to describe inflammation of the lymph nodes
Lymphadenitis
Which cell type has a major population in blood leukocytes
PMNs (neutrophils)
Where do leukocytes exit the vasculature during extravasation
Through veins (not arteries)
What receptor is involved in the immediate pathway of neutrophil migration and what stimulates this pathway
P selectin
Stimulated by histamine, C5a and PAF at the site of injury
What receptor is involved in the delayed pathway of neutrophil migration and what stimulates this pathway
E selectin
Stimulated by IL-1, TNF-alpha and other chemo attractants at the site of injury
Name 3 functions of neutrophils during inflammation
Phagocytosis
Liquefaction by lysosomal enzymes
Amplification of inflammation by making PGs, LTs, and PAF
Why is monocyte migration slower than neutrophils
Because MCP-1 production is relatively slow and there are way more neutrophils than monocytes
List 4 roles of macrophages in acute inflammation
- Phagocytosis
- Secrete toxic factors
- Secrete cytokines and chemokines to alert effector cells
- Secrete colony stimulating factors to promote differentiation of immature immune cells
List the 5 systemic effects of acute inflammation
Leukocytosis
Acute phase response
Induction of fever
Anemia
Septic shock
Describe the “shift to the left” of neutrophils during acute inflammation
Since the body is trying to compensate and replace neutrophils during infection, it releases them from the bone marrow before they are matured resulting in more immature neutrophils in circulation
What is the acute phase response
Increased production of several plasma proteins by the liver
Name 2 plasma proteins released during acute phase response and their function
C-reactive - bacterial clearance
Serum amyloid A - leukocyte migration
What are 3 characteristics of septic shock
Fever
Increased vascular permeability
Disseminated intravascular coagulation (DIC)
What is the difference between resolution and repair
Resolution - return to normal
Repair - formation of scar tissue
What are the 3 broad groups of resolution mediators
Lipoxins, resolvins and protectins
What are the precursors to resolvins and protectins
Fatty acids eicosapentanoic acid (only resolvins) and docosahexanoic acid
What is the precursor of lipoxins and what is an example
Arachidonic acid
ex. LXA4
When is LXA4 produced and by what
When neutrophils recognize PGE2 without an antigen present, it will product LXA4 which will stop further neutrophil recruitment and reduce vascular permeability
How are resolvins and protectins anti-inflammatory
They induce PMNs to expose their PS apoptosis markers so their removed by macrophages
Define macrophage switch
After a macrophage ingests an apoptotic PMN it will start releasing anti-inflammatory and reparative cytokines
What mediates regeneration and what produces them
Wound cytokines (TGF-beta, VEGF) - produced by macrophages
What produces a fibrous scar
Granulation tissue
What is granulation tissue
Small, red granular foci that bleed easy
Newly formed blood vessels that proliferate
Fibroblast proliferation
New connective tissue production
What is suppuration
It is pus formation from intense and prolonged neutrophil emigration that happens when pyogenic bacteria resist uptake
What are two events leading to chronic inflammation
Persistent suppuration and a foreign body response
What characterizes chronic inflammation
A progressive change of cell types present at the site of inflammation and simultaneous destruction and repair of the tissues
Name 3 common denominators of chronic inflammation
Persistent infection, autoimmune reactions and prolonged foreign body responses
Name 4 cellular mediators of chronic inflammation
T cells, B cells, Monocytes/macrophages and NK cells (mononuclear cells)
Which receptors mediate lymphocyte migration in chronic inflammation
VLA-4 (lymphocyte) and VCAM-1 (vasculature)
How do T helper cells help propagate the immune response and how are they activated
Macrophages and dendritic cells present antigens to Th cells which then become active and secrete cytokines that stimulate other cell populations (B cells, CD8 cells and macrophages)
Which chemical effector promotes lymphocyte/monocyte migration through the endothelia during chronic inflammation
IFN-gamma
What mediates a foreign body reaction
Macrophages
Define amyloidosis
A build up of abnormal protein (amyloid fibrils) in tissues
Define amyloidosis in the context of chronic inflammation
Secondary/reactive amyloidosis happens as a complication of existing chronic inflammatory disease, and involves the deposition of serum amyloid A fragments (misfolded proteins that aggregate to insoluble fibrils)
Which phase of the immune response is responsible for hypersensitivity reactions
The effector phase - late primary, chronic, or recall of the adaptive immune response
Which hypersensitivity reaction is mediated by IgE antibodies
Type I
Which hypersensitivity reaction is mediated by IgG or IgM
Type II
Which hypersensitivity reaction is mediated by Ag/Ab complexes, IgG or IgM
Type III
Which hypersensitivity reaction is mediated by antigen-specific T cells and macrophages
Type IV
What response coordinates IgE mediated hypersensitivity reactions
Th2 response (associated with alternatively activated macrophages)
Name 3 granulocytes involved in type I hypersensitivity
Eosinophils, mast cells and basophils
What specific event happens to cause immediate hypersensitivity in type I reactions
Binding of the antigen to IgE and cross-linking of FceRI receptor on mast cells
Define atopy
A predisposition to suffer IgE mediated allergic reactions
Define anaphylaxis
Generally describes instances where the allergen is distributed systemically through blood circulation, rapid onset, mild to severe, systemic histamine release
What is hypotonic shock
Reduced blood pressure - vascular consequence of anaphylaxis
List 3 events that can happen during a type II hypersensitivity reaction
- opsonization via IgG abs
- opsonization/lysis via complement (MAC)
- Antibody-dependent (IgG) cell-mediated cytotoxicity
List 2 examples of a type II hypersensitivity reaction
- Autoimmune hyperthyroidism
- Immune mediated thrombocytopenia
What happens to cause Ag/Ab complexes to persist in circulation
There is no/little cross linking of Ag/Abs so the complexes are very small and therefore not cleared by the body (complement & phagocytosis)
List 3 examples of type III hypersensitivity reactions
- Serum sickness
- Chronic obstructive pulmonary disease (COPD)
- Arthus reaction (vaccine reaction)
When does the inflammatory response typically occur in type IV hypersensitivity reactions
24-48 hours after contact (in sensitized individuals)
Which T cell response is seen in type IV hypersensitivity reactions
Th1 cell response
What do macrophages differentiate into in granulomatous inflammation
Epithelioid cells and giant cells
List 3 examples of type IV hypersensitivity reactions
- tuberculin reaction
- contact sensitivity
- granulomatous inflammation
