NON SPECIFIC HOSTDEFENSE

MECHANISM
Host Defense Mechanism
 Ways which the body protects
itself from pathogesns.
 First 2 lines of defense are
nonspecific
 Third line of defense
mechanism the immune
response, is very specific
 In the 3rd line of defense,
special proteins called
antibodies are produced in
response to foreign
substances called antigens.
Nonspecific Host Defense Mechanisms
 It is general and serve to protect the body from a variety of
foreign substances or pathogens
 Innate or inborn
 Resistance observed among some species of animals and some
persons who have a natural resistance to certain disease.
 Other nonspecific host defense mechanisms include mechanical
and physical barriers to invasion, chemical factors, microbial
antagonism, fever, the inflammatory response, and phagocytic
white blood cells.
Specific Host Defense Mechanism
 Directed against a particular foreign substance or pathogen
that has entered the body.
First Line of Defense
 These are a combination of physical and chemical
barriers that prevent all types of foreign agents from
penetrating the outer layer of the body.
 No specific foreign agent is targeted at this level
Physical Barrier
 It serves as a physical or mechanical barrier to pathogens
 Very few pathogens are able to penetrate intact skin
 Helminth infections are acquired by penetration of the skin
by parasites.
 Hookworm infection and schistosomiasis
 Most pathogens can only pass through when theses
membranes are cut or scratched
Physical Barrier
 Repels many organisms: difficult to get through.
 Epithelium lines all body systems exposed to external
environments including the respiratory, digestive and urinary
systems.
 Secretes liquid which are mildly acidic which hinder bacterial
growth.
 Lack of nutrition for microbial growth.
Physical Barrier
 Skin
 Cells filled with keratin, making skin impenetrable, waterproof, and
resistant to disruptive toxins and most invaders.
 Dead cells are shed and replaced (1 million every 40 min).
 Mucous Membranes
 The inner surfaces of the body are guarded by mucous membranes
that line the respiratory, digestive, urinary, and reproductive systems
and protect the internal lining
 But, mucous membranes are more vulnerable than skin
 linings of the GI, genitourinary, and respiratory tracts
 Mechanical removal:
 Sloughing off of cells
 Coughing and sneezing
 Flushing from urinary system
 Vomiting
 Mucus and cilia
Several microorganisms are capable of
penetrating mucous membranes:
Enteroinvasive E. coli Papillomavirus
Several microorganisms are capable of
penetrating mucous membranes:
Treponema pallidum Entamoeba histolytica
Cellular and Chemical Factors
 Sweat produced by glands in the skin wash away microbes
and their acidity slows bacterial growth.
 Mucous membranes produce sticky mucous that traps many
microbes
 Saliva and tears contain an enzyme called lysozyme that kills
bacteria by rupturing their cell walls
 Cerumen (ear wax) – produced in the ear canal and protects
the canal by trapping dirt and dust particles
 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.
 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.
Cellular and Chemical Factors
 Following factors protect the digestive system from bacterial
colonization and are therefore considered to be nonspecific
host defense mechanisms:
 Digestive enzymes
 Acidity of the stomach (approx. pH 1.5)
 Alkalinity of the intestines
Microbial Antagonism
 When resident microbes of the indigenous microflora
prevent colonization by new arrivals to a particular
anatomical site.
 The inhibitory capability of the indigenous microflora has
been attributed to the following factors:
 Competition for colonization sites.
 Competition for nutrients.
 Production of substances that kill other bacteria
Second Line of Defense
 Pathogens able to penetrate the first line of defense are
usually destroyed by nonspecific cellular and chemical
responses.
 A complex sequence of events develop involving production
of fever, production of interferons, activation of the
complement system, inflammation, chemotaxis, and
phagocytosisx
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.
Fever
 Normal body temperature is between 36.2 C and 37.5 C
(92.7 F and 99.5 F).
 Average body temperature is 37.8 C (98.6 F)
 Fever is a defense mechanism that can destroy many types of
microbes
 Fever also helps fight viral infections by increasing interferon
production.
 Substance that stimulate the production of fever are called
pyrogens or pyrogenic substances.
Antimicrobial Substances: 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 effect on infected
cells.
 Host specific, but not virus
specific.
Antimicrobial Substances: Interferons
 Interferon alpha and beta:
 Produced by virus infected cells and diffuse to neighboring
cells. Cause uninfected cells to produce antiviral proteins
(AVPs).
 Interferon gamma:
 Produced by lymphocytes. Causes neutrophils to kill bacteria
Antimicrobial Substances: Complement
System
 Not a single entity, but rather a group
of approx. 30 different proteins that are
found in normal blood plasma.
 These proteins make up the
complement system because it is
complementary to the action of the
immune system.
 Large group of serum proteins that
participate in the lysis of foreign cells,
inflammation, and phagocytosis.
 Opsonization is a process by which
phagocytosis is facilitated by the
deposition of opsonins (e.g., antibodies
or certain complement fragments) onto
objects (e.g., pathogens)
Acute-Phase Proteins
 are plasma proteins, the synthesis and the circulating
concentrations of which are adaptively regulated
in response to most forms of inflammation, infection and
tissue injury.
Cytokinesis
 Chemical mediators that are released from many different
types of cells in the human body
 Enable cells to communicate with each other
 Act as a chemical messengers both within the immune
system and between the other systems of the body
Inflammation
 The body normally responds to any local injury, irriation,
microbial invasion, or bacterial toxin by a complex series of events
collectively.
 Referred also as inflammatory response
 Triggered by tissue damage due to infection, heat, wound, etc.
 An increase in the diameter of capillaries (vasodilation) which
increases blood flow to the site
 Increased permeability of the capillaries, allowing the escape of
plasma and plasma proteins
 Exit of leukocytes from the capillaries and their accumulation at
the site of injury
Inflammation
Three Major Events in acute inflammation
 An increase in the diameter of capillaries (vasodilation)
which an increases blood flow to the site
 Increased permeability of the capillaries, allowing the escape
of plasma and plasma proteins.
 Egress (exit) of leukocytes from the capillaries and their
accumulation at the site of injury.
 The 4 major signs and symptoms of inflammation are:
redness, heat, swelling (edema), and pain
 Plasma that escapes from the capillaries into the site
causes the area to become edematous (swollen)
Sequence of Events in Inflammation
1. Tissue Injury

2. Vasodilation

3. Increased Permeability

4. Emigration of Leukocytes

5. Chemotaxis

6. Phagocytosis
• The accumulation of fluid, cells,
and cellular debris at the
inflammation site is known as an
inflammatory exudate.
– If the exudate is thick and
greenish-yellow, containing
many live and dead
leukocytes, it is known as a
purulent exudate or pus.
• In many inflammatory responses
(e.g., arthritis or pancreatitis)
there is no exudate and no
invading microorganisms.
• Pyogenic microorganisms (pus-
producing microorganisms) like
staphylococci and streptococci
result in additional pus formation.
Phagocytosis
 Derived from the Greek
words “Eat and cell”.
 Phagocytosis is carried out by
white blood cells:
 Macrophages - Originate
from monocytes that leave
blood and enter infected
tissue, and develop into
phagocytic cells
 Neutrophils - predominate
early in infection
 occasionally eosinophils.
 Chemotaxis - Phagocytes are
chemically attracted to site of
infection.
Phagocytic Cells: Macrophages (Monocytes),
Neutrophils, and Eosinophils
Cellular Elements of
Human Blood
Stages of Phagocytosis- Chemotaxis
 Phagocytes are Attracted to Site of Infection by Chemotaxis
it is the directed migration.
 The result of chemical attractants are called Chemotactic
agents (also called chemotactic factors, chemotactic
substances, and chemoattractants).
Stages of Phagocytosis- Chemotaxis
 Phagocytes are Attracted to Site of Infection by Chemotaxis
Stages of Phagocytosis - Adhere
 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
Stages of Phagocytosis - Ingestion
 Plasma membrane of phagocytes extends projections
(pseudopods) which engulf the microbe.
 Microbe is enclosed in a sac called phagosome
Stages of Phagocytosis - Ingestion
 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
discharged.
Mechanisms by Which Pathogens
Escape Destruction by Phagocytes
 Capsules; initially serve to protect the organism from
phagocytosis (they serve an antiphagocytic function)
 Some bacteria produce an exoenzyme called leukocidin,
which kills phagocytes.
Some bacteria (e.g., Mycobacterium tuberculosis) are not
destroyed within the phagolysosome.
 The mechanism by which each pathogen evades
digestion by lysosomal enzymes differs from pathogen to
pathogen, and is not yet fully understood.
 Disorders and Conditions That
Adversely Affect Phagocytic and
Inflammatory Process
 Leukopenia
 Abnormally low number of circulating leukocytes
 It may result from bone marrow injury as a result from bone
marrow injury as a result of ionizing radiation or drugs,
nutritional deficiencies, or congenital stem cell defects.
 Disorders and Conditions Affecting Leukocyte Motility
and Chemotaxis
 Inabililty of leukocytes to migrate in response to chemotactic agents may be
related to a defect in the production of actin, a structural protein associated
with motility
 Disorders and Conditions Affecting Intracellular Killing
By Phagocytes (e.g., chronic granulomatous disease,
CGD)
 Additional Factors
 Additional Factors That Can impair
Host Defense Mechanisms
Factor Comments

Nutritional Status Malnutrition is accompanied by decreased resistance to infections

Increased Iron Levels High concentration of iron make it easier for bacteria to satisfy their
iron requirements; high concentrations of iron reduce the chemotactic
and phagocytic activities of phagocytes; increased iron levels may result
from a variety of conditions or habits
Stress People living under stressful conditions are more susceptible to
infections than people living under less stressful conditions
Age Newborn infants lack a fully developed immune system, the efficiency
of the immune system and other host defenses declines after age 50
 Additional Factors That Can impair
Host Defense Mechanisms
Factor Comments

Cancer and Cancer Cancer chemotherapeutic agents kill healthy cells and malignant one
Therapy
AIDS Destructions of the AIDs patient’s helper T cells decreases the patient’s
ability to produce antibodies to certain pathogens
Drugs Steroids and alcohol

Various B-cell and T-cell deficiencies

Genetic Defects