STB2153 Virology &

Immunology

LU 3: Mechanism of immunity
Lecture 3:
Non-specific Immunity/Innate
Immunity
Barriers Against Infections

External Barrier

Second Line of Defense (Innate,

Natural immunity)

Third Line of Defence

(Adaptive = Acquired
Immunity)
 INNATE IMMUNITY

 A Non-specific defence mechanism that a

host uses immediately or within several hours
after exposure to almost any microbe.

 Recognize the unique molecules associated

with microbes called pathogen-associated
molecular patterns (PAMPS).
Pathogen-associated molecular
patterns (PAMPS).
PAMPs include the following:
 Peptidoglycan, found in bacterial cell
walls;
 Flagellin, a protein found in bacterial
flagella;
 Lipopolysaccharide (LPS) from the outer
membrane of gram-negative bacteria;
 Lipopeptides, molecules expressed by most
bacteria; and
 Nucleic acids such as viral DNA or RNA.
Pathogen-associated molecular
patterns (PAMPS).
 Function of the non-specific
immune response
 Restrict entry of pathogens
 Early or first response in killing of pathogens to
reduce the inoculum potential to below threshold of
infection
 Restrict spread of pathogen from point of entry to
other part of the body
 Antigen presentation for the induction of the immune
response
 The final action in the series of actions that occur in
the killing process of a pathogen
Types of Immunity
Types of Immunity
Non-Cellular component of immune
system:
Cytokine
 Small molecules secreted by cells in response to
stimulus
 specific effect on the interactions between cells, on
communications between cells or on the behavior of
cells.
 Many different cells release cytokine
 The cytokines includes the interleukins, lymphokines
and cell signal molecules, such as tumor necrosis
factor and the interferons, which trigger inflammation
and respond to infections.
Interferons
 Protect cells from viral infection-produce by
virus-infected cell, provides an early innate
immune response against viruses.

 Host-specific but not pathogen specific;

 Interferon produced by human cells protect
human cells.
 Active against a number of different viruses.
Interferons
 Three types
 Alpha (IFN-α)
 Beta (IFN-β)
 Gamma (IFN-γ)

 Both IFN-α and IFN-β are produced by

virus-infected host cell in small quantities
and diffuse to uninfected neigbouring cells.
Interferon Action

x
Translation
inhibitory
protein
(TIP)
Interferon Action

x
Translation
inhibitory
protein
(TIP)
 Other example of cytokine

 Interleukin – serve as communicators

between leukocytes.

 Tumor necrosis factor – mediates acute

inflammation.

 Chemokines – induce the migration of

leukocytes into areas of infection or tissue
damage.
 The Complement System
 A series of proteins circulating in the blood and
bathing the fluids surrounding the tissue.

 A system that helps or ‘complement’ the ability of

antibody and phagocytic cells to clear pathogen.

 Complement protein made in the liver & circulate in

plasma(more than 30 proteins)

 Circulate in the blood as inactive form – proenzymes

 Series of proteases that are themselves activated by

proteolytic cleavage

 Heat labile & present in normal plasma

 activated early in infection

 Complement Pathways
Three pathways

 Classical pathway

 Alternative pathway

 Lectin pathway
(Mannose-Binding Lectin (MBL) pathway)
 Phases of Complement
Pathways
 Complement activation is a
Three Step Process
 Step 1:Recognition
 Step 2:Enzyme activation
 Step 3:Expression of biological
activities
 Phases of Complement
Pathways
 Each pathway has unique proteins and
enzymes for the recognition in step 1
and enzyme activation step 2.

 But the resulting activities are the same

for the three pathways.
 Which is the activation of C3 and C5.
 The Classical Pathway
Complement
proteins involved: 1) Step 1:
C1 is activated by binding
to antigen-antibody
 C1 complex complexes.
(c1q, c1r & c1s) 2) Step 2:
Activated C1 splits C2
 C2 into C2a and C2b. C4
 C3 into C4a and C4b.
 C4 C2a4b = C3 Convertase
 C5-C9
C3 splits into C3a and
C3b, to produce C2a4b3b
(C5 convertase)
 The activation of classical pathway

Step 2:
C5 convertase
splits C5 into
C5a and C5b

Step 3

 Membrane
attack
complex
C5b + C6 +C7+ C8 + C9  opsonization
C5a = MEMBRANE ATTACK  inflammation
C5b
COMPLEX
Activation of Classical
Pathway
Outcome of Complement
Activation
Membrane Attack Complex
 Inflammation
 fragments of C3a, C4a and C5a - produced as part of the
activation of the complement system

 known as anaphylatoxin because

 cause smooth muscle contraction (eg. bronchospasms)
 histamine release from mast cells
 enhanced vascular permeability

 mediate chemotaxis – mediate movement of leukocytes to

inflamed site
 Outcome of Complement
Activation
Opsonization

 fragments of C3b binds to surface of a microbe, and receptor on

phagocytes attach to the C3b.

 Thus C3b enhances phagocytosis by coating a microbe (opsonization).

 Opsonization promotes attachmet of a phagocyte to microbe.

 RECOGNITION
STEP

ENZYME ACTIVATION
STEP

EXPRESSION OF BIOLOGICAL
ACTIVITIES:
MAC & LYSIS OF MICROBE
OPSONIZATION & PHAGOCYTOSIS
INFLAMMATION
 Alternative pathway
Alternative pathway
STEP 1:
 Activated by:
 Lipopolysaccharide
 zymosan
 Aggregated antibodies
 endotoxin
 Alternative pathway
STEP 2
Complement  C3 (spontaneous hydrolysis) 
proteins involved: C3a + C3b

 C3
 C3b + Factor B  C3bB
 Factor B
 Factor D acts on factor B 
 Factor D
Ba + Bb
 Properdin
 C5-C9
 C3bBb (C3 convertase ) +
properdin = stable

 C3bBb3b=(C5 Convertase)
 Lectin Pathway
(Mannose-binding lectin, MBL)
STEP 1:
 Initiated by binding of MBL (a serum protein) to
mannose containing CHO on bacteria or viruses
 Bypasses C1q activation step (in classical pathway)
and feeds into the classical pathway
 MBL forms a complex with serine proteases (MBL
associated serine protease or MASP)that
resembles the classical C1 complex
 Lectin Pathway
(Mannose-binding lectin, MBL)
STEP 2:
 Activate C2 and C4, and continue in similar pattern
as classical pathway.
Overview of Complement System
Overview of Complement System
Overview of Complement System

C4b/C2a C4b/C2a

C4b/C2a C4b/C2a
 Importance of complemets

 trigger inflammation
 chemotactically attract phagocytes to the infection
site
 promote the attachment of antigens to phagocytes
 cause lysis of gram-negative bacteria/virus and
human cells displaying foreign epitopes
 plays a role in the activation of B-lymphocytes
 remove harmful immune complexes from the body
 Lysis of virus: