Burton’s Microbiology

for the Health

Sciences

Chapter 16.
Specific Host
Defense
Mechanisms:
An Introduction to
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Chapter 16
Outline

• Introduction
• The Key to Understanding Immunology
• Primary Functions of the Immune System
• Major Arms of the Immune System
• Immunity
• Cells of the Immune System
• Where do Immune Responses Occur?
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Chapter 16 Outline

• Humoral Immunity
• Cell-Mediated Immunity
• Hypersensitivity and Hypersensitivity Reactions
• Autoimmune Diseases
• Immunosuppression
• The Immunology Laboratory

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 Introduction
(Immunology)
• Immunology is the scientific study of the immune
system and immune responses.
• The primary functions of the immune system are to:
– Differentiate between “self” and “nonself”
– Destroy that which is “nonself”
• Cells involved in immune responses originate in bone
marrow; three lines of lymphocytes are derived from
lymphoid stem cells of bone marrow: B lymphocytes
(B cells), T lymphocytes (T cells), and natural killer
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• cells (NK cells).

 Lymphoid Stem Cells
(Hematopoietic Stem Cells HSCs)
A. Myeloid stem cells → become:
✔ RBC Red blood cells (erythrocytes) – carry oxygen
✔ Platelets (thrombocytes) – help with clotting
✔ Granulocytes:
• Neutrophils – fight bacteria
• Eosinophils – fight parasites and cause allergic reactions
• Basophils – involved in inflammation and allergies
✔Monocytes – become macrophages (big eaters of
pathogens and debris)
B. Lymphoid stem cells → become:
✔B lymphocytes (B cells) – produce antibodies
✔T lymphocytes (T cells) – attack infected or cancerous
cells
 Introduction

• There are two categories of T cells:

– Helper T cells and cytotoxic T cells
• There are two major arms of the immune system:
– Humoral immunity—where special glycoproteins
called antibodies are produced by B cells to
destroy specific microbes
– Cell-mediated immunity—involves a variety of
cell types, with antibodies playing only a minor
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role, if any
 The Two Major Arms of
the Immune
System

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 Immunity
(Acquired Immunity)

❖ Acquired immunity—immunity that results

from the active production or receipt of
antibodies during one’s lifetime.
❖ Acquired immunity (also called
adaptive immunity) is the type of
immunity that a person develops after
being exposed to a specific pathogen,
or through vaccination.
❖ It is not present at birth—it is
Acquired Immunity

A. Active acquired immunity:

• Antibodies are produced within the person
• Usually provides long-lasting protection
B. Passive acquired immunity:
• Antibodies are received that were
produced by another person(s) or by an
animal
• Usually provides only temporary protection
 Active Acquired
Immunity

• Two types of active acquired immunity:

1. Natural active acquired immunity—occurs naturally
2. Artificial active acquired immunity—artificially
induced
• Artificial active acquired immunity results when a person
receives a vaccine.
– A vaccine is defined as material that can artificially
induce immunity to an infectious disease, usually
following injection or ingestion of the vaccine.
– Most vaccines are made from living or dead
pathogens or the toxins that they produce.
 How Vaccines
Work
• Vaccines stimulate the recipient’s
immune system to produce protective
antibodies (i.e., antibodies that will
protect the person from disease).

Types of available vaccines:

✔Attenuated vaccines
✔Inactivated vaccines
✔Subunit vaccines
✔Conjugate vaccines
✔Toxoid vaccines
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 Types of Vaccine

1. Attenuated (Live) Vaccines

▪Made from weakened live pathogens that can
still replicate but don’t cause disease in healthy
people.
▪Provide strong, long-lasting immunity.
▪Not safe for people with weak immune systems
(e.g., HIV, cancer).

▪Examples:
•
 Types of Vaccine

2.Inactivated (Killed)
Vaccines 3. Subunit Vaccines
▪ Contain only specific
▪ Made from pathogens that
parts of the pathogen
have been killed or
inactivated by heat or (like proteins or sugars),
chemicals. not the whole organism.
▪ Fewer side effects; may
need boosters.
▪ Safer than live vaccines but ▪ Examples: Hepatitis
may require booster shots. B ;Human
▪ Examples: papillomavirus
• Inactivated polio vaccine (HPV);Whooping cough
(IPV) (part of DTaP)
 Types of Vaccine

4. Conjugate Vaccines
▪ Combine a weak antigen (like a sugar coating from bacteria) with a
strong protein carrier to boost immune response.
▪ Effective in infants and young children.
▪ Examples:
Haemophilus influenzae type b (Hib) ;Pneumococcal vaccine;
Meningococcal Vac. v

5. Toxoid Vaccines
▪ Made from inactivated toxins (toxoids) produced by bacteria, not the
bacteria itself.
▪ Protects against the harmful effects of the toxin.
▪ Examples:
Tetanus (T)
Child Receiving a
Vaccine

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 Passive Acquired
Immunity

• Antibodies produced in one person are transferred to

another person to protect the latter from infection –
provides temporary protection.
• Two types:
– Natural passive acquired immunity
• Small antibodies, IgG, present in mother’s blood
cross the placenta to reach the fetus
– Artificial passive acquired immunity
• Antibodies from an immune person are transferred
to a susceptible person (e.g., hepatitis B
immunoglobulin).
There are two major arms of
the immune system
A. Humoral Immunity
• Antigens
– Foreign organic substances that are large
enough to stimulate the production of
antibodies
– Substances capable of stimulating
antibodies are said
to be antigenic (or immunogenic).
– A bacterial cell has many molecules
(antigenic determinants) on its
surface that are capable of
stimulating the production of
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antibodies.
 Humoral Immunity
(cont.)

• Antibodies
– Proteins produced by
lymphocytes in
response to the
presence of an antigen
– Belong to a class of
proteins called
immunoglobulins— Ig
globular glycoproteins
in the blood that
participate in immune
reactions
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Basic
Structure of
an Antibody

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 Humoral Immunity
(cont.)

• Antibodies (cont.)
– The amount and type of antibodies produced by a
given antigenic stimulation depend on the nature of
the antigen, the site of antigenic stimulus, the amount
of antigen, and the number of times the person is
exposed to the antigen.
– The majority of antigens are referred to as T-
dependent antigens because T cells are required in
their processing; the processing of T-independent
antigens requires only B cells.
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 Humoral Immunity
(cont.)
• Antibodies (cont.)
– The processing of either T-dependent or T-
independent antigens results in B cells developing
into plasma cells, which are capable of secreting
antibodies.

– The initial immune response to an antigen is called

the primary response; it takes 10 to 14 days for
antibodies to be produced.

– The increased production of antibodies following the

second
Copyright exposure
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Reserved

secondary response.
 Humoral Immunity
(cont.)
• Where do immune responses occur?
– Immune responses to antigens in the blood are
usually initiated in the spleen; responses to microbes
and other antigens in tissues are generated in lymph
nodes located near the infected area.
• Antibody structure and function
– Antibodies are a class of glycoproteins called
immunoglobulins; five types—IgA, IgD, IgE, IgG,
and IgM.
– All antibodies are immunoglobulins, but not all
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immunoglobulins are antibodies!

Monoclonal Antibodies
• Long-lived, antibody-producing cells called hybridomas
are produced by combining a single plasma cell and a
rapidly dividing tumor cell.

• Hybridomas are capable of producing large amounts of

specific antibodies called monoclonal antibodies.

• Monoclonal antibodies are used in

immunodiagnostic procedures (i.e., immunologic
procedures used in laboratories to diagnose
diseases).
•Copyright
Monoclonal antibodies
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• All Rights Reserved

use in fighting diseases, killing tumor cells, boosting the

immune system, and preventing organ rejection.
Antigen–Antibody
Complexes
• When an antibody combines with an antigen, an antigen–
antibody complex (or immune complex) is formed.
• Antigen–antibody complexes are capable of activating
the complement cascade, which results in some of
the following effects:
– Activation of leukocytes
– Lysis of bacterial cells
– Increased phagocytosis as a result of opsonization

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Cell-Mediated Immunity

• Antibodies are unable to enter cells.

• Cell-mediated immunity (CMI)

– A complex system of interactions among many types

of cells and cellular secretions (cytokines)

– An arm of the immune system capable of controlling

chronic infections by intracellular pathogens (e.g.,
certain bacteria, protozoa, fungi, and viruses)

– Examples of cells that participate in CMI:

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macrophages, TH cells, TC cells, NK cells, and
granulocytes
Cell-Mediated Immunity (cont.)
• NK (Natural Killer) Cells

– NK cells are a subpopulation of lymphocytes called

large granular lymphocytes.

– They resemble lymphocytes, but lack typical T or B

cell surface markers.

– Do not proliferate(multiply) in response to antigen

and appear not to be involved in antigen-specific
recognition.

– NK cells kill target cells, including foreign cells, host

cells infected with viruses or bacteria, and tumor
 Hypersensitivity and
Hypersensitivity Reactions
• Hypersensitivity refers to an overly sensitive immune
system.
• Different types of hypersensitivity reactions:
1.Immediate-type: occurs from within a few minutes
to 24 hours after contact with a particular antigen;
three types: types I, II, and III hypersensitivity
reactions
2.Delayed-type: usually takes more than 24 hours
to manifest themselves
• Also known as type IV hypersensitivity reactions.
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 Type I Hypersensitivity
Reactions

• Type I hypersensitivity reactions are also known as

anaphylactic reactions; they 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

– Anaphylactic shock

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Type I Hypersensitivity Reactions
(cont.)

• The Allergic Response

– Type I immediate hypersensitivity is probably the

most common type of hypersensitivity.
– People prone to allergies (atopic persons) produce
IgE antibodies when exposed to allergens (antigens
that cause allergic reactions).
– The allergic reaction results from the presence of IgE
antibodies bound to basophils in the blood or to mast
cells in connective tissues—IgE antibodies that were
produced in response to the person’s first exposure
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to the allergen.
Factors in the Development of
Type I Hypersensitivity

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Events That Occur in
Type I Hypersensitivity Reactions

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Transmission
Electron
Micrograph
Showing
Degranulation of a
Rat Mast Cell
Transmission
Electron
Micrograph
Showing
Phagocytosis of
Rat Mast Cell
Granules
Copyright by aKluwer
© 2015 Wolters Rat • All Rights Reserved

Eosinophil
 Type I Hypersensitivity Reactions
(cont.)
• Type I hypersensitivity reactions may be
localized or systemic.
1.) Localized reactions involve mast cell
degranulation (Reside in tissues =skin,
lungs, GI tract, mucosa); they result in allergic
reactions, such as hay fever symptoms,
asthma, and food allergies.
2.) Systemic reactions involve basophil
degranulation (Circulate in the blood, enter
tissues during inflammation); they occur
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throughout the body, can lead to anaphylactic
shock, and can be life-threatening.
Type I Hypersensitivity
Reactions (cont.)
• Systemic anaphylaxis
– Results from the release of chemical mediators from
basophils in the bloodstream
– Occurs throughout the body—much more serious
than localized anaphylaxis
– Common allergens involved are drugs and insect
venom.
• Latex allergy
– Latex can trigger any of three types of reactions:
Copyright irritant
© 2015 Wolterscontact dermatitis,
Kluwer • All Rights Reserved allergic contact dermatitis,
or immediate type hypersensitivity.
 Type I Hypersensitivity Reactions
(cont.)

• Allergy skin testing and allergy shots

– Anaphylactic reactions can be prevented by avoiding
known allergens, which is often difficult to do.
– Skin tests (scratch tests) are used to identify
offending allergens in patients.
• A positive test is indicated if cutaneous
anaphylaxis occurs at the site of the scratch.
– Immunotherapy (i.e., allergy shots - IM doses of the
allergen) may be used to treat the patient.
– IgG blocking antibodies are produced in response to
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allergy shots.
Type II Hypersensitivity
Reactions
• Type II hypersensitivity reactions are cytotoxic
reactions, meaning that body cells are destroyed during
these reactions.
• Sequence of events in a type II hypersensitivity
reaction:
1. A particular drug binds to the surface of a cell.
2. Antidrug antibodies then bind to the drug.

3. Complement activation on the cell surface is

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4. The complement cascade leads to lysis of the cell.

Type III Hypersensitivity
Reactions

• Type III hypersensitivity reactions are immune complex

reactions—such as those that occur in serum sickness
and certain autoimmune diseases (e.g., systemic lupus
erythematosus and rheumatoid arthritis).

• Involve IgG or IgM antiboides, complement, and

neutrophils
• Some complications of untreated or inadequately treated
strep throat and other Streptococcus pyogenes
infections are the result of type III hypersensitivity
reactions (e.g., rheumatic fever and glomerulonephritis).
Type III Hypersensitivity Test

What is Type III Hypersensitivity?

• It is caused by immune complex formation
— when antigen-antibody complexes
(especially IgG or IgM) form in the blood and
deposit in tissues.
• These deposits trigger inflammation and
tissue damage, mostly by activating the
complement system and attracting
neutrophils.
Type IV Hypersensitivity
Reactions

• Type IV hypersensitivity reactions are delayed-type

hypersensitivity (DTH) or cell-mediated immune
reactions, and are part of cell-mediated immunity.

– Reactions are usually observed 24 to 48 hours or

longer after exposure or contact.

• DTH is the prime mode of defense against intracellular

bacteria and fungi.
• DTH involves a variety of cell types, including
macrophages, cytotoxic T cells, and NK cells—antibodies
do not play a major role.
• A classic example of DTH is a positive TB skin test.
Mantoux Skin Test OR Tuberculine Skin
Test

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 Autoimmune
Diseases

Autoimmune diseases result 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.
• May occur with certain tissues that are not exposed to the
immune system during fetal development and, thus, are not
recognized as “self.”
• There are more than 80 recognized autoimmune
diseases.
• Can be classified as organ-specific or non-organ-specific.
• Examples: Hashimoto thyroiditis, Graves disease,
systemic lupus erythematosus, etc.
 Hashimoto’s Thyroiditis

Hashimoto's Thyroiditis
• Cause: Autoimmune attack on thyroid cells.
• Autoantibodies: Anti-thyroid peroxidase (anti-TPO),
anti-thyroglobulin.
• Symptoms: Fatigue, weight gain, cold intolerance,
bradycardia.
• Treatment: Lifelong thyroid hormone replacement.
Graves’ Disease

Graves' Disease
• Cause: Autoantibodies mimic TSH →
thyroid overactivity.
• Autoantibody: TSH receptor antibody
(TRAb).
• Symptoms: Weight loss, heat intolerance,
palpitations, exophthalmos (bulging eyes).
• Treatment: Antithyroid drugs, radioactive
iodine, or surgery
Systemic Lupus
Erythematosus

Systemic Lupus Erythematosus (SLE)

• Cause: Autoantibodies against nuclear
components (DNA, histones).
• Autoantibodies: ANA, anti-dsDNA, anti-Smith.
• Symptoms: Butterfly rash, arthritis, nephritis,
anemia, fatigue.
• Treatment: Immunosuppressants,
corticosteroids.
Immunosuppressi
on
• Persons whose immune systems are not functioning
• properly are said to be immunosuppressed.
• Acquired immunodeficiencies may be caused by
drugs (e.g., cancer therapeutic agents), irradiation,
or certain infectious diseases (e.g., HIV infection).
• Inherited immunodeficiency diseases can be the
result of deficiencies in antibody production,
complement activity, phagocytic function, or NK cell
function (e.g., DiGeorge syndrome and Wiskott–
Aldrich syndrome).
• People born lacking the ability to produce
antibodies (i.e., gamma globulins) have
agammaglobulinemia; persons not producing a
Immunodiagnostic
Procedures

• Immunodiagnostic procedures (IDPs) help diagnose

infectious diseases by detecting either antigens or
antibodies in clinical specimens; test results are usually
available on the same day!

• Three possible reasons for the presence of antibodies to

a particular pathogen: present infection, past infection,
and vaccination.
• A variety of different laboratory tests have been designed
to observe the presence of an antibody–antigen reaction.

– Examples of these tests include agglutination,

precipitin tests, immunofluorescence, and enzyme-
Agglutination Procedure for
ABO Blood Typing

Agglutination is the clumping of

red blood cells (RBCs) in response to
the interaction between antigens
on RBCs and specific antibodies
in the reagent. This procedure is a
simple lab test used to
determine a person's blood type
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(A, B, AB, or O) using the ABO

 ABO Blood System

Blood Type RBC Antigens Antibodies in

Plasma
A A antigen Anti-B antibodies

B B antigen Anti-A
antibodies
AB A and B No ABO
Universal antigens antibodies
Recipient
O No antigens Anti-A and Anti-B
Universal Donor antibodies
 Universal Donor and Universal
RecipieNT: Blood Type O
Universal Donor: Universal Recipient:
Blood Type O Negative (O−) Blood Type AB Positive (AB+)
A person with O− blood is called the A person with AB+ blood is the
universal donor because: universal recipient because:
✔ Their red blood cells have no A, ✔ Their red blood cells have both A
B, or Rh antigens. and B antigens, and the Rh
antigen.
✔ So, their blood won’t trigger an ✔ Their plasma has no anti-A, anti-
immune reaction in any recipient. B, or anti-Rh antibodies.
✔ Can donate to: A+, A−, B+, B−, ✔ So they can receive blood from
AB+, AB−, O+, O− (all blood types) any ABO and Rh group without
reacting.
✔ Can receive blood from: Only O− ✔ Can receive blood from: A+, A−,
B+, B−, AB+, AB−, O+, O− (all blood
types)
Blood
Typing

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Immunodiagnostic Procedures
(cont.)

• Skin Testing
– Performed in vivo
– Antigens are injected within or beneath the skin.
– Example: the TB skin test
• Procedures Used in the Diagnosis of Immunodeficiency
Disorders
– For assessment of patient’s immune status and
evaluation of immunodeficiency disorders
– Include B-cell deficiency states, cell-mediated
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immunodeficiencies, complement deficiencies,
etc.