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Inflammation, Ab & Complement
Dr. Gregory's fifth lecture for Spring Exam #1
12
Medical
Professional
01/29/2009

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Term
Acute Inflammatory Responses
Definition

Fast proceeding

 Painful

Fever

Influx of PMNs (mostly neutrophils)

Purulence (formation of pus)

CRP is induced

Term
Chronic Inflammatory Responses
Definition

Major influx of T cells (primarily TH2--antibody response) and plasma cells

Sites contain complex mix of TH2 cells, plasma cells, monocytes, macrophages, eoxinophils, neutrophils, basophils and mast cells

Depending on major cell type present, may have IgE-mediated response (through mast cells) or complement-mediated tissue destruction (primarily through neutrophils with macrophage involvement)

Term
Complement System Pathways
Definition

Classical pathway - participates in specific immune defense system (demands antigen-antibody interaction)

Alternative pathway - participates primarily in the innate nonspecific defense system

Mannose lectin pathway - binds to mannose on pathogens

Term
Classical Pathway
Definition
  1. Immunoglobulin (1 IgM [pentomer] or 2 or more IgG - IgG1, IgG2 or IgG3) binds to antigenic epitopes on microbial surface
  2. C1 binds to the Fc regions of immunoglobulins
  3. C1 cleave C4 into C4a and C4b; C4a floats away, C4b remains bound to microbial surface
  4. C1,4b complex cleaves C2 into C2a and C2b; C2a floats away, C2b remains bound to microbial surface
  5. C4b,2b complex (C3 convertase) cleaves C3 into C3a and C3b; C3a floats away, C3b remains bound to microbial surface
  6. C4b,2b,3b (C5 convertase) cleave C5 into C5a and C5b; C5a floats away, C5b remains bound to microbial surface
  7. C6 and C7 bind to C5b forming a complex
  8. C8 binds to the C5b,6,7 complex and inserts into the cell membrane
  9. C9 binds to the membrane bound C5b,6,7,8 complex
  10. 10-16 molecules of C9 bind to form a pore in the membrane
  11. Water will enter the microbial cell, enlarging and engoring the cell → the cell will explode
Term
Alternative Complement Pathway
Definition
  1. Spontaneous cleavage of C3 into C3a and C3b by proteiolytic enzymes found in the blood
  2. C3b bind to carbohydrates on the surface of microorganisms
  3. Factor B binds to C3b
  4. Factor D cleaves Factor B into Ba and Bb; Ba floats away, Bb remains bound to the microbial surface
  5. Properdin stabilizes this complex
  6. Additonal C3b's attach to this complex (C5 convertase)
  7. C3b,Bb,C3bn (C5 convertase) cleave C5 into C5a and C5b; C5a floats away, C5b remains bound to microbial surface
  8. C6 and C7 bind to C5b forming a complex
  9. C8 binds to the C5b,6,7 complex and inserts into the cell membrane
  10. C9 binds to the membrane bound C5b,6,7,8 complex
  11. 10-16 molecules of C9 bind to form a pore in the membrane
  12. Water will enter the microbial cell, enlarging and engoring the cell → the cell will explode
Term
C3a and C5a (Important Mediators of Inflammation)
Definition
[image]
Term
C4a and C2a (Biological Activities)
Definition

C4a: anaphylatoxin less potent than C5a and C3a (degranulation of mast cells, increased vascular permeability)

C2a: converted to C2 kinin, which regulates blood pressure by causing blood vessels to dialate and induces pain related to bradykinin

Term
Common Chemotactic Factors
Definition

C5a

Formyl-methonin derivatives on bacterial proteins

Term
Killing of Bacteria by Neutrophils
Definition
Respiratory Burst - conversion of O2 into oxygen radicals → damages sulfhydryl groups on surface of bacterial cell destroying the activity of those enzymes AND punches holes in bacterial cell membrane (=cell death)
Term
Three Major Effects of Complement System
Definition

Lysis = MAC formed through completion of classic and alternative pathways

Activation of Immune System = release of C3a and C5a recruiting neutrophils to the site of infection

Opsonization = C3 or C3b binds directly to bacterial cell as a marker for phagocytic cells (have C3 and C3b receptors)

Term
Idiotypic Network Theory
Definition

Antigen ingected into an animal → animal produces antibody (Ab1) to the antigen → Ab1 is injected into a second animal → second animal produces and antibody to Ab1 (Ab2)

Way to develop vaccines

Term
ABO Blood Typing
Definition

Type A → A antigen and anti-B antibody (30-40%)

Type B → B antigen and anti-A antibody (10-15%)

Type AB → A and B antigens and neither antibody (<5%)

Type O → neither antigen and both anti-A and anti-B antibodies (45%)

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