Chapter 15

Lecture Outline

Copyright © 2016 McGraw-Hill Education. Permission required for reproduction or display. 1

I. Defense Mechanisms
 A. Introduction

1. Protect against disease-causing agents called

pathogens
2. Make up the immune system
3. Two types:
a. Innate (nonspecific) immunity - inherited
b. Adaptive (specific) immunity – learned from
exposure to specific pathogens; function of
lymphocytes
 1. Innate Immunity

1. Includes external and internal defenses

2. Serves as a first line of defense against
pathogens
a. Examples: epithelial membranes (secrete
antimicrobial peptides), high acidity in stomach,
cells that can engulf/kill pathogens, fever
Innate Immunity
 1. Activation of Innate Immunity

a. Cells distinguish “self” from “nonself” using

pathogen-associated molecular patterns
(PAMPs) unique to the pathogens.
1) Immune cells have pathogen recognition
receptors, such as toll-like receptors for
PAMPs on their surface.
2) So far, 10 distinct toll-like receptors have been
identified.
3) These cells respond by secreting chemokines
to recruit more immune cells or activate
specific immune cells.
PAMPs and toll-like receptors (TLRs)
 NOD-like receptors (NLRs)
crucial cytoplasmic sensors

NOD: nucleotide-binding oligomerization domain

PGN: peptidoglycan (PGN) fragment
meso-DAP: γ-D-glutamyl-meso-diaminopimelic acid
 1. Complement System

1) Integrates innate and adaptive immune responses

2) Consists of proteins in the plasma that become
activated when antibodies bind to antigens
3) Complement proteins promote phagocytosis, lysis
of target cells, and inflammation.
 outcomes of complement activation
C3

Splits into activated C3a and C3b

cytolysis opsonization inflammation

C3a C3b C3a C3b C3a C3b

C5 C5

C5a C5b C5a C5b

C6 Histamine

C7 C8 C3a C5a
Microbe

C3a C5a
C9 receptor Mast cell receptor

Channel C3b protein Microbes Phagocytesa

C6
C7 C5b
C8
C9
Phagocyte

Microbes burst as extracellular Coating microbes with C3b Blood vessels become more
fluid flows in through transmembrane channel enhances phagocytosis. permeable, and chemotactic agents
formed by membrane attack complex. attract phagocytes to area.

KEY CONCEPTS

The complement system is another way the body fights infection and destroys pathogens. This component of innate immunity
“complements” other immune reactions.
Complement is a group of over 30 proteins circulating in serum that are activated in a cascade: one complement protein triggers
the next.
The cascade can be activated by a pathogen directly or by an antibody–antigen reaction.
Together these proteins destroy microbes by (1) cytolysis, (2) enhanced phagocytosis, and (3) inflammation.
 1. Local inflammation

1) Tissue damage that causes necrosis

2) Immune system exposed to DAMPs – danger
associated molecular patterns
3) Stimulates innate immune responses and
inflammation
Schematic of
recognized danger-
associated
molecular patterns
(DAMPs), the
receptors to which
they bind, and
association with the
innate and adaptive
immune response.
 1. Phagocytosis

a. Three types of phagocytic cells:

1) Neutrophils are the first to arrive at an infection.
2) Mononuclear phagocytic cells (monocytes in
the blood and macrophages and dendritic cells
in the tissues) arrive later.
3) There are organ-specific phagocytes in the
liver, spleen, lymph nodes, lungs, and brain.
a) Some of these, called fixed phagocytes, are
immobile in the walls of these organs.
Phagocytotic Cells & Locations
 1. Phagocytosis in Tissues

1) Neutrophils and monocytes squeeze through

gaps in post-capillary venule walls to enter tissue
in a process called extravasation, or diapedesis.
2) Attracted to site by a process called chemotaxis
by cytokines called chemokines
3) The pathogen becomes engulfed by
pseudopods.
4) The vacuole containing the pathogen fuses with
a lysosome.
5) The pathogen is digested.
Migration of white blood cells

Selectins and
integrins
Phagocytosis by a neutrophil or macrophage
Suicide (apoptosis) signals

PS: phosphatidylserine

Inflammatory responses are suppressed

 1. Fever

a. Regulated by hypothalamus (“thermostat”)

b. A chemical called an endogenous pyrogen sets
the body temperature higher.
1) Produced as a cytokine by leukocytes
(interleukin-1)
2) Endotoxins from some bacteria stimulate
leukocytes to produce these cytokines (IL-1, IL-
6, and TNF).
3) Along with fever, they also induce sleepiness
and a fall in plasma iron concentration (which
limits bacterial activity), increased activity of
neutrophil.
 1. Interferons

a. Antiviral polypeptides produced by infected cells

b. Three types identified
1) Alpha and beta – inhibit viral replication and
assembly (produced by infected cell)
2) Gamma – helps fight infections and cancer
(produced by NK cell)
c. New antiviral drugs are being developed using
interferons. (FDA approved and clinical trial)
Effects of Interferons
 1. Adaptive Immunity

1. The acquired ability to defend against specific

pathogens after exposure to these pathogens

a. Mediated by antigens and antibodies

 1. Antigens

a. Cell surface molecules that stimulate the

production of specific antibodies and combine with
those antibodies
1) Foreign antigens illicit an immune response.
The immune system can distinguish “self” from
“nonself.”
2) Antibodies bind to their specific antigens.
3) Large molecules can have several antigenic
determinant sites or epitopes, that stimulate the
production of and binding to antibodies.
 1. Haptens

1. Smaller, nonantigenic molecules that can become

antigens when bound to other proteins
2. These are useful for creating antigens for
research and diagnosis.
1. Immunoassays

1. Tests that use specific antibodies to identify

specific antigens
2. Binding causes agglutination, which can be seen.
3. Used to determine blood type and detect
pregnancy
Immunoassays using the
agglutination technique
 1. Lymphocytes & Lymphoid Organs

1. Lymphocytes
a. Derived from stem cells in the bone marrow.
b. These stem cells seed the thymus, spleen, and
lymph nodes.
1) The thymus is the site of new T lymphocytes
through late childhood. It degenerates in
adulthood, and new T lymphocytes are
made through mitosis in secondary lymphoid
organs.
2) The bone marrow and thymus are
considered primary lymphoid organs.
1. T Lymphocytes

1) Lymphocytes that seed the thymus become T

lymphocytes. These then seed the blood,
lymph nodes, and spleen.
2) T lymphocytes attack host cells that have
become infected with a virus or fungus,
transplanted human cells, and cancer cells.
3) T lymphocytes do not produce antibodies.
4) They must be in close proximity to the victim
cell in order to destroy it.
5) This is called cell-mediated immunity.
 1. B Lymphocytes

1) Lymphocytes that come directly from bone marrow

to seed other organs (not the thymus) are called B
lymphocytes.
2) They combat bacterial and some viral infections.
3) They secrete antibodies into blood and lymph so
can be far from the victim.
4) This is called humoral immunity or antibody-
mediated immunity.
Comparison of T and B Lymphocytes
 1. Secondary Lymphoid Organs

a. Lymph nodes, spleen, tonsils, and Peyer’s

patches (in mucosa of intestines) (near 450 lymph
node)
b. Capture and present pathogens to macrophages
and house lymphocytes
c. Lymphocytes migrate between lymphoid organs to
sample blood and lymph.
1) The spleen filters blood for pathogens.
2) Other organs filter lymph for pathogens.
 1. Local Inflammation

1. Occurs when bacteria enter a break in the skin

2. Initiated by nonspecific mechanisms of
phagocytosis by toll-like receptors
a. Macrophages and mast cells release cytokines
and chemokines to attract phagocytic
neutrophils.
b. Complement proteins are activated, which also
attract phagocytic cells.
c. More phagocytic cells arrive via extravasation
from nearby venules. T lymphocytes are the
last to arrive.
 Local Inflammation, cont

3. Mast cells (especially concentrated in the skin,

bronchioles and intestinal mucosa) degranulate
and secrete heparin, histamine, prostaglandins,
leukotrienes, cytokines, and TNF-α.
a. These produce warmth, swelling, and pain
(classic symptoms).
b. They also recruit more leukocytes.
Pathogen Splinter
Movement
of fluid

Signaling Macro-
Mast molecules phage
cell
Capillary
Phagocytosis

Red blood Neutrophil

cells
1 Mast cells release 2 Neutrophils and 3 Neutrophils
histamines. anti- digest
Capillaries microbial pathogens
dilate. peptides and cell
enter tissue. debris.
Tissue heals.
Events of Local Inflammation
Infiltration of an inflamed site by leukocytes

 Macrophage
 Local inflammation, cont

4. Neutrophils
a. Kill microorganisms through phagocytosis
b. Release NETS (neutrophil extracellular traps)
to trap pathogens
c. Undergo programmed cell death and spill
protein-digesting enzymes into the surrounding
tissues, causing pus
d. Release granule proteins that draw monocytes
to the area
 Local inflammation, cont

5. Monocytes
a. Enlarge into macrophages
b. Phagocytose apoptotic neutrophils and release
growth factors and other agents that will end
inflammation and promote repair.
6. As inflammation progresses, B lymphocytes
produce antibodies against bacterial antigens.
a. Formation of antigen-antibody complexes
amplifies phagocytosis by neutrophils,
monocytes, and macrophages, a process
called opsonization.
Opsonization
 Local Inflammation, cont

7. Symptoms of inflammation
a. Redness and warmth due to histamine
stimulated vasodilation
b. Swelling – vasodilation
c. Pain – release of PGE2
d. Pus - phagocytosis
Summary of Events in Local Inflammation
II. Functions of B
Lymphocytes
1. Introduction

1. Exposure to the specific antigen activates a B

lymphocyte
2. Enters the germinal center of a secondary
lymphoid organ
3. Undergo multiple cell divisions (cloning).
a. Some become memory cells, which are
used in a later infection by the same
pathogen.
b. Others become plasma cells, which produce
2,000 antibodies/second.
B Lymphocytes Become Plasma
& Memory Cells
 1. Antibodies

1. Introduction
a. Also known as immunoglobulins (Ig)
b. Five classes: IgG, IgA, IgM, IgD, and IgE
Types of Antibodies
 1. Antibody Structure

a. Y-shaped protein
1) 2 long, heavy (H) chains joined by 2 shorter,
light (L) chains
2) The bottom (Fc) is constant across different
antibodies, whereas the top (Fab) varies and
allows antigen specificity.
b. B lymphocytes have antibodies on the plasma
membranes that are receptors for antigens.
1) When the antigen bonds to the antibody, the B
cell is stimulated to divide and produce more
antibodies
Antibodies bond to antigens on bacteria
Antigen-Antibody complex
 1. Diversity of Antibodies

a. Everyone has 1020 antibody molecules.

1) There are a few million different specificities.
2) There should be an antibody for every antigen
you might encounter.
 Diversity of Antibodies, cont

b. Mechanisms for antibody diversity

1) A large percentage of our genetic code is
dedicated to making antibodies. Some genes
code for light chains and some for heavy chains
2) Antigen-independent genetic recombination in
the bone marrow – different combinations of
light and heavy chains
3) Antigen-dependent cell division of lymphocytes
in secondary lymphoid organs, somatic
hypermutation, gene recombinations, class
switch recombination
 1. The Complement System

1. Part of the nonspecific defense system

a. Activity is triggered by binding of antibodies to
antigens (classic pathway) and by
polysaccharides on bacterial membranes
(alternative pathway).
2. Binding of antibodies to antigens does not destroy
the pathogen.
a. This labels targets for attack by phagocytic
cells and stimulates opsonization.
pathway of complement activation

classical
1. Antibodies bind to antigens,
Microbe
activating C1
Antigen 2. C1 splits and activates C2
Antibody and C4
C1
3. C2a and C4b combine and
C2 C4
activate C3
1. C3a functions in
C2b C2a C4b C4a inflammation
2. C3b functions in cytolysis
and opsonization
C3

C3a C3b

inflammation cytolysis opsonization

 alternative
1. C3 present in the blood
combines with factors B, D,
Microbe
and P on microbe surface
Lipid–
carbohydrate
complex
2. C3 splits into C3a and C3b,
functioning the same as in the
classical pathway

Microbe

B D P
Factors

C3

C3a C3b

inflammation cytolysis opsonization

 lectin
1. Macrophages ingest pathogens,
Microbe releasing cytokines that
Carbohydrate
stimulate lectin production in
containing
mannose the liver
Mannose-binding 2. Mannose-binding lectin (MBL)
lectin (MBL)
binds to mannose, activating C2
C2 C4
and C4
C2b C2a C4b C4a 3. C2a and C4b activate C3, which
functions the same as in the
classical and alternative
C3
pathways

C3a C3b

inflammation cytolysis opsonization

The Complement System, cont

3. Complement is a group of plasma proteins

activated by the binding of antibodies to
antigens.
a. Proteins are designated C1−C9.
b. C1 serves as a recognition protein.
c. C2, C3, and C4 serve as activators.
d. C5−C9 attack by attaching to a cell
membrane and destroying it.
 1. Classic Pathway of Complement Action

a. Complement-dependent cytotoxicity - more rapid

and efficient; involves antibodies binding to
antigens to destroy cells
1. IgG and IgM activate C1, which splits C4 into two
fragments, C4a and C4b.
2. C4b binds to the cell membrane and becomes
active, splitting C2 into C2a and C2b.
3. C2a attaches to C4b and cleaves C3 into C3a and
C3b.
Classic Pathway, cont

e. C3b converts C5 into C5a and C5b.

f. C5b and C6−C9 are inserted into the bacterial
cell membrane, forming the membrane attack
complex – complement fixation
g. This creates a large pore in the membrane,
causing influx of water into the cell = lysis.
Complement Fixation
Membrane Attach Complex
 1. Effects of Complement Fragments

a. Chemotaxis – attracting phagocytic cells

b. Opsonization – phagocytes have receptors for
C3b; forms a bridge between phagocyte and victim
cell to facilitate phagocytosis
c. C3a and C5a stimulate mast cells to release
histamine to increase blood flow to the area.
III. Functions of T
Lymphocytes
 A. Killer, Helper, and Regulatory T Lymphocytes

1. Killer (cytotoxic) T Lymphocytes

a. Have surface molecules called CD8
b. Destroy body cells that harbor foreign antigens
1) Usually from a pathogen (virus or fungus),
but can be due to a malignancy (cancer)
2) Transplant cells
c. Cell-mediated destruction means the T cells
must touch the target victim.
1) Secrete perforins to create large pore in cell
2) Secrete granzymes to trigger apoptosis in
cell through the action of caspase enzymes
 2. Helper T Lymphocytes

a. Surface molecule is CD4

b. Improve ability of B lymphocytes to become
plasma cells and enhance ability of cytotoxic T
cells to kill targets
1) Secretion of lymphokines
 3. Regulatory T Lymphocytes, T(reg)

a. Surface molecules CD4 and CD25

b. Previously called suppressor T lymphocytes
c. Inhibit response of B lymphocytes and killer T
lymphocytes
d. Activates the FOXP3 gene that codes for a
transcription factor needed for development of
T(reg) lymphocytes
e. People with genetic deficiencies in regulatory T
lymphocyte production may develop autoimmune
diseases and allergies.
Effects of an Antigen in Summary
 1. Lymphokines

a. Autocrine regulators
b. Cytokines specific to lymphocytes
c. Called interleukins – see Table 15.7
d. Many stimulate B cell or cytotoxic T cell activity.
 Lymphokines, cont

e. Subtypes of helper T cells also produce

lymphokines
1) TH1 – produces IL-2 and gamma interferon –
activates killer T cells and stimulates NO
production in macrophages
2) TH2 – produces IL-4, IL-5, IL-13 and others –
stimulates B cells and humoral immunity,
recruits eosinophils and induces IgE production
3) TH17 – secretes IL-17 – fights infections in skin,
lungs, and mucous membranes; stimulates
neutrophils
Some Cytokines that Regulate
the Immune System
1. T Cell Receptor Proteins

a. Antigen recognition proteins on the membranes

of T cells
1) These cannot bind directly to antigens.
2) Antigen-presenting cells, such as dendritic
cells and macrophages, help T cells bind to
antigens.
Migration of antigen-presenting dendritic cells
 1. Dendritic Cells

1) Originate in the marrow and migrate to most

tissues (especially where pathogens might enter
body)
2) Engulf protein antigens, partially digest them, and
display polypeptide fragments on their surface for
T cell to “see”
a) Associated with histocompatibility antigens
b) Secrete cytokines to attract T lymphocytes in
secondary lymphoid organs
3) Once activated, the T cells divide for form effector
T cells and memory T cells
 1. Histocompatibility Antigens

a. On surface of all body cells (except mature

RBCs); also called human leukocyte antigens
(HLAs)
b. Coded for by four genes (A, B, C, D) on
chromosome 6 called major histocompatibility
complex (MHC)
1) Many versions of each gene are possible, so
most people have different combinations.
2) An organ transplant requires an MHC match.
 B. Interactions between antigen-presenting cells
and T cells

1. Classes of MHC molecules

a. Class 1 is made by all cells except RBCs.
1) Class 1 MHC molecules and foreign
antigens are presented together to activate
cytotoxic T cells.
b. Class 2 is made by antigen-presenting cells
and B cells
1) Class 2 MHC molecules and foreign
antigens are presented together to helper T
lymphocytes
Classes of MHC molecules, cont

c. Classes have different coreceptors

1) Killer T cells have CD8 for MHC-1
2) Helper T cells have CD4 for MHC-2
Coreceptor on helper T and killer T cells
Interaction between antigen-presenting cells
and T cells and B cells

T cell-dependent
antigen
2. T cell response to a virus (macrophage
interactions)

a. Virus phagocytosed by macrophages or dendritic

cells
b. Viral foreign antigens moved to the surface of the
presenter cell
c. Foreign antigen forms a complex with MHC-2
molecule
d. Macrophage secretes IL-1 to stimulate cell
division and proliferation of T cells
 T cell response to a virus, cont

e. Macrophages secrete interleukin-1, which

stimulates helper T cell mitosis.
f. Helper T cells secrete macrophage colony-
stimulating factor and gamma interferon, which
promote macrophage activity.
g. T helpers secrete interleukin-2, which makes the
macrophage produce tumor necrosis factor
(against cancer) and activates cytotoxic T cell
activity/mitosis.
T Lymphocytes and Macrophage Interactions

M-CSF
INF

IL-1
1. Interactions with B Cells

1) Activated helper Ts promote humoral response of

B cells by binding to foreign antigens and MHC-
2s
2) This stimulates mitosis of B cells, conversion to
plasma cells, and production of antibodies.
Macrophages, helper T cells and interactions with
B Cells

Long-term humoral immunity

Somatic hypermutation
Class switch recombination
 1. Destruction of T Cells

a. Activated T cells must be destroyed when the

infection is over.
b. Active T cells produce a surface receptor called
FAS and later a protein called FAS ligand.
c. Binding of FAS to FAS ligand induces apoptosis.
d. Helps maintain immunologically privileged sites –
inner region of the eye and tubules of the testis –
protects molecules that could be seen as foreign
by the immune system
IV. Active and Passive
Immunity
Virulence and Antigenicity
A. Active Immunity & the Clonal Selection Theory

1. Primary response
a. After infection, it takes 5−10 days before
antibodies are detected in the blood.
b. The person will get sick.
2. Secondary response
a. Later exposure to the same infection results in
maximum antibody production in less than 2
hours.
b. The person will likely never get sick.
Primary & Secondary Responses
1. Clonal Selection Theory

a. Explains how the secondary immune response

works:
1) A person inherits lymphocytes specific to
almost every pathogen, but there are few of
each type.
2) When exposed to foreign antigens, immune
cells respond by making many copies of
themselves.
3) Germinal centers in secondary lymphoid
organs develop to produce the clones
Clonal Selection Theory, cont

b. The primary response triggers a massive

production of cells that can respond to that
antigen.
c. These cells respond much quicker after
exposure a second time.
 1. Active Immunity

a. Development of the secondary response provides

active immunity
b. Requires prior exposure to the antigen and then
protects the body from future infections
c. Active immunity is also used to make vaccines.
d. These vaccines include an antigen but are not
virulent (disease-causing).
Clonal Selection
Clonal Selection Theory & B cells
Summary of the Clonal Selection Theory & B Cells
 1. Vaccines
a. Stimulate a primary response and active immunity
without making the person sick.
b. Three ways to accomplish this:
1) Use a killed virus (Salk polio vaccine)
2) Use a live virus with attenuated virulence—i.e.,
the virus either cannot replicate or cannot infect
target tissues Sabin polio vaccine, MMR)
3) Use a genetically engineered recombinant virus
(hepatitis B)
c. Adjuvants – molecules that boost immune
response when delivered with the vaccine
antigens; found to be PAMPs
A systematic review of SARS-CoV-2 vaccine candidates

adeno or pox virus

Signal Transduction and Targeted Therapy volume 5, Article number: 237 (2020)
https://covid19vaccinetrial.co.uk/about
 1. Immunological Tolerance

1. Immunological (ability to mount an immune response)

develops during early postnatal life – being able to
distinguish self-antigens from foreign antigens
2. Immunological tolerance – continued recognition and
tolerance of self-cells
3. In some instances, “self” cells are attacked by antibodies
and autoreactive T cells:
a. If mutations occur in lymphocytes (usually good and
adds to what the body can defend against)
b. If cells in particular organs are never exposed to the
immune system
c. These lymphocytes are called autoreactive.
 Immunological Tolerance, cont

4. If lymphocytes do begin attacking cells,

there are mechanisms to stop this:
a. In clonal deletion, these lymphocytes that
recognize self-antigens are destroyed
(apoptosis).
b. In clonal anergy, these lymphocytes are
prevented from becoming active. Regulatory T
lymphocytes likely do this.
 Immunological Tolerance, cont

5. Types of tolerance
a. Central – occurs in the thymus (T cells) and
bone marrow (B cells)
b. Peripheral – anywhere outside the thymus or
bone marrow
1. Passive Immunity

1. Passing of antibodies from one individual to

another; person does not make their own
antibodies
2. Provides temporary protection:
a. From mother to fetus
b. From mother to child (in breast milk -
colostrum)
c. Artificially via immunization (snake anti-
venom) (antiserum; antitoxin; intravenous
immunoglobulin)
Comparison of Active & Passive Immunity
 1. Monoclonal antibodies

a. Animals are injected with an antigen

b. A single B lymphocyte that makes the desired
antibodies is extracted
c. The B cell is fused with a cancerous myeloma cell
in vitro
d. The hybridoma produces many clones that
produce antibodies specific for the antigen
V. Tumor Immunology
 1. Introduction

1. Oncology has shown that tumor biology is similar

to and interrelated with functions of the immune
system
2. Tumors are abnormal clonal cells that
dedifferentiate to an embryonic state.
3. Tumor growth and dedifferentiation reveal
antigens that can stimulate the destruction of the
cell (by cytotoxic T cells).
4. Benign tumors are slow growing and limited to
specific areas of the body.
 Introduction, cont

5. Malignant tumors are fast growing and spread to

other parts of the body (metastasize).
6. Cancers arise when the immune cells fail to stop
the growth/spread of the tumors.
7. Results from altered expression of oncogenes,
tumor suppressor genes, or genes that code for
microRNA
1. Tumor Antigens

a. Some tumor antigens are due to dedifferentiated

embryonic antigens not recognized by the
immune system.
1) Some antigens provide the basis for
diagnostic blood tests (alpha-fetoprotein)
b. Some arise due to mutations from carcinogens.
c. Others are viral antigens from the virus that
caused the tumor (human papillomavirus).
d. Normally, over-expressed antigens may trigger
an immune response.
 1. Lymphocytes and Tumor Cells

a. Lymphocytes provide immunological surveillance

against cancer.
b. Tumor cells can evade immune surveillance by
suppressing immunity with secretions:
1) FAS ligand stimulates lymphocyte apoptosis.
2) TGFβ – transforming growth factor beta
3) IL-10
Destruction of a cancer cell
 1. Natural Killer (NK) Cells

1. Related to T lymphocytes but part of innate

immunity without the ability to recognize specific
antigens
a. Can recognize malignant cells and cells
infected with a virus
b. Must be activated by pro-inflammatory
cytokines from dendritic cells
2. Kill compromised cells in the same manner as
cytotoxic T cells
3. Cytokines released by natural killer cells activate
both innate and adaptive immune cells.
Antibody-dependent cell-
mediated cytotoxicity
 1. Immunotherapy for Cancer

1. Therapeutic monoclonal antibodies, interferons,

and interleukin-2 have been used to treat cancer.
2. None of these “cure” cancer, but they do help
some people.
3. Other cytokines are currently being tested against
cancer. Nobel prize 2018
Natural Killer T cells (NKT cells)
 1. Effects of Aging and Stress

1. Susceptibility to cancer varies greatly

2. Cancer risk increases with age.
3. This may be due to aging mutated lymphocytes.
4. Thymus functions are reduced – causes a
decrease in cell-mediated immune competence
5. Tumors also grow faster in lab animals under
stress. Stress induces the release of cortisone,
which is known to suppress the immune system.
VI. Diseases Caused by the
Immune System
(1) Autoimmune disease
(2) Immunecomplex disease
(3) Allergy or hypersensitivity
1. Autoimmunity

1. Produced by failure of immune cells to recognize

and tolerate “self” antigens
a. Autoreactive T lymphocytes and
autoantibodies are produced, causing
inflammation and organ damage.
b. Common autoimmune diseases include
rheumatoid arthritis, type 1 diabetes, multiple
sclerosis, Grave’s disease, pernicious
anemia, thyroiditis, psoriasis, and lupus
Some Examples of Autoimmune Diseases
 1. Reasons why self-tolerance may fail

a. An antigen not normally exposed to the immune

system becomes exposed.
1) Hashimoto’s thyroiditis
b. A normally tolerated antigen is combined with a
foreign hapten. This may occur when a drug such
as aspirin combines with platelets, resulting in the
destruction of platelets.
1) Thrombocytopenia
 Reasons why self-tolerance may fail, cont

c. Antibodies are produced that are directed against

other antibodies.
1) Cause of inflammation in rheumatoid arthritis
d. Antibodies produced against foreign antigens
cross-react with self antigens and begin attacking
self cells (can occur in the heart or kidneys after a
strep infection).
1) Rheumatic fever
2) Glomerulonephritis
 Reasons why self-tolerance may fail, cont

e. Self antigens may be presented to T helper cells

along with MHC-2 molecules.
1) May occur after viral infection of cells
2) Occurs in diabetes type I
3) Graves Disease (Thyroid cell produce MHC II)
f. Inadequate regulatory T cell activity.
(mutated FOXP3)
 1. Immune Complex Diseases

1. Involve free antigen-antibody complexes that

stimulate complement proteins and inflammation
a. Usually self-regulating because complexes are
removed via phagocytosis
b. Complex formation may be prolonged or
spread to other organs, leading to prolonged
inflammation.
 Immune Complex Diseases, cont

2. May result from infections from bacteria, viruses,

or parasites
a. Hepatitis B results in free complexes that cause
damage to arteries due to inflammation.

3. May also result from complexes formed by self

antigens and autoantibodies
a. Rheumatoid arthritis and lupus
 1. Allergies

1. Abnormal response to allergens (antigens)

a. Also called hypersensitivity
b. Two types:
1) Immediate hypersensitivity
2) Delayed hypersensitivity
1. Immediate Hypersensitivity

a. Abnormal B cell response to allergen

1) Effects seen seconds to minutes after exposure
2) Can be caused by foods, bee stings, pollen,
etc.
b. Dendritic cells stimulate TH2 helper T cells to
secrete interleukin-4 and interleukin-13, which
stimulate B and plasma cells to secrete IgE
antibodies
Immediate Hypersensitivity, cont

c. These antibodies do not circulate in the blood

but attach to mast cells and basophils.
d. When re-exposed to the same allergen, these
antibodies bind with it and stimulate the
production of histamine, leukotrienes, and
prostaglandin D, producing allergy symptoms.
Mechanism of Immediate Hypersensitivity
Flare-and wheal reaction
Common Allergens
 1. Delayed Hypersensitivity

a. Abnormal T cell response that produces

symptoms 24−72 hours after exposure
b. Symptoms are caused by secretion of
lymphokines, not histamine, so taking
antihistamines has little effect.
c. Example: contact dermatitis caused by poison
oak, ivy, or sumac
Comparison of Immediate & Delayed
Hypersensitivity Reactions