CIS 1 Flashcards
How do we activate the classical pathway of the compliment system?
Ab-Ag complexes
How do we activate the alternative pathway of the compliment system?
- Immunogically, when antibodies that can’t interact with Clq in their native form aggregate.
- Non-immunologically via lipopolysacharides of gram (-) bacteria, teichoic acids of gram (+) bacteria or zymosan from yeast cell walls.
What is the main purpose of the compliment system?
- Defects againsts infects (via opsinization, chemotaxis and activation of leukocytes, and lysis)
- Connects the innate and adaptive immune systems
- Disposes wastes (clears immune complexes and dead cells)
Can our compliment system cause damage, if uncrontrolled?
Even it is properly regulated and activated, it can, especially in people with immune complex diseases.
Deposition of antigen-ab complexes in the glomeruli and blood vessel walls can cause
- Glomerulonephritis
- Systemic vasculitis
When the ab in these complexes activate the compliment system, it can lead to acute inflammatory respones that fuck up the walls –> thrombosis, ischemic damage and scarring.
Deficiencies in compliment proteins are mostly due to
genetic mutations
Defects in classical pathway are assx with
Lupus
Glomerulonephritis
Pyogenic infections
Vaculitis
Defects in alternative pathway are assx with
Pyrogenic infections
Defects in MAC are assx with
Neiseria infections
Lupus
Glomerulonephritis
C3 deficiencies
- loss of opsinon
- cannot activate MAC
C3
Properidin
MAC proteins
cannot form MAC
C1 inhibitor deficiency
cannot regulate C1 and failure to activate kallikrein
CD59 deficneicny
CC59 restricts the formation of the MAC Complex
A defiency causes a failure to restrict the formation of MAC complexes on autologous cells
FH and FI deficiency
cannot avtivate C3; severe secondary C3 deficiency
Increases susceptibility to haemophilus influenza and streptococcus pneumania occurs in patients that have defects in what?
- Ab production
- Compliment proteins in the classical pathway
- Complement receptors on phagocytes
What is the normal pathway of defense against pyogenic bacteria?
- Opsinization with antibody
–>2. MAC formation
- Phagocytosis
What are the most important opsonin to protect us against bacteria?
C3b and iC3b
Neisseria meningitis
-Caused by defects in components of MAC complex, which we need to form lytic pore in the bacteria. People without the MAC complex have 10k fold-increase of getting the infection
Thus, we would have to kill via extracellular lysis
What is hereditary angiodema (HAE)
A deficiency in C1 inhibitor, causing attacks of skin and mucosal edema
PAROXYSMAL NOCTURNAL HEMOGLOBINURIA
a complement- mediated intravascular hemolysis caused by deficiencies in DAG
C1 Inhibitor deficiency can be
- inherited (hereditary angioedema)
- Acquired (acquired angioedema AAE)
Both lead to recurrent agioedema when the larynx is involved
Acquired C1 IN deficiency is due to what?
an accelerated consumption of C1 Inhibitor due to
- autoantibodies that bind C1-Inh and activate it.
- diseases that use C1-inhibitors with other mechanisms
How do we treat HAE?
Treating is hard because it is usually misdiagnosed as an allergic reaction. It unrecognized, it can kill you.
Prophylatic treatement is based on attenuated androgens in HAE and anti-fibrinolytic agents in AAE
Laryngeal and abdominal attacks are treated with ______
How do we treat if we have auto-antibody mediated AAE?
C1 inhibitor plasma concentrate
We would need HIGH doses,depending on the rate of C1 inhibitor consumption
main function of C1 INHIBITOR
inhibition of spontaneous activation of the complement system. C1‐inhibitor irreversibly binds to and inactivates C1r and C1s proteases in the classical pathway
and MASP‐1 and MASP‐2 proteases in the lectin pathway.
What happens without C1 inhiibitor
Spontaneous and uncontrolled activation of C1 forms C3 convertase, producing C4a, but not C3a or C5a
C4a will then cause histamine to be released from mast cells–> edema
Paroxysmal nocturnal hemoglobinuria is an example of the consequences of the FAILURE to regulate _____
formation of the MAC complex.
Paroxysmal nocturnal hemoglobinuria
Somatic mutations cause a deficiency in glycosylphosphatidylinositol, a lipid tail that anchors proteins to the membrane
Two compliment molecules, DAF and CD59 are usually anchored to the tail.
Thus, we do not express these on the surface.
CD59 (membrane inhibitor of reactive lysis) restrics the formation of the MAC complex.
What causes intravascular hemolysis that we see in patients with PNH?
Deficiency in CD59.
