CHAPTER 15

INNATE IMMUNITY
Outline
An overview of Body`s defenses
The body`s first line of defense
The body`s second line of defense

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A pathogen can cause disease only if it can

1. Gain access, either by penetrating the surface of the skin
or some portal of entry
2. Attach itself to the host cells
3. Evade the body`s defense mechanism

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The Movement of Microbes into Hosts

Portals of Entry
Sites through which pathogens enter the body
Three major pathways
Skin
Mucous membranes
Placenta

Parenteral route

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An overview of Body`s defenses

Species resistance :
cells (with receptors for pathogens) and certain physiological processes
(pH, temperature) of humans are incompatable with those of plants and
animals
humans have resistance to those species of plants and animals.
-chemical receptors these pathogens require are not present in
humans
Eg. Tobacco mosaic virus, feline immunodeficiency syndrome

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An overview of Body`s defenses

Three main lines of defense First line of defense : external physical barriers to
pathogens eg. Skin, Mucous membranes
Second line of defense : Internal protective cells,
bloodborne chemicals, processes that inactivate or kill
invaders.
First and Second Innate immunity present at birth
and work on wide variety of pathogens Protozoa,
parasitic worms, fungi, bacteria, viruses
Third line of defense : adaptive immunity responds
against unique species and strains of pathogens and alters
the body defenses.
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The Bodys First Line of Defense

The Role of Skin in Innate Immunity
Skin composed of two major layers
Epidermis : Multiple layers of tightly packed cells ;
Few pathogens can penetrate these layers ;
Shedding of dead skin cells removes microorganisms ;
Epidermal dendritic cells phagocytize pathogens
Dermis : Collagen fibers help skin resist abrasions that could
introduce microorganisms

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The Bodys First Line of Defense

The Role of Skin in Innate Immunity
Skin has chemicals that defend against pathogens
Perspiration secreted by sweat glands
Salt inhibits growth of pathogens
Antimicrobial peptides (defensins) act against
microorganisms dermicidins broad spectrum
Lysozyme destroys cell wall of bacteria
Sebum secreted by sebaceous (oil) glands
Helps keep skin pliable and less likely to break or tear
Lowers skin pH to a level (pH5) inhibitory to many
bacteria

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The Role of Mucous Membranes

Mucous membranes line all body cavities open to environment
Eg. Respiratory, Urinary, digestive, reproductive tracts
Two distinct layers
Epithelium
Thin, outer covering of the mucous membranes
Epithelial cells are living
Tightly packed to prevent entry of pathogens
Continual shedding of cells carries away microorganisms
Dendritic cells below the epithelium
Stem cells mucous cells, ciliated epithelial cells
Deeper connective layer that give mechanical and nutritive
support to the epithelium

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The structure of the respiratory system

Mucus secreting goblet cells

antimicrobial peptides (defensins)

nasal Mucus contains Lysozyme

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Figure 15.2

The lacrimal apparatus

Group of structures that produces and drains tears
Blinking spreads tears and washes surface of the eye
Lysozyme in tears destroys bacteria

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Figure 15.3

The Bodys First Line of Defense

The Role of Normal Microbiota in Innate Immunity
Microbial antagonism
Normal microbiota compete with potential pathogens
Activities of normal microbiota make it hard for pathogens to
compete
Consumption of nutrients
Create an environment unfavorable to other microorganisms
Help stimulate the bodys second line of defense
Promote overall health by providing vitamins (vitamin B5,
folic acid, precurssor of vitamin K) to host
Animals raised in an axenic environment (free of all other organisms and
viruses) are slower to defend themselves when exposed to a pathogen.

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Other First-Line Defenses

Antimicrobial peptides
Present in skin, mucous membranes, neutrophils
Triggered by sugar or protein molecules of the pathogens
Act against a variety of microbes
Work in several ways (punch holes in cytoplasmic
membranes, interrupt internal signaling or enzymatic action,
chemotactic factors that recruit leucocytes).
Other processes and chemicals
Many organs secrete chemicals with antimicrobial properties
Eg. Stomach acid, Saliva lysozyme and digestive enzyme

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The Bodys Second Line of Defense

Operates when pathogens penetrate the skin or mucous membranes
Composed of cells (Phagocytes), antimicrobial chemicals (peptides,
complement, interferons), processes (fever, inflammation)
Many of these components are contained or originate in the blood
Act on wide variety of pathogens viruses to parasitic worms
Defense Components of Blood
Blood is a complex liquid tissue with cells and fluid called plasma
Plasma - Mostly water containing electrolytes, dissolved gases,
nutrients, and proteins
Serum - is the fluid remaining when clotting factors are removed from
plasma
Includes iron-binding proteins (transferrin, ferritin, siderophores,
lactoferrin, hemolysin), complement proteins and antibodies

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Defense Components of Blood

Cells and cell fragments in plasma are called formed elements
Formed from blood stem cells in the bone marrow
Three types of formed elements
1. Erythrocytes : Carry oxygen and carbon dioxide in the
blood
2. Platelets : formed from megakaryocytes and are involved in
blood clotting
3. Leukocytes : Involved in defending the body against
invaders. They are commonly called WBCs.
- Divided into granulocytes and agranulocytes

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Schematic representation of hematopoiesis

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Figure 15.4

Defense Components of Blood

Granulocytes : Contain large granules that stain different colors
Three types
1. Basophils stain blue with basic dye methylene blue
2. Eosinophils stain red/orange with acidic dye eosin
3. Neutrophils stain lilac with mix of acidic and basic
dyes. Also called as polymorphonuclear leukocytes
(PMNs)
Neutrophils and eosinophils
Phagocytize pathogens
Capable of diapedesis (squeeze between the cells lining
the capillaries)

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Leukocytes as seen in stained blood smears

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Figure 15.5

Defense Components of Blood

Agranulocytes : Cytoplasm appears uniform under a light microscope
Two types
1. Lymphocytes : Most involved in adaptive immunity; small
cells, nucleus fill the cells; natural killer cells has a role in
innate immunity
2. Monocytes : Leave the blood and mature into
macrophages ; large cells, lobed nucleus
scavenger function
wandering macrophages (diapedesis), alveolar
macrophages of the lungs, microglia of CNS
they engulf and degrade foreign objects including
bacteria, fungi, spores, dust, dead body cells.

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Defense Components of Blood

Lab analysis of leukocytes
Differential white blood cell count can signal signs of disease
Increased eosinophils indicate allergies or parasitic worm
infection
Bacterial diseases often show increase in leukocytes and
neutrophils
Viral infections show increase in lymphocytes

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Phagocytosis
Cells capable of phagocytosis are called phagocytes
Phagocytosis can be divided into six stages
1. Chemotaxis :
Is movement of cell towards (+ve) or away (-ve) from a chemical stimulus.
Use Pseudopodia.
Chemicals such as microbial components, secretions, components of
damaged tissues, WBCs and chemotactic factors such as defensins,
peptides, chemokines by leucocytes.
2. Adherence : attachment to microorganisms
through glycoproteins on the membranes of cells.
Virulence factors (eg. Proteins or slippery capsules) hinder phagocytosis.
Opsonization ( coating or covering of pathogens with opsonins or
antimicrobial proteins such as complement or antibodies).
3. Ingestion: They extend pseudopodia , engulf the microbe phagosome

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4. Maturation :
phagolysosome which contains enzymes, highly reactive and toxic forms of
oxygen, low pH 5.5
Digestion complete in 10-30 minutes.
5. Killing residual body
6. Elimination:
exocytosis - elimination of phagosomes.
Antigen processing and presentation - on membrane.

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The events of phagocytosis

1. cytoplasmic receptors for recognising microbial surface components cell wall components or flagella
2. Opsonins help

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Figure 15.6

Nonphagocytic Killing
Killing by eosinophils
Attack parasitic helminths by attaching to their surface
Secrete toxins that weaken or kill the helminth
Eosinophilia (elevated eosinophils) is often indicative of
a helminth infestation
Eosinophil mitochondrial DNA and secreted proteins form
structure (barrier) that kills some bacteria
First evidence that DNA can kill bacteria

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Nonphagocytic Killing
Killing by natural killer lymphocytes
Secrete toxins onto surface of virally infected cells and tumors
Differentiate normal body cells from infected cells or tumor cells
because they have membrane proteins similar to the NK cells
Killing by neutrophils
Produce chemicals that kill nearby invaders
Enzymes create Superoxide radical, hydrogen peroxide an
enzyme convert these into hypochlorite
Generate extracellular fibers called neutrophil extracellular traps
(NETs) that bind to and kill bacteria (NETs made from DNA,
histones, membranes and proteins)

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Second Line of Defense :Nonspecific Chemical Defenses Against Pathogens

Toll-like receptors (TLRs)
Integral membrane proteins produced by phagocytic cells
Bind pathogen-associated molecular patterns (PAMPs)
bacterial or viral components such as flagellin, unmethylated C
& G, dsRNA, ssRNA
TLRs cytoplasmic membranes, phagosome membranes,
alone or in pairs and bind PAMPs
Binding of TLRs to PAMPs Initiate defensive responses
Apoptosis (cell suicide), Secretion of inflammatory
mediators or interferons; Production of stimulants of
adaptive immune response
NOD proteins (nucleotide oligomerization domains) are receptors
which are cytosolic proteins for PAMPs. Bind RNA of viruses,
bacterial cell walls
Trigger apoptosis, other innate immune responses.

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Nonspecific Chemical Defenses Against Pathogens

Interferons (for viruses)
Protein molecules released by host cells to nonspecifically inhibit the spread of
viral infections
Cause many symptoms associated with viral infections (malaise, muscle
aches, headache, fever)
Viral nucleic acid binds to TLR3, 7 or 8 stimulate the production of
interferons
Two types
Types I (alpha and beta) appear early in viral infections. Monocytes,
macrophages, some lymphocytes secrete alpha. Fibroblasts of
connective tissues secrete beta
Type II (gamma) or Macrophage activation factor later in the course of
infection by activated T-lymphocytes and NK lymphocytes, stimulates
activity of macrophages

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The actions of alpha and beta interferons

AVP = antiviral proteins
Oligoadenylate
synthetase,(degradation of
mRNA)
Protein kinase

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Figure 15.7

Nonspecific Chemical Defenses Against Pathogens

Complement system: Set of serum proteins designated
numerically according to their order of discovery
Complement activation results in lysis of the foreign cell
Complement can be activated in three ways
1. Classical pathway antibodies activate complement
2. Alternate pathway pathogens or pathogenic
products (bacterial glycoproteins, endotoxins)
3. Lectin pathway microbial polysaccharides bind to
activating molecules.

Membrane attacking complex

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Pathways by which complement is activated

-Three pathways merge.
- cascade reactions : complement proteins react with one another in an amplifying sequence
of chemical reactions, in which product of one reaction becomes enzyme that catalyzes the
next reaction
Classical pathways: Proteins act to
complement or in conjunction with,
action of antibodies.
Alternative pathway: occurs
independent of antibodies. Useful in
the early stages of infection before
the adaptive immune response.
Cleavage of C3 into C3a and C3b.
Lectin pathway: lectins are
chemicals that bind to specific sugar
subunits of polysaccharides as
mannose of mannans on the surface
of fungi, bacteria or viruses. Trigger
by cleaving C2 and C4.
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Figure 15.8

The complement cascade

Lectins bound to
mannose act to trigger
complement cascade by
cleaving C2 and C4.
C3 C3a, C3b
C3b adhere to
membrane surface
for factor B
Factor D cleaves B
to Bb and C3b.
End product
Membrane attack
complex

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Figure 15.9

The Bodys Second Line of Defense

Inactivation of complement
Bodys own cells withstand complement cascade
Proteins on many cells bind and break down
activated complement proteins

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Inflammation
Nonspecific response to tissue damage from various causes (heat, sunburn,
pathogens, cuts)
Characterized by redness(rubor), localized heat (calor), edema (swelling), and
pain(dolor)
Two types
1. Acute develops quickly, short lived, beneficial, elimination or resolution of
condition
Is important in the second line of defense
a) Dilation and increased permeability of the blood vessels
b) Migration of phagocytes (monocytes, neutrophils)
c) Tissue repair
2. Long-lasting (chronic) damage (or death) to the tissues, resulting in
disease.

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The stimulation of inflammation by complement

1. Localized dilation
2. Blood clotting triggers the formation
of Bradykinin potent mediator of
inflammation; vasodilator
3. Patroling Macrophages with TLRs
and NOD proteins release
prostaglandins & Leukotrienes to
identify invaders (make small veins
permeable)
4. Basophils, platelets, mast cells
release histamine (vasodilator) on
exposure to C3a, C5a

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Figure 15.11

The dilating effect of inflammatory mediators

Bradykinin & histamine
- cause vasodilation of arterioles
more phagocytes, more nutrients, more
oxygen
-cause cells to make more adhesion
molecules receptors for leukocytes
- with prostaglandins and leukotrienes
make small veins permeable
phagocytes enter
Edema fluid leak in the tissue causes
pressure pain (dolor)
Vasodilation redness (rubor) and
localized heat (calor)

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Figure 15.12

Increased vascular permeability during inflammation

Fibrinogen blood clotting protein.
Clots at injury site prevent pathogens and their toxins from spreading.
Pus fluid with dead tissue cells, leukocytes and pathogens erupt or
absorbed
Abscess isolated site of infection. eg. Pimples, boils, pustules

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Figure 15.13

An overview of the events of inflammation

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Figure 15.14

The Bodys Second Line of Defense

Fever is beneficial in fighting infection
A body temperature over 37C
Results when pyrogens trigger the hypothalamus to increase the bodys core
temperature
Various types of pyrogens
Bacterial toxins
Cytoplasmic contents of bacteria released by lysis
Antibody-antigen complexes
These signal for the production of interleukin-I (IL-1)

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One explanation for fever in response to infection

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Figure 15.15