5. Characteristics Innate immune
system
Adaptive immune
system
Components First line defense:
- Epithelial barriers
that block entry
of microbes
- The enzymes of GIT
and HCl in the
stomach (destroy
the toxic
substances from
food)
- “Lysozymes” in
saliva, nasal
secretion, tears,
etc.
-Wax in ears
Antigen-presenting
cells (APCs)
Definition:
APCs are defined
as cells, which
have highly
specific receptors
for antigen
6. Characteristics Innate immune
system
Adaptive immune
system
Humoral
Components
(refers to body fluid)
-Complement
factors
-Cytokines
-Acute phase
proteins
-WBCs
B-lymphocytes
(B-cells)
Immunoglobulins
(antibodies)
Cellular components
(refers the cells)
-NK (natural
killer) cells,
-Micro- and
macrophages
T-lymphocytes
(T-cells)
8. Definition:
The complement system is a set of
plasma proteins that help the ability
of antibodies and phagocytic cells to
clear pathogens from an organism.
4% of all plasma proteins are
complement proteins, that are
numbered as C1, C2….. C9.
9. Where complement proteins are
synthesized?
Complement proteins
are synthesized by:
Liver hepatocytes
Tissue macrophages
Blood monocytes
Epithelial cells of
genitourinal tract and
gastrointestinal tract
10. Complement proteins present in the
blood in inactive form.
Activation of proteins is result of
proteolytic cleavaged by convertases.
C3 convertase
C3 C3aC3b +
active subunits
inactive
C5 convertase
C5 C5b C5a+
active subunits
inactive
11. Three ways of activation
Classical
pathway
Alternative
pathway
Lectin
pathway
Antibody independentAntibody
dependent
generation of protease
C3 convertase
caSCADE
activation
of complement factors
EFFECTS
C5 convertase
13. Initiators of Classic pathway
Immunoglobulin-antigen complex
C1 protein exist in blood serum as a molecular complex
containing:
6 molecules of C1q
2 molecules of C1r
2 molecules of C1s
S S
R R
binds with IgM or
IgG (CH2-region)
activation
of C1r and C1s
When C1q1.
2. 3.C4
C4b + C4a
Activation of C4 and C2C2
C2b + C2a
C4b-C2b
C3 convertase
C3
C3b + C3a
C4b-C2b-C3b
C5 convertase
C5
C5b + C5a
15. Alternative pathway of
complement activation
A pathway of complement activation
initiated by
Bacterial endotoxins,
Microbial polysaccharides,
lipopolysaccharides,
Microbial cell walls
Factors: B, D (adipsin)
Stabilization of C3-convertase: Factor P
(properdin)
16. Complement activation cascade
C3
B
C3 Bb
Ba
C3
C3b
C3a B
C3b
1
2 3
Bb
P
D
c3 convertase
4
C3
C3b
Bb
P
C3b
c5-convertase
C5
C5b
C5a
5
6
C3a
exotoxin
of bacteria
wall of bacteria
18. It activates complement through the
mannose-binding lectin (MBL) which
is produced by the liver and can
initiate the complement cascade.
MBL binds to specific carbohydrates
(fucose, mannose) found on the
surface of many pathogens.
19. MBL binds with
Yeasts such as Candida albicans
Viruses such as influenza A, HIV
Many bacteria such as Streptococci,
Salmonella
Parasites like Leishmania
21. Effects of activated complements
Effects of
C3a and C5a
Effects of
C3b and C5b
Produce inflammatory
mediators
Opsonization (C3b)
Formation of MAC
(complement fixation)
(C5b)Chemotaxis
22. Opsonization (Greek: “ to prepare
for eating”)
Opsonization- is the
process of coating the
pathogens and
preparing them for
phagocytosis.
Opsonins- substances
that bind a microbe to a
phagocyte and promotes
phagocytosis.
23. C3b is important opsonin. C3b is
riched by thioester groups which
react with –OH or -NH2 groups.
NH2
bacterial
membrane
S C
O
NH
SH C
O
Phagocytes
may recognize
this complex
25. BIOLOGICAL ROLE
C3a / C5a
INFLAMMATORY RESPONSE
C3a and C5a activate releasing of
HISTAMINE by mast cells, basophiles
and platelets.
C3a and C5a activate leukocytes
26. Effect of histamine
Vasodilatation (increase in the
diameter of blood vessels, especially
arteries).
Increases vascular permeability and
hence increases migration of plasma
proteins (active complement,
cytokines, leukocytes) into the tissue
for pathogen inactivation.
28. COMPLEMENT DEFICIENCIES
Classic and
alternative pathways
complements
deficiency:
Clinical signs:
(i) Pyogenic (causing the
formation of pus)
infections
(ii) Immune-complex
syndrome**
30. Immune-complex
syndrome
Include:
(i) SYSTEMIC LUPUS ERYTHEMATOSIUS
(SLE) – chronic inflammatory disease of
connective tissue, affecting the skin,
kidney, lungs, heart, brain (eg. formation
of fibrous scar)
(ii) GLOMERULONEPHRITIS- group of
kidney diseases involving the glomeruli
(iii) VASCULITIS – inflammation of the walls
of small blood vessels