Defense Mechanisms of the

Body

AMEET KUMAR
LECTURER
UCNM
 Objective
At the completion of this unit students will be able to:
• Explain the role of good health in protection against the
microbial infection.
• Define resistance and susceptibility.
• Define nonspecific resistance.
• Describe the role of the skin and mucous membrane in non
specific resistance.
• Explain the process of phagocytosis.
• Define the specific resistance, innate resistance and immunity.
• Explain four types of acquired immunity.
• Differentiate between humoral and cell mediated immunity.
 Objective Cont
……….
• Define antigens and antibodies.
• List the five classes of antibodies and their functions.
• Explain the role of memory, tolerance and specificity in
immunity.
• Distinguish between primary and secondary immune response.
• Define Hypersensitivity.
• Differentiate between delayed and immediate Hypersensitivity.
 The concept of Disease and Infection
• Many diseases that are not caused by pathogen, including
among them
 Malfunction of an organ HTN and DM.
 Vitamin deficiency Scurvy and rickets.
 Allergic response Asthma and hay fever
 Uncontrolled cell growth Tumors and cancer

• Microorganisms infection
The concept of Virulence/ Virulent/ Avirulent
Virulence
the ability of a pathogen to invade, infect the host, cause the
damage and produce disease is term its virulence
Virulent
those microbes that can cause disease with relative ease are
referred to as virulent pathogen
Avirulent
microbes incapable of causing disease are described as
avirulent
 The concept of Communicable and Contagious
diseases
Communicable Disease
An infectious disease that can be transmitted from one person
to another person, such as measles gonorrhea and diphtheria
Contagious Diseases
A communicable disease that is easily transmitted from person
to person such as common cold and influenza by air droplet

Note: the severity of any infectious disease determined by the

host resist against invasion and toxins produced by pathogen
 Why infection does not always occur?
• Some people who are exposed to pathogens but do not get
sick for numerous reasons.
 Microbes landing in wrong place and be unable to multiply.

 Unavailability to attach specific host receptor sites.

 Presence of antibacterial factors that destroy the growth of

microbes ( lysozyme in tears, saliva and perspiration).

 The indigenous flora inhibit the growth by occupying space

and using up available nutrients.
Cont ………..
 Microbes already growing in region produce antibacterial
factors (bacteriocins) that have a local antibiotic effects.

 Antibodies present because the person previously infected

with same organism or been immunized against it.

 Phagocytes present in the blood and tissues may engulf.

 The development of Infection
• Infection occur when pathogens are able to enter the host,
attach, multiply, and cause damage to the tissue of the host.
• The often respond to the infection via the inflammatory
process, the symptoms of inflammation include
 Swelling due to fluid escape from capillaries
 Redness because more blood supply against infection
 Heat caused by increased blood flow + M-activity
 Pain results from pressure on the nerve endings
• Phagocytes help to destroy the invaders and rid the area of
dead tissue, pus is often found at the site of inflammation.
• Pus consist of lymph, plasma, dead tissue cell, leukocytes and
sometimes bacteria.
 Mechanisms of disease causation
Pathogenicity
• The capacity of pathogens to cause disease. It is related to
their following abilities.
• To infect the host or protect themselves against body
defense.
• To invade and multiply in tissues.
• To cause damage or destruction to tissues.
Virulence
• It is a measure or degree of pathogenicity. Virulence can be
defined as follows.
Virulence = Infectivity + Invasiveness + Toxigenicity
 Mechanisms of disease causation
• Each species of pathogens have specific characteristics that
determine their pathogenicity and virulence.
• Characteristics contribute to the virulence of pathogen are
called virulence factors.
• Once the pathogen finds itself in a moist, warm environment,
it must be able to attach to the site and be able to resist the
body lytic enzyme, antibodies and phagocytes.
 Morphological characteristics associated
with infection
• Some structural features of pathogens enable microbes to
attach or invade tissues of the host, and multiply there thus
causing an infection.

• These structures include

 Capsules help to attach and resist phagocytosis
 Flagella enable bacteria to be motile
 Pili (Fimbriae) enable to adhere to cells within mucous
membrane
 Enzymes associated with invasiveness
• Some pathogens release enzymes that increase their ability to
invade body tissues.
• These substances includes
 Coagulase
 Kinases
 Hyaluronidase
 Collagenase
• Note that the ase ending on these words indicate that these
substances are enzymes, it means they are proteins that
catalyze particular chemical reaction.
 Enzymes associated with invasiveness

Coagulase
• Enable the microbe to clot plasma and form a sticky coat of
fibrin around themselves for protection from phagocytes and
other body defense mechanisms.

Kinases
• Fibrinolysin or kinases has the opposite effect of coagulase.
Streptokinase lyses fibrin clot, thus enable streptococci to
invade and spread throughout the body.
 Enzymes associated with invasiveness
Hyaluronidase
• Enables pathogens to spread through connective tissue by
breaking down hyaluronic acid the “cement” that hold tissue
cells together.

Collagenase
• It breaks down collagen, the supportive protein found in
tendons, cartilage and bones.
• Clostridium perfringens spreads deeply within the body by
secreting both collagenase and hyaluronidase.
 Toxins and enzymes associated with
toxigenicity
• The ability to damage host tissues may depend on the
production and release of
 Hemolysin hemo = blood, lysis = breakdown
( Alpha and Beta hemolytic streptococci)
 Leukocidin Leuko = WBCs, lysis = breakdown
( Staphylococci and streptococci)
 Exotoxins Exo = outside (Staphylococcus aureus,
Vibrio cholerae)
 Endotoxins Endo = within, (typhoid fever,
meningitis)
 Resistance and Susceptibility

Resistance: Ability to ward off disease.

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

Susceptibility: Vulnerability or lack of resistance.

 Protection Against Invading Pathogens
First Line of Defense:
 Nonspecific 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 and neutrophils),
inflammation, and interferon.
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.
Three Lines of Defense Against Infection
 First Line of Defense
• It is comprises on Skin and Mucous Membranes
• It may be mechanical defenses or chemical defenses
• Mechanical defense includes
 Skin Coughing and sneezing
 Mucous membrane Epiglottis
 Lacrimal apparatus Urination
Vaginal Secretions
 Saliva
 Mucus
 Nose Hair
 Ciliary Escalator
 First Line of Defense
• Chemical defenses include
 Sebum
 pH
 Perspiration
 Lysozyme
 Gastric Juice
 Transferrins
 First Line of Defense
Mechanical Defenses
Skin
• Skin has two Layer
 Epidermis: Thin outer layer of epithelial tissue.
Contains Langerhans cells
 Dermis: Thick inner layer of connective tissue.
Infections are rare in intact skin. Exceptions:
» Hookworms can penetrate intact skin
» Dermatophytes: “Skin loving” fungi
 First Line of Defense
Mechanical Defenses
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 offer less
protection than skin.
 Several microorganisms are capable of penetrating mucous
membranes:
Papillomavirus
Treponema pallidum
Enteroinvasive E. coli
Entamoeba histolytica
 First Line of Defense
Mechanical Defenses
Lacrimal apparatus
• Continual washing and blinking prevents microbes
from settling on the eye surface.
Saliva
• Washes microbes from teeth and mouth mucous
membranes.
Mucus
• Thick secretion that traps many microbes.
Nose Hair
• Coated with mucus filter dust, pollen, and microbes.
 First Line of Defense
Mechanical Defenses
Ciliary Escalator
• Cilia on mucous membranes of lower respiratory tract
move upwards towards throat
Coughing and sneezing
• Expel foreign objects.
Epiglottis
• Covers larynx during swallowing.
Urination
• Cleanses urethra.
Vaginal Secretions
• Remove microbes from genital tract.
 First Line of Defense
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.
 First Line of Defense
Lysozyme
• Enzyme that breaks down gram-positive cell walls. Found
in nasal secretions, saliva, and tears.
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.
Transferrins
• Iron-binding proteins in blood which inhibit bacterial
growth by reducing available iron.
 Second Line of Defense
• It is a nonspecific cellular and chemical responses to microbes
invasion.
• To trap or destroy the pathogens a complex sequence of
events develops involving
 Inflammatory response
 Fever production
 Iron balance
 Cellular secretion (Interferons, Fibronectin, B.Lysin, Interleukin)
 Blood protein (Complement, Properdin)
 Chemotaxis, Phagocytosis and Neutralization of toxins
 Clean-up and repair of damaged area.
 Second Line of Defense
Fever Production
• Fever may be triggered by various pyrogenic secretion of
pathogens.
• Increased body temperature augments the host defenses by
 Stimulating WBCs (leukocytes) to deploy and destroy
invaders.
 Reducing free plasma iron to restrict pathogen growth.
 Inducing the production of interleukin-I which causes
proliferation, maturation and activation of lymphocytes.
 Second Line of Defense
Iron balance
• The virulence of many bacteria in enhanced in the presence of
free iron.
• In response to pathogenic invasion some of the host’s
leukocytes produce interleukin-I.
• Interleukin-I induces the release of lactoferrin.
• Lactoferrin stimulates iron storage in the liver and thus
reduces the amount of free iron available for pathogens.
• Interleukin-I is also known as endogenous pyrogen.
 Second Line of Defense
Blood Protein
• A group of protein found in normal blood plasma help in
restricting pathogenic growth.
• Complement is a nonspecific defense mechanism because it
binds to different antigen-antibody complexes.
• Once complement bound, it becomes activated
 To enhance the inflammatory response.
 To aid in the destruction (lysis) of cells and microbes.
 to attract phagocytes into the region (chemotaxis).
 To aid in neutralizing the toxins of certain microbes.
 Second Line of Defense
Properdin
• A blood protein enhances phagocytosis, inflammation and the
destruction of bacteria and certain viruses.

Prostaglandins
• Act like local hormone, biologically active in platelet
aggregation, the immune response inflammation, increased
capillary permeability, pain production, autoimmune response
and many other condition in health and disease.
 Second Line of Defense
Inflammation
• Body normally respond to any local injury, irritation, microbial
invasion or toxins by complex series of events called inflammation.
• The purpose of inflammatory response are to
• Localize an infection
• To prevent the spread of microbial invaders
• To neutralize toxins
• To aid in the repair of damaged tissue
• Inflammatory response include all of the nonspecific defenses.
• These interrelated physiological reaction result in characteristic
sign and symptoms of inflammation.
Edema Redness heat pain Pus formation May
also lose of function.
 Second Line of Defense
• Inflammation……. Cont
• A complex series of physiological events occurs immediately
after the initial damage to the tissues.
• Some injured cells (mast cells, basophils, and platelet) release
chemical (histamine, bradykinin and heparin).
• Released chemical increases the permeability of capillaries
and venules.
• Vasodilation and increased capillary permeability allow more
blood to enter the area including more leukocytes for
phagocytosis and antibody production.
• The surrounding tissues becomes engorged with fluids and
edema results.
 Second Line of Defense
Inflammation ………cont
• Red blood cells collecting in the irritated area cause redness.
• Metabolic heat and fever is generated by increased cellular
activity in the destruction and detoxification of foreign bodies.
• When the inflammatory response is over the phagocytes
continue cleaning up the area and helping to restore orders.
Process of Inflammation
 Second Line of Defense
Phagocytosis
• Derived from the Greek words “Eat and cell”.
• Phagocytosis is carried out by white blood cells:
macrophages, neutrophils, and occasionally eosinophils.
• 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.
 Second Line of Defense
• Stages of Phagocytosis
Chemotaxis:
• Phagocytes are chemically attracted to site of infection.
Adherence:
• Phagocyte plasma membrane attaches to surface of pathogen
or foreign material.
• Adherence can be inhibited by capsules (S. pneumoniae) or
(S. pyogenes).
• Opsonization: Coating process with opsonins that facilitates
attachment.
• Opsonins include antibodies and complement proteins.
 Second Line of Defense
Phagocytes are Attracted to Site of Infection by
Chemotaxis
 Second Line of Defense
Ingestion:
• Plasma membrane of phagocytes extends projections
(pseudopods) which engulf the microbe. Microbe is
enclosed in a sac called phagosome.
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
discharged.
 Second Line of Defense
Process of Phagocytosis
 Third Line of Defense
• The immune response is the third line of defense against
pathogens.
• In this protective type of immunity, antibodies are produced
by lymphocytes to recognize, bind, inactivate, and destroy
specific microorganisms.
• These humoral (circulating) antibodies are found in blood
plasma, lymph and other body secretion.
• Thus a person has an immunity to a particular disease
because of the presence of specific protective antibodies.
• There are protective cell mediated immune responses that do
not involve the presence of antibodies.
 Overview of Immunology
Immunity
• The ability of the body to defend itself against specific foreign
invaders (molecules or cells)

Immunogenicity
• The ability to stimulate proliferation of specific lymphocytes
and specific antibody production

Reactivity
• The ability of activated lymphocytes and their products,
antibodies, etc., to interact with specific antigens
 Overview of Immunology
Specificity
• The antigen triggers focused immune defenses (from
particular lymphocytes lineages) that respond only to the
antigens of this foreign substance/cell

Memory
• The immune system produces clones of specific memory
lymphocytes (T & B) which react rapidly when the particular
foreign substance/cell is encountered again

• Specificity and memory differentiate this system from the

nonspecific (innate) defenses
 Overview of Immunology
• Any foreign organic substance which is protein in nature, that
stimulate the production of antibodies is called antigen or
immunogen.
• An antigen must have one or more antigenic sites, known as
antigenic determinants or epitopes, to which antibody can
bind.
• Some small molecules called Haptens may act as antigen.
• Antibodies are glycoprotein's produced by lymphocytes in
response to the presence of an antigen.
• All antibodies are in a class of proteins called
immunoglobulins, present in blood, lymph, tears, saliva and
colostrum.
 The Immune system
• The immune system encompasses the whole body but the
lymphatic system is the site and source of most immune
activity.
• The cells involved in immune response originate in bone
marrow, from which most of blood cells develop.
• Three lines of lymphocytes B-cells, T-cells, and natural killer
cells derived from lymphoid stem cells of bone marrow.
• Half of the stem cells migrate to the thymus gland where they
differentiate into T-cells, T-Helper cells, T-Suppressor cells,
T-Cytotoxic cells and T-Delayed hypersensitivity cells.
• T-cells are small lymphocytes found in the blood, lymph and
lymphoid tissues.
 The Immune system
• T-cells involved in cell mediated immune response ( tissue
transplant rejection, cellular immunity to mycobacteria, fungi,
viruses and cytotoxicity of viral infected cells and tumor cells).
• Other lymphocytic stem cells differentiate in the liver and
intestinal lymphoid areas into B-cells.
• B-cells migrate to lymphoid tissues where they produce
antibodies that circulate through lymph and blood to protect
the individual humoral immunity.
• When B-cells stimulated by an antigen, each B-cells is capable
of producing thousands of specific antibodies per minute.
 The Immune Response
Humoral Immunity
• A complex series of events must occur for antibodies
production.
• T-cells, B-cells and macrophages are often involved in
cooperative efforts in humoral immunity.
• When bacteria invade they are first ingested and processed by
macrophages.
• Macrophages prepare and present antigen to T-helper cells.
• T-helper cells are sensitized by the antigen on the macrophage
and serves to stimulate the production of antibody by B-cells.
• T-helper cells induce B-cells to produce antibodies, whereas
T-suppressor cells inhibit antibody production.
 The Immune Response
Humoral Immunity……..cont
• B-cells are activated and stimulated to enlarge , differentiate
and divide into clones of antibody producing plasma cells
(large B-cells).
• Antibodies are expelled for several days until plasma cell die.
• Each plasma cell clone makes only one type of antibody, and
are responsible for activating the B-cell.
• The activated B-cells that did not become plasma cells, and
some T-cells remain as memory cells, respond more quickly
when the antigen appears again.
• When antigen-antibody complex is formed, complement may
be activated to destroy invading cells, phagocytosis and
neutralization of bacterial toxins increases.
 The Immune Response
Cell Mediated Immunity
• Antibodies are unable to enter cells, thus cell mediated
immunity controlling chronic infections of intracellular
parasites.
• Cell mediated immunity results from several types of antigen
stimulated T-cells.
• T-helper cells cooperate with B-cells to initiate antibody
mediated response.
• T-suppressor cells reduce the intensity of antibody mediated
response and moderate the activities of T-cytotoxic cells.
• T-cytotoxic cells and natural killer cells kill infected host cells
when pathogen are established inside the cells.