COMPLEMENT SYSTEM
SGD
Complement system
Essential part in innate
immunity
Group of 20 plasma proteins
Most common = B, C1-9, D
These are mainly enzyme
precursors and catalyze a
series of enzymatic reactions
Mainly synthesized in Liver and
distributed to other body parts
Present among plasma proteins in
blood and proteins that leak into
tissue spaces
Enzyme precursors are normally
inactive
Activated by classical pathway
Only comes in effect when it is
activated
NOMENCLATURE
There are 9 main complement proteins
Named with a C followed by a number
Order in which proteins are discovered
Once cleaved products are given an a or b
The a fragment is smaller, anaphylatoxin
The b fragment is larger binding protein
C2 is exception to the above
E.g; C3 cleavage C3a + C3b
Fragments complex together to form
enzymes
When naming a protein complex its
fragments are listed in order they bind
C3 convertase = C4b2a = C4b + C2a
C3b + C4b2a C5 Convertase =
C4b2a3b
Activation
Antigen antibody reaction
(classical pathway)
Bacterial endotoxin
(Alternative pathway)
Lectin pathway
(mannose binding lectin)
CLASSICAL PATHWAY
Activated by antigen-antibody reaction
Specific reactive site on “constant portion”
of antibody is uncovered
Binds with C1 molecule
Begins a cascade of sequential reactions
Amplified reaction occurs
C1
C4
C4a CASCADE
C4b
C14b C2 OF
C3a
ENZYMATI
C2a
C2b C
C14b2 C3
C3 a C3b REACTION
CONVERTASE S
C14b2a3b C5
C5
CLASSICA
C5a
CONVERTASE
C5b C6 L
C7
C8 PATHWAY
C9
C5b6789 MEMBRANE
ATTACK COMPLEX
FUNCTIONS/ EFFECTS
OPSONIZATION AND PHAGOCYTOSIS:
antigen-antibody complex attaches to
bacteria
Binds with C3b
Binds to neutrophils and macrophages
Phagocytosis
LYSIS:
Lytic complex , C5b689
Rupture cell membrane of bacteria
LYSIS:
Membrane attack complex (MAC)
C5b on surface of bacteria binds to C6
Activation of C6, it binds to C7
C7 binds to C8 which in turn binds to many
C9
Together they form a circular complex
Create pores in membrane of bacteria
Bacterial cell bursts
FUNCTIONS/EFFECTS:
AGGLUTINATION:
causes changes in surfaces of bacteria
Bacteria adhere to each other
NEUTRALIZATION OF VIRUSES:
Makes them non-virulent
CHEMOTAXIS:
C5a
Act as a chemotactic substance
Macrophages and neutrophils accumulate
FUNCTIONS /EFFECTS
MAST CELL & BASOPHIL ACTIVATION:
C3a, C4a, C5a
Cause these cells to release histamine, and
other substances
Increased blood flow
Leakage of proteins and fluid into tissue
spaces
Inflammation
INFLAMMATORY EFFECTS:
Increase blood flow and leakage of proteins
TOLERENCE:
Immune system does not destroy body’s
own cells
“recognition” of own tissues
CLONE SELECTION DURING
PREPROCESSING:
Preprocessing occurs in thymus and bone
marrow
During preprocessing of lymphocytes in
fetus, presence of strong antigen prevents
the development of clones of lymphocytes
specific to that antigen
During presence of strong antigen,
The whole gene for forming each type of T cell or B cell
is never present in the original stem cells from which the
functional immune cells are formed.
Instead, there are only gene segments —actually,
hundreds of such segments—but not whole genes.
During preprocessing of the respective T- and B- cell
lymphocytes, these gene segments become mixed with
one another in random combinations, finally forming
whole genes.
Because there are several hundred types of gene
segments, as well as millions of different combinations
in which the segments can be arranged in single cells,
one can understand the millions of different cell gene
types that can occur.
IMMUNIZATION
ACTIVE
PASSIVE
IMMUNIZATION BY INJECTION OF
ANTIGENS:
Dead Organisms:
Typhoid fever, whooping cough
Toxins treated with chemicals:
Tetanus, Botulism
Alive, Attenuated Organisms:
Small pox, poliomyelitis, measels
IMMUNIZATION
PASSIVE IMMUNITY
Without injecting antigens
Injecting antibodies, activated T cells or
both
Temporary immunity:
Lasts only 2-3 weeks if obtained from
humans
Last a few hours if obtained from animals
ALLERGY AND
HYPERSENSITIVITY
Caused by activated T cells
Delayed Reaction allergy
• Upon repeated exposure
• Active helper and cytotoxic T cells
• Diffuse to the site of antigen
• Cell mediated type of immune reaction
• Release of toxic substances from T cells
• Invasion of tissue macrophages
• Serious tissue damage
ATOPIC ALLERGIES:
IgE antibodies present in large numbers
Genetic
Allergic tendency
Antibodies are called “reagins” or “sensitizing
antibodies”
Antigen-reagin reaction
Subsequent allergic reaction
IgE attach to mast cells/basophils
Release substances such as histamines, slow
reacting substance of anaphylaxis (toxic
leukotienes), platelet activating factors, eosinophil
and neutrophil chemotactic substances
Results
dilation of blood vessels
Attraction of eosinophils, neutrophils
Increased permiability of capillary walls
Loss of fluid into tissues
Contraction of local smooth muscles
ANAPHYLAXIS
Antigen directly into circulation
Antigen-reagin reaction
Allergic reaction throughout vascular system and
closely associated tissues
Histamine causes body wide vasodilation
Marked loss of plasma from circulation
Circulatory shock
Death in few minutes unless treated by epinephrine
Leukotienes causes spasm of smooth muscles of
bronchioles
Asthma like attack
Death by suffocation
UTRICARIA
Antigen entering specific skin area
Localized anaphylactoid reaction
All effects are localized
Swelling of skin within few minutes, called
hives
Treated with antihistamine drugs
HAY FEVER
Antigens in nose
Intra nasal vascular dilation
Increased capillary pressure
Increased capillary permiability
Rapid fluid leakage into nasal cavities,
nasal secretions
Treated with antihistamine drugs
Sneezing syndrome:
Products of allergy cause irritation of nose
ASTHMA
Antigens present in bronchioles of lungs
Slow reacting substance of anphylaxis,
toxic leukorienes
Spasm of smooth muscles of bronchioles
Difficulty in breathing
Antihistamines have no effect