MICROBIOLOGY AND

PARASITOLOGY

MODULE 3
Infection and Host Resistance

Maria Corazon Lourdes C. LUCIN, RN, MAN,LPT

Subject Instructor

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 Infection and Host Resistance

Specific Host Defense Mechanisms

INTRODUCTION

▪ Immunology is the scientific study of the immune system and responses. Scientists who
study various aspects of the immune system are called immunologists.
▪ The immune system is considered to be the third line of defense. It is considered a
specific host defense mechanism because it springs into action to defend against a
specific pathogen (or other foreign object) that has gained entrance to the body.
▪ Immune responses involve complex interactions among many different types of body
cells and cellular secretions.

THE KEY TO UNDERSTANDING IMMUNOLOGY

▪ An understanding of immunology boils down to an understanding of two terms: antigens

and antibodies. For the moment, think of antigens as molecules (usually proteins) that
stimulate a person's immune system to produce antibodies. Think of antibodies as protein
molecules that a person's immune system produces in response to antigens.

PRIMARY FUNCTIONS OF THE IMMUNE SYSTEM

▪ According to accepted doctrine, the primary functions of the immune system are to:
o Differentiate between “self” and “nonself” ( something foreign), and
o Destroy that which is nonself.

MAJOR ARMS OF THE IMMUNE SYSTEM

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 ▪ There are two major arms of the immune system: humoral immunity and cell-mediated
immunity (CMI)
▪ Humoral immunity always involves the production of antibodies in response to antigens.
After their production, these humoral (circulating) antibodies remain in blood plasma,
lymph, and other body secretions where they protect against the specific pathogens that
stimulated their production. Thus in humoral immunity, a person is immune to a
particular pathogen because of the presence of specific protective antibodies that are
effective against that pathogen. Because humoral immunity is mediated by antibodies, it
is also known as antibody-mediated immunity (AMI).
▪ The second major arm of the immune system -CMI-involves various cell types, with
antibodies playing only a minor role, if any. These immune responses are referred to as
cell-mediated immune responses.

IMMUNITY

▪ A significant result of immune responses is to make a person resistant to certain

infectious diseases. 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.
▪ Humans are immune to certain infectious diseases simply because they are humans. For
example, humans are not infected with some of the pathogens that infect their pets. One
explanation for this is that human cells do not possess the appropriate cell surface
receptors for some of the pathogens that cause diseases of pets.
▪ The various types of immunities that humans acquire as life progresses from conception
onward are collectively referred to as acquired immunity. Such immunity is often the
result of the presence of protective antibodies that are directed against various pathogens.

Acquired Immunity

▪ Immunity that results from the active production or receipt of protective antibodies
during one's lifetime is called acquired immunity. If the antibodies are actually
produced within the person's body, the immunity is called active acquired immunity;
such protection is usually long lasting.
▪ In passive acquired immunity, the person receives antibodies that were produced by
another person or by more than one person, or, in some cases, by an animal; such
protection is usually only temporary. In either case, active or passive, the immunity
may result from either a natural or an artificial event.

Active Acquired Immunity

▪ There are two types of active acquired immunity:

1. Natural (or naturally occurring) active acquired immunity, which, as the
name implies, occurs naturally.

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 2. Artificial (or artificially occurring) active acquired immunity, which does
not occur naturally; rather, it is artificially induced.
▪ People who have had a specific infection usually have developed some resistance
to reinfection by the causative pathogen because of the presence of antibodies and
stimulated lymphocytes. This is called natural active acquired immunity.
Symptoms of the disease may or may not be present when these antibodies are
formed. Such resistance to reinfection may be permanent, lasting for a person’s
entire lifetime, or it may only be temporary. Antibodies that protect us from
infection or reinfection are called protective antibodies. Sometimes, there is no
immunity to reinfection after recovery from certain infectious diseases, even
though antibodies are produced against the pathogens that cause these diseases.
This is because the antibodies produced are not protective antibodies.
▪ Artificial active acquired immunity is the second type of active acquired
immunity. This type of immunity results when a person receives a vaccine which
stimulates a person’s immune system to produce specific protective antibodies –
antibodies that will protect the person should he or she become colonized with
that particular pathogen in the future.

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 Vaccines

▪ A vaccine is defined as material that can artificially induce immunity to an infectious

disease, usually after injection or, in some cases, ingestion of the material (e.g., oral polio
vaccine)
▪ A person is deliberately exposed to a harmless version of a pathogen (or toxin), which
will stimulate his or her immune system to produce protective antibodies and memory
cells, but will not cause disease in him or her. In this manner, the person’s immune
system is primed to mount a strong protective response should the actual pathogen (or
toxin) be encountered in the future.
▪ An ideal vaccine is one that:
o contains enough antigenic determinants to stimulate the immune system to
produce protective antibodies (i.e., antibodies that will protect individuals from
infection by the pathogen)
o contains antigenic determinants from all the strains of the pathogen that cause that
disease (e.g., the three strains of virus that cause polio); such vaccines are referred
to as multivalent or polyvalent vaccines
o has few (preferably, no) side effects
o does not cause disease in the vaccinated person

Types of Vaccines

▪ Various materials are used in vaccines (Table 16-2). Most vaccines are made from living
or dead (inactivated) pathogens or from certain toxins they produce. The use of such
vaccines illustrates a very important and practical application of the principles of
microbiology and immunology. In general, vaccines made from living organisms are
most effective, but they must be prepared from harmless organisms that are antigenically
closely related to the pathogens or from weakened (attenuated) pathogens that have been
genetically changed so that they are no longer pathogenic.
▪ As microbiologists made further studies of the characteristics of vaccines, they found that
it was practical to vaccinate against several diseases by combining specific vaccines in a
single injection. For example, the diphtheria-tetanus-pertussis (DTaP) vaccine contains
toxoids to prevent diphtheria and tetanus and antigenic portions of killed bacteria
(Bordettella pertussis) to prevent whooping cough (pertussis). Another example is the
measles-mumpsrubella (MMR) vaccine
▪ According to our own DOH, a child should receive the following vaccines between birth
and before his/her first birthday.

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 Types of Available Vaccines
Type of vaccine Examples
Attenuated vaccine: The process of weakening Attenuated viral vaccines: Adenovirus, chicken
pathogens is called attenuation, and the pox (varicella), measles (rubeola), mumps,
vaccines are referred to as attenuated vaccines. German measles (rubella), polio (oral Sabin
Most live vaccines are avirulent vaccine}, rotavirus, smallpox. yellow fever
(nonpathogenic) mutant strains of pathogens Attenuated bacterial vaccines: BCG (for
that have been derived from the virulent protection against TB), cholera, tularemia,
(pathogenic) organisms; this Is accomplished typhoid fever (oral vaccine)
by growing them for many generations under
various conditions or by exposing them to
mutagenic chemicals or radiation. Attenuated
vaccines should not be administered to
immunosuppressed individuals because even
weakened pathogens could cause disease in
these persons.
Inactivated vaccines: Vaccines made from Inactivated viruses or viral antigens: Hepatitis
pathogens that have been killed by heat or A, influenza, Japanese encephalitis, other
chemicals-called inactivated vaccines-can be (EEE, WEE, Russian) encephalitis vaccines,
produced faster and more easily, but they are polio (subcutaneous Salk vaccine), rabies
Jess effective than live vaccines. This is Inactivated bacterial vaccines: Anthrax,
because the antigens on the dead cells are cholera, pertussis, plague, typhoid fever

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 usually less effective and produce a shorter (subcutaneous vaccine), Q fever
period of Immunity.
Subunit vaccines: A subunit vaccine (or Anthrax, hepatitis B, whooping cough
acellular vaccine) is one that uses antigenic
(antibody-stimulating) portions of a pathogen,
rather than using the whole pathogen. For
example, a vaccine containing pili of Neisseria
gonorrhoeae could theoretically stimulate the
body to produce antibodies that would attach to
N. gonorrhoeae pill, thus preventing the
bacteria from adhering to cells. If N.
gonorrhoeae cells cannot adhere to cells that
line the urethra, they cannot cause urethritis.
The material that is used to protect health care
workers and others from hepatitis caused by
HBV is being produced by genetically
engineered yeasts. The genes that code for
hepatitis B surface protein were introduced into
yeast cells, which then produced large
quantities of that protein. The proteins are then
injected into people. Antibodies against the
protein are produced In their bodies, and these
antibodies serve to protect the people from
HBV hepatitis.
Conjugate vaccine&: Successful conjugate Hib (for protection against H. /influenzae type
vaccines have been made by conjugating b), meningococcal meningitis (Neisseria
bacterial capsular antigens {which by meningitidis serogroup C), pneumococcal
themselves are not very antigenic) to molecules pneumonia
that stimulate the immune system to produce
antibodies against the less antigenic capsular
antigens.
Toxoid vaccines: A toxoid is an exotoxin that Diphtheria and tetanus: Commercial antisera
has been inactivated (made nontoxic) by heat containing antitoxins are used to treat diseases,
or chemicals. Toxoids can be injected safely to such as tetanus and botulism. Such antisera are
stimulate the production of antibodies that are also used in certain types of laboratory tests,
capable of neutralizing the exotoxins of known as lDPs.
pathogens, such as those that cause tetanus,
botulism, and diphtheria. Antibodies that
neutralize toxins are called antitoxins, and a
serum containing such antitoxins Is referred to
as an antiserum.
DNA vaccines: Currently, DNA vaccines or Four veterinary DNA vaccines have been
gene vaccines are only experimental in approved for use in animals, including a West
humans. A particular gene from a pathogen is Nile virus vaccine for horses. Clinical trials for
inserted into plasmids, and the plasmids are DNA vaccines are currently in progress for M.
then injected into skin or muscle tissue. Inside tuberculosis, malaria, Zika virus, among

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 host cells, the genes direct the synthesis of a others.
particular microbial protein (antigen). Once the
cells start churning out copies of the protein,
the body then produces antibodies directed
against the protein, and these antibodies protect
the person from Infection with the pathogen.
Autogenous vaccines: An autogenous vaccine
Is one that has been prepared from bacteria
Isolated from a localized Infection, such as a
staphylococcal boll. The pathogens are killed
and then injected into the same person to
induce production of more antibodies.

▪ Many additional vaccines are available for use when needed. They include vaccines for
protection against adenovirus, anthrax, cervical cancer (human papillomavirus), cholera,
H5N1, avian influenza, Japanese encephalitis, plague, rabies, small pox, TB, typhoid
fever, yellow fever, and zoster. A successful vaccine for colds has not been developed
because so many different types of viruses cause colds. Maintaining a successful vaccine
for influenza is difficult because influenza viruses frequently change their surface
antigens-a phenomenon known as antigenic variation.

How Vaccines Work

▪ Vaccines stimulate the recipient's immune system to produce protective antibodies. The
protective antibodies or memory cells produced in response to the vaccine then remain in
the recipient’s body to “do battle with” a particular pathogen, should that pathogen enter
the recipient’s body at some time in the future.
▪ For example, when a person receives tetanus toxoid (an altered form of the toxin,
tetanospasmin), protective antibodies referred to as antitoxins are produced and rmain in
the person’s body. Should Clostridium tetani enter the person’s body at some time in the
future and start to produce tetanospasmin, the antitoxins are there to attach to and
neutralize the toxin.
▪ Some vaccines stimulate the body to produce protective antibodies that are directed
against surface antigens. When the pathogen enters the person's body, the antibodies
attach to the surface antigens. This prevents the pathogen from adhering to host cells. In
the case of viruses, if they are unable to attach, they are unable to enter the cell and are
thus unable to multiply and cause cell destruction.
▪ In some cases, protective antibodies attached to pathogens' surface antigens act as
opsonins, enabling phagocytes to attach to the pathogens. Once attached to a pathogen,
the phagocyte can ingest and digest it. In other cases, attachment of protective antibodies
to surface antigens activates the complement cascade, with the end result being lysis of
the pathogen.

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 Passive Acquired Immunity

▪ Passive acquired immunity differs from active acquired immunity, in that antibodies
formed in one person are transferred to another to protect the latter from infection.
Thus, in passive acquired immunity, a person receives antibodies, rather than
producing them. Because the person receiving the antibodies did not actively produce
them, the immunity is temporary, lasting only about 3 to 6 weeks. The antibodies of
passive acquired immunity may be transferred naturally or artificially.
▪ In natural passive acquired immunity, small antibodies (such as immunoglobulin G
[IgG], which is described later in this chapter) present in the mother’s blood cross the
placenta to reach the fetus while it is in the uterus (in utero). Also, colostrum, the thin,
milky fluid secreted by mammary glands a few days before and after delivery,
contains maternal antibodies to protect the infant during the first months of life.
▪ Artificial passive acquired immunity is accomplished by transferring antibodies from
an immune person to a susceptible person. After a patient has been exposed to a
disease, the length of the incubation period usually does not allow sufficient time for
postexposure vaccination to be an effective preventive measure. This is because a
span of about 2 weeks is needed before sufficient antibodies are formed to protect the
exposed person.
▪ To provide temporary protection in these situations, the patient is given human
gamma globulin or "pooled" immune serum globulin (ISG); that is, antibodies taken
from the blood of many immune people. In this manner, the patient receives some
antibodies to all of the diseases to which the donors are immune. The ISG may be
given to provide temporary protection against measles, mumps, polio, diphtheria, and
hepatitis in people, especially infants, who are not immune and have been exposed to
these diseases.
▪ Hyperimmune serum globulin (or specific immune globulin) has been prepared from
the serum of persons with high antibody levels (titer) against certain diseases. For
example, hepatitis B immune globulin is given to protect those who have been, or are
apt to be, exposed to hepatitis B virus; tetanus immune globulin is used to prevent
tetanus in nonimmunized patients with deep, dirty wounds; and rabies immune
globulin may be given to prevent rabies after a person is bitten by a rabid animal.
Other examples include chickenpox immune globulin, measles immune globulin,
pertussis immune globulin, poliomyelitis immune globulin, and zoster immune
globulin.

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 CELLS OF THE IMMUNE SYSTEM

▪ The major cell types that participate in immune responses are as follows:
• T lymphocytes (T cells)
• B lymphocytes (B cells)
• NK cells (a category of lymphocytes)
• Macrophages and dendritic cells (DCs)
▪ DCs are similar in form and function to macrophages. They are named for their long thin
cytoplasmic projections called dendrites. DCs are present in tissues that are in contact
with the external environment, such as skin and the linings of the nose, lungs, stomach,
and intestines. Like macrophages, they process ingested antigens and display antigenic
determinants on their surface. Once activated, they migrate to lymph nodes where they
interact with T cells. Thus, like macroph2ges, they serve as antigen-presenting cells.
▪ The cells involved in immune responses originate in bone marrow, from which most
blood cells develop. Three lines of lymphocytes-B lymphocytes (B cells), T lymphocytes
(f cells), and NK cells---are derived from lymphoid stem cells of bone marrow.
▪ There are three major categories ofT cells: helper T cells, cytotoxicT cells, and regulatory
T cells. Helper T cells are also known as T-helper cells, T H cells, and CD4+ cells. The
term CD4+ cells refers to the fact that these cells possess on their surface an antigen
designated as CD4.
▪ The primary function of helper T cells is secretion of cytokines. T H 1 cells and T H2
cells are subcategories of helper T cells. Cytokines secreted by T H 1 cells (referred to as
type 1 cytokines) support cell-mediated immune responses (described later in this
chapter), involving macrophages, cytotoxic T cells, and NK cells. Cytokines secreted by
T H2 cells (referred to as type 2 cytokines) support humoral immune responses by
inducing B-cell activation and differentiation of activated B cells into plasma cells.
▪ Cytotoxic T cells are also known as T cytotoxic cells, T c cells, and CD8† cells. The term
CD8† cells refers to the fact that these cells possess on their surface an antigen
designated as CD8. The primary function of cytotoxic T cells is to destroy vitally infected
host cells, foreign cells, and tumor cells.
▪ Regulatory T cells serve as a brake on the immune response to infection. Regulatory T
cells include more than one cell type and have multiple functions, including the
downregulation of the immune response once an infection has been contained, and they
also appear to function in the capacity of preventing autoimmune diseases. The majority
of regulatory T cells have the CD4 + antigen, but some contain the CDS+ antigen on their
cell surface.

WHERE DO IMMUNE RESPONSES OCCUR?

▪ Although it encompasses the whole body, the lymphatic system is the site and source of
most immune activity. Immune responses to antigens in the blood are usually initiated in

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 the spleen, whereas responses to microbes and other antigens in tissues are generated in
lymph nodes located near the affected area.

HUMORAL IMMUNITY

▪ In humoral immunity, special glycoproteins (molecules composed of carbohydrate and

protein) called antibodies are produced by B cells in response to antigens. In many cases,
these antibodies are capable of recognizing, binding to, and inactivating or destroying
specific pathogens.

Processing of Antigens in the Body

▪ For antibodies to be produced within the body, a complex series of events must occur,
some of which are not completely understood. It is known that macrophages, DCs, T
cells, and B cells often are involved in a cooperative effort.
▪ The initial immune response to a particular antigen is called the primary response. In the
primary response to an antigen, it takes about 10 to 14 days for antibodies to be produced.
When the antigen is used up, the numbers of antibodies in the blood declines as the
plasma cells die.
▪ Other antigen-stimulated B cells become memory cells, which are small lymphocytes that
can be stimulated to rapidly produce large quantities of antibodies when later exposed to
the same antigens. This increased production of antibodies after the second exposure to
the antigen (e.g., a booster shot) is called the secondary response, anamnestic response,
or memory response. A second booster shot of antigen many months later causes the
antibody concentration to exceed the level of the secondary response. This is the reason
why booster shots are given to protect against certain pathogens that one might encounter
throughout lire, such as the bacterium, C. tetani (the cause of tetanus). In addition to
memory B cells, memory T cells also contribute to immunologic memory.

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 A Closer Look at Antibodies

▪ Humoral immunity (or AMI) involves the production of antibodies. Antibodies are
proteins produced by lymphocytes in response to the presence of antigen. (As previously
described, the antibody-producing cells are a specific type of lymphocyte called B
lymphocytes [or B cells], which usually work in coordination with T lymphocytes [T
cells] and macrophages or DCs.)
▪ A bacterial cell has numerous antigenic determinants on its cell membrane, cell wall,
capsule, and flagella that stimulate the production of many different antibodies. Usually,
an antibody is specific in that it will recognize and bind to only the antigenic determinant
that stimulated its production.
▪ Example: Antibodies produced against molecules located on bacterial fimbriae can
recognize and bind to only those particular molecules. Occasionally, however, an
antibody will bind to an antigenic determinant that stimulated its production; in this case,
it is referred to as a cross-reacting antibody.
▪ All antibodies are in a category of proteins called immunoglobulins-globular
glycoproteins in the blood that participate in immune reactions. The term antibodies is
used to refer to immunoglobulins with particular specificity for an antigen. In addition to
being found in blood, immunoglobulins are found in lymph, tears, saliva, and colostrum.
Antibodies found in the blood are called humoral or circulating antibodies. As previously
mentioned, antibodies that provide protection against infectious diseases are called
protective antibodies.

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 How Antibodies Protect Us From Pathogens and Infectious Diseases

As previously mentioned, once they are produced, antibodies are very specific. Usually, a
given antibody can recognize and bind to only the antigenic determinant that stimulated its
production.

Example 1

A pathogen has entered a person's body and has started producing a twin. That person's immune
system responds by producing antibodies against the toxin; such antibodies are called antitoxins.
Once produced, the antitoxins recognize, bind to, and neutralize the toxin molecules, so that they
can no longer cause harm (i.e., they are no longer toxic).

Example 2

Recall that viruses can bind only to the host cells that bear the appropriate receptor on their
surface. The molecule on the virus that recognizes and binds to the receptor is called an adhesin.
A person has received a vaccine containing an attenuated virus (a virus that is no longer
infectious). The vaccine stimulates that person's immune system to produce antibodies against
the adhesin molecules. At some later date, should that same virus enter the person 1 body, those
antibodies will adhere to the adhesin molecules, making it impossible for the virus to bind to host
cells. If the virus is unable to bind to the appropriate host cell, it is unable to enter the cell, and
the person is protected from infection with that virus.

Example 3

A person is infected with a fimbriated bacterium. (Recall that fimbriae enable bacteria to attach
to host cells, which, with certain bacterial pathogens, is necessary for the bacteria to cause
disease.) That person1 immune system responds by producing antibodies against the fimbriae.
The antibodies bind to the fimbriae, making it impossible for the bacterial cells to bind to tissue.
If the bacteria are unable to attach to tissue, they are unable to cause disease.

Example 4

A person is infected with an encapsulated bacterium. (Recall that bacterial capsules serve an
antiphagocytic function, meaning that phagocytic white blood cells are unable to phagocytize
encapsulated bacteria. The reason for this is that the phagocytes have no receptors on their
surface that recognize the polysaccharide molecules. If the phagocyte is unable to attach to the
encapsulated bacterium, it is unable to phagocytize it. That person’s immune system responds by
producing antibodies against the capsular polysaccharide molecules. The antibodies attach to the
capsule. This makes it possible for the phagocytes t bind to the encapsulated bacteria. Why?
Because the phagocytes have receptors on their surface that can recognize and bind to antibody
molecules.

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 CELL-MEDIATED IMMUNITY

▪ Antibodies are unable to enter cells, including cells containing intracellular pathogens.
Fortunately, there is an arm of the immune system capable of controlling chronic
infections by intracellular pathogens (e.g., bacteria, protozoa, fungi, and viruses). It is
called CMI-a complex system of interactions among many types of cells and cellular
secretions (cytokines). Included among the various cells that participate in CMI are
macrophages,DCs, TH cells, TC cells, NK cells, and granulocytes. Although CMI does
not involve the production of antibodies, antibodies produced during humoral immunity
can play a minor role in some cell-mediated responses.
▪ A typical cell-mediated cytotoxic response would involve the following steps:
o Step 1. A macrophage or DC engulfs and partially digests a pathogen. Fragments
(antigenic determinants) of the pathogen u-e then displayed on the surface of the
macrophage or DC (i.e., the macrophage or DC acts as an antigen-presenting cell).
o Step 2. A T H cell binds to one of the antigenic determinants being displayed on
the macrophage or DC surface. The T H cell produces cytokines, which reach an
effector cell of the immune system (e.g., a T c cell or NK cell).
o Step 3. The effector cell binds to a target cell (i.e., a pathogen-infected host cell
displaying the same antigenic determinant on its surface).
o Step 4. Vesicular contents of the effector cell are discharged. These include
perforin and other proteins and enzymes, which literally punch holes in the target
cell membrane. Other cytokines released by effector cells are tumor necrosis
factor and NK cytotoxic factor.
o Step 5. Toxins produced by the effector cells enter the target cell, causing
disruption of DNA and organelles. The target cell dies.
▪ Both humoral and cell-mediated immune responses play a role in the body's defense
against viral infections. In cytolytic viral infections (e.g., herpes infections), the viruses
can be neutralized and destroyed by antibodies and the complement system when they
move in body fluids from a lysed cell to an intact cell. When the virus is established
within body cells, the cell-mediated immune response can destroy the virus-infected cells,
preventing viral multiplication. If the virus is not completely destroyed, however, it may
become latent in nerve ganglion cells, as in herpes infections (e.g., shingles).
▪ T c cells and NK cells kill infected host cells when pathogens are established inside the
cells. Thus, infected liver cells are destroyed in hepatitis infections during the body's
battle against the disease. The acquired immunodeficiency syndrome (AIDS) virus
(human immunodeficiency virus [lllV]) that targets T H cells is particularly destructive
because it destroys the very cells that would have helped fight the infection. The lack of
T H cells impairs both humoral immunity and CMI, making AIDS patients very
susceptible to many opportunistic infections and malignancies.

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 HYPERSENSITIVITY AND HYPERSENSITIVITY REACTIONS

▪ The term hypersensitivity refers to an overly sensitive or overly reactive immune system.
In such situations, the immune system, in an attempt to protect the person causes
irritation or damage to certain cells and tissues in the body.
▪ There are several different types of hypersensitivity reaction. Some types involve
antibodies, whereas others do not. All types depend on the presence of antigen and T
cells that are sensitized to that antigen. Hypersensitivity reactions are divided into two
general categories – immediate – type and delayed – type – depending on the nature of
the immune reaction and the time required for an observable reaction to occur.
▪ Immediate-type hypersensitivity reactions occur from within a few minutes to 24 hours
after contact with a particular antigen. There are three categories of immediate-type
hypersensitivity reactions, referred to as type I, type IT, and type m hypersensitivity
reactions. A delayed-type hypersensitivity (DTH) reaction usually takes more than 24
hours to manifest itself. DTH reactions are also known as type IV hypersensitivity
reactions and cell-mediated reactions.

Type I Hypersensitivity Reactions

▪ Type I hypersensitivity reactions (also known as anaphylactic reactions) include classic

allergic responses, such as hay fever symptoms, asthma, hives, and gastrointestinal
symptoms that result from food allergies; allergic responses to insect stings and drugs;
and anaphylactic shock. These reactions all involve IgE antibodies and the release of
chemical mediators (especially histamine) from mast cells and basophils.

The Allergic Response

▪ People who are prone to allergies (atopic persons) produce IgE (sometimes called reagin)
antibodies when they are exposed to allergens (antigens that cause allergic reactions).
The IgE molecules bind to the surface of basophils and mast cells by their Fc regions.
The type and severity of an allergic reaction depend on a combination of factors,
including the nature of the antigen, the amount of antigen entering the body, the route by
which it enters, the length of time between exposures to the antigen, the person’s ability
to produce IgE antibodies, and the site of lgE attachment.

Localized Anaphylaxis

▪ Type I hypersensitivity reactions (anaphylactic reactions) may be localized or systemic.

Localized reactions usually involve mast cell degranulation, whereas systemic reactions
usually involve basophil degranulation. Hay fever, asthma, and hives are examples of
localized anaphylaxis.
▪ The symptoms depend on how the atlergen enters the body and the sites of IgE
attachment. If the allergen (e.g., pollens, dust, and fungal spores) is inhaled and deposits

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 on the mucous membranes of the respiratory tract, the IgE antibodies that are produced
attach to mast cells in that area. Subsequent exposure to those inhaled allergens allows
them to bind to the attached IgE, causing mast cell degranulation. The released histamine
initiates the classic symptoms of hay fever. Antihistamines function by binding to and
blocking the sites where histamine binds.
▪ Allergens (e.g., food and drugs) entering through the digestive tract can also sensitize the
host, and subsequent exposure may result in the symptoms of food allergies (hives,
vomiting, and diarrhea).

Systemic Anaphylaxis

▪ Systemic anaphylaxis results from the release of chemical mediators from basophils in
the bloodstream. It occurs throughout the body and thus tends to be a more serious
condition than localized anaphylaxis. It may lead to a severe, potentially fatal condition
known as anaphylactic shock. Most often, the allergens involved in systemic anaphylaxis
are drugs or insect venom to which the host has been sensitized.
▪ Penicillin is an example of a hapten-a substance that must first bind to a host blood
protein (a carrier protein) before IgE antibodies are produced. The IgE antibodies then
bind to circulating basophils. Subsequent injections of penicillin into the sensitized host
may cause degranulation of the basophils and release of large amounts of histamine and
other chemical mediators into the circulatory system.
▪ The shock reaction usually occurs immediately (within 20 minutes) after re-exposure to
the allergen. The first symptoms are flushing of the skin with itching headache, facial
swelling, and difficulty breathing, followed by &lli.ng blood pressure, nausea, vomiting
abdominal cramps, and urination (caused by smooth muscle contractions). In many cases,
acute respiratory distress, unconsciousness, and death may follow shortly. Swift
treatment with epinephrine (adrenaline) and antihistamine usually stops the reaction.

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 Latex Allergy

Latex can trigger any of the following three types of reactions:

• Irritant contact dermatitis. This is the most common reaction to latex products. The
affected individual experiences dry, itchy, irritated areas on the skin, usually the hands.
This is not a true allergy because the immune system is not involved.
• Allergic contact dermatitis. This results from exposure to chemicals added to latex
during harvesting, processing, or manufacturing. These chemicals can cause skin
reactions similar to those caused by poison ivy. This is a DTH or type IV allergy.
• Latex allergy. This is an immediate-type hypersensitivity that can be a more serious
reaction to latex than irritant contact dermatitis or allergic contact dermatitis. Certain
products in latex may cause sensitization. Subsequent exposure to latex can then trigger
mild-to-severe reactions. Mild reactions include skin redness, hives, or itching. More
severe reactions include respiratory symptoms (runny nose and sneezing), itchy eyes,
scratchy throat, and asthma.

Type II Hypersensitivity Reactions

▪ Type II hypersensitivity reactions are cytotoxic reactions, meaning that body cells are
destroyed during these reactions. These include the cytotoxic reactions that occur in
incompatible blood transfusions, Rh incompatibility reactions, and myasthenia gravis; all
of these reactions involve IgG or IgM antibodies and complement. A typical type II
hypersensitivity reaction might follow this sequence:
o Step 1. A particular drug binds to the surface of a body cell.
o Step 2. Antidrug antibodies then bind to the drug.
o Step 3. This initiates complement activation on the cell surface.
o Step 4. The complement cascade leads to lysis of the body cell.

Type III Hypersensitivity Reactions

▪ Also known as immune complex reactions. Examples of type ill hypersensitivity

reactions are serum sickness and certain autoimmune diseases (e.g., systemic lupus
erythematosus [SLE] and rheumatoid arthritis). These reactions involve IgG or IgM
antibodies, complement, and neutrophils
▪ Serum sickness is a cross-reacting antibody immune reaction in which antibodies formed
to globular proteins in horse serum may also bind with similar proteins in the patient’s
blood. The formation of these immune complexes (antigen † antibody † complement)
causes the symptoms of hives, fever, kidney malfunction, and joint lesions of serum
sickness. Horse serum containing antitoxins is used to treat botulism. About 10% of
patients receiving this antiserum develop serum sickness.
▪ Certain complications (sequelae) of untreated or inadequately treated strep throat and
other Streptococcus pyogenes infections are the result of type ill hypersensitivity
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 reactions. IgG and IgM antibodies produced in response to S. pyogenes infection may
bind with streptococcal antigens (e.g., M-protein). The resultant immune complexes
become deposited in heart tissue, joints, or the glomeruli of the kidney. This causes
inflammation at the site, leading to scarring and, in some cases, abnormalities in or loss
of function.

Type IV Hypersensitivity Reactions

▪ Type IV hypersensitivity reactions are referred to as DTH (delayed-type hypersensitivity)

or cell-mediated immune reactions, and are part of CMI. (Recall that the two major arms
of the immune system are humoral immunity and CMI.) Type IV hypersensitivity
reactions are called DTH reactions because they are usually observed 24 to 48 hours or
longer after exposure or contact. They occur in tuberculin and fungal skin tests, contact
dermatitis, and transplantation rejection. DTH is the prime mode of defense against
intracellular bacteria and fungi. DTH involves various cell types, including macrophages,
DCs ( dendritic cells), cytotoxic T cells, and NK cells, but antibodies do not play a major
role.
▪ A classic example of a DTH reaction is a positive TB skin test (also called the Mantoux
skin test). Tuberculin purified protein derivative (PPD), which consists of protein extracts
prepared from Mycobacterium tuberculosis cultures, is injected intradermally into a
person. If an “immunologic memory” of the M. tuberculosis proteins exists in the
person’s body, a DTH reaction will occur, producing the typical swelling and redness
(wheal and flare) associated with a positive test result.
▪ The following events occur to produce the positive reaction:
o Step 1. Within 2 to 3 hours afu:r injection of the PPD, there is an influx of
polymorphonuclear celts (PMNs) into the site.
o Step 2. This is followed by an influx of lymphocytes and macrophages while the
PMNs disperse.
o Step 3. Within 12 to 18 hours, the area becomes red (erythematous) and swollen
(edematous).
o Step 4. The erythema (redness) and edema (swelling) reach maximum intensity
between 24 and 48 hours.
o Step 5. With time, as the swelling and redness disappear, the lymphocytes and
macrophages disperse.

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 ▪ A positive TB skin test result does not necessarily mean that a person has TB, although
that is one possibility. Actually, a positive TB skin test result may indicate any of the
following five possibilities:
1. The person has active TB (in which case, a chest radiograph will reveal the
disease, the person will probably be coughing, and his or her sputum will contain
acid-fast bacilli).
2. The person had TB at some time in the past and recovered (in this case, the person
should remember having had TB or his or her medical records will contain this
information).
3. The person was infected with M. tuberculosis at some time in the past, but the
organisms were killed by his or her host defense mechanisms (even though this
person currently harbors no live M. tuberculosis cells, he or she will receive a 6-
month. course of isoniazid because there is no way to differentiate possibility 3
from possibility 4).
4. The person currently harbors live M. tuberculosis organisms but does not actually
have TB (in this case, a 6-month course of isoniazid will be initiated in an attempt
to kill any M. tuberculosis cells in his or her body).

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 5. The person had received Bacillus Calmette-Guerin ( BCG) vaccine at some point
in the past ( he or she should remember having received BCG vaccine or he or she
is from a country where the BCG vaccine is routinely administered.

AUTOIMMUNE DISEASES

▪ An autoimmune disease 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 with certain tissues that are not exposed to the immune system
during fetal development. so that they are not recognized as self. Such tissues may
include the lens of the eye, the brain and spinal cord, and spenn. Subsequent exposure to
this tissue (by surgery or injury) may allow antibodies (IgG or lgM) to be formed, which
together with complement could cause destruction of these tissues, resulting in blindness,
allergic encephalitis, or sterility.

IMMUNOSUPPRESSION

▪ If a person's immune system is functioning properly, he or she is said to be an

immunocompetent person. If a person's immune system is not functioning properly, he or
she is said to be immunosuppressed, immunodepressed, or immunocompromised. The
most common cause of immune deficiency worldwide is malnutrition. In addition, there
are acquired and inherited immunodeficiencies.
▪ Acquired immunodeficiencies may be caused by drugs (e.g., cancer, chemotherapeutic
agents and drugs given to transplant patients), irradiation, or certain infectious diseases
( e.g., HIV infection). Immune responsiveness and the ability to produce antibodies also
decline as the normal body ages, perhaps the result of a declining ability of T cells to
regulate the immune response. This, in tum, results in a greater susceptibility of the
elderly to get serious infectious diseases.
▪ Inherited immunodeficiency diseases can be the result of deficiencies in antibody
production, complement activity, phagocytic function, or NK cell function. Examples of
inherited immunodeficiency diseases are chronic granulomatous disease and Chediak-
Higashi syndrome. Others include severe combined immunodeficiency (SCID),
DiGeorge syndrome, and Wiskott-Aldrich syndrome. SCID patients have deficiencies of
either B cells or T cells or both, resulting in severe recurrent infections.
▪ In DiGeorge syndrome, there is a congenital absence of the thymus and parathyroid
glands; patients suffer frequent infections and delayed development. Wiskott-Aldrich
syndrome patients have deficiencies in B cells, T cells, monocytes, and platelets; effects
on the patient include bleeding, recurrent infections, and eczema. Bone marrow
transplantation and gene therapy may be valuable in treating certain immunodeficiency
diseases.

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 ▪ Some people are hom lacking the ability to produce protective antibodies. Because they
are unable to produce antibodies, they have no gamma globulins in their blood. This
abnonnality is called agammaglobulinemia. These persons are very susceptible to
infections by even the least virulent microbes in their environment.

Blood Typing

▪ Agglutination tests are used in the Blood Bank. to learn a person's blood type, which is
determined by the types of antigens present on the surface of his or her RBCs. Three
reagents are used for ABO and Rh typing:
Anti-A antiserum (a serum containing antibodies against A antigen)
Anti-B antiserum (a serum containing antibodies against B antigen)
Anti-Rh antiserum (a serum containing antibodies against Rh antigen)
▪ In three separate tests, each antiserum is mixed together with the person\ RBCs. In each
test, agglutination (clumping) of the RBCs will occur if that particular antigen is present
on the RBCs

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 Example 1. A person is said to be A positive (A+) if his or her RBCs have A antigen and Rh
antigen on their surface, but lack B antigen.

Example 2. A person is said to be 0 negative (0- ) if his or her RBCs lack A antigen, B antigen,
and Rh antigen.

The Rhesus blood group system is based on another important group of RBC antigens. "Rh"
stands for "Rhesus factor. In reality, the Rh blood group system consists of 50 defined blood
group antigens. "Rh factor" strictly refers only to the most immunogenic of these antigens, called
D antigen. A person either has or does not have Rh factor on the surface of his or her RBCs. If
Rh factor is present, he or she is considered Rh positive; if not, he or she is considered Rh
negative. The original antiserum used to detect this antigen was produced in the 1940s by
injecting rabbits with RBCs from a rhesus monkey; the term "Rhesus" is still in use.

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