INNATE
IMMUNITY
INTRODUCTION
✓ The body protects itself from microbial
invasion in ways that are similar to those
used to protect a country from invasion.
✓ Humans and animals have survived on
Earth for hundreds of thousands of years
because they have many built-in or
Component of the Innate Immunity
naturally occurring mechanisms of defense
Epithelial:
against pathogens and the infectious
- Physical Barrier
diseases that they cause.
- Chemical Barrier
✓ The ability of any animal to resist these
- Biological Barrier
invaders and recover from disease is
Cellular:
attributable to many complex interacting
- Granulocytes
functions within the body.
- Agranulocytes
Humoral
- Interferons
- Chemokines
- Complements
Innate Immunity
First line of defense Second line of
defense
• Intact skin • Phagocytes, such
• Mucous as neutrophils,
membranes eosinophils,
• Normal dendritic cells,
microbiota and
macrophages
• Inflammation
INNATE IMMUNITY • Fever
- Most primitive type of immune response • Antimicrobial
- Nonspecific defenses of the host; always substances
present and active
- Defenses that are present at birth ESSENTIAL FUNCTIONS OF INNATE
- Immediate and rapid IMMUNITY
- No prior exposure to antigen is needed 1) Initial response to microbes
- Same every time; no “memory” as found in 2) Eliminate damaged cells and initiate the
the adaptive immune system process of tissue repair
- Physical and chemical barriers 3) Stimulates adaptive immune response
- Cellular defense
Four types of defensive barriers of innate invaders and also contain antibacterial or
immunity: antiviral substances
1) Anatomic barriers – skin and mucous - It is covered by cilia (respiratory tract)
membranes - Normal flora
2) Physiologic barriers – temperature, low
pH, chemical mediators
3) Phagocytic/endocytic barrier –
neutrophils, macrophages, etc
4) Inflammation barriers
Overview of the Innate Immune
Response
ANATOMICAL BARRIERS:
SKIN
Anatomical/Physical Barriers
- The body’s first line of defense
- Include epithelial layers of the skin and
mucosal and glandular tissue surfaces
- Prevent infection by blocking pathogens
from entering the body
ANATOMICAL BARRIERS:
Mucous Membranes
- Found in the conjunctive and alimentary,
respiratory and urogenital tracts
- Consist of an outer epithelial layer and an
underlying layer of connective tissue.
- Saliva, tears and mucous secretions
(mucus)act to wash away potential
Skin and other Epithelial barriers Organ or Tissue Innate mechanisms
protecting
skin/epithelium
Skin Antimicrobial
peptides, fatty acids
in sebum
Mouth and upper Enzymes,
alimentary canal antimicrobial
peptides, and
sweeping of surface
by directional flow of
fluid toward stomach
Stomach Low pH, digestive
enzymes,
antimicrobial
peptides, fluid flow
toward intestine
Small intestine Digestive enzymes,
antimicrobial
peptides, fluid flow
to large intestine
The ciliary escalator Large intestine Normal intestinal
flora compete with
invading microbes,
fluid/feces expelled
from rectum
Airway and lungs Cilia sweep mucus
outward, coughing,
sneezing expel
mucus,
macrophages in
alveoli of lungs
Urogenital tract Flushing by urine,
aggregation by
urinary mucins; low
Lacrimal apparatus
pH anti- microbial
peptides, proteins in
vaginal secretions
Salivary, Lacrimal, Flushing by
and mammary secretions, anti-
glands microbial peptides
and proteins in
vaginal secretions
Interferon Second Line of Defense:
- Interferes with viral replication 1. Phagocytic cells - macrophages
- Enhances phagocyte activity of 2. Inflammation
macrophages 3. Fever (physiological barrier)
- Stimulates production of antibodies 4. Antimicrobial substances (physiological
- Enhances the killing power of natural killer barrier)
cells and cytotoxic T cells 5. Complement System
- Slows cell division and tumor growth
Function of Interferon: Cells involved in the innate immune
system:
a. Monocytes
b. Macrophages
c. Polymorphonuclear granulocytes
(polymorphonuclear neutrophils
(PMNs), basophils and eosinophils)
d. NK cells
e. Mast cells
f. Platelets
Cells of Innate immunity based on
population
▪ Neutrophils
▪ Lymphocytes
▪ Monocytes
▪ Eosinophils
▪ Basophils
Function of Cell Types of Innate
Immunity
Normal Microbiota of a Human:
a) Provides a first line of defense against
microbial pathogens
b) Assist in digestion
c) Play a role in toxin degradation,
d) Contribute to maturation of the immune ✓ Monocytes have many of the same
system functions as macrophage
How does Innate IR recognize Mechanism of killer activation without
pathogens? killer inhibitory receptors:
Pattern recognition receptors (PRRs) -
important in detecting the presence of
pathogen and activating innate immunity.
▪ binds to pathogen-associated molecular
patterns (PAMPS)
▪ Some are expressed on the plasma
membrane while others are located inside our
cells
Cellular defense mechanism of innate
immunity:
➢ RECOGNITION via receptors:
✓ Pattern Recognition Receptors (PRRs) PHAGOCYTIC BARRIER
✓ Toll-like Receptors (TLRs) ➢ Phagocytosis - ingestion of
extracellular particulate material
✓ Killer Activation Receptors (KARs)
➢ Endocytosis – the general term for the
✓ Killer Inhibition Receptors (KIRs)
uptake by a cell of material from its
✓ Complement Receptors (CRs)
environment.
✓ Fc Receptors (FcRs) a. Receptor – mediated endocytosis
➢ RESPONSE via: b. Pinocytosis
✓ Phagocytosis
✓ Inflammation
Role of Phagocytes in Innate Immunity Elimination of Intracellular Pathogens
➢ Order of events in infection Autophagy
1. Entry of pathogen • From the Latin word that means
2. Recognition of pathogen "self-eating,"
3. Phagocytosis and killing of a pathogen • It is a natural process that involves breaking
(macrophages) down unneeded or damaged components
➢ Reactive oxygen species (ROS), nitric oxide within a cell and reusing them as the building
(NO) and lysosomal enzymes blocks for cellular repair or the formation of
4. Induction of inflammation new cells
➢ Production of pro-inflammatory cytokines
(TNF, IL-1, chemokines) Natural Killer Cells
5. Attraction of cells to infection site - Lymphocyte – like
➢ Adhesive molecules (selectins and - Release perforin
integrins) and chemokines - Target cancerous and virally infected cells
6. Pathogen elimination and/or adaptive - lyse the target cell’s membrane
immunity activation
7. Tissue repair and remodeling
➢ Enzymes and cytokines (growth factors,
metalloproteinases
8. Attraction of cells to infection site
➢ Adhesive molecules (selectins and
integrins) and chemokines
Mechanism of Phagocytosis:
1. Chemotaxis
2.Adherence
3.Ingestion
4.Digestion
Inflammation
Steps in phagocytosis of a bacterium Inflammation is the body’s response to tissue
damage or microbial invasion. The way the
body responds depends on:
1. What has caused the damage
2. Its location
3. Its severity
✓ Damage can be caused by physical means
or by infection. If an infection is present, the
body’s innate systems for limiting damage
and repairing tissues work in concert with the
adaptive immune responses. This involves a
number of overlapping stages, which
typically take place over a number of days or
weeks.
– facilitates an influx of fluid and cells from the
Hallmarks of inflammation: engorged capillaries into the tissue
• Influx of fluid (edema) c. Influx of phagocytes – facilitated by the
• Increased temperature (hyperthermia) increased permeability of the capillaries
• Decreased oxygenation (local hypoxia)
• Influx of white blood cells (extravasation) Initiation of a local inflammatory response
Functions of Inflammation
1. Destroy the injurious agent
2. If destruction is not possible, to limit the
effects on the body by confining or walling off
the injurious agent and its by – products
3. To repair or replace tissue damaged
Four cardinal signs (Celsus)
a. Rubor – redness
b. Tumor – swelling
c. Calor – heat
Neutrophil Extravasation
d. Dolor – pain
• Rolling
➢ 5th sign (Galen)
• Activation of chemoattractant stimulus
• - Functio laesa – loss of function • Arrest and adhesion
• Trans endothelial migration into tissue
DIAPEDESIS - migration of cells through the
walls of blood capillaries into the tissue
spaces.
Process of inflammation:
a. Damage to tissue Chemical mediators – acutephase proteins
b. Vasodilation and increased permeability of 1. Histamine - vasodilation, increased
blood vessels permeability of blood
c. Phagocyte migration and phagocytosis vessels
d. Repair of damaged tissue 2. Kinins - vasodilation, increased permeability
of blood
MAJOR EVENTS OF AN INFLAMMATORY vessels
RESPONSE 3. Prostaglandins – intensify the histamine and
a. Vasodilation – an increase in the diameter of kinin effect
blood vessels 4. Leukotrienes - increased permeability of
b. An increase in capillary permeability blood vessels, phagocytic attachment
5. Cytokines ➢Substances that stimulate the production of
fever are called pyrogens or pyrogenic
substances
FEVER as defense against disease
1. Stimulate white blood cells (leukocytes) to
deploy and destroy invaders
2. Slow down the rate of growth of certain
pathogens and can even kill some especially
fastidious pathogens
3. Reduce available free plasma iron
4. Induce the production of IL-1
5. Help in body tissues repair
Complications of fever
a. Tachycardia
b. Increased metabolic rate – acidosis
c. Dehydration
d. Electrolyte imbalances
e. Seizures in young children
f. Delirium
Physiologic Barrier g. Coma
➢Include temperature, pH and various
soluble and cell-associated molecules. Death results if the body temperature rises
a. lysozyme – hydrolytic enzyme found in above 44oC to 46oC.
mucous secretions and tears
Other mechanisms TO REMOVE THE
✓ Able to cleave the peptidoglycan layer of
PATHOGENS IN THE BODY:
the bacterial cell wall
1. Vaginal secretions
b. Lactoferrin and calprotein – bind and
2. Peristalsis
sequester metal ions needed by bacteria and
3. Defecation
fungi, limiting their growth
4. Vomiting
c. Interferon – comprises a group of proteins
5. Diarrhea
produced by virus-infected cells.
✓ It has the ability to bind to nearby cells and
KEY POINTS
induce a generalized antiviral state
c. Complement – a group of serum proteins • Epithelial layers provide a chemical barrier
that circulate in an inactive state to infection, producing a variety of
protective substances, including acidic pH,
enzymes, binding proteins, and
Fever antimicrobial proteins and peptides.
✓ An abnormally high body temperature • Phagocytosis—engulfment and
✓3rd component of the second line of defense internalization of particulate materials such
✓Controlled by the hypothalamus (sometimes as microbes—is mediated by receptors on
called as the body’s thermostat) phagocytes that either directly recognize
PAMPs on the surface of microbes or
recognize soluble proteins (opsonins) that
bind to the microbes.
• PAMP binding triggers microbe uptake into
phagosomes, which fuse with lysosomes or
prepackaged granules, leading to their
killing through the actions of lysosomal
enzymes, antimicrobial proteins and
peptides, etc.
• Intracellular bacteria may be killed by the
process of autophagy, in which bacteria are
surrounded with membrane to form an
autophagosome that then fuses with
lysosomes.
• Inflammatory responses are initiated by
innate immune responses to local infection
or tissue damage—in particular, by the
proinflammatory cytokines IL-1β, TNF, and
IL-6.
• Key early components of inflammatory
responses are increased vascular
permeability, allowing soluble innate
mediators to reach the infected or
damaged site, and the recruitment through
the action of chemokines of neutrophils and
monocytes from the blood into the site.
• Natural killer (NK) cells, the first ILC
discovered, have the unique function of
killing cells that have become altered due
to infection or stress.
• NK cells induce apoptosis of target cells if
their activating receptors, which recognize
markers of infection or stress on cells, send
stronger signals than their inhibitory
receptors, which recognize markers of
normal cells, such as MHC proteins.
