CIS 1

Question 1

How do we activate the classical pathway of the compliment system?

Answer 1

Ab-Ag complexes

Question 2

How do we activate the alternative pathway of the compliment system?

Answer 2

1. Immunogically, when antibodies that can’t interact with Clq in their native form aggregate.
2. Non-immunologically via lipopolysacharides of gram (-) bacteria, teichoic acids of gram (+) bacteria or zymosan from yeast cell walls.

Question 3

What is the main purpose of the compliment system?

Answer 3

1. Defects againsts infects (via opsinization, chemotaxis and activation of leukocytes, and lysis)
2. Connects the innate and adaptive immune systems
3. Disposes wastes (clears immune complexes and dead cells)

Question 4

Can our compliment system cause damage, if uncrontrolled?

Answer 4

Even it is properly regulated and activated, it can, especially in people with immune complex diseases.

Question 5

Deposition of antigen-ab complexes in the glomeruli and blood vessel walls can cause

Answer 5

1. Glomerulonephritis
2. 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.

Question 6

Deficiencies in compliment proteins are mostly due to

Answer 6

genetic mutations

Question 7

Defects in classical pathway are assx with

Answer 7

Lupus

Glomerulonephritis

Pyogenic infections

Vaculitis

Question 8

Defects in alternative pathway are assx with

Answer 8

Pyrogenic infections

Question 9

Defects in MAC are assx with

Answer 9

Neiseria infections

Lupus

Glomerulonephritis

Question 10

C3 deficiencies

Answer 10

1. loss of opsinon
2. cannot activate MAC

Question 11

C3

Properidin

MAC proteins

Answer 11

cannot form MAC

Question 12

C1 inhibitor deficiency

Answer 12

cannot regulate C1 and failure to activate kallikrein

Question 13

CD59 deficneicny

Answer 13

CC59 restricts the formation of the MAC Complex

A defiency causes a failure to restrict the formation of MAC complexes on autologous cells

Question 14

FH and FI deficiency

Answer 14

cannot avtivate C3; severe secondary C3 deficiency

Question 15

Increases susceptibility to haemophilus influenza and streptococcus pneumania occurs in patients that have defects in what?

Answer 15

1. Ab production
2. Compliment proteins in the classical pathway
3. Complement receptors on phagocytes

Question 16

What is the normal pathway of defense against pyogenic bacteria?

Answer 16

1. Opsinization with antibody

–>2. MAC formation

3. Phagocytosis

Question 17

What are the most important opsonin to protect us against bacteria?

Answer 17

C3b and iC3b

Question 18

Neisseria meningitis

Answer 18

-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

Question 19

What is hereditary angiodema (HAE)

Answer 19

A deficiency in C1 inhibitor, causing attacks of skin and mucosal edema

Question 20

PAROXYSMAL NOCTURNAL HEMOGLOBINURIA

Answer 20

a complement- mediated intravascular hemolysis caused by deficiencies in DAG

Question 21

C1 Inhibitor deficiency can be

Answer 21

1. inherited (hereditary angioedema)
2. Acquired (acquired angioedema AAE)

Both lead to recurrent agioedema when the larynx is involved

Question 22

Acquired C1 IN deficiency is due to what?

Answer 22

an accelerated consumption of C1 Inhibitor due to

1. autoantibodies that bind C1-Inh and activate it.
2. diseases that use C1-inhibitors with other mechanisms

Question 23

How do we treat HAE?

Answer 23

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

Question 24

Laryngeal and abdominal attacks are treated with ______

How do we treat if we have auto-antibody mediated AAE?

Answer 24

C1 inhibitor plasma concentrate

We would need HIGH doses,depending on the rate of C1 inhibitor consumption

Question 25

main function of C1 INHIBITOR

Answer 25

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.

Question 26

What happens without C1 inhiibitor

Answer 26

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

Question 27

Paroxysmal nocturnal hemoglobinuria is an example of the consequences of the FAILURE to regulate \_\_\_\_\_

Answer 27

formation of the MAC complex.

Question 28

Paroxysmal nocturnal hemoglobinuria

Answer 28

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.

Question 29

CD59 (membrane inhibitor of reactive lysis) restrics the formation of the MAC complex. What causes intravascular hemolysis that we see in patients with PNH?

Answer 29

Deficiency in CD59.