Clinical Immunology - The Complement System

Soluble proteins present in blood and other bodily fluids

In a general sense, what are complements?

Sensitive

Complements in plasma are (sensitive/resistant) to heat

Zymogens

Many of the complement components are ___, which are enzymes synthesized in inactive form

Presence of pathogens, presence of antibody bound to pathogens, or presence of dying cells

By what processes can a complement become active?

B fragments

Which fragment of a complement tends to be the larger component?

Smaller

A fragments of complements tend to be (smaller/larger) than B fragments

C2

In which named complement is the A fragment larger?

Proteases; cleave and activate the next component of the sequence

Large B fragments of a complement are what type of molecule? What is their main job?

A fragments

Which component of a complement is usually considered to be potent chemoattractants and cell activators?

Can induce inflammation, cause smooth muscle contraction, vasodilation, histamine release, enhance vascular permeability

What effects can A fragments have on the body?

Classical pathway, lectin pathway, and alternative pathway

What are the three ways in which the complement system can be activated?

Production of 'a' fragments and 'b' fragments and induction of microbial lysis

What are the major end results of complement activation?

Coats the microbes and induces phagocytosis

What does the production of 'b' fragments achieve in the immune response?

Once an antibody binds to its antigen, it undergoes a conformational change

Describe the first step in the classical complement pathway

Once it is bound to its antigen and has changed shape

Complement C1 is only able to bind to an antibody when?

2

How many antibodies binding to an antigen are required to activate a C1 complement?

IgM

Which type of antibody is more efficient in C1 activation?

C3

What is the most critical complement component in the classical pathway?

C4b2a / C3 converts

After the activation of C1, which molecule is responsible for cleaving C3?

C4b2a3b; cleaves and activates C5

C5 convertase in the classical pathway is? What is its main job?

Membrane attack complex; C5b6789

What is MAC and what is its molecule formula?

To form a pore and poke a hole in the microbe's membrane

What is the function of the membrane attack complex?

Potent opsonins

Complement fragments, especially C3b and C5b, can also be?

Mannose binding lectin binds carbohydrates on microbes

What is the first step of the lectin complement pathway?

MASP2

In the lectin binding pathway, which molecule is responsible for activating C2 and C4?

True

True or False: Under normal conditions, C3 can spontaneously self-activate to C3b

Endogenous inhibitor proteins; deactivate C3b immediately

Which molecule controls the self-activation of C3? How so?

If it binds to a microbe first

Under which conditions do inhibitor proteins not destroy C3b?

Factor B

Once C3b is bound to a microbe via the alternative pathway, it binds to ___

Further activates C3bB, which activates more C3 and C5

Factor D has what effect on the alternative complement pathway?

Properdin / factor P

___ is released by neutrophils to stabilize C3bBb

False

True or False: The alternative pathway does not work on first exposure

C3bBb

In the alternative pathway, C3 convertase is?

C3b2Bb

In the alternative pathway, C5 convertase is?

Induces lysis of microbes via MAC, opsonization of microbes and immune complexes for phagocytosis, recruitment and activation of inflammatory cells

What are the main functions of the complement system?

On the surface of a pathogen or on damaged host cells

Complement activation will only proceed where?

DAF, MCP, and CR1

Which regulatory proteins compete with Factor B for binding to C3b?

Binds C3b so that factor I can cleave it into an inactive fragment

How does Factor H function?

C1INH

Active C1 is inactivated by what protein?

C3; it is critical in all 3 pathways and its fragments act as opsonins and anaphylotoxins

___ deficiency has the greatest impact on the immune system. Why is this?

Sepsis, pneumonia, pyometra and wound infections

Patients with C3 deficiency are more susceptible to what diseases?

There is uncontrolled activation of the alternative cascade, and C3b binds to self-cells, causing damage to the host in those areas

How is factor H deficiency detrimental?

Those which attract complement regulators to their own surfaces, those which inhibit complement activations, and those which produce a capsule that hinders access of complement molecules to their surface

Pathogens can produce proteins which inhibit complement activation. What are the major types of these proteins?

Innate

The alternative pathway and lectin pathways are considered ____ pathways

Kidney lesions

C3-deficient dogs develop immune complex-mediated ____

C3a and C5a

The complement system triggers inflammation through the release of?

D

A child presents with a history of multiple bacterial infections. You suspect a complement deficiency, specifically C3. You test each individual component of the immune system to see if its function is intact. If you are correct, you will find that which of the following is true?

A. The patient's macrophages are unable to phagocytize

B. The patient's neutrophils are unable to release NETs

C. The patient's Mast cells are unable to degranulate

D. The patient's serum is unable to assist in antibody-mediated bactericidal activity

B

Activation of the alternative pathway involves?

A. C1

B. C3

C. C2

D. C4

C

The classical pathway of complement is primarily

activated by?

A. Microbial surfaces

B. Cytokines

C. Antibodies

D. C3

C

What are two products of C3 convertase?

A. C2a and C2b

B. C4a and C4b

C. C3a and C3b

D. C5a and C5b

B

What does the C5 convertase do?

A. It binds C6, C7, C8, and C9 to form the MAC complex

B. It cleaves C5 into C5a and C5b

C. It opsonizes bacteria

D. It cleaves factor B

B

Complement component C3 is cleaved by?

A. C3bBb3b

B. C3bBb

C. Factor D

D. Factor P

B

A complement component which is strongly chemotactic

for neutrophils is:

A. C9

B. C5a

C. C3b

D. C5b

A

The initial complement component that is bound by complement-fixing antibodies is:

A. C1

B. MBL

C. C3b

D. iC3b

C

Which mechanism best explains how Neisseria meningitidis factor H binding protein evades complement activation?

A. Binds to C3 convertases

B. Cleaves immunoglobulins

C. Inactivates bound C3b

D. Produces a polysaccharide capsule

C

Which consequence most directly follows from C3 deficiency in the

complement system?

A. Excessive inflammatory responses

B. Increased risk of autoimmune disease

C. Susceptibility to bacterial infection

D. Uncontrolled complement activation

B

What is the primary impact of C3 deficiency?

A. Decreased IgG production

B. Greatest overall impact

C. Loss of C3b opsonin function

D. Loss of C3a anaphylotoxin