Complement System

December 17, 2020 | Reading Time: 3 min 14 s

Classic pathway

Antigen enters body. Antibody attaches to antigen.
C1 protein has 3 subdomains Q,R,and S. Q subdomain attach to antibody.
The order of chain is Fc of antibody - C1 - C4 - C2 - C3 - C5 - C6-9
- C2 to C5 follows Baby with Apple system
- C5b-C9 is the Membrane attack complex. C5b onwards is late events
  - MAC is effective only against Gram negative. Their absence is marked by repeated infection of Neisseria gonorrhea (Gram negative cocci).
    -C3b facilities phagocytosis by neutrophils and macrophages. It is thus an opsonin. Another opsonin is IgG which can do the same.

Antigen-antibody complexes
Antibody must be IgG or IgM (Single IgM or Double IgG)
- GM Motors makes Classical cars
IgG subclasses 1-3 will trigger classic pathway, ~~IgG4 will not~~.

Antibody production could take upto 2 weeks for a brand new antigen.
So body started accepting triggers other than antigen-antibody complexes. Lipopolysaccharides of gram negative organims (Alternate pathway) and Mannan protein of gram positive organisms also act as triggers now.

Mast cells are activated by c3a and c5a -> histamine -> vasodilation -> more inflammatory cells to scene. Thus they are anaphylotoxins.
- Major mast cell activator is IgE
C5a is a chemotactic agent for neutrophils.
C5a makes endothelial cells more adhesive to neutrophils.
Some complement can block viral entry to cells. These viruses are later attached by antibodies and opsonised.
C3b can induce B cell proliferation -> more antibodies.

Alternate pathway can also be activated by aggregated IgA complexes.

In Bergers IgA nephropathy, IgA deposits on glomerular membrane of kidney -> Compliment system triggered and attacks glomerular membrane
IgA deposit under skin and GIT mucosa seen in Dermatitis herpetiformis.
IgA deposit on multiple tissues after Viral URTI which liver failed to remove from circulation - Henoch Schonlein Purpura
- 7 yr old with viral URTI 2 wks back. Fever, abdominal cramps, rashes on lower limbs, polyarthritis, proteinuria, generalized lymphadenopathy, pericardial pain.

C1 esterase inhibitors inhibit C1 until a threshold amount of antigen is reached to avoid unncessary triggers.
C1 inhibitors deficiency
-> Compliment activation at slightest triggers
-> More C3a -> Mast cell activation -> More histamine
-> Non itchy rashes, edema and bronchoconstriction - Angioneurotic Edema. It is called neurotic because sometimes it is precipitated under anxiety.
Decay acceleration factor (CD55 and CD59) in membranes of RBC, WBC and platelets protects them against complement system by decaying C5 convetase and C3 convertase. DAF is deficient in Paroxysmal Nocturnal Hemoglobinurina resulting in lysis of RBC (Hemoglobinuria), Platelets (Venous thrombosis), and Neutrophils.
Deficiency of Early Factors (before C5, esp C3): Repeated Staphylococcus infection of sinus.
Deficiency of Late Factors (esp MAC): Repeated Neisseria infection
C2 and c4 deficiency:
-> No C3 -> No opsonisation
-> Antigen wanders in blood for more time
-> More antibodies which eventually attack our tissues –> SLE

Liver disease (Under production)
SLE (Overuse)
- If you have glomerulonephritis and low C3, it is probably SLE
ABO incompatibility
Donor RBC is considered offending antigen.
- Antibodies -> Complement -> C3
  -> Mast cell activation -> Histamine -> Shock. Bronchoconstriction.
- Free Hemoglobin filtered through kidneys damaging PCT -> AKI