Non-specific Host

Defenses
Prepared by:
GEORGINE L. MANANTAN, RMT,RN,RM,MSN

Introduction:

Resistance
Ability to ward of disease.
The capacity of an
organism to defend itself
against a disease.
The capacity of an
organism or a tissue to
withstand the efects of a
harmful environmental
agent.

Nonspecific Resistance:
Defenses that protect
against all pathogens.
Specific Resistance:
Protection against
specific pathogens.

Susceptibility:
Vulnerability or lack of
resistance.
the state of being
predisposed to, sensitive to,
or of lacking the ability to
resist a pathogen, familial
disease, or a drug.

Against
Invading
Pathogen

First Line of
Defense:
Non-specific natural
barriers which restrict
entry of pathogen.
Examples: Skin and
mucous membranes.

Second Line of
Defense:
Innate non-specific immune
defenses provide rapid local
response to pathogen after
it has entered host.

Examples: Fever, phagocytes

(macrophages & neutrophils),
inflammation, and interferon.

cells

Third line of
defense:

Antigen-specific immune
responses, specifically
target and attack
invaders that get past
first two lines of defense.
Examples: Antibodies
and lymphocytes.

antibodies

Three Lines of Defense

Against Infection

First Line of
Defense:
Skin and Mucous
Membranes

I. Mechanical
Defenses
1. Skin has two
Layers:

A.Epidermis
Thin outer layer of epithelial
tissue.
Contains Langerhans cells,

B. Dermis
Thick inner layer of connective
tissue.
Infections are rare in intact
skin.
Exceptions:
Hookworms can penetrate
intact skin
Dermatophytes: Skin
loving fungi

Intact Skin is an Efective

Barrier Against Most
Pathogens

I. Mechanical
Defenses

2. Mucous
Membranes
Line
gastrointestinal,
genitourinary, and
respiratory tracts.

Two layers: Outer epithelial

and inner connective layer.

Epithelial layer

secretes mucus which

maintains moist
surfaces.
Although they inhibit
microbial entry, they
ofer less protection

Several microorganisms are capable of

penetrating mucous membranes:

Papillomavirus
Treponema pallidum
Enteroinvasive E. coli
Entamoeba histolytica

Papillomavirus

Treponema
pallidum

Entamoeba coli

Entamoeba histolytica

I. Mechanical
Defenses

3. Lacrimal
apparatus
Continual washing
and blinking
prevents microbes
from settling on the

Lac
rim
al
app
arat
us

4. Saliva
Washes microbes from
teeth and mouth mucous
membranes.

5. Mucus
Thick secretion that traps
many microbes.

6. Nose Hair

Coated with
mucus filter
dust, pollen,
and
microbes.

7. Ciliary Escalator
Cilia on
mucous
membranes
of lower
respiratory
tract move
upwards
towards
throat at 1-3
cm/hour.

8. Coughing and
sneezing:

Expel
foreign
objects.

9. Epiglottis
Covers
larynx
during
swallowing
.

Epiglottis Protects Respiratory System

from Infection During Swallowing

10. Urination
Cleanses urethra.

11. Vaginal
Secretions

Remove microbes from

genital tract.

B. Chemical
Defenses:
Sebum:
Oily substance produced by
sebaceous glands that forms a
protective layer over skin.
Contains unsaturated fatty
acids which inhibit growth of
certain pathogenic bacteria
and fungi.

pH
Low, skin pH usually
between 3 and 5. Caused
by lactic acid and fatty
acids.

Perspiration:
Produced by
sweat glands.
Contains
lysozyme and
acids.

Lysozyme
Enzyme that
breaks down
gram-positive
cell walls.
Found in nasal
secretions,
saliva, and
tears.

B. Chemical
Defenses
Gastric Juice
Mixture of hydrochloric acid,
enzymes, and mucus. pH
between 1.2 to 3 kills many
microbes and destroys most
toxins. Many enteric bacteria
are protected by food particles.

Helicobacter pylori
neutralizes stomach acid and
can grow in the stomach,
causing gastritis and ulcers.

Helic
obact
er
pylori

Transferrins
Iron-binding proteins in
blood which inhibit
bacterial growth by
reducing available iron.
also called Siderophilin, protein
(beta1 globulin) in blood plasma
that transports iron from the
tissues and bloodstream to the
bone marrow, where it is reused
in the formation of hemoglobin.

Cellular Elements of Blood

Cell Type

# Cells/mm3 Function

Erythrocytes (RBC) 4.8-5.4 million Transport O2 and CO2

Leukocytes (WBC) 5,000-10,000

Various

A. Granulocytes:
1. Neutrophils (70% of WBC)
Phagocytosis
2. Basophils (1%)
Produce histamine
3. Eosinophils (4%)
Toxins against parasites
some phagocytosis
B. Monocytes/Macrophages (5%)
C. Lymphocytes (20%)

Platelets

Phagocytosis

Antibody production (B cells)

Cell mediated immunity (T cells)

300,000

Blood clotting

Composition of Human
Blood

Platelets Form Blood Clots

II. Second Line

of Defense

1. Phagocytosis
Derived from the Greek
words Eat and cell.
Phagocytosis is carried out
by white blood cells:
macrophages,
neutrophils,
occasionally

Neutrophils
predominate early in
infection.

Wandering macrophages
Originate from monocytes
that leave blood and enter
infected tissue, and develop
into phagocytic cells.

Fixed Macrophages (Histiocytes):

Located in liver,
nervous system, lungs,
lymph nodes, bone
marrow, and several
other tissues.

1. Chemotaxis
Phagocyte
s are
chemically
attracted
to site of
infection.

Phagocytic Cells: Macrophages

(Monocytes), Neutrophils, and
Eosinophils

(Macrophages)

Stages of

Phagocyto
sis

Phagocytes are Attracted to

Site of Infection by Chemotaxis

2. Adherence:

Phagocyte plasma
membrane attaches to
surface of pathogen or
foreign material.
Adherence can be inhibited
by capsules (S.
pneumoniae) or M protein
(S. pyogenes).

Opsonization:
Coating process with
opsonins that facilitates
attachment.

Opsonins
include antibodies and
complement proteins.

3. Ingestion
Plasma membrane of
phagocytes extends
projections (pseudopods)
which engulf the
microbe.
Microbe is enclosed in a
sac called phagosome.

4. Digestion
Inside the cell, phagosome fuses with
lysosome to form a phagolysosome.
Lysosomal enzymes kill most bacteria
within 30 minutes and include:
Lysozyme: Destroys cell wall
peptidoglycan
Lipases and Proteases
RNAses and DNAses

After digestion, residual body

with undigestable material is

Process of Phagocytosis

Inflam
mation

Triggered by tissue damage

due to infection, heat,
wound, etc.

Functions of
Inflammation
1. Destroy and remove pathogens
2. If destruction is not possible, to
limit efects by confining the
pathogen and its products.
3. Repair and replace tissue damaged
by pathogen and its products.

HOST DEFENSE

HOST DEFENSE
CELLULAR PARTICIPANTS
POLYMORPHONUCLEAR
LEUKOCYTES
Neutrophils
Eosinophils
Basophils

POLYMORPHONUCLEAR LEUKOCYTES

Neutrophil

Eosinophil

Basophil

HOST DEFENSE
CELLULAR PARTICIPANTS

MONONUCLEAR
LEUKOCYTES
Lymphocytes
Monocytes

LYMPH
OCYTE
S

MON
OCYT
E/
HISTI
OCYT
E/
MAC
ROP
HAG
E

PLATELETS

HOST DEFENSE
Neutrophils
I
n
t
e
n
s
i
t
y

Fibroblasts
Lymphocytes
Macrophages

Acute
INJURY

Chronic
Time

Fibrosis

Scar
REPAIR

ACUTE
INFLAMMATION

ACUTE INFLAMMATION

INJURY

Mediators

Acute
inflammation

ACUTE INFLAMMATION

Inflammation
Major Symptoms of Inflammation:
LOCAL MANIFESTATION

1.
2.
3.
4.
5.

Redness
Pain
Heat
Swelling
Loss of function

ACUTE INFLAMMATION

SYSTEMIC MANIFESTATIONS
Fever
Chills
Myalgia
Malaise

ACUTE INFLAMMATION
LABORATORY MANIFESTATIONS

Leukocytosis

(granulocytosis vs.
lymphocytosis)
Elevated serum acute phase proteins

(C-reactive protein, fibrinogen,

etc)
Increased ESR

(erythrocyte sedimentation
rate)
Hypercoagulability

ACUTE INFLAMMATION
SEQUELAE

RESOLUTION
Mediators
INJURY

Acute inflammation

t
ia
ed

Chronic irritation
Viral infection

Mediators

s
or

Autoimmune disease

Chronic inflammation

ACUTE INFLAMMATION

ACUTE INFLAMMATION
SEQUENCE OF EVENTS

Vasoconstrictio
n
Vasodilation
Increased
vascular
permeability
Hemoconcentr
ation and
stasis

Leukocyte
Adhesion
Transmigratio
n
Chemotaxis
Aggregation

Stages of Inflammation
1. Vasodilation
.Increase in diameter of blood
vessels.
.Triggered by chemicals
released by damaged cells:
histamine, kinins,
prostaglandins, and
leukotrienes.

ACUTE INFLAMMATION
VASODILATION

ACUTE INFLAMMATION
VASODILATION

ACUTE INFLAMMATION

Increase in
Permeability

INCREASED VASCULAR PERMEABILITY

Histamine (Mast Cells)

Seratonin (Platelets)

Time

ACUTE INFLAMMATION
HEMOCONCENTRATION AND STASIS

Normal flow

Stasis

ACUTE INFLAMMATION
LEUKOCYTE ADHESION

ACUTE INFLAMMATION
LEUKOCYTE ADHESION

ACUTE INFLAMMATION
EMIGRATION (TRANSMIGRATION)

ACUTE INFLAMMATION
EMIGRATION (TRANSMIGRATION)

ACUTE INFLAMMATION
CHEMOTAXIS

ACUTE INFLAMMATION
AGGREGATION

ACUTE INFLAMMATION
PHAGOCYTOSIS - ATTACHMENT

ACUTE INFLAMMATION
PHAGOCYTOSIS - ENGULFMENT

ACUTE INFLAMMATION
PHAGOCYTOSIS KILLING AND DEGRADATION

ACUTE INFLAMMATION

2. Phagocyte Migration and

Margination
Margination is the process in
which phagocytes stick to
lining of blood vessels.
Diapedesis (Emigration):
Phagocytes squeeze between
endothelial cells of blood
vessels and enter surrounding
tissue.

Phagocytes are attracted to site

of infection through
chemotaxis.
Phagocytes destroy microbes,
as well as dead and damaged
host cells.

3. Tissue Repair
.Dead and damaged cells
are replaced.

Process of
Inflammation

ACUTE INFLAMMATION
PATTERNS
Serous
Catarrhal
Fibrinous
Hemorrhagic
Suppurative
Gangrenous
Pseudomembran
ous

ACUTE INFLAMMATION

SEROUS

ACUTE INFLAMMATION
SEROUS

ACUTE INFLAMMATION
CATARRHAL

ACUTE INFLAMMATION
FIBRINOUS

ACUTE INFLAMMATION
HEMORRHAGIC

ACUTE INFLAMMATION
SUPPURATIVE / PURULENT

ACUTE INFLAMMATION
SUPPURATIVE / PURULENT - ABSCESS

ACUTE INFLAMMATION
SUPPURATIVE / PURULENT - ABSCESS

ACUTE INFLAMMATION
SUPPURATIVE / PURULENT - EMPYEMA

ACUTE INFLAMMATION
ULCERATIVE

Thomas McGovern M.D.

ACUTE INFLAMMATION
GANGRENOUS

ACUTE INFLAMMATION
GANGRENOUS

Appendix

Gallbladder

ACUTE INFLAMMATION
PSEUDOMEMBRANOUS

Atlanta South Gastroenterology, P.C.

Antimicrobial Substances:
I. Complement System:
Large group of serum proteins
that participate in the lysis of
foreign cells, inflammation, and
phagocytosis.

II. Interferons:
Antiviral proteins that interfere with
viral multiplication.
Small proteins (15,000 to 30,000
kDa)
Heat stable and resistant to low pH
Important in acute and short term
infections.
Have no efect on infected cells.
Host specific, but not virus specific.

Interferon alpha and beta:

Produced by virus infected
cells and difuse to
neighboring cells. Cause
uninfected cells to produce
antiviral proteins (AVPs).
Interferon gamma: Produced by
lymphocytes. Causes
neutrophils to kill bacteria.

Two mechanisms of
complement
activation:

1. Classical Pathway: Initiated

by an immune reaction of
antibodies.
2. Alternative Pathway: Initiated
by direct interaction of
complement proteins with
microbial polysaccharides.
Both pathways cleave a complement
protein called C3, which triggers a series
of events.

Classical Complement Pathway is

Triggered by Antibodies Binding to
Foreign Cells

Both Classical and Alternative

Complement Pathways Trigger the
Cleavage of C3

Consequences
of Complement
Activation

1. Cytolysis: Due to the

formation of a membrane
attack complex (MAC)
which produces lesions in
microbial membranes.
2. Inflammation: Complement
components (C3a) trigger the
release of histamine, which
increases vascular

3. Opsonization: Complement
components (C3b) bind to
microbial surface and
promote phagocytosis.
4. Inactivation of Complement:
Regulatory proteins limit
damage to host cells that
may be caused by
complement.

Classical and Alternative Complement

Pathways
Cause Inflammation, Opsonization, and
Cytolysis

Cytolysis Caused by Membrane

Attack Complex

Thank you