Charles A.

Janeway, Paul Travers, Mark Walport, Mark Shlomchik

IMMUNOBIOLOGY:
THE IMMUNE SYSTEM IN HEALTH & DISEASE
SIXTH EDITION

Innate Immunity
Lectured by :
Riandini Aisyah

Copyright © 2005 by Garland Science Publishing

 Topics

1. The front line of host defense

2. Pattern recognition in innate immune
system
3. The complement system and innate
immunity
4. Induced innate response to infection
The arms of Immune System
The function of Immune
System
1. THE FRONT LINE OF HOST
DEFENSE
 Pathogen

Innate defense mechanisme

Adaptive immune response

Phases in immune responses
 Innate v.s. Adaptive immune defense

Innate Adaptive
•directly available •must be induced
•no long-lasting protection •long-lasting protection
•limited specificity: •highly specific:
general recognition criteria recognition by individual
lymphocytes
•removal by killing and/or •removal by killing
phagocytosis and/or
•macrophages, phagocytosis
granulocytes, NK cells •T- and B lymphocytes
Pathogen can enter the body via many routes
Epithelial form barrier to infection
• Infectious disease microorganisms succeed
to establish a local site of infection and
replicates to allows its further transmission
• Pathogen spread is countered by an inflammatory
response
 Main Actors in Innate Immunity
•Phagocytic cells key role in innate immunity

Macrophage Neutrophil
Residence:
Connenctive tissue, In blood
submocosa of Not in normal healthy tissue
gastrointestinal, lung, certain
blood vessel in the liver,
spleen

Macrophages & neutrophil recognize pathogen by their

surface receptors
Macrophage activation
induces endocytosis and
degradation of the pathogen
Bactericidal agents released/produced by macrophages
 Main Combating Infection Process in Innate
Immunity

Inflammation in site of infection induced by

macrophage
• Inflammation plays 3 essential roles in combating
infection:
1. Deliver additional effector to site of infection
2. Provide physical barrier microvascular
coagulation
3. Promote repair of injured tissue
Characteristic of inflammatory responses are: pain,
redness, heat, and swelling
2. PATTERN RECOGNITION IN
INNATE IMMUNE SYSTEM

PATTERN RECOGNITION MOLECULE (PRM) OF

ANTIGEN RECOGNIZED BY :
PATTERN RECOGNITION RECEPTOR (PRR) OF
MACROPHAGE
 Recognition of pathogens

The cells of innate immune system recognize features common

to many pathogens (pattern-recognition molecules) such as:
• certain carbohydrate structures
• certain sugar molecules (mannose)

The receptors on innate immune cells involved in recognition

are called pattern-recognition receptors (PRRs):
• scavenger receptor
• mannose receptor
• Toll-like receptor
• CD14 / LPS receptor
Mannose Receptor
Mannose-binding lectin binds on to pattern
recognition molecules
MBL has a rigid structure
Toll-Like Receptor (TLR)
Macrophage
activation by LPS

Toll-like receptors
(TLRs) form a family of
receptors that signal the
presence of pathogen,
e.g. TLR4 signals the
presence of LPS.
LPS binding triggers
the formation of
cytokines a.o. of TNF-a
and might, thus, induce
septic shock.
Clustering of CD14 and Toll-like receptor

NFkB induces DNA transcription

Toll pathway leads to the
expression of co-
stimulatory molecules
essentials for adaptive
immune response
induction : B7.1 (CD80) &
B7.2 (CD86)
3. THE COMPLEMENT SYSTEM AND
INNATE IMMUNITY
Complement: activation routes and effector functions
Complement: generation of C3 convertases
Immune defense functions of complement
Cellular distribution and function of complement receptors
Small complement
components can
induce local
inflammatory
responses by:
-Chemoattractive
and
-Anaphylactive
activities

Features of
inflammation:
Pain, redness, heat
and swelling at the
site of
inflammation
4. INDUCED INNATE RESPONSE TO
INFECTION

CYTOKINE  SIGNALLING PATHWAY 

CELL-CELL COMMUNICATION
 Different types of cytokines

• Haemopoietic cytokines (growth and differentiation factors):

IL-3: interleukin-3
GM-CSF: granulocyte/macrophage colony stimulating factor
G-CSF: granulocyte colony stimulating factor

• Inflammatory cytokines:
IL-1: interleukin-1
IL-6: interleukin-6
TNF-a: tumor necrosis factor a
IL-8: interleukin-8
ECF: eosinophil chemotaxtic factor

• Regulatory cytokines:
IL-2: interleukin-2 IL-4: interleukin-4
INF-g : interferon-g IL-5: interleukin-5
IL-12: interleukin-12 IL-10: interleukin-10
 Chemokines (Chemoattractive cytokine)
Chemokines: small polypeptides that are synthesized by many
cell types,
e.g. dendritic cells, macrophages, granulocytes,
lymphocytes, endothelial cells, stromal cells

Based on N-terminal amino acid sequence chemokines

can be divided into CXC, CC, C and CXXC types.
Receptors for these types are present on many cell types.

Main functions of chemokines:

1. cell recruitment and migration
2. cell activation and degranulation

Cytokines are mostly involved in

lymphocyte development, maturation and regulation
 Chemokines: pro-inflammatory proteins that
regulate leukocyte traffic
- small structurally related molecules (8-12 kD)
- immune cell mediators with prominent chemotactic properties
as well as cytokine-like activation properties.
- most chemokines have two cysteine pairs linked CXC or CC
- expressed and secreted by virtually all cell types
- epithelial, mesothelial and endothelial cells are potent
chemokine producers

CXC CC
NH2 NH2

COOH COOH
About 15 members About 25 members
example: IL-8 example:MCP-1
 Two major chemokine families

• CXC chemokines

• CC chemokines
 Chemokines play a prominent role in
cell migration

Chemokines regulate normal lymphocytes migration and homing

Chemokines attract inflammatory cells to the site of infection

Chemokines may activate cells to release inflammatory factors

Chemokines may have an additional regulatory function

 Molecules involved in cell migration

Adhesion molecules play a role in cell-cell contacts

Adhesion molecules involved in leukocyte interactions
 Leukocyte interaction with inflamed endothelium

Chemokines upregulate adhesion molecules on endothelial cells

Local and
systemic effects
of TNF-a
Cytokine released by phagocytosis activate the acute phase
response
Figure 2-47Figure 2-47 part 2
of 2

Opsonization
 NK CELLS IN INNATE IMUNITY
Challenge Activation Function

IFN-a/b Cytotoxicity
virus + Killing
blastogenesis Antiviral
o
o o
o
o
NK
-
o o
o
o

IFN- g Cell mediated

virus production
IL-12
IL-12 immunity

NK cell activation is an early response that is

abrogated by activation of the adaptive response.
CROSSTALK BETWEEN INNATE AND
ADAPTIVE IMMUNITY

INNATE INDUCE ADAPTIVE

RESPONSE
Dendritic cells bridging innate and
adaptive immune system
Activated Dendritic Cells (DCs) activate naïve T
cell in the secondary lymphoid organs (lymph
nodes, spleen, mucosa associated lymphoid
organ)  activate adaptive immune response
 Summary

 Innate system of host defense:

 Barriers by epithelial
 Cells and molecules destroy pathogen which can
breach the epithelial, e.g: macrophages
 Recognition by innate immunity elimination of
pathogen through various effector mechanisms