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Burton's Microbiology

for the Health Sciences


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

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins


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?

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins


Chapter 16 Outline, cont.

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

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins


Learning Objectives:
1. Define the terms immunology, immunity, antigenic determinant,
immunoglobulins, primary response, secondary response,
agammaglobulinemia, hypogammaglobulinemia, T cell, B cell, plasma
cell, and immunosuppression.
2. Identify the two primary functions of the immune system.
3. Differentiate between humoral immunity and cell-mediated immunity.
4. Distinguish between active acquire immunity and passive acquired
immunity.
5. Differentiate between natural active acquired immunity and artificial
acquired immunity and cite an example of each.

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins


Learning Objectives:
6. Outline the steps involved in the processing of T-independent antigens
and T-dependent antigens.
7. Construct a diagram of a monomeric antibody molecule.
8. Identify and describe the five immunoglobulin classes (isotypes).
9. List the types of cells that are killed by natural killer (NK) cells.
10. Name the four types of hypersentivity reactions.
11. Outline the steps involved in an allergic reactions, starting with the
initial sensitization to an allergen and ending with the typical symptoms of
an allergic reaction.

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins


Learning Objectives:
12. Cite six examples of allergens.
13. List five possible explanations for a positive tuberculosis (TB) skin
test.

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins


Introduction

• 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 “non-self”
– Destroy that which is “non-self”
• Cells involved in immune responses originate in
bone marrow; 3 lines of lymphocytes are
derived from lymphoid stem cells of bone
marrow: B lymphocytes (or B cells), T
lymphocytes (or T cells) and natural killer cells
(NK cells)

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins


Introduction, cont.
• There are 2 categories of T cells:
– Helper T cells and Cytotoxic T
cells
• There are 2 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 only playing a
minor role, if any

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins


The Two Major Arms of the Immune System

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins


Immunity
• Acquired immunity = immunity that
results from the active production or
receipt of antibodies during one’s
lifetime

• Active acquired immunity:


• Antibodies are produced within
the person
• Usually provides long lasting
protection
• Passive acquired immunity:
• Antibodies are received that
were produced by another
person or persons or by an
animal
• Usually provides only temporary
protection
Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins
Active Acquired Immunity
• Two types of active acquired immunity:
– Natural active acquired immunity –
occurs naturally
– 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.

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins


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
http://www.riversideonline
.com/health_reference/Infe
– Toxoid vaccines ctious-
http://youtu.be/C061bmvk7Hw Disease/ID00023.cfm

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins


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;
example, hepatitis B immune globulin

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins


Cells of the Immune System

• The major cell types that participate in immune responses are:


 T lymphocytes (T cells)
 B lymphocytes (B cells)
 NK cells (a category of lymphocytes)
 Macrophages and dendritic cells (DCs)
• 3 major categories of T cells
 Helper T cells
- Also know as T-helper cells, Th cells, and CD4+ cells
- Secretion of cytokines
- Subcategories:
Th1 cells
Th2 cells

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins


Cells of the Immune System, cont.

• Cytotoxic T cells
 Also known as T cytotoxic cells, Tc cells, and CD8+ cells.
 To destroy virally infected host cells, foreign cells, and
tumor cells
• Regulatory T cells
 Serves as a brake on the immune response to infection
 CD4+ antigen, but some contain CD8+ antigen on their
cell surface

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins


Humoral Immunity

• 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.
• The lymphatic system is the site and
source of most immune activity.
 Other sites: spleen, lymph nodes,
tonsils and adenoids.

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins


Humoral Immunity

• Antibody Structure and Function


– Antibodies are a class of
glycoprotein called
immunoglobulins; 5 types = IgA,
IgD, IgE, IgG, IgM.
– All antibodies are
immunoglobulins, but not all
immunoglobulins are antibodies!

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins


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
– A bacterial cell has many
molecules (antigenic
determinants) on its surface
that are capable of stimulating
the production of antibodies

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins


Humoral Immunity, cont.

• Antibodies

– Proteins produced by
lymphocytes in response
to the presence of an
antigen
– Are in a class of proteins
called immunoglobulins –
globular glycoproteins in
the blood that participate
in immune reactions

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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 10-14 days for
antibodies to be produced.
– The increased production of
antibodies following the second
exposure to a particular antigen
is called the secondary response.
Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins
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; results in some of the
following effects:
– Activation of leukocytes
– Lysis of bacterial cells
– Increased phagocytosis as a result
of opsonization

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins


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) http://www.mhhe.com/biosci/e
sp/2001_saladin/folder_structu
– Examples of cells that
participate in CMI: re/tr/m4/s9/index.htm
macrophages, TH cells, TC cells,
NK cells, and granulocytes
Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins
Cell-Mediated Immunity, cont.

• NK (Natural Killer) Cells


– NK cells are in a subpopulation of
lymphocytes called large granular
lymphocytes.
– They resemble lymphocytes, but
lack typical T or B cell surface
markers.
– Do not proliferate 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 cells.
Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins
Hypersensitivity and Hypersensitivity
Reactions
• Hypersensitivity refers to an overly sensitive immune system.
• Different types of hypersensitivity reactions:
– Immediate-type: occurs from within a few minutes to 24 hours
after contact with a particular antigen; 3 types: type I, II and III
hypersensitivity reactions
– Delayed-type: usually takes more than 24 hours to manifest
themselves
• Also known as Type IV hypersensitivity reactions.

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins


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 to the allergen.

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins


Factors in the Development of
Type I Hypersensitivity

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Events That Occur in
Type I Hypersensitivity Reactions

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Type I Hypersensitivity Reactions, cont.

• Type I hypersensitivity reactions may be localized or systemic.


– Localized reactions involve mast cell degranulation; they result in
allergic reactions, such as hay fever symptoms, asthma, and food
allergies.
– Systemic reactions involve basophil degranulation; they occur
throughout the body, can lead to anaphylactic shock, and can be life-
threatening.

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins


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 or insect venom
• Latex Allergy
– Latex can trigger any of 3 types of reactions: irritant contact
dermatitis, allergic contact dermatitis, and immediate type
hypersensitivity

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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 allergy shots.

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins


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. Anti-drug antibodies then bind to the drug.
3. Complement activation on the cell surface is initiated.
4. The complement cascade leads to lysis of the cell.

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins


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).

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins


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 24-48 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.

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins


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 “non-self” 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’s thyroiditis, Graves disease, etc.

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins


Immunosuppression
• 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; examples – DiGeorge syndrome and Wiskott-Aldrich syndrome.
• People born lacking the ability to produce antibodies (i.e., gamma
globulins) have agammaglobulinemia; persons not producing a sufficient
amount of antibodies are said to have hypogammaglobulinemia.

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins


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!
• 3 possible reasons for the presence of antibodies to a particular
pathogen: present infection, past infection, 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-linked immunosorbent assays
(ELISAs).

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Immunodiagnostic Procedures, cont.
• Skin Testing
– Performed in vivo
– Antigens are injected within or beneath the skin
– Example: the tuberculosis 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 immunodeficiencies,
complement deficiencies, etc.

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins

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