COMPLEMENT SYSTEM

Engole Bernard
Objectives
• Definition of complement
• Functions of complement
• Characteristics C’
• Activation of complement
• Diseases of the complement system
Introduction
Discovered in 1894 by Bordet

It represents lytic activity of fresh serum

Its lytic activity destroyed when heated at 56C for 30 min

• Complement is a system of over 25 functionally related serum proteins that help
cells and other biologic activities.
• Complement is involved in defense through a number of mechanisms that involve
either the full activation of the complement system to destroy the membrane of
invading organism or partial activation which makes the organism more susceptible to
phagocytosis.
• Complements helps fight off bacterial and viral infections and eliminates protein
complexes
Roles of complement
• The three major roles of complements are:-
• Promoting acute inflammatory responses.
• Altering the cell surfaces to encourage phagocytosis (opsonization)
• phagocyte attraction and activation
• lysis of bacteria and infected cells
• regulation of antibody responses
• clearance of immune complexes
• clearance of apoptotic cells
Characteristics of Complement
• It is in the beta region on protein electrophoresis and is categorized as a
beta globulin.
• The complement component that is found in the highest concentration is
C3.
• Complement components are identified by latter C and their numbers are: -
C1, C2, C3 etc.
• Complement products resulting from the splitting of these proteins during
activation processes are followed by a lower case letter: C3a, C3b and C1q.
• If complement complexes develop (that have enzymatic activity) are
written with a bar above ie C5b678
Pathways for complement activation
• Complement activation is when the components of complement are
switched on to start the process of protecting the body
• Three are three pathways for complement activation
 Proteins of the complement system
(nomenclature)
• C1(qrs), C2, C3, C4, C5, C6, C7, C8, C9
• factors B, D, H and I, properdin (P)
• mannose binding lectin (MBL), MBL associated serine proteases
(MASP-1 MASP-2)
• C1 inhibitor (C1-INH, serpin), C4-binding protein (C4-BP), decay
accelerating factor (DAF), Complement receptor 1 (CR1), protein-S
(vitronectin)
Complement activation pathways
Classical pathway
Cont..
Cont..
Summary of classical pathway
The alternative pathway –
properdin
Introduction
Steps in alternative pathway
• C3 is the principal protein of
concern
• C3b can bind to bacteria and
enhance phagocytosis.
• The production of C3b can be
catalyzed by “C3 convertase.”
How bacteria are phagocytosed in alternative
pathway
• C3b can bind to bacteria and
enhance phagocytosis
• C3 convertase is produced by
C3b associating with factor B
in the presence of Mg++ to
form C3bB which in the
presence of factor D is
cleaved to C3[bBb].
• The bacteria is finally
destroyed
The lectin pathway
Sumarry
Diseases of the complement system
• Autoimmune diseases
• Alzheimer’s syndrome
• Schizophrenia
• Atypical hemolytic uremic syndrome
• Macular degeneration
• Crohn’s disease
Autoimmune diseases
• Rheumatoid arthritis (RA). ... • result when your immune system is
• Systemic lupus erythematosus overactive, causing it to attack and
(lupus) damage your body's own tissues.
• Inflammatory bowel disease (IBD) • Normally, your immune system
creates proteins called antibodies
• Multiple sclerosis (MS). ... that work to protect you against
• Type 1 diabetes. ... harmful substances such as viruses,
cancer cells, and toxins.
• Guillain-Barre syndrome (GBS). ...
• But with autoimmune disorders, your
• Chronic inflammatory demyelinating immune system can't tell the
polyneuropathy (CIDP). ... difference between invaders and
• Psoriasis. healthy cells.
Alzheimer’s disease
• Alzheimer’s disease is the most
common type of dementia.
• It is a progressive disease beginning
with mild memory loss and possibly
leading to loss of the ability to carry
on a conversation and respond to the
environment.
• Alzheimer’s disease involves parts of
the brain that control thought,
memory, and language.
• It can seriously affect a person’s ability
to carry out daily activities.
Schizophrenia
• Schizophrenia is a chronic, severe
mental disorder that affects the
way a person thinks, acts,
expresses emotions, perceives
reality, and relates to others.
• People with schizophrenia often
have problems functioning in
society, work, school, and
relationships. They might feel
scared and withdrawn or appear
to have lost touch with reality
PATHOLOGICAL SITUATIONS ASSOCIATED WITH
EXAGGERATED COMPLEMENT ACTIVATION
• Once the complement cascade is activated, the complement
components are under very tight regulation and control
• An important aspect of this regulation is the constant presence of
plasma inhibitors for the activated complement components
• For each type of activated fragment there is at least one inhibitor or
inhibitory mechanism
• Some of conditions include
A. Hereditary Angioedema
• This is a rare genetic disorder due to a genetically inherited C1-INH
deficiency, of which two main variants are known.
• In the most common, the genetic inheritance of a silent gene results
in a very low level of C1-INH
• Attacks in patients with C1-INH deficiency occur after surgical trauma,
particularly after dental surgery or after severe stress
B. Paroxysmal Nocturnal Hemoglobinuria
• Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder
• The patients develop hemolytic anemia associated with the
intermittent passage of dark urine (due to hemoglobinuria), which
usually is more seen at night
• The spontaneous hemolysis is due to an increased susceptibility of the
abnormal erythrocytes to complement-mediated lysis.
• The erythrocytes are not responsible for the activation of the
complement system; rather, they are lysed as innocent bystanders
when complement is activated.
End

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