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57 Cards in this Set

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The complement is aka what?
Acute-Phase Proteins
In which are of the immunity system would you place the complement system into?
It is involved in both innate and acquired immunity (humoral).
Who coined the term 'Acute-Phase Proteins'?
Paul Erlich--("the activity of the blood serum that completes the action of the antibodies").
Complement consists of more than 30 what?
It consist of more than 30 soluble and cell-bound proteins.
After complement is activated what occurs?
After activation, various components interact in a highly regulated cascade of events.
How does complement exist when inactive? Why?
It exist in plasma as inactive forms until it is activated. Otherwise you would feel sick.
4 Functions of the complement cascade?
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.
What is opsonization?
The process of coating bacteria to promote phagocytosis. (makes bacteria "tasty")
What is complement synthesized by?
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)
What percentage of the serum globulin is made up of complement?
5%
How does most complement circulate?
As inactive form. Called Zymogens (proenzymes).
How is complement designated?
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.
How are the peptide fragments of complement proteins designated?
By small letters.
List the 3 pathways of the complement activation pathway?
1. Classical

2. Alternative

3. Lectin
What do all the pathways form (converge)?
They all form C5b. (All have different starting steps though)
What does the final steps of the complement activation pathway form?
MAC (Membrane Activation Complex)
In the Complement activation pathway, what are already in the plasma in an inactive form?
C1, C2, C3, and C4
The Classical pathway is initiated by what?
Initiated by Ag-Ab soluble complexes of by bacterial cell walls.
In what arm of the immunity system does the classical pathway belong to?
The acquired arm.
The classical pathway can be activated by what?
IgM, IgG1, IgG2, IgG3 (NOT IgG4)
C1 is a ? ?.
C1 is a macromolecular complex. C1qr2s2
List the steps of the classical pathway beginning with C1 to C4b2a.
1. C1 activates C4

2. C4b activates C2

3. C4b adn C2a combine to give C4b2a (which is aka C3 convertase)
C3 convertase activates what? How.
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.
What is common to all 3 pathways?
C5
What is C5 convertase aka?
C4b2a3b
What does C5 convertase activate?
C5. It removes C5a from the cascade and leaves C5b.
List the sequence from where all the paths converge until the MAC is formed?
C5 to C6 to C7 to C8 to C9 to MAC complex
What is the MAC complex essentially and what does it do?
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.
What is not required by the Alternative pathway? What does this indicate?
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.
The alternative pathway requires what for initiation?
Microbial surfaces. It needs cell surface constituents that are foreign to the host.
How is an Ag-Ab complex involved in the alternative pathway?
The pathway is not triggered by the binding of it but it may recognize it if it is already formed.
List 8 pathogenic indicators of the alternative pathway?
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)
Name 6 nonpathogenic initiators of the alternative pathway of the complement system?
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)
4 key features of the alternative pathway?
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
What are lectins?
Proteins that bind carbohydrates.
The lectin pathway does not depend upon what? What does this indicate?
Does not depend on Ab pathway. This indicates that it is part of the innate immune system.
When does the Lectin pathway start to be identical with the classical pathway?
After the activation of C4. So it is only different up until it reaches C4.
What is the Lectin pathway activated by?
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
The formation of MAC involves what?
C5b, C6, C7, C8, and C9 which interact to form a macromolecule.
Once formed what does the MAC do?
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".
What can MAC lyse? Explain.
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)
What does the MAC do to viruses?
"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.
Give 3 examples of viruses that MACs will attack?
1. herpesvirus

2. orthomyxoviruses (measles, mumps)

3. paramyxoviruses (flu)

4. retroviruses
What complement products mediate the degranulation of eosinophils?
C3a and C5a
What complement products mediate the aggregation of platelets?
C3a and C5a
People with C1 and C4 deficiencies tend to suffer from what?
Tend to suffer from rheumatologic and vascular-collagen diseases.
C3 deficiencies lead to what?
They lead to a profound susceptibility to bacterial infections.
C2 deficiencies lead are associated with what?
They are associated with chronic nuetropenia.
What is PNH aka?
Paroxymal Nocturnal Hematouria
What is PNH caused by?
A decreased number of CD50 and CD59.
PNH inflicts what ratio of the population?
1 : 100,000
What indicates the presence of PNH?
Blood in the urine. Caused by lysed product. Produces dark orange color.
Life expectancy after onset of PNH?
10-15 years
What is the immune system doing in PNH?
It attacks RBCs.
Cilaris was developed to fight PNH. What was it derived from?
Derived from a single clone of an Ab for this disorder. (Prior to this it was treated with Prednisone)
What is the problem with Cilaris and the way that it txs PNH?
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.
What are the side effects of Cilaris?
The side effects are common to all immune drugs and they include : headaches, vomiting, nausea, diarrhea, flu-like symptoms, and joint aches.