MIDTERM - complement system Flashcards by CHARLENE SAN JOSE

_ is a complex series of more than 30 soluble
and cell-bound proteins that interact in a very specific way
to enhance host defense mechanisms against foreign cells.

complement

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complement is a complex series of more than how many soluble and cell bound proteins?

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Complement systems is also called __.

complement pathway.

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are complement proteins heat-labile or not?

heat labile

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A termed “Complement” was given by ___ in the year (1980’s

Paul Erlich

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In year, she was awarded a Noble Prize for
elucidating the nature of complement.

1919, Jules Bordet

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In elucidating the nature of complement it was
___

jules bordet

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what are the 3 effects of complement activation

Activation of immune system
Opsonization (C3b, C4b, C5b)
LYSIS of Foreign cells and Immune complexes

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what are the 3 example of opsonins

(C3b, C4b, C5b)

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What are the complement proteins that are mainly incorporated with the process of opsonization?

(C3b, C4b, C5b)

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an effect of complement activation that is to
ENHANCE the host mechanism against the
foreign cells

Activation of immune system

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an effect of complement activation that is for
facilitating and preparing the cell eating.

Opsonization (C3b, C4b, C5b)

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Chronic activation of complement pathway will lead to

inflammation and tissue damage

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Complement pathway play an essential role as a ____.
That’s why the complement pathway is connected also with the acute phase reactants,

pro-inflammatory agent

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acute phase reactants or APR or toll like receptors are produced by

hepatocytes

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acute phase reactants are produced within how many hours in response to an increase in certain intracellular signaling polypeptides

12-24 hrs

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hepatocytess are also called as

liver cell or liver parenchymal cells

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it is the one that regulates the amount or the production of apr. It will give signal or serve as a chemical messenger

cytokines

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what are the 2 major apr?

Serum Amyloid A and C reactive protein

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what is the function of C reactive protein

opsonization and for complement activation,

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what is the function of Serum amyloid A

removal of cholesterol.

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what is the most important component or protein complement under the activation unit?

Complement C3

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the point where all pathways meet.

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is associated with a
specific pathway which is the lectin pathway

mannose binding protein

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where can we be able to find mannose?

within the outer coating of bacteria, yeast, viruses and even protozoa.

Most plasma complement proteins are synthesized in the __-.

liver

Most plasma complement proteins are synthesized in the liver except __

C1 components

C1 is synthesized by epithelial cells and factor D. Whereas Factor D is made up of ___

adipose tissue

C1 is synthesized and produced by the ____

epithelial cells and factor D

Example of additional source of early complement components ___

C1, C2, C3 and C4.

the common objective associated with complement activation, it is the end product of activation of complement activation

lysis of the foreign cells and immune complexes

2 factors contributing the end product of the complement pathway

lysis of the foreign cells and immune complexes

the one responsible for controlling or inhibiting a particular complement protein preventing chronic activation

complement component protein regulators

response time of c reactive protein for opsonization and complement activation

6-10 hrs

a generalized marker of acute inflammation

C reactive protein

complement component proteins are like enzymes as they are produced in what form?

inactive form or zymogen

They are release in inactive precursors of complement proteins are called __.

zymogen

once the zymogen are released and activated it will be called as

holoenzyme

The complement system can be activated in three different ways. What are those?

Classical pathway alternative or properdin pathway Mannose-binding lectin pathway

a complement pathway that is antibody dependent

classical pathway

How many proteins are involved in classical pathway?

9 proteins

The 9 proteins in classical pathway is triggered by what combination

antigen and antibody combination/formation

In the year 1950s, ___ discovered an antibody-independent pathway and this plays a major role as a natural defense system.

Pillemer and colleagues

alternative pathway is also called as

properdin system

function of properdin in alternative pathway

stabilize the key enzyme complex called C3bBb (or C3 convertase)

lectin pathway's major constituent

mannose

If lectin's major constituent is MBL, where can we seen the constituent of alternative pathway?

serum constituent

lectin pathway is also called as

mannose-binding lectin pathway

In lectin pathway, it is the ___ that will adhere to mannose which found in the outer coating of the bacteria, yeast, viruses and protozoa

MBL mannose binding lectin or the mannose binding protein

Under the classical pathway it is always involved with what complement component

Complement component C1

C1 is composed of ___ how many strands

6 strands

6 strands of C1 complement will form _

6 globular head with a collagen-like tail portion

what are the 3 sub units of C1

C1q, C1r and C1s.

A subunit of C1 that will recognized/binds the fragment crystallizable or FC region or FC fragments of two adjacent antibody molecules.

C1q

how many globular heads are needed for C1q to initiate classical pathway

2 globular heads

the first one that act upon the activation of classical pathway

C1q

complement components found in alternative pathway

factor B factor D properdin

c3 convertase is also called as

C3bBb

aside from the mannose that is the major constituent of mannose binding lectin pathway. It is as well associated with different serine proteases?

MASP 1, MASP 2 and MASP 3

what are the 2 antibody INDEPENDENT pathway?

alternative and mannose-binding lectin pathway

the 2 pathway that is part of natural defense system

alternative and mbl pathway

the antibody that is best for complement fixation

antibody IgM

can IgG can help in complement fixation as well?

yesw

which IgG is the one that has no capability for complement fixation?

IgG4

which IgG is the best for complement fixation

IgG3 followed by IgG1 and IgG2

if IgG is the one that will help in complement fixation, how many IgG is needed to attach to an antigen to activate the complement?

2 IgG molecule

IgG needs 2 IgG molecules in order to activate the complement pathway, the attachment of antigen as well must be within how many nanometers between each other to activate it fully?

30-40 nanometers

what are the stages of complement activation for classical pathway?

Recognition stage or recognition unit Activation stage or activation unit Formation of MAC - membrane attack complex

what is the only complement component associated with the recognition unit of classical pathway?

complement component C1

C4, C2 and C3 is collectively known as

activation stage or the activation unit

the last stage of classical pathway wherein the lysis of the foreign cell take place

formation of MAC

"MAC" in stages of classical pathway activation stands for __

membrane attack complex

what is the end product of the 3 stages of classical pathway activation?

lysis of the foreign cell and immune complexes

the stage or unit where we can see the C1 components

Recognition unt/stage

what are the 3 components of C1/what are the 3 subunits of C1

C1q, C1r, C1s

is composed of six strands that form six globular heads with a collagen like tail portion.

C1q

a sub unit of C1 that will “recognizes” the fragment crystallizable (FC) region of two adjacent antibody molecules.

C1q

what are the 2 adjacent antibodies that the C1q will recognize?

CH2 of IgG and CH3 of IgM

Once the C1q bonds with the fc region of the adjacent antibodies, it will activate ___

C1r

C1r will start to cleave ___

thioester bond of C1s

once the C1r cleave the thioester bond of C1s, it will then activate ___

C1s

Please summarized the steps for recognition stage/unit

It will start with the C1q. It will bind with the FC region of the adjacent antibodies (IgG and IgM) The bonding will activate C1r C1r will cleave the thioester bond of C1s It will activate the C1s

what is the end stage of the last step of recognition unit?

the activation of C1s

what is the last stage of the end product of the activation unit?

c5 convertase or the C5b2a3b

after the activation of the C1s, it will form __ and __ that must be near the proximity of C1s in order to form.

C4 and C2

C4 must be near enough to C1s of about how many nanometers?

atleast 40 nm

C2 must be near enough to C1s of about how many nanometers?

at least 60 nm

what is the most abundant complement protein under the activation unit?

C1s will cleave C4 to form ___

C4a and C4b

C4b must bind to __ or __ immediately or it will react with water molecules or it will be inactivated permanently

protein or carbohydrates

C4b must bind to protein or carbohydrate within a few seconds, or it will react with water molecules to form ____ , which is rapidly degraded.

iC4b (inactivated C4b)

C2 gene is closely related to ___ in alternative pathway

factor B

C4b and C2a will combine through what ions

magnesium ions

the combination of C4b and C2a is also called as

C3 convertase (C4b2a)

is the c3 convertase a stable complex?

what is the half life of c3 convertase

15 seconds to 3 minutes

the c4b2a will cleave the most important complex in the activation unit

most significant step in the entire process of complement activation

cleavage of C3

Major function is for the formation of the MAC.

C3b

aside from the formation of MAC, the other function of C3b is it act as ___

opsonin

In C3b, ___ have specific receptors for this complement. Thus, enhance phagocytosis.

Macrophages

C3b will bound to C4b2a for how many nanometers?

40 nm

If C3b is bound within 40 nm of the C4b2a, then this creates a new enzyme known as____

C5 convertase.

the beginning of the formation of the membrane attack complex and the last stage of activation unit

c5 convertase

is C5b extremely labile?

yes

C6 will bind to C5b to form

C5b6

C7 will bind to C5b6 to form

C5b67

It is a forming a trimolecular complex that has a high affinity for lipid constituents of the cell membrane.

The forming of C7 and c5b6 to create C5b67

c8 will combined with C5b67 to form

C5b678

__ and ___ Interacts with the cell membrane to form a small hole in the membrane.

C7 and C8

is inserted into the lipid bilayer of the cell membrane.

a beginning of the formation of form to cause cell to lyse and result the cell to leaks

forming of C5b678

C5b678 will form pores to rbc causing cell leaks, what are the contents of the cell that can possible leak?

(potassium, amino acids, ribonucleotides)

Pore formed are small→ able to lyse RBC but not nucleated cells

C5b678

in order to complete the lysis of the cell, C5b678 must combine with

c9 forming C5b6789

What would be the end stage of this classical pathway?

lysis of the foreign cells and immune complexes

the most abundant complement component protein in recogition unit is the

C1q

Under the classical pathway kapag tayo ay nagkaroon ng increase vascular permeability this is cause by .

anaphylatoxins

We have different proteins involved in case of increase vascular permeability. what are those?

C3a, C4a, and C5a

5 to 15

alternative pathwAy In addition to properdin, the serum proteins that are unique to this pathway include ____ and ___

factor B and factor D.

Triggering substances for the alternative pathway include:

Bacteria, fungi, viruses, tumor cell lines and some parasites

major factor in complement system (alternative and classical pathway).

In alternative pathwaY, which is analogous to c2

FACTOR B

in alternative pathway, it Bind to activated C3 to become (C3b)

Factor B

In alterative pathway Cleaves factor B that are bounded to C3b

Factor D

In alterative pathway Cleaves factor B to Bb and Ba

Factor D

Cleaves additional C3 into C3a and C3b

C3bBb

___ is considered an acute phase protein because it is produced in the liver and is normally present in the serum but increases during an initial inflammatory response

Mannose binding lectin

Lectins are proteins that bind to ___.

carbohydrates

This pathway provides an additional link between the innate and acquired immune response

lectin pathway

among the serine proteases, which one is homologous to C1s? as it plays an active role in cleaving the C4 and C2

Masp 2

the only pathway that has the acute phase reactants involve?

lectin pathway

C1 inhibitor will inhibits which complement components?

inactivates C1 and Masp 2

___ is a glycoprotein with a molecular weight of 105,000 that inhibits activation at the FIRST STAGES of both the classical and lectin pathways

C1 inhibitor

c3 convertase are inhibits by 4 regulators, what are they?

C4b binding protein CR1 "cd 35" MCP "membrane cofactor protein" DAF "decay-accelerating factor"

c3 convertase has 4 regulators, all of this works with _____

factor I

Binds to Factor I then inactivates the C4b resulting into the dissociation of C4b from the C4b2a complex. Causing the classical pathway to stop and not able to continue the pathway.

C4b-binding protein (C4BP)

Also known as CD35, once CR1 binds to C3b or C4b it is then degraded by factor I.

Complement receptor 1 (CR1) Also known as CD35,

Most efficient cofactor for Factor I-mediated cleavage of C3b.

Membrane cofactor protein (MCP)

Membrane cofactor protein (MCP) - Most efficient cofactor for Factor I-mediated cleavage of C3b. It also serves as cofactor for Factor I in cleaving the C4b not as efficient as the ____ (most efficient in inhibiting the activity of the classical pathway)

C4bB

Dissociates the C3 convertase by cleaving the C3b or C4b or both.

Decay accelerating factor (DAF)

Which one is the most common complement deficiency?

C2 lupuslike syndrome ; recurrent infections atherosclerosis C2 deficient individuals are prone to recurrence staphylococcal and streptococcal infection. They also has low levels of Factor B kasi yung gene location or alleles nila ay close to each other.

Which one is the most serious form of the complement deficiency?

C3 because they are prone to severe recurrent of life-threatening infections with encapsulated bacteria such as streptococcus pneumoniae.

MBL Deficiency Lack of MBL are associated to ___

pneumonia, sepsis and meningococcal diseases.

Causes increase susceptibility to systemic Neisseria infections.

C5-C8

deficiency in MASP 2

pneumococcal diseases

lack of C1INH

hereditary angioedema

lack of c9

no known disease associarion

lack of these complement components will lead to lupus like sydrome

c1, c2, c4,

lack of these complement components will lead to paroxysmal nocturnal hemoglobinuria

DAF and MIRL

lack of c3 will lead to

glomerlonephritis

binds immune complexes, making them soluble and facilitating their removal by the spleen and liver.

C3b

___ and ___ are anaphylatoxins: they increase vascular permeability, smooth muscle contraction, and recruit immune cells.

C3a and C5a

__coats the pathogen surface, enhancing phagocytosis by macrophages and neutrophils (via complement receptors).

C3b

controls C1 activation (classical pathway).

C1 inhibitor (C1-INH

Factor I and Factor H – degrade __.

C3b

– inhibits MAC formation on host cells

CD59 (protectin)

duscuss the alternative pathway

hydrolysis of C3 upon contact with bacterial LPS/cell wall c3---> c3a and c3b c3b will proceed c3b + factor B = C3bB eeksena si factor D ---- ice-cleave si factor B magiging C3bBb si properdin or factor P magcecleave ng more C3 final product C3bBbc3b

what is the equivalent c3 convertase of alternative pathway

c3bBb

Binds to activated C1r and C1s, causing their dissociation from C1q.

1. C1 Inhibitor (C1-INH)

Deficiency of C1-INH leads to ____, characterized by excessive bradykinin-mediated swelling

hereditary angioedema

Target: C4b (part of C3 convertase, C4b2a).

c4 Binding protein

c4 inhibitor Acts as a cofactor for Factor _____, which inactivates C4b.

Factor I

Inactivation of C3 convertase in the classical and lectin pathways.

2. C4 Binding Protein (C4BP + factor I

` C5b-8 complex (before C9 polymerization).

CD59 (Protectin)

Prevents insertion of C9 molecules into the cell membrane

cd59

Binds to C5b-7, preventing its insertion into the membrane.

S Protein (Vitronectin)

Acts as a cofactor for Factor I, promoting degradation of C3b and C4b on host cells.

Membrane Cofactor Protein (MCP/CD46)

DAF or CD59 deficiency

paroxysmal nocturnal hemoglobinuria (complement-mediated RBC lysis).

MIDTERM - complement system Flashcards

(171 cards)