CHAPTER 16

SPECIFIC HOST DEFENSE MECHANISMS : AN INTRODUCTION TO IMMUNOLOGY

( outlined by ALgerico F. Baiño, Jr., RN )

I. INTRODUCTION
 Immunology is the scientific study of the immune system and responses
 Immunologists are the scientists who study the various aspects of the immune system
 Immune system is the third line of defense or specific host defense mechanism because its target is a specific
host

II. THE KEY TO UNDERSTANDING IMMUNOLOGY

 Antigens - are molecules ( proteins ) that stimulate the person’s immune system to produce antibodies
 Antibodies are protein molecules that a person’s immune system produces in response to antigens

III. PRIMARY FUNCTIONS OF THE IMMUNE SYSTEM

 To differentiate between self and non self

 To destroy that which is non self

IV. MAJOR ARMS OF THE IMMUNE SYSTEM

1. HUMORAL IMMUNITY /  Involves the production of antibodies in response to antigens

Antibody - Mediated Immunity  Antibodies remain in the blood, plasma, lymph where they protect
against specific pathogens that stimulated their production
 A person is immune to a particular pathogen because of the presence of
specific protective antibodies that are effective against that pathogen
2. CELL MEDIATED IMMUNITY  Involves many different cell types - macrophages, T helper cells,
cytotoxic T cells, delayed hypersensitivity T cells, natural killer cells,
killer cells and granulocytes
 Antibodies play only a minor role

V. IMMUNITY

 When one is resistant to a certain disease, he or she is said to be immune

 The condition of being immune is usually referred to as immunity

ACQUIRED IMMUNITY
 Results from the active production of or receipt of protective antibodies during one’s lifetime
TYPES DESCRIPTION
A. ACTIVE  If the antibodies are actually produced within the person’s body and is long lasting
ACQUIRED  There are 2 sub types
IMMUNITY NATURAL ACTIVE ACQUIRED ARTIFICIAL ACTIVE ACQUIRED IMMUNITY
IMMUNITY
 Occurs Naturally  Does not occur naturally
 People who have had a specific  It is artificially induced
infection usually have developed  Results when a person receives a
resistance to reinfection by the vaccine - because vaccines stimulates a
causative pathogen because of the person’s immune system to produce
presence of antibodies and stimulated specific protective antibodies
lymphocytes  A vaccine is defined as material that
 When antibodies are formed, can artificially induce immunity to an
symptoms of the disease may or may infectious disease, usually after injection
not be present or ingestion of a material
 Resistance to infection may be  After vaccination, it deliberately
permanent or temporary exposes a person to a harmless version
 Protective antibodies are the of a pathogen or toxin to stimulate his
antibodies that protect us from or her immune system to produce
infection or re infection protective antibodies and memory cells,
 Sometimes, when there is no immunity thus, the person’s immune system is
to re infection after recovery from primed to mount a strong protective
certain infectious disease, it could only response should the actual pathogen or
mean that the antibodies produced toxin be encountered in the future
are not protective antibodies
 WHAT IS AN IDEAL VACCINE
 Contains enough antigenic determinants to stimulate the immune system to produce
protective antibodies
 Contains antigenic determinants from all the strains of the pathogen that cause that
disease, hence it is called Multivalent or Polyvalent vaccines
 Few side effects
 Does not cause disease in the vaccinated person
TYPES OF VACCINES ( examples are on the book )
Attenuated Vaccines  Attenuation is The process of weakening the pathogen
 Thus, these vaccines contains weakened pathogen and when
injected it does not cause an infection
 But, it should not be administered to immunosuppressed
individuals because even weakened pathogens cold cause
disease in these persons
Inactivated Vaccines  These are the vaccines made from pathogens that have been
killed by heat or chemicals
 Can be produced faster and more easily but less effective
than attenuated because antigens on the dead cells are
usually less effective and produce a shorter period of
immunity
Subunit Vaccines /  Is the one that uses antigenic ( antibody stimulating ) portions
Acellular Vaccines of pathogen, rather than using the whole pathogen
Conjugate Vaccines  Have been made by conjugating bacterial capsular antigens
to molecules that stimulates the immune system to produce
antibodies against the less antigenic capsular antigens
Toxoid Vaccines  Is an exotoxin that has been inactivated ( made non toxic ) by
heat or chemicals
 Toxoids can be injected safely to stimulate the production of
an antibodies that are capable of neutralizing the exotoxins
or pathogens.
 Antitoxins are antibodies that neutralize toxins
 Antiserum are antitoxins that contains serum
DNA Vaccines /  Are only experimental in humans
Gene Vaccines
Autrogenous  Is the one that has been prepared from bacteria isolated from
Vaccines a localized infection and then the pathogens are killed and
injected into the same person to induce production of more
antibodies
VACCINES SHOULD BE GIVEN TO CHILDREN BETWEEN BIRTH AND ENTRY INTO SCHOOL
1. Hepatitis B Vaccine
2. Rotavirus Vaccine
3. DTaP vaccine
4. Haemophilus Influenzae type B conjugate Vaccines
5. MMR
6. Varicella ( Chiken Pox )
7. Influenza ( yearly )
8. Pneumococcal
9. Hepatitis A
10. Meningococcal
HOW VACCINES WORK
 It stimulates the recipient’s immune system to produce protective antibodies.
 Protective antibodies / memory cells produced in response to the vaccine then remain
in the recipient’s body to battle with a particular pathogen should that pathogen
enter the recipient’s body at some time in the future
 Some vaccines stimulate the body to produce protective antibodies that are directed
against surface antigens, and when pathogens enter, the antibodies attaches to the
surface antigens thus it cannot adhere to host cells
 Antibodies produced in response to molecules on the surface of the bacterial fimbrae
would adhere to the fimbrae
 Protective antibodies attached to pathogens’ surface antigens act as opsonins
enabling phagocytes to attach to pathogen
 Attachment of protective antibodies to surface antigens activates the compliment
cascade, with the end result of lysis of the pathogen
 TYPES DESCRIPTION
B. PASSIVE  Antibodies formed in one person are transferred to another to protect the latter
ACQUIRED from infection
IMMUNITY  Person receives antibodies rather than producing them
 Immunity is temporary lasting to only about 3 to 6 weeks
NATURAL PASSIVE ACQUIRED ARTIFICIAL PASSIVE ACQUIRED
IMMUNITY IMMUNITY
 Small antibodies, IgG present in the  Immunity is accomplished by transferring
mother’s blood cross the placenta to antibodies from an immune person to a
reach the fetus while the fetus is in susceptible person
utero  2 weeks is needed before sufficient
 Colostrum, the thin milky fluid secreted antibodies are formed to protect the
by mammary glands a few days exposed person
before and after delivery contains  Human Gamma Globulin is given or ISG
maternal antibodies to protect the ( immune serum globulin ) is given to
infant during the first months of life provide temporary protection against
measles, mumps, polioi, diptheria and
hepatitis
 Hyperimmune serum globulin ( specific
immune globulin ) has been prepared
from the serum of persons with high
antibody levels ( titers ) against certain
diseases. Ex : Hepatitis B Immune
globulin, tetanus Immune globulin, rabies
immune globulin, chicken pox immune
globulin, measles immune globulin,
pertussis immune globulin, poliomyelitis
immune globulin and zoster immune
globulin

VI. CELLS OF THE IMMUNE SYSTEM

 These are the major cell types that participate in the immune response
1. T Lymphocytes ( T Cells )
2. B Lymphocytes ( B Cells )
3. NK cells
4. Macrophages and Dendritic cells
 Cells involved in immune response originate in the bone marrow
 T and Lymphocytes and NK cells are derived from lymphoid stem cells of bone marrow

3 MAJOR CATEGORIES OF T CELLS

Helper T Cells  Secretes cytokines TH1 and TH2
 TH1 cells ( type 1 cytokines ) support cell mediated immune responses involving
macrophages, cytotoxic T Cells and NK cels
 Cytokines secreted by TH2 supports humoral immune responses by inducing B cell
activation and differentiation of activate B cells into plasma cells
Cytotoxic T cells  Also known as Tc Cells and CD8 cells
 These cells possess on their surface an antigen designated as CD8
 Primary function is to destroy virally infected host cells, foreign cells and tumor cells
Regulatory T cells  Serves as a brake on the immune response to infection
 Has multiple functions including down regulatio of the immune response once an
infection has been contained
 Also function in the capacity of preventing autoimmune diseases
 Majority of regulatory T cells have CD4 antigen

VII. WHERE DO IMMUNE RESPONSES OCCUR ?

 The Lymphatic system is the site and source of most immune activity
 Spleen - immune responses to antigens in the blood
 Lymph nodes near affected area - immune responses to microbes and other antigens in tissues
 Mucoa associated lymphoid tissue - antigens entering ther body through mucosal surfaces ( inahalation
or ingestion )
 Tonsils and adenoids - immune responses to intranasal and inhaled antigens
 Peyer’s patches in the intestinal mucosa - immune responses to ingested antigens
VIII. HUMORAL IMMUNITY / Antibody - Mediated Immunity

 Antibodies , special glycoproteins composed of carbohydrates and protein, are produced by B cells in
response to antigens
 These antibodies are capable of recognizing, binding to and destroying specific pathogens

A. A CLOSER LOOK AT ANTIGENS

 Antigen generates antibody production, thus, it is an antibody generating substance

 Antigenic / Immunogenic are substances capable of stimulating the production of antibodies
 Epitopes- are molecules present on the bacterial cell’s surface capable of stimulating the production
of antibodies
 Processing of either T dependent or T independent results in B cells developing into plasma cells that
are capable of secreting antibodies
 Processing of Antigens in the body

T Dependent  Majority of the antigens are referred to as T dependent antigens

Antigens  T cells ( Helper T cells ) ar involved in their processing
 Also involves macrophages and B cells
T independent  Requires only B cells, Helper T Cells not involved
Antigens  Processing occurs independently on T cells
 Are large polymeric molecules containing repeating antigenic determinants,
examples oncludes lipopolysaccharide found in the cell walls of Gram negative
bacteria, bacterial flagella and bacterial capsules

 Primary Response - also known as the initial immune response and takes 10 to 14 days for the
antibodies to be produced
 When antigens are used up, antibodies in the blood decline as the plasma cells die
 Secondary Response - is the subsequent response to the same antigen ( booster shot ) also called as
anamnestic response or memory response and it causes the antibody concentration to exceed the
level of the secondary response. It occurs rapidly and results in the production of large quantities of
IgG antibodies directed against the antigen

B. A CLOSER LOOK AT ANTIBODIES

 Antibodies are proteins produced by lymphocytes in response to the presence of an antigen

 Antibodies is used to refer to immunoglobulins with particular specificity for an antigen
 A bacterial cell has numerous antigenic determinants on its cell membrane, cell wall, capsule, flagella
that stimulates ther production of many different antibodies.
 Humoral or circulating antibodies - antibodies fond in the blood
 Protective Antibodies - antibodies that provide protection against infectious diseases
 An antibody is specific, in that it will recognize and bind to only the antigenic determinant that
stimulated its production
 Cross Reacting antibody - an antibody will bind to an antigenic determinant that is similar, but not
identical instructure to the antigenic determinant that stimulated its production
 Factors to be considered in Antibody production
1. Nature of the antigen
2. Site of Antigenic Stimulus
3. Amount of antigen
4. Number of times the person is exposed to the antigen
 It takes about 10 - 14 days for antibodies to be produced
 Immunoglobulins - are globular glycoproteins in the blood that participate in immune response. It is
found in the blood, lymph, tears, saliva and colostrum

IMMUNOGLOBULIN CLASSESS AND ITS FUNCTION

CLASS LOCATION FUNCTION
IgA  Saliva, tears, seminal  Protects external openings an mucous membranes from
fluid, colostrum, breast attachment, colonization and invasion of pathogens
milk and mucous  Colostrum helps protect nursing newborns
secretions of the nose,  In the intestine,IgA attaches to viruses, bacteria and
lungs and GI tract protozoal parasites , hence, it prevents the pathogens from
adhering to mucosal surface preventing invasion
IgD  Large quantities on  Serve as antigen receptors and determine which specific
surface of B cells antigen that particular B cell is able to respond to

IgE  Basophils and Mast cells  Is produced in response to allergens

 Plays a major role in allergic responses
IgG  Is abundant in the serum  The only that can cross the placenta and help protect the
newborn during its first months of life
 Complement fixation - Antigen bound IgG can bind to and
activate complement
 Can also bind to a wide variety of cellular receptors
promoting phagocytosis and antibody dependent toxicity
 IgG are produced very rapidly due to memory cells ( 1 -3
days )
 Are long lived, persisting for the lifetime of the individual
IgM  Could bind to 10 separate virus particles thus preventing
the viruses from attaching to target cells
 Are the first antibodies to be formed in the primary
response to antigens and provides protection in the earliest
stages of infection
 Relatively short - lived and does not cross the placenta
 IS considered to be the most efficient complement fixing
immunoglobulin

C. ANTIGEN ANTIBODY COMPLEXES -

 when an antibody combines with an antigen and is capable of activating the complement cascade
resulting in the activation of leukocytes, lysis of bacterial cells and increased phagocytosis as a result
of opsonization

D. HOW ANTIBODIES PROTECT US FROM PATHOGENS AND INFECTIOUS DISEASE

 Example 1 : Pathogen entered the body, Immune system responds, antibodies are produced
( antitoxins )which recognize, binds and neutralizes the toxin

 Example 2 : Person receives vaccine, antibodies produced against adhesin ( receptor ) molecules on
virus adheres to, unabling the virus to bind to appropriate host cell

 Example 3 : Fimbriated bacterium infects a person, immune system responded by producing

antibodies directed to that fimbrae, unabling it to bind to tissue

 Example 4 : encapsulated bacterium ( anti-phagocytic function ) infects a person, immune system

responds producing antibodies targeted against the capsular polysaccharide molecules, phagocytes
can now bind to the encapsulated bacteria

ANTIGEN - ANTIBODY INTERACTIONS AND EFFECTS

Prevention of Attachment  Antigen coated with antibody is prevented from attaching to a cell
Clumping of Antigen  Antibodies link antigens together forming a cluster that phagocytes
can igest
Neutralization of toxins  Antibodies bind to toxin molecules to prevent tem from damaging
cells
Phagocytosis  Phagocytes can attach easily if antigen is coated with antibody
Compliment activation  A series of reaction begins when a compliment attaches to antibody
on a cell surface
Activation of NK cells  NK cells responds to antibody adhering to a cell surface and
attack the cell

E. MONOCLONAL ANTIBODIES
 These are purified antibodies that are directed against specific antigens that produces a product
called hybridoma, which is a long - lived, antibody - producing cells
 It treats several diseases such as : Asthma, Breast cancer, Cardiovascular disease, Colon cancer,
Chron’s disease, leukemia, lymphomas, macular degeneration, melanoma, multiple myeloma, multiple
sclerosis, osteoporosis, psoriatic arthritis, psoriasis, rheumatoid arthritis, several autoimmune disorders,
transplant rejection
IX. CELL MEDIATED IMMUNITY

 An arm of the immune system capable of controlling chronic infections by intracellular pathogens
( bacteria, protozoa, fungi and viruses )
 It includes Macrophages, Dendritic cells, T helper cells, Cytotoxic T cells, NK cells and granulocytes
 Does not involved in the production of antibodies
 Cytotoxic T cells and NK cells kill infected host cells when pathogens are established inside the cells
 STEPS IN CELL MEDIATED CYTOTOXIC RESPONSE
1. Macrophage or DC engulfs and digests a pathogen
2. Helper T cell binds to macrophage and produces cytokines which reach an effector cell of the immune
system
3. Effector cell binds to target cells ( pathogen - infected host cell )
4. Vesicular content of the effector cell are discharged ( perforin )punch holes in the target cell
membrane
5. Toxins produced by the effector cells enter the target cell causing disruption of DNA and organelles
until the target cell dies.
 NATURAL KILLER CELLS
 Are also called large granular lymphocytes
 They lack typical T cell or B cell surface markers
 Does not proliferate in response to antigen and appear not to be involved in antigen specific
recognition
 NK cells targets cells including foreign cells, host cells infected with viruses or bacteria and tumor
cells
 NK cells have receptors for some antibodies that enable them to attach to and kill antibody coated
target cells. This process is known as Antibody - dependent cellular toxicity. This allows the NK cells
to inserts a molecule, perforin, to the cell membrane of the target cell, opening its pores and
cytotoxic granules called granzymes are injected

X. HYPERSENSITIVITY AND HYPERSENSITIVITY REACTIONS

 Hypersensitivity - overly sensitive or overly reactive immune system, causing irritation or damage to
certain cells and tissues in the body
 All types of hypersensitivity depends on the presence of antigen and T cells that are sensitized to that
antigen
 There are two Types : IMMEDIATE TYPE and DELAYED TYPE

TYPES OF HYPERSENSITIVITY REACTIONS

A. IMMEDIATE TYPE
 Occur from within a few minutes to 24 hours after contact with a particular antigen
TYPE 1 TYPE II TYPE III
HYPESENSITIVITY REACTIONS HYPESENSITIVITY REACTIONS HYPESENSITIVITY REACTIONS
 Also known as anaphylactic reactions  Are also called Cytotoxic  The dark side of the immune
 Responses : hay fever , asthma, hives, reactions meaning that body complexes ( result in the
GI symptoms
 Causes : Food allergies, Insect stings,
cells are destroyed during binding of an antibody with the
drugs and anaphjylactic shock these reactions antigen that stimulated its
 Involves IgE antibodies and the  Ex : Incompatible blood production )
release of chemical mediators from transfusions, Rh Incompatibility  Ex : Serum Sickness and
mast cells and basophils and Myasthenia Gravis autoimmune diseases ( systemic
A. THE ALLERGIC RESPONSE
 It involves IgG, IgM and lupus erymatosus and
 People who are prone to allergies compliment rheumatoid arthritis )
produce IgE antibodies when they are  It involves IgG, IgM,
exposed to allergens complement and neutrophils
 These IgE molecules bind to the  Are immune complex reactions
surface of the basophils and mast
cells
( antigen + antibody +
 The type and severity of the allergic complement ) = hives, fever,
reaction depends on the combination kidney malfunction, joint lesions
of factors : Nature of the Antigen, of serum sickness
amount of antigen entering the body,  Complications : the resultant
route at which it enters, the length of
time between exposures to the
immune complexes become
antigen and the ability to produce IgE deposited in heart tissue, joints
antibodies and the site of its or the glemeruli of the kidneys
attachment and leads to rheumatic heart in
heart tissue, arthritis in joints
B. LOCALIZED ANAPHYLAXIS
and glumerulonephritis in
 Involves mast cell degranulation - if kidneys
allergen is inhaled, IgE antibodies
produced attach to mast cells in the
area of the mucous membranes of the
respiratory tract and releases
histamine
 The relased histamine initiates the
 classic symptom of hay fever
 Ex : Hay fever, Asthma and Hives
 Symptoms depend on how the
allergen eters the body and the sites
of IgE attachment
 Antihistamines are often used by
blocking the sites where histamines
binds but are not effective against
asthma

C. SYSTEMIC ANAPHYLAXIS

 Results from the release of chemical

mediators from basophils in the blood
stream
 Occurs throughout the body and is
serious than localized leading to
anaphylactic shock which is a fatal
condition
 Often involved are drugs or insect
venom to which the host has been
sensitized
 Shock occurs immediately after
exposure
 SYmptoms : Flusing of the skin with
itching, headache, facial swelling,
difficulty breathing, falling BP,
nausea , vomiting, abdominal cramps
and urination leading to ARDS and
death may follow shortly
 Treatment : Epinephrine
( adrenaline ) and antihistamine

D. LATEX ALLERGIES

 Some healthcare workers are allergic

to latex, like latex gloves or other
products containing latex
 Symptoms : skin rashes, hives, flushing,
itching, nasal, eye or sinus symptoms
 3 types of reactions triggered by
Latex allergy :

1. Irritant Contact Dermatitis -

common reaction. Dry, itchy, irritated
areas on the skin. Immune system is
not involved

2. Allergic contact Dermatitis -

exposure to chemicals added to latex.
A DTH or type 4 hypersensitivity

3. Latex Allergy - an immediate type

hypersensitivity. Is a systemic type IgE
mediated reaction. Can be diagnosed
using antibody detection procedures
and skin testing

E. ALLERGY SKIN TESTING AND

ALLERGY SHOTS

 Skin tests are often used to identify

the offending allergens
 A positive skin test result is swelling
and redness ( wheal and flare ) at the
site that the allergen was introduced
into the skin
 Once identified, immunotherapy is
accomplished by injecting small doses
of allergen.
 B. TYPE 4 HYPERSENSITIVITY REACTIONS /DTH / CELL- MEDIATED IMMUNE REACTIONS
 Usually observed 24 to 48 hours longer after exposure or contact
 Occurs in tuberculin and fungal skin tests, contact dermatitis and transplantation rejection
 Is the prime mode of defense against intracellular bacteria and fungi
 Involves various cell types, including macrophages, DCs, Cytotoxic T cells and NK cells
 Antibodies have no major role
 Example : Positive TB skin test ( Mantoux skin test )
A. MANTOUX SKIN TEST
 PPD ( Tuberculin Purified protein derivative ) consists of protein extracts prepared from M. tuberculosis
and is injected intradermally
 The test is performed by injecting 0.1 ml of PPD and observing the results 48 to 72 hours later.
 If the person has an exposure of mycobacteria in the past, redness and swelling occurs constituting a
positive TB skin test
 DTH reaction will occur producing the typical swelling and redness ( wheal and flare ) associated with a
positive reaction
 Diameter of induration , which is the palpable raised hardened area is measured, not the redness
 A positive TB skin test does not necessarily mean that a person has TB
 Positive TB skin test indicates that an individual has been exposed to mycobacterial antigens but that
individual may or may not have active TB
B. INTERFERON GAMMA RELEASE ASSAYS
 An assay used to detect latent TB and is more specific than Mantoux skin test and can be used on
people previously vaccinated with BCG
 It detects interferon gamma ( IFN-y ) produced by lymphocytes exposed to two specific antigens present
on M. tuberculosis
 Presence of IFN-y indicates the patient has been exposed to M. tuberculosis

XI. AUTOIMMUNE DISEASES

 Results when a person’s immune system no longer recognizes certain body tissues as self and attempts to
destroy those tissues as if they were nonself or foreign
 This may occur within tissues that are not exposed to the immune system during fetal development, so that
they are not recognized as self ( lens of eye, brain, spinal cord and sperm )
 Are a result of types II, III or IV hypersensitivity
 Classifications :
1. Organ Specific Autoimmune diseases
 Hashimoto’s thyroiditis - thyroid
 Grave’s disease - thyroid
 Primary myxoedema - thyroid
 Pernicious anemia - gastric mucosa
 Addison’s disease - adrenal glands
 Type 1 DM ( IDDM ) - pancreas
2. Non - Organ Specific (skin, kidneys,joints and muscles )
 Myasthenia gravis - muscle
 Dermatomyositis - skin
 SLE- kidneys, lungs, skin and brain
 Scleroderma - skin, lungs, kidneys and GIT

XII. IMMUNOSUPPRESSION

 if a person’s immune system is not functioning properly

 Common cause is malnutrition. And also acquired and inherited immunodeficiencies

A. ACQUIRED IMMUNODEFICIENCIES

 Caused by drugs ( cancer chemotherapeutic agents ), irradiation or certain infections ( HIV )

 HIV leads to decrease in Helper T cells, thus, preventing production of antibodies against T dependent
antigens leading to inability to fight off certain pathogens
 People with AIDS usually die of various infectious diseases ( viral, fungal, bacterial, parasitic )
 In elderly, immune reponsiveness and the ability to produce antibodies also decline as a result of the ability
of the T cells to regulate the immune response, thus, they are susceptible.
B. INHERITED IMMUNODEFICIENCIES

 Result in a deficiency in antibody production, complement activity, phagocytic function or NK cell function
 Examples :
1. Chediak - Higashi Syndrome / Chronic Granulomatous disease
2. SCID / severe combined immunodeficiency - deficiencies in either B or T cells resulting in severe recurrent
infections
3. Di George Syndrome - congenital absence of thymus and parathyroid glands leading to frequent
infections and delayed development
4. Wiskott - Aldrich syndrome - Deficiencies in B cells, T cells, monocytes and platelets leading to bleeding,
recurrent infections and eczema
5. Agammaglobulinemia - born with the lacking ability to produce protective antibodies, thus, they have no
gamma globulins. Treatment is by bone marrow transplant
6. Hypogammaglobulinemia - insufficient amount of antibodies and resistance to infection is lower than
normal. Example is Bruton hypogammaglobulinemia