Immunology (Test 1) Lecture 5: The Complement System

Front 1

The complement is aka what?

Back 1

Acute-Phase Proteins

Front 2

In which are of the immunity system would you place the complement system into?

Back 2

It is involved in both innate and acquired immunity (humoral).

Front 3

Who coined the term 'Acute-Phase Proteins'?

Back 3

Paul Erlich--("the activity of the blood serum that completes the action of the antibodies").

Front 4

Complement consists of more than 30 what?

Back 4

It consist of more than 30 soluble and cell-bound proteins.

Front 5

After complement is activated what occurs?

Back 5

After activation, various components interact in a highly regulated cascade of events.

Front 6

How does complement exist when inactive? Why?

Back 6

It exist in plasma as inactive forms until it is activated. Otherwise you would feel sick.

Front 7

4 Functions of the complement cascade?

Back 7

1. Lysis of cell, bacteria and virus

2. Opsonization to promote phagocytosis of Ag

3. Activation of the Inflammatory response by it's ability to bind, trigger and secrete immunoregulatory molecules by causing degranulation and release

4. Clearance from the circulation. Which occurs in the liver and spleen.

Front 8

What is opsonization?

Back 8

The process of coating bacteria to promote phagocytosis. (makes bacteria "tasty")

Front 9

What is complement synthesized by?

Back 9

Mainly by the liver's hepatocytes. There are some other minor sources of complement proteins also, like monocytes, macrophages, and epithelial cells. (remember that hepatocytes make most of the globulins)

Front 10

What percentage of the serum globulin is made up of complement?

Back 10

5%

Front 11

How does most complement circulate?

Back 11

As inactive form. Called Zymogens (proenzymes).

Front 12

How is complement designated?

Back 12

Designated by numerals (C1-C9), by letters (factor D) or by trivial names. However, these names have nothing to do with their position in the cascade, it is just the order in which they were discovered.

Front 13

How are the peptide fragments of complement proteins designated?

Back 13

By small letters.

Front 14

List the 3 pathways of the complement activation pathway?

Back 14

1. Classical

2. Alternative

3. Lectin

Front 15

What do all the pathways form (converge)?

Back 15

They all form C5b. (All have different starting steps though)

Front 16

What does the final steps of the complement activation pathway form?

Back 16

MAC (Membrane Activation Complex)

Front 17

In the Complement activation pathway, what are already in the plasma in an inactive form?

Back 17

C1, C2, C3, and C4

Front 18

The Classical pathway is initiated by what?

Back 18

Initiated by Ag-Ab soluble complexes of by bacterial cell walls.

Front 19

In what arm of the immunity system does the classical pathway belong to?

Back 19

The acquired arm.

Front 20

The classical pathway can be activated by what?

Back 20

IgM, IgG1, IgG2, IgG3 (NOT IgG4)

Front 21

C1 is a ? ?.

Back 21

C1 is a macromolecular complex. C1qr2s2

Front 22

List the steps of the classical pathway beginning with C1 to C4b2a.

Back 22

1. C1 activates C4

2. C4b activates C2

3. C4b adn C2a combine to give C4b2a (which is aka C3 convertase)

Front 23

C3 convertase activates what? How.

Back 23

It is aka C4b2a. It cleaves it in an AMPLIFICATION step which ACTIVATES C3 (removes a piece of C3a) leaving C3b. Some C3b binds C5 convertase, some coats immune complexes, adn some binds directly to cell membranes.

Front 24

What is common to all 3 pathways?

Back 24

C5

Front 25

What is C5 convertase aka?

Back 25

C4b2a3b

Front 26

What does C5 convertase activate?

Back 26

C5. It removes C5a from the cascade and leaves C5b.

Front 27

List the sequence from where all the paths converge until the MAC is formed?

Back 27

C5 to C6 to C7 to C8 to C9 to MAC complex

Front 28

What is the MAC complex essentially and what does it do?

Back 28

It is a big polypeptide and it forms pores where fluid can enter into cells and change the tonicity causing it to swell and burst.

Front 29

What is not required by the Alternative pathway? What does this indicate?

Back 29

Ab-Ag complexes are not required. This indicates that it is part of innate immunity. It generates bound C5b indepent of the presence of Ab.

Front 30

The alternative pathway requires what for initiation?

Back 30

Microbial surfaces. It needs cell surface constituents that are foreign to the host.

Front 31

How is an Ag-Ab complex involved in the alternative pathway?

Back 31

The pathway is not triggered by the binding of it but it may recognize it if it is already formed.

Front 32

List 8 pathogenic indicators of the alternative pathway?

Back 32

1. Many strains of gram-negative bacteria

2. Lipopolysaccharides from gram-negative bacteria

3. many strains of gram-positive bacteria

4. Teichoic acid from gram-positive cell walls

5. Fungal and yeast cell walls (zymosan)

6. Some viruses and virus-infected cells

7. Some tumor cells (Raji)

8. Parasites (trypanosomes)

Front 33

Name 6 nonpathogenic initiators of the alternative pathway of the complement system?

Back 33

1. Human IgA, IgG, and IgE in complexes

2. Rabbit and guinea pig IgG in complexes

3. Cobra venom factor

4. Heterologous erythrocytes (rabbit, mouse, chicken)

5. Anionic polymers (dextran, sulfate)

6. Pure carbohydrates (agarose, insulin)

Front 34

4 key features of the alternative pathway?

Back 34

1. Path is started by C3 which gives factor B which leads to factor D which leads to properdin (Factor B, D, and Properdin are only found in this path)

2. Initiated by cell surface constituents that are foriegn to the host (bacterial cell walls have low levels of sialic acid)

3. Properdin is important for stability of pathway.

4. Makes it possible to arrive at MAC in fewer steps

Front 35

What are lectins?

Back 35

Proteins that bind carbohydrates.

Front 36

The lectin pathway does not depend upon what? What does this indicate?

Back 36

Does not depend on Ab pathway. This indicates that it is part of the innate immune system.

Front 37

When does the Lectin pathway start to be identical with the classical pathway?

Back 37

After the activation of C4. So it is only different up until it reaches C4.

Front 38

What is the Lectin pathway activated by?

Back 38

Activated by the binding of mannose-binding lectin (MBL, an acute phase protein) found on the surface of microorganisms. (pathogens, such as salmonella, listeria, Candida albicanes (fungus that causes thrush), RSV (respiratory synsytial virus in infants), and HIV-1

Front 39

The formation of MAC involves what?

Back 39

C5b, C6, C7, C8, and C9 which interact to form a macromolecule.

Front 40

Once formed what does the MAC do?

Back 40

It displaces membrane phospholipids and forms a large transmembrane channel. So it disrupts the target cell membrane and enable ions and small molecules to diffuse and "sinks the ship".

Front 41

What can MAC lyse? Explain.

Back 41

Gram-negative bacteria like E.coli and salmonella. They are not able to lyse gram-positive because they have thick peptidoglycan coats.
(However it does have trouble with gram-negative gonorrhea)

Front 42

What does the MAC do to viruses?

Back 42

"It puts a hole in them.". Remember that the viral envelope is derived from our own plasma membranes and are very susceptible to holes being formed.

Front 43

Give 3 examples of viruses that MACs will attack?

Back 43

1. herpesvirus

2. orthomyxoviruses (measles, mumps)

3. paramyxoviruses (flu)

4. retroviruses

Front 44

What complement products mediate the degranulation of eosinophils?

Back 44

C3a and C5a

Front 45

What complement products mediate the aggregation of platelets?

Back 45

C3a and C5a

Front 46

People with C1 and C4 deficiencies tend to suffer from what?

Back 46

Tend to suffer from rheumatologic and vascular-collagen diseases.

Front 47

C3 deficiencies lead to what?

Back 47

They lead to a profound susceptibility to bacterial infections.

Front 48

C2 deficiencies lead are associated with what?

Back 48

They are associated with chronic nuetropenia.

Front 49

What is PNH aka?

Back 49

Paroxymal Nocturnal Hematouria

Front 50

What is PNH caused by?

Back 50

A decreased number of CD50 and CD59.

Front 51

PNH inflicts what ratio of the population?

Back 51

1 : 100,000

Front 52

What indicates the presence of PNH?

Back 52

Blood in the urine. Caused by lysed product. Produces dark orange color.

Front 53

Life expectancy after onset of PNH?

Back 53

10-15 years

Front 54

What is the immune system doing in PNH?

Back 54

It attacks RBCs.

Front 55

Cilaris was developed to fight PNH. What was it derived from?

Back 55

Derived from a single clone of an Ab for this disorder. (Prior to this it was treated with Prednisone)

Front 56

What is the problem with Cilaris and the way that it txs PNH?

Back 56

It is directed against C5. It binds it up so that RBCs can not be destroyed. However, C5 being disabled also prevents it from forming MAC complexes so you are also impairing your immune system.

Front 57

What are the side effects of Cilaris?

Back 57

The side effects are common to all immune drugs and they include : headaches, vomiting, nausea, diarrhea, flu-like symptoms, and joint aches.