Innate (Nonspecific) Immunity

Dr. Zahraa A Mohammed

 Introduction to immune system
• The daunting role of the immune system is to
afford protection. It is designed to recognize and
respond to non-self antigen in a coordinated
manner. Additionally, cells that are diseased,
damaged, distressed or dying are recognized
and eliminated by the immune system. To
accomplish this goal, the immune system is
equipped with a rapid response mechanism,
exquisite specificity, adaptability, an intricate
regulatory network, and memory.
 The Immune response
• A response generated against a
potential pathogen is called an ( immune
response).
• The immune system is divided into 2
complementary arms:
1- Innate Immunity.
2- Acquired Immunity.
 1- Innate Immunity:
It is an immediate response to the pathogen
represent the first line of defense, which is not
directed against any particular pathogen but is a
general defense mechanism. It is active right
from the time a child is born, and is rapidly
mobilized at the initial site of infection, but lacks
immunologic memory and includes barriers to
infectious agents, such as :Skin (epithelium) and
mucous membranes. It also includes many
immune components important in the adaptive
response include: phagocytic cells , NK cells,
TLR, cytokines and Complements.
 Innate host defenses against
infection
• Anatomical barriers
– Mechanical, chemical, biological
• Humoral components
– Complement, coagulation system, cytokines
• Cellular components
– Neutrophils, monocytes & macrophages, NK
cells, eosinophils
Mechanical/physical barriers
 Physiological Barriers:
1) Skin:
Few microorganisms are capable of
penetrating intact skin, but many can enter
sweat or sebaceous glands and hair follicles
and establish themselves there.
Sweat and sebaceous secretions have
antimicrobial properties (acid pH and certain
chemical substances like fatty acid)
Lysozyme : a hydrolytic enzyme present in
all mucous secretions including tears,
saliva, skin, in respiratory and cervical
secretions that can lyse gram positive by
cleaving peptidoglycan layer found in
bacterial cell wall
Psoriasin :protein with antibacterial
prosperities produced by skin.
 2) Mucous Membrane:
In the respiratory tract:
• Bacteria tend to stick to a film of mucous
covers the surface and is constantly being
driven upward by ciliated cells toward the natural
orifices.
• Lysozymes
• IgA
• The phagocytes.
• Hair at the nares and cough reflex ( special
protective mechanism)
The gastrointestinal tract:
• Saliva contains numerous hydrolytic
enzymes.
• Acidity of the stomach.
• Proteolytic enzymes and active MQs in
small intestine.
The most mucous membrane of the body
Carry a constant normal microbiota that
itself opposes establishment of pathogenic
microorganisms(“Bacterial
interference”)and has important
physiologic functions. e.g. in the vagina
the acid pH is maintained by normal
Lactobacilli, inhibiting establishment of
yeasts, anaerobes, and Gram-negative
bacteria.
 Mechanisms of Innate
Immunity
The Innate system has both cellular and
humoral factors.
Cells:
 Phagocytic leukocytes, such as PMN.
 Macrophages.
 NK cells.
Innate cellular components
Cell Mechanism
Neutrophils Phagocytosis and intracellular killing
Inflammation and tissue damage
Macrophages Phagocytosis and intracellular killing
Extracellular killing of infected or altered self
targets
Tissue repair
Antigen presentation for specific immune response
NK and LAK cells Killing of virus-infected and altered self targets
Eosinophils Killing of certain parasites
The interaction of the invading microbs with
these cells and other cells throughout the
body triggers the release of:
 Complement.
 Cytokines.
 Chemokines.
Armed with these tools, the host initiates
its defense against the invading pathogens
 Humoral components
Component Mechanism
Complement Lysis of bateria and some viruses
Opsonin
Increase in vascular permeability
Recruitment and activation of phagocytic cells
Coagulation system Increase vascular permeability
Recruitment of phagocytic cells
B-lysin from platelets – a cationic detergent
Lactoferrin and Compete with bacteria for iron
transferrin
Lysozyme Breaks down bacterial cells walls
Cytokines Various effects
Microbial Sensors:
When a pathogen enters the skin, it is
confronted with macrophages and other
phagocytic cells possessing “Microbial
sensors”.
There are three major groups of microbial
sensors:
1)Tool like receptors (TLRs).
2)NOD-like receptors (NLRs).
3)RIG-1 like helicases and MDA-5.
 Pathogen associated molecular patterns(PAMPs):
The microbial molecules that stimulate innate immunity
and present in infectious agents
Pattern recognition receptors(PRR):The receptors of
innate immunity that recognize the structures shared by
microbes
Damage-associated molecular patterns(DAMPs):The
innate immune system recognizes molecules that are
released from damaged or necrotic host cells. Example
include high mobility group box protein 1(HMGB1 )
 TLRs
The TLRs are a family of evolutionary
conserved pattern recognition receptors
(PRRs) that recognize pathogen-
associated molecular patterns (PAMPs).
They constitute a first line of defense
against a variety of pathogens and play a
critical role in initiating the innate immune
response.
 TLRs
To date, 10 human TLRs have been identified,
and each receptor appears to be involved in the
recognition of a unique set of microbial patterns
e.g.:
 TLR2 recognizes several glycolipids and
peptidoglycan that are made by Gram- positive
bacteria.
 TLR3 engages dsRNA in viral replication.
 TLR1 and TLR6 recognize multiple diacyle
peptides (e.g. Mycoplasma) .
 TLR4 is specific for Gram-negative
lipopolysaccharide (LPS).
 TLR5 recognizes bacterial protein called
flagellin.
 TLR7 and TLR8 interact with ssRNA in
viral replication.
 TLR9 binds bacterial DNA.
 TLR10 remains an orphan receptor.
NOD-like receptors
A large family of innate receptors sense
DAMPs and PAMPs that are located in the
cytosol of cells and serve as intracellular
sensors for microbial products.
They activate the nuclear factor kappa-light
chain-enhancer of activated B cells (NF-
ҡB) pathway and drive inflammatory
responses similar to the TLRs.
RIG-1-like helicases (Retinoic acid-inducible
gene-1(and MDA-5( melanoma- differentiation-
associated gene 5)

These are cytoplasmic sensors of viral

ssRNA. The engagement of ssRNA with
these sensors triggers type 1 IFN
production. These IFNs are highly
effective inhibitors of viral replication.
 Phagocytosis :
During infections, the number of circulating
phagocytic cells often increases. The main
functions of phagocytic cells include:
Chemotaxis, migration, ingestion and microbial
killing.
M.Os and other exogenous Ags that enter the
lymphatic, lung, or blood stream are engulfed by
a variety of phagocytic cells
Phagocytosis involves:
1- Extension of pseudopodia to engulf attach
materia.
2- Fusion of the pseudopodia to trap the
material in a phagosome.
3- Fusion of the phagosome with a
lysosome to create a phagolysosome.
4- Digestion.
5- Exocytosis of digested contents.
 Phagocytosis
A. A. Attachment via
receptors
B. – FcR, complement R,
scavenger R, Toll-like R
B. Pseudopod extension
Cytoplasm
C. Phagosome formation
C.
D. Granule fusion and
Phagolysosome
formation

D.
Phagocytosis is the process whereby a
phagocytic cells especially the PMN,
recognizes the pathogen, ingests it ,and
then destroy the engulfed organisms. This
is multistep process:
Steps of extravasation:
Step 1: Rolling.
Step 2: Activation by chemoattractants.
Step 3: Arrest and adhesion.
Step 4: Transendothelial migration.
Antimicrobial mechanisms used by
phagocytes
1) Acidification occurs within the
phagosome. The phagosome pH is 3.5-4,
and this level of acidity is bacteriostatic or
bactericidal.
2) Toxic oxygen-derived products are
generated and include superoxide Oˉ2,
hydrogen peroxide H2O2, and singlet
oxygen Oˉ2
3) Toxic nitrogen oxides .
4) Antimicrobail peptides participate in
killing.