Welcome
To
Microbiology 112
Quiz time
Next week is the Midterm!
Be sure to use the study guide materials to help focus your studying on
the most relevant material.
The exam is 75 multiple choice questions.
There is no lab afterwards, however there is a smartlab (blood) and be
sure to read chapters 17-19.
Students auditing the course do not need to show up.
Chapter 14: Host Defenses
• Host Defenses
– Innate, natural defenses: present at birth, provide
nonspecific resistance to infection
Chapter 14: Host Defenses
• Host Defenses
– Innate, natural defenses: present at birth, provide
nonspecific resistance to infection
Chapter 14: Host Defenses
• Host Defenses
– Innate, natural defenses: present at birth, provide
nonspecific resistance to infection
– Adaptive immunities: specific, must be acquired after birth
Chapter 14: Host Defenses
•
Functions of a healthy functioning
immune system:
1. Surveillance of the body
What are some structures that accomplish
this?
Surveillance
Body compartments
are screened by
circulating WBCs.
Chapter 14: Host Defenses
•
Functions of a healthy functioning
immune system:
1. Surveillance of the body
General phagocytes, lymphatic tissues in
organs, lymph nodes, lymph nodules
(tonsils), spleen
Surveillance
Body compartments
are screened by
circulating WBCs.
Chapter 14: Host Defenses
•
Functions of a healthy functioning
immune system:
1. Surveillance of the body
2. Recognition of foreign material
Contact
with self cells
WBC
Phagocytic cells possess specialized
receptors to identify “self cells” and
separate receptors to identify foreign
cells/virsuses
Normal
Self
molecules
Contact with
a foreign cell
WBC
Pathogen
recognition receptor
(PRR)
Surveillance
Body compartments
are screened by
circulating WBCs.
Detection and
recognition
of foreign cell
or virus
Chapter 14: Host Defenses
•
Functions of a healthy functioning
immune system:
1. Surveillance of the body
2. Recognition of foreign material
3. Destruction of entities deemed
to be foreign
Contact
with self cells
No reaction
WBC
Normal
Self
molecules
Contact with
a foreign cell
Adaptive immunity dramatically increases
the amount of destruction
PAMPs*
on
microbe
WBC
Pathogen
recognition receptor (PRR)
Surveillance
Body compartments
are screened by
circulating WBCs.
Detection and
recognition
of foreign cell
or virus
Destruction
Chapter 14: Host Defenses
•
•
The Immune System is a large, complex, and diffuse
network of cells and fluids
Four major subdivisions of immune system:
1. Reticuloendothelial system (RES)
1. Extracellular fluid (ECF)
2. Lymphatic system
3. Bloodstream
Chapter 14: Host Defenses
• Reticuloendothelial System (RES):
Fiber mesh interconnecting cells and
connective tissue networks
Dendritic
surrounding organs
cell
• “surface streets”
• affects flow of materials
• filled with extracellular fluid
Compartmentalized, but not
consistently compartmentalized
Macrophage
Neutrophil
• Inhabited by phagocytic cells
Tissue
cell
Reticular
fibers
Chapter 14: Host Defenses
•
Four major subdivisions of immune system:
1. Reticuloendothelial system (RES)
1. Extracellular fluid (ECF)
2. Lymphatic system
-“one-way canal system”
3. Bloodstream
Chapter 14: Host Defenses
Lymphatic System Functions????
Chapter 14: Host Defenses
Lymphatic System Functions
1.
Returns excess
extracellular fluid to the
blood stream
2.
Acts as a drain-off
system for the
inflammatory response
3.
and…
Chapter 14: Host Defenses
Lymphatic System Functions
1.
Returns excess
extracellular fluid to the
blood stream
2.
Acts as a drain-off
system for the
inflammatory response
3.
Renders surveillance,
recognition, and
protection against
foreign material (a.k.a.
the immune response)
Structures of the lymphatic system?
Chapter 14: Host Defenses
Lymphatic System Functions
1.
Returns excess
extracellular fluid to the
blood stream
2.
Acts as a drain-off
system for the
inflammatory response
3.
Renders surveillance,
recognition, and
protection against
foreign material
Functions???
Structures of the lymphatic system
-red bone marrow
-thymus
-lymphatic vessels
-lymph nodes
-tonsils
-associated lymphatic tissues
-spleen
Chapter 14: Host Defenses
Lymphatic System Functions
1.
Returns excess
extracellular fluid to the
blood stream
2.
Acts as a drain-off
system for the
inflammatory response
3.
Renders surveillance,
recognition, and
protection against
foreign material
Structures of the lymphatic system
-red bone marrow
-hemopoiesis
-thymus
-maturation of T cells
-lymphatic vessels
-transport lymph
-lymph nodes
-filter lymph
-surveillance (lymph)
-tonsils
-surveillance (pharynx)
-associated lymphatic tissues
-surveillance (organs)
-spleen
-filter blood
-surveillance (blood)
Chapter 14: Host Defenses
•
Four major subdivisions of immune system:
1. Reticuloendothelial system (RES)
1. Extracellular fluid (ECF)
2. Lymphatic system
1. “one-way train system”
3. Bloodstream
1. “super highway” throughout the
entire body
Chapter 14: Host Defenses
What chemicals/substances are found in blood plasma?
Plasma
Serum
Red blood
cells
Clot
Buffy coat
(a) Unclotted Whole Blood
(b) Clotted Whole Blood
Chapter 14: Host Defenses
What chemicals/substances are found in blood plasma?
-water
-electrolytes
-nutrients/wastes
-plasma proteins
-immunoglobulins
Plasma
Serum
Red blood
cells
Clot
Buffy coat
(a) Unclotted Whole Blood
(b) Clotted Whole Blood
What formed elements are found in blood?
Chapter 14: Host Defenses
What chemicals/substances are found in blood plasma?
-water
-electrolytes
-nutrients/wastes
-plasma proteins
-immunoglobulins
-complement proteins
Plasma
Serum
Red blood
cells
Clot
Buffy coat
(a) Unclotted Whole Blood
(b) Clotted Whole Blood
What formed elements are found in blood?
-various leukocytes
-red blood cells (erythrocytes)
-platelets
Chapter 14: Host Defenses
in blood
nonspecific
specific
Chapter 14: Host Defenses
Memory check!
What are some examples of First Line Defenses?
Chapter 14: Host Defenses
Memory check!
What are some examples of First Line Defenses?
Chapter 14: Host Defenses
Second Line of Defense
Parallel & Interconnected Components
•
•
•
•
Inflammation
Phagocytosis
Interferon
Complement
Chapter 14: Host Defenses
Second Line of Defense
4 Classic signs/symptoms of Inflammation:
•
Dolor – pain
•
Rubor –vasodilation (redness)
Injury
Rubor
Dolor
Chapter 14: Host Defenses
Second Line of Defense
4 Classic signs/symptoms of Inflammation:
•
Dolor – pain
•
Rubor –vasodilation (redness)
•
Calor – heat from increased blood flow (warmth)
–
•
higher temp. slows many pathogens
Tumor – increased fluid (edema or swelling)
–
WBC’s, microbes, debris, fluid accumulation (pus)
Injury
Rubor
Tumor,
Calor
Dolor
Chapter 14: Host Defenses
inflammation
Second Line of Defense
Bacteria in wound
Mast cells release
chemical mediators
Vasoconstriction
-initially
(a) Injury/Immediate
Reactions
Chapter 14: Host Defenses
inflammation
Second Line of Defense
Clot
Bacteria in wound
Mast cells release
chemical
mediators
Bacteria
Phagocytes
Seepage
Vasoconstriction
Vasodilation
(a) Injury/Immediate
Reactions
(b) Vascular Dilation (after clot forms)
Chapter 14: Host Defenses
inflammation
Second Line of Defense
Clot
Bacteria
Phagocytes
Bacteria in wound
Seepage
Mast cells release
chemical
mediators
Vasoconstriction
Vasodilation
(a) Injury/Immediate Reactions
(b) Vascular Reactions
Scab
(c) Edema and Pus Formation
Neutrophils
& macrophages
Scar
Pus
Lymphocytes
Fibrous exudate
Macrophage
(d) Resolution/Scar Formation
Chapter 14: Host Defenses
Chemical Mediators of
Inflammation
Second Line of Defense
Start
Initiating Event
Trauma, infection,
necrosis, foreign particle,
neoplasm
Production
of
Mediators
Chapter 14: Host Defenses
Chemical Mediators of
Inflammation
Second Line of Defense
Vasoactive Actions
3. Vasodilation
Initiating Event
Trauma, infection,
necrosis, foreign particle,
neoplasm
Increased permeability
of capillaries and small veins
2. Stimulation of
nerves; pain
Production
of
Mediators
1. Vasoconstriction
(initially)
4. Edema
Chapter 14: Host Defenses
Chemical Mediators of
Inflammation
Second Line of Defense
Vasoactive Actions
3. Vasodilation
Initiating Event
Trauma, infection,
necrosis, foreign particle,
neoplasm
Chemotactic Actions
Cells migrate to site of damage
2. Neutrophils
Increased permeability
of capillaries and small veins
Major phagocytes
1. Platelets
Release mediators
2. Stimulation of
nerves; pain
Production
of
Mediators
3. Macrophages
Major phagocytes
and support for
immune reactions
1. Vasoconstriction
(initially)
4. Lymphocytes
4. Edema
Specific response
to pathogens
Chapter 14: Host Defenses
Fever
Second Line of Defense
• Systemic component of nonspecific immune response
• Initiated by pyrogens (chemicals) which increase body temperature via
hypothalamus
– Exogenous pyrogens – products of infectious agents (endotoxins)
– Endogenous pyrogens – liberated during phagocytosis (macrophages)
Chapter 14: Host Defenses
Second Line of Defense
• Benefits of fever:
– Inhibits temperature-sensitive microorganisms
– Impedes nutrition of bacteria (reducing iron)
– Increases body metabolism and stimulates immune
reactions
Chapter 14: Host Defenses
Second Line of Defense
Activities of phagocytes:
1. Surveillance
-microbes, particulate matter, and dead or injured cells
2. To ingest these materials
3. To extract any immunogenic information from
foreign matter
-for specific immune response
Chapter 14: Host Defenses
Second Line of Defense
Neutrophils – general-purpose
phagocytosis
Eosinophils –parasitic
infections and antigenantibody products
Chapter 14: Host Defenses
Second Line of Defense
Development of Macrophages
Neutrophils – general-purpose
phagocytosis
Marrow
Stem cell
Eosinophils –parasitic infections
and antigen-antibody
products
Macrophages – phagocytosis (in
tissues)
-process & present
antigens for lymphocytes
Promoncyte
Blood
(inactive)
Monocytes
Tissue
(active)
Macrophage
Dendritic cells
Chapter 14: Host Defenses
Second Line of Defense
• Macrophages possess Toll-like receptors
– general recognition
• Detect foreign molecules
– then produces chemicals to stimulate an immune response
Toll-like receptor
Foreign molecule
Nucleus
Macrophage
Cytokines
Interleukins
Inflammatory mediators
Phagocytosis
Chapter 14: Host Defenses
Second Line of Defense
1. Chemotaxis by phagocyte
Phagocytosis
Chapter 14: Host Defenses
Second Line of Defense
Pathogen-associated
Molecular Patterns
(antigen on pathogen)
Bacterial cells
1. Chemotaxis by phagocyte
PAMPs
2 Adhesion of bacteria
Toll-like Receptor on host cell
3
Engulfment
into
phagocytic
vacuole
4Phagosome
Lysosomes
Phagocytosis
Chapter 14: Host Defenses
Second Line of Defense
Pathogen-associated
Molecular Patterns
(antigen on pathogen)
Bacterial cells
1. Chemotaxis by phagocyte
PAMPs
2
Adhesion of bacteria
Toll-like Receptor on host cell
3
Engulfment
into
phagocytic
vacuole
4Phagosome
5 Phagolysosome
formation
6
Destruction
of bacterial
cells
7. Release of
residual debris
Lysosomes
Phagocytosis
Chapter 14: Host Defenses
Second Line of Defense
Pathogen-associated
Molecular Patterns
(antigen on pathogen)
Bacterial cells
1. Chemotaxis by phagocyte
PAMPs
2
Adhesion of bacteria
Toll-like Receptor on host cell
3
Engulfment
into
phagocytic
vacuole
4Phagosome
Finally, macrophage will
present antigens on surface
for specific immune response
5
Phagolysosome
formation
6 Destruction of
bacterial cells
7. Release of
residual debris
Lysosomes
Chapter 14: Host Defenses
Second Line of Defense
Interferon
• Small protein produced by certain WBCs and tissue cells
• Produced in response to viruses, RNA, immune products, and
various antigens
Virus
infection
IFN
gene
Assembly
Viral
of viruses
nucleic acid
Virus
release
Synthesis Attachment of
IFN to special
of IFN
receptor
alarm
Infected
cell
Chapter 14: Host Defenses
Second Line of Defense
Interferon
• Small protein produced by certain WBCs and tissue cells
• Produced in response to viruses, RNA, immune products, and various
antigens
• Induce expression of antiviral proteins and inhibit expression of
cancer genes
Virus
infection
Assembly
Viral
of viruses
nucleic acid
Virus
release
Degrades virus
nucleic acid
Blocks virus
replication
Synthesis of antiviral proteins
IFN
gene
alarm
Synthesis Attachment of
of IFN
IFN to special
receptor
Infected
cell
Signals
activation of genes
Nearby defense
cell
Chapter 14: Host Defenses
Second Line of Defense
• Complement: consists of blood proteins that work in concert to
destroy bacteria and viruses
Stages
1.
Initiation: specific molecule(s) start cascade
2.
Amplification and cascade: binding to target cell
3.
Polymerization: structure formation on cell membrane
4.
Membrane attack: lysis of cell
C
O
M
P
L
E
M
E
N
T
49
Break
Chapter 15: Adaptive, Specific Immunity
Major Histocompatibility Complex (MHC)
• Receptors found on all cells except RBCs, platelets
• Plays a role in recognition of self by the immune system and
in rejection of foreign tissue
Peptides
Cell
membrane
need to
match for
transplants
Class I MHC
Class II MHC
molecule found on all
nucleated human cells
found on some types
of white blood cells
Chapter 15: Adaptive, Specific Immunity
Lymphocytes
B cells
T cells
Bone marrow
Chapter 15: Adaptive, Specific Immunity
Lymphocytes
B cells
T cells
Bone marrow
Bone marrow
stromal cells
specific
antibody
receptor
Maturation
In separate
sites
Thymus
Expression of cell
receptors (specificity)
B cell
Migration to specific
compartments of lymphoid
organs
specific T-cell
receptor
T cell
Lymph node, etc.
Chapter 15: Adaptive, Specific Immunity
Complex antigen is processed
by a phagocytic cell
Antigen
Antigen
Phagocytic cell
displays antigen
T-cell
receptor
for that antigen
Cell-Mediated Immunity
Chapter 15: Adaptive, Specific Immunity
Complex antigen is processed
by a phagocytic cell
Antigen
Antigen
Phagocytic cell
displays antigen
T-cell
receptor
for that
antigen
Memory
T cells
Cytokines
T helper cell
Inactive
Cytotoxic
T cells
Cell-Mediated Immunity
Chapter 15: Adaptive, Specific Immunity
Complex antigen is processed
by a phagocytic cell
Antigen
Antigen
Phagocytic cell
displays antigen
T-cell
receptor
for that
antigen
Memory
T cells
Cytokines
T helper cell
Active
Cytotoxic
T cells
(kill infected cells)
Cell-Mediated Immunity
Chapter 15: Adaptive, Specific Immunity
Complex antigen is processed
by a phagocytic cell
Antigen contact
Free
soluble
antigen
Antigen
Antigen
B-cell
receptor
B cell
Needs both for
Stimulation to
become active
Phagocytic cell
displays antigen
T-cell
receptor
Memory
T cells
Cytokines
Cytokines
T helper cell
Active
Cytotoxic
T cells
(kill infected cells)
Cell-Mediated Immunity
Humoral Immunity
Chapter 15: Adaptive, Specific Immunity
Complex antigen is processed
by a phagocytic cell
Antigen contact
Free
soluble
antigen
Antigen
Antigen
B-cell
receptor
B cell
Needs both for
Stimulation to
become active
Phagocytic cell
displays antigen
T-cell
receptor
Plasma cells
Memory
T cells
secrete antibodies
Memory
B cells
Cytokines
Cytokines
T helper cell
Antibodies: binds to antigens
Active
Cytotoxic
T cells
(kill infected cells)
Cell-Mediated Immunity
Humoral Immunity
59
Chapter 15: Adaptive, Specific Immunity
• B & T Lymphocyte specificity is genetic
– no gene, no immunity possible
• Each lymphocyte (clone) expresses a single specificity
Lymphocyte 1
stem cell
Receptors
Chapter 15: Adaptive, Specific Immunity
• B & T Lymphocyte specificity is genetic
– no gene, no immunity possible
• Each lymphocyte (clone) expresses a single specificity
Lymphocyte 1
stem cell
Self
Receptors
Self
Eliminated
clones
2
3
Repertoire of lymphocyte clones, each with unique receptor display
Chapter 15: Adaptive, Specific Immunity
Chapter 15: Adaptive, Specific Immunity
• Antigen (Ag) is a substance that provokes an immune response
– Foreignness, size, shape, and accessibility
– epitope – small molecular group in antigen that is recognized by
lymphocytes
Chapter 15: Adaptive, Specific Immunity
• Antigen (Ag) is a substance that provokes an immune response
– Foreignness, size, shape, and accessibility
– epitope – small molecular group that is recognized by lymphocytes
bad guys
• Superantigens – potent T-cells stimulators
–
provoke an overwhelming response
• Allergen – antigen that evokes allergic reactions
• Autoantigens – molecules on self tissues for which tolerance is
inadequate
Microbial cells,
viruses
Foreign human
or animal cells
Plant molecules
Chapter 15: Adaptive, Specific Immunity
Humoral Immunity
Principle antibody activity is to unite with the Antigen
Bacterial cell “tagged” with Abs
Chapter 15: Adaptive, Specific Immunity
Effects of Antibody Binding Antigen
Opsonization
Neutralization
bacterial cells
Antibodies
block binding
Abs
Viruses
Opsonized bacteria
engulfed more readily
Agglutination Cross-linked
Chapter 15: Adaptive, Specific Immunity
Effects of Antibody Binding Antigen
Opsonization
Neutralization
Agglutination Cross-linked
bacterial cells
Antibodies
block binding
Abs
Viruses
Opsonized bacteria
engulfed more readily
Complement fixation
(stimulates activation of complement response)
Precipitation
toxins
Antibodies aggregate antigen molecules
Lysing
bacterial
cells
Chapter 15: Adaptive, Specific Immunity
most common type of Ab
(in blood)
Chapter 15: Adaptive, Specific Immunity
found in breast milk
Chapter 15: Adaptive, Specific Immunity
causes agglutination
Chapter 15: Adaptive, Specific Immunity
Chapter 15: Adaptive, Specific Immunity
Chapter 15: Adaptive, Specific Immunity
Chapter 15: Adaptive, Specific Immunity
• Cell-mediated immunity requires the direct
involvement of T lymphocytes
1. T helper cells: regulate immune reaction to antigens,
including other T and B cells
-also involved in stimulating macrophages
Chapter 15: Adaptive, Specific Immunity
• Cell-mediated immunity requires the direct
involvement of T lymphocytes
1. T helper cells: regulate immune reaction to antigens,
including other T and B cells
-also involved in stimulating macrophages
2. Cytotoxic T cells destroy specific foreign or abnormal
body cells by secreting perforins that lyse cells
3. Natural killer cells –destroy any abnormal body cells (no
specificity)
T-Cell Activation and Differentiation
TM
phagocytic cell
presenting antigen
Memory T cell
IL-2,
Activated B cell
CD4 cell
APC
various cytokines
TH 2
MHC-II Ag
IL-4
helper T cells
TH 1
various cytokines
activates CD4 receptor
possessing T cells
TH 1
Stimulate
macrophages
T-Cell Activation and Differentiation
TM
phagocytic cell
presenting antigen
Memory T cell
IL-2,
CD4 cell
APC
TH 2
MHC-II Ag
IL-4
various interleukins
Activated B cell
helper T cells
TH 1
various interleukins
activates CD4 receptor
possessing T cells
Stimulate macrophages
helper T cells
TH 1
cytokines
TM
Memory T cell
Perforins
MHC-I
phagocytic cell
presenting antigen
activates CD8 receptor
possessing T cells
Ag
cytotoxic Activated
T cell
cytotoxic
(CD8 cell)
T cell
TC
TC cell
recognizes
infected self
Destroyed
host cell
Infected
host cell
Chapter 15: Adaptive, Specific Immunity
T Cells and Superantigens
• Superantigens are a form of a virulence factor
• Provoke overwhelming immune responses by large numbers of
different T cells
– Release of excessive cytokines
• Blood vessel damage
• Toxic shock
• Multiorgan damage
79
Chapter 15: Adaptive, Specific Immunity
Categories of Acquired Immunities
Acquired Immunity
Natural Immunity
acquired through the normal life experiences
Artificial immunity
produced purposefully through medical procedures
Examples???
Chapter 15: Adaptive, Specific Immunity
Categories of Acquired Immunities
Acquired Immunity
Natural Immunity
acquired through the normal life experiences
Active Immunity
is the consequence of a
person developing his own
immune response to a
microbe.
Passive Immunity
is the consequence of
one person receiving
preformed immunity
made by another person.
Artificial immunity
produced purposefully through medical procedures
Chapter 15: Adaptive, Specific Immunity
Categories of Acquired Immunities
Acquired Immunity
Natural Immunity
acquired through the normal life experiences
Active Immunity
is the consequence of a
person developing his own
immune response to a
microbe.
Passive Immunity
is the consequence of
one person receiving
preformed immunity
made by another person.
Artificial immunity
produced purposefully through medical procedures
Active Immunity
is the consequence of
a person developing his
own immune response
to a microbe.
Passive Immunity
is the consequence of
one person receiving
preformed immunity
made by another person.
Chapter 15: Adaptive, Specific Immunity
Most vaccines are prepared from:
1. Killed whole cells or inactivated viruses
2. Live, attenuated cells or viruses
-could mutate & cause disease
3. Antigenic molecules derived from bacterial
cells or viruses
4. Genetically engineered microbes or microbial
agents
Chapter 15: Adaptive, Specific Immunity
• Some vaccines require adjuvant to enhance
immunogenicity
-improves the contact between the antigen and
lymphocytes
Chapter 15: Adaptive, Specific Immunity
• Possible Vaccination side effects include local
reaction at injection site, fever, allergies
-rarely back-mutation to a virulent strain (only some vaccines)
-neurological effects or other side effects
Chapter 15: Adaptive, Specific Immunity
• Herd Immunity: Immune individuals will not
harbor disease, reducing the occurrence of
pathogens in a population
vulnerable
no one vaccinated
immune
diseased
Chapter 15: Adaptive, Specific Immunity
• Herd Immunity: Immune individuals will not
harbor disease, reducing the occurrence of
pathogens in a population
vulnerable
no one vaccinated
a few vaccinated
immune
diseased
Chapter 15: Adaptive, Specific Immunity
• Herd Immunity: Immune individuals will not
harbor disease, reducing the occurrence of
pathogens in a population
vulnerable
no one vaccinated
a few vaccinated
most vaccinated
immune
diseased
Break!
Chapter 16: Disorders in Immunity
Antigenic
Stimulation
Chapter 16: Disorders in Immunity
Antigenic
Stimulation
Type I.
Immediate
(hay fever
anaphylaxis)
Type II.
Antibody-mediated (blood type
incompatibilities)
Type III.
Immune complex
(rheumatoid arthritis,
serum sickness)
Chapter 16: Disorders in Immunity
Type I.
Immediate,
(hay fever
anaphylaxis)
Antigenic
Stimulation
Type II.
Antibody-mediated (blood type
incompatibilities)
Type III.
Immune complex
(rheumatoid arthritis, serum
sickness)
Type IV.
Cell-mediated, cytotoxic
(contact dermatitis, graft rejection)
Chapter 16: Disorders in Immunity
Chapter 16: Disorders in Immunity
Two levels of severity of Allergies (Type I):
• Atopy – any chronic local allergy such as hay fever or asthma
• Anaphylaxis – a systemic, often explosive reaction that involves
airway obstruction and circulatory collapse
Antibodies
Chapter
16:
Disorders
in
Immunity
First exposure
(a) Sensitization/IgE Production
1
Allergen particles enter.
Mucous membrane
Lymphatic vessel
2
carries them to
B cell
Lymph node
3
B cell recognizes
allergen with help
of T cell.
4
Proliferates
into
Plasma cells
TH cell
5
Fc fragments
Synthesize
IgE
No allergic reaction yet
Antibodies
Chapter
16:
Disorders
in
Immunity
First exposure
(a) Sensitization/IgE Production
1
Allergen particles enter.
Mucous membrane
Lymphatic vessel
2
carries them to
B cell
Lymph node
3
B cell recognizes
allergen with help
of T cell.
4
No allergic reaction yet
Proliferates
into
Plasma cells
TH cell
5
Synthesize
IgE
Granules
With
Inflammatory
mediators
IgE binds to 6
mast cell surface
receptors.
Fc fragments
Mast cell in tissue
primed with IgE
also basophils
Antibodies
Chapter 16: Disorders in Immunity
(b) Subsequent Exposure to Allergen
(a) Sensitization/IgE Production
1
Allergen particles enter.
7
Allergen is encountered again.
Mucous membrane
8
Lymphatic vessel
2
carries them to
Allergen attaches
to IgE on mast
cells and triggers
release of allergic
mediators.
Time
B cell
Lymph node
3
Antibodies
B cell recognizes
allergen with help
of T cell.
4
Proliferates
into
9
Plasma cells
TH cell
5
Granules
With
Inflammatory
mediators
SynthesiZe
IgE
6
IgE binds to
mast cell surface
receptors.
Mast cell in tissue
primed with IgE
Fc fragments
also basophils
Systemic distribution of
mediators in bloodstream
Chapter 16: Disorders in Immunity
(b) Subsequent Exposure to Allergen
(a) Sensitization/IgE Production
1
Allergen particles enter.
7
Allergen is encountered again.
Mucous membrane
8
Lymphatic vessel
2
carries them to
Allergen attaches
to IgE on mast
cells and triggers
release of allergic
mediators.
Time
B cell
Lymph node
3
Antibodies
B cell recognizes
allergen with help
of T cell.
4
Proliferates
into
9
Plasma cells
TH cell
5
Systemic distribution of
mediators in bloodstream
Granules
With
Inflammatory
mediators
SynthesiZe
IgE
6
IgE binds to
mast cell surface
receptors.
Mast cell in tissue
primed with IgE
End result: Symptoms in various organs
10
Red, itchy eyes
Fc fragments
also basophils
Hives
98
Runny
nose
Chapter 16: Disorders in Immunity
Constricted
bronchioles
Headache (pain)
Dilated
blood vessel
Nerve cell
Prostaglandin
Mast cell
Leukotriene
Typical
Response
in asthma
Constriction
of bronchioles
Airway obstruction:
mucus buildup
Allergic Mediators
(inflammatory cytokines)
Chapter 16: Disorders in Immunity
Constricted
bronchioles
Headache (pain)
Allergic Mediators
(inflammatory cytokines)
Dilated
blood vessel
Wheal and flare
reaction, itching
Dilated
blood vessel
Increased blood flow
Nerve cell
Constricted
bronchiole
Prostaglandin
Smooth muscle
Wheezing, Difficult
breathing, coughing
Histamine
Serotonin
Bradykinin
Mast cell
Secretory
Glands on epithelial tissues
Increased peristalsis of
intestine; diarrhea, vomiting
Leukotriene
Typical
Response
in asthma
Constriction
of bronchioles
Airway obstruction:
mucus buildup
Excessive mucus, tear formation,
glandular secretions
Chapter 16: Disorders in Immunity
• Atopic disease:
– hay fever, rhinitis
• seasonal, inhaled plant pollen or mold
– Asthma – severe bronchoconstriction
• inhaled allergen
– Eczema – dermatitis
• ingestion, inhalation, skin contact
Antibodies
Chapter 16: Disorders in Immunity
Antibodies
• Atopic disease – hay fever, rhinitis; seasonal, inhaled plant pollen or mold
– Asthma – severe bronchoconstriction; inhaled allergen
– Eczema – dermatitis; ingestion, inhalation, skin contact
• Food allergy:
– Vomiting, diarrhea, abdominal pain
• possibly severe
– intestinal portal can affect skin and respiratory tract
• Eczema, hives, rhinitis, asthma, occasionally anaphylaxis
• Drug allergy – common side effect of treatment; any
tissue can be affected; reaction from mild atopy to
fatal anaphylaxis
Chapter 16: Disorders in Immunity
Antibodies
• Atopic disease – hay fever, rhinitis; seasonal, inhaled plant pollen or mold
– Asthma – severe bronchoconstriction; inhaled allergen
– Eczema – dermatitis; ingestion, inhalation, skin contact
• Food allergy – intestinal portal can affect skin and respiratory tract
– Vomiting, diarrhea, abdominal pain; possibly severe
– Eczema, hives, rhinitis, asthma, occasionally anaphylaxis
• Drug allergy:
– common side effect of treatment
– any tissue can be affected
– reaction from mild to fatal anaphylaxis
Chapter 16: Disorders in Immunity
• Important to determine if a person is experiencing
allergy or infection
– could have similar signs/symptoms
Antibodies
Chapter 16: Disorders in Immunity
Antibodies
• Important to determine if a person is experiencing
allergy or infection
• Skin testing
Environmental Allergens
No. 1 Standard Series
+++
+++
++++
++++
++
+
+
++
+++
+
+
+
++++
+++
+
+
+
+++++
+++
© STU/Custom Medical Stock Photo
(a)
(b)
No. 2 Airborne Particles
1. Ant
2. Aphid
3. Bee
4. Housefly
5. House mite
6. Mosquito
+++
7. Moth
++++
8. Roach
+++
9. Wasp
++
10. Yellow jacket
0
Airborne mold spores
++
11. Alternaria
+++
12. Aspergillus
++
13. Cladosporium
+++
14. Fonsecaea
0
15. Penicillium
+
16. Phoma
17. Rhizopus
+++
18. .........................
- not done
++ - mild reaction
+++ - moderate reaction
0 - no reaction
+ - slight reaction ++++ - severe reaction 105
1. Acacia gum
2. Cat dander
3. Chicken feathers
4. Cotton lint
5. Dog dander
6. Duck feathers
7. Glue, animal
8. Horse dander
9. Horse serum
10. House dust #1
11. Kapok
12. Mohair (goat)
13. Paper
14. Pyrethrum
15. Rug pad, ozite
16. Silk dust
17. Tobacco dust
18. Tragacanth gum
19. Upholstery dust
20. Wool
+++
+++++
++++
++++
Chapter 16: Disorders in Immunity
Antibodies
General Treatments for allergies include:
1. Avoiding allergen
2. Drugs: antihistamines (treat symptoms)
3. Desensitization therapy – injected allergens
B Cell / Plasma Cell
IgG
“Blocking
antibodies”
Mast Cell
with previous IgE
Allergen
X
No
Reaction
With
Mast
cell
IgG binds
allergens
X
IgE
No
degranulation
No
Allergic
symptoms
Chapter 16: Disorders in Immunity
Type II Hypersensitivity
• Reactions that lyse foreign cells
• Involve antibodies & complement
– leads to lysis of foreign cells
Antibodies
Chapter 16: Disorders in Immunity
Type II Hypersensitivity
• Reactions that lyse foreign cells
• Involve antibodies & complement
– leads to lysis of foreign cells
• Transfusion reactions
– ABO blood groups
-what are blood types?
Antibodies
Chapter 16: Disorders in Immunity
Antibodies
Type II Hypersensitivity
• Reactions that lyse foreign cells
• Involve antibodies & complement
– leads to lysis of foreign cells
• Transfusion reactions
– ABO blood groups
A+, A-, B+, B-, AB+, AB-, O+, O- compatibility?
adverse side effects include:
fever, anemia, jaundice,
systemic shock, kidney failure,
death
Chapter 16: Disorders in Immunity
Antibodies
Type II Hypersensitivity
• Reactions that lyse foreign cells
• Involve antibodies & complement
– leads to lysis of foreign cells
• Transfusion reactions
– ABO blood groups
adverse side effects include:
fever, anemia, jaundice,
systemic shock, kidney failure,
death
– example: Rh factor – hemolytic disease of the newborn
Chapter 16: Disorders in Immunity
hemolytic disease of the newborn
Rh– mother
Placenta breaks
away
Rh factor
on RBCs
Rh+ fetus
Anti-Rh antibody
First Rh+ fetus
(a)
Chapter 16: Disorders in Immunity
hemolytic disease of the newborn
Rh– mother
Late in second pegnancy
r
Of Rh+ child
Placenta breaks
away
Rh factor
on RBCs
Rh+ fetus
Anti-Rh antibody
First Rh+ fetus
(a)
Second Rh+ fetus
Chapter 16: Disorders in Immunity
hemolytic disease of the newborn
Treatment
Rh– mother
Late in second pegnancy
r
Of Rh+ child
Anti-Rh
Antibodies
(RhoGAM)
Placenta breaks
away
Rh factor
on RBCs
Rh– mother
Rh+ RBCs
Rh+ fetus
Anti-Rh antibody
First Rh+ fetus
(a)
Second Rh+ fetus
(b)
First Rh+ fetus
(mother never generates
antibodies against Rh)
Type III Hypersensitivity
Antibodies
• Reaction of soluble antigen with antibody
• Immune complexes (antigens bound to
antibodies) become trapped in tissues and incite
a damaging inflammatory response
– Arthus reaction – localized dermal injury due to
inflamed blood vessels
– Serum sickness – systemic injury initiated by antigenantibody complexes that circulate in the blood
114
Pathogenesis of Immune Complex Disease
Antibodies
Phases:
Ab
Ag
Immune complexes
Antibody combines with excess soluble
antigen, forming large quantities of
Ag-Ab complexes.
Pathogenesis of Immune Complex Disease
Antibodies
Phases:
Antibody combines with excess soluble
antigen, forming large quantities of
Ag-Ab complexes.
Ab
Ag
Immune complexes
Lodging of complexes in
basement membrane
Ag-Ab complexes
Basement
membrane
Epithelial
tissue
Circulating immune complexes
become lodged in the basement
membranes of epithelia in blood
vessels, kidney, skin and other sites.
Pathogenesis of Immune Complex Disease
Phases:
Antibody combines with
excess soluble antigen,
forming large quantities of
Ag-Ab complexes.
Ab
Ag
Immune complexes
Lodging of complexes in
basement membrane
Neutrophils
Ag-Ab complexes
Basement
membrane
Epithelial
tissue
Blood Vessels Heart/Lungs
Joints
Circulating immune
complexes become lodge
din the basement
membranes of epithelia in
blood vessels, kidney, skin
and other sites.
Neutrophils migrate to sites of
Ag- Ab complexes and release
enzymes and chemokines that
severely damage the target
tissues and organs.
Skin
Kidney
Major organs where immune complexes are deposited
Antibodies
Pathogenesis of Immune Complex Disease
Antibodies
Phases:
Antibody combines with
excess soluble antigen,
forming large quantities of
Ag-Ab complexes.
Ab
Ag
Circulating immune
complexes become lodge
din the basement
membranes of epithelia in
blood vessels, kidney, skin
and other sites.
Immune complexes
Lodging of complexes in
basement membrane
Neutrophils
Ag-Ab complexes
Basement
membrane
Epithelial
tissue
Neutrophils migrate to sites of
Ag- Ab complexes and release
enzymes and chemokines that
severely damage the target
tissues and organs.
Complement factors trigger release of histamine
and other inflammatory mediators.
Blood Vessels Heart/Lungs
Joints
Skin
Kidney
Major organs where immune complexes are deposited
119
T cells
Immunopathologies Involving T cells
• Type IV Hypersensitivity
– T cell-mediated
– Delayed response to
Antigen involving activation
of T cells
– Delayed allergic response –
skin response to allergens
Mechanism for Type IV Reactions
Blister
1
Chemical antigens
Skin
layers
2
Inflammatory
fluid
TH1
Dendritic cell
3
TH1
(a)
Memory
T-helper cell
1 Lipid-soluble chemicals are absorbed by the skin.
2 Dendritic cells close to the epithelium pick up the allergen, process it,
and display it on MHC receptors.
3 Previously sensitized TH1 (CD4+) cells recognize the presented allergen.
-need previous exposure
T cells
Mechanism for Type IV Reactions
Blister
1
Chemical antigens
Skin
layers
2
Inflammatory
fluid
Induce
Inflammatory
reaction
TH1
6
CD8
T cell
Dendritic cell
3
4
TH1
Cytotoxic
Macrophage T cell
5
(a)
Memory
T-helper cell
Blood vessel
1 Lipid-soluble catechols are absorbed by the skin.
2 Dendritic cells close to the epithelium pick up the allergen, process it,
and display it on MHC receptors.
3
Kill
Skin
cells
Previously sensitized TH1 (CD4+) cells recognize the presented allergen.
4 Sensitized TH1 cells are activated and secrete cytokines
5 These cytokines attract macrophages and cytotoxic T cells
Macrophages release mediators that stimulate a strong, local
6 Inflammatory reaction. Cytotoxic T cells directly kill cells and
damage the skin. Fluid-filled blisters result.
T cells
T Cells and Organ Transplantation
• Graft/transplantation rejection – host may reject
graft; graft may reject host
• MHC markers of donor tissue (graft) are different
Organ Transplant
Cytotoxic
T cell of
recipient (host)
Host
Heart
graft
T cells
T Cells and Organ Transplantation
T cells
• Graft/transplantation rejection – host may reject
graft; graft may reject host
• MHC markers of donor tissue (graft) are different
Organ Transplant
Bone Marrow Transplant
Cytotoxic
T cell of
recipient (host)
Host
Heart
graft
Host
Bone marrow
graft
T cell of donor
124
Autoimmunity
• The immune system forms autoantibodies and sensitized T cells against
self
– causes include:
• isolated structures/antigens become exposed
• survival of “forbidden lymphocyte clones” that attack self
• mutation in leukocyte stem cells so that now attack self
• molecular mimicry where pathogen possesses antigen similar to
self
Autoimmunity
• Disruption of function can be systemic or organ specific:
Autoimmunity
• Disruption of function can be systemic or organ specific:
Immunodeficiency Diseases
Antigenic
Stimulation
Cancer
X
X
Immunodeficiency
Immunodeficiency Diseases
• Components of the immune response system are absent.
• 2 general categories:
– Primary immunodeficiency – congenital;
usually genetic errors
– Secondary diseases – acquired after birth;
caused by natural or artificial agents
129
Primary Immunodeficiency Diseases
Some types of
severe combined
immunodeficiency
X
Lymphoid stem cell
Primary Immunodeficiency Diseases
Di George
syndrome
(no mature
T cells)
Adenosine deaminase
deficiency (no functional
helper T cells)
Thymus
Some types of
severe combined
immunodeficiency
Pre-T cell
X
X
X
T cell
Lymphoid stem cell
Cell-mediated
immunity
Recurrent fungal,
protozoan, viral
infections
Primary Immunodeficiency Diseases
Di George
syndrome
(no mature T cells)
Adenosine deaminase
deficiency (no functional
helper T cells)
Recurrent fungal,
protozoan, viral
infections
Thymus
Some types of
severe combined
immunodeficiency
Pre-T cell
X
X
Cell-mediated
immunity
X
T cell
Lymphoid stem cell
X
X
Pre-B cell
B cell
Bone marrow
(gene therapies)
Congenital
agammaglobulinemia
(no B cells)
Hypogammaglobulinemia
(no IgG antibodies
deficiencies)
Recurrent
bacterial infections
Secondary Immunodeficiencies
• Due to damage after birth
– Caused by: infection, organic disease,
chemotherapy, or radiation
– AIDS most common – T helper cells are
targeted
• numerous opportunistic infections and cancers
The Immune System and Cancer
• Tumors may be benign (nonspreading) or malignant
(spreads from tissue of origin)
• Have genetic alterations (mutations) that disrupt the
normal cell division cycle
134
The Immune System and Cancer
• Tumors may be benign (nonspreading) or malignant
(spreads from tissue of origin)
• Have genetic alterations (mutations) that disrupt the
normal cell division cycle
• Immune surveillance, immune system keeps cancer “in
check”
-cytotoxic T cells, natural killer cells, macrophages
-immunotherapies developed to use immune system
to fight cancer