Download Chapter 22: The Lymphatic System

Chapter 22:
The Lymphatic System
Biology 142 A&P
R.L. Brashear-Kaulfers
Pathogens
• Microscopic organisms that cause
disease:
–
–
–
–
viruses
bacteria
fungi
parasites
• Each attacks in a specific way
The Lymphatic System
Protects us against disease
• Lymphocytes:
• Lymphatic system cells respond to:
– environmental pathogens
– toxins
– abnormal body cells, such as cancers
What is the difference
between nonspecific
and specific defense, and
the role of lymphocytes
in the immune response?
Specific Defenses
• Lymphocytes:
– part of the immune response
• Identify, attack, and develop immunity
to a specific pathogen
• Immunity- The ability to resist
infection and disease
The Immune System
• All body cells and tissues involved in
production of immunity:
– not just lymphatic system
Nonspecific Defenses
• Block or attack any potential infectious
organism
• Cannot distinguish one attack from
another
PLAY
Immunity: Nonspecific Defenses
What are the major components of
the lymphatic system and their
functions?
Organization of the
Lymphatic System
Figure 22–1
4 Parts of the Lymphatic System
1. Lymph:
–
–
a fluid similar to plasma
does not have plasma proteins
2. Lymphatic vessels (lymphatics):
–
network that carries lymph from peripheral
tissues to the venous system
3. Lymphoid tissues and lymphoid organs:
–
found throughout the body
4. Lymphocytes, phagocytes, and other
immune system cells
Function of the
Lymphatic System
• To produce, maintain, and distribute
lymphocytes**Lymphocyte Production:
- Lymphocytes are produced:
– in lymphoid tissues (e.g., tonsils)
– lymphoid organs (e.g., spleen, thymus)
– and in red bone marrow
** Lymphocytes Distribution:
– detect problems
– travel into site of injury or infection
Lymphocyte Circulation
• From blood to interstitial fluid (lymph)
through capillaries
• Returns to venous blood through
lymphatic vessels
The Circulation of Fluids
• From blood plasma to lymph and back
to the venous system
• Also transports hormones, nutrients,
and waste products
Lymphatic Vessels
• Are vessels that carry lymph
• Lymphatic system begins with smallest
vessels: lymphatic capillaries (terminal
lymphatics)
• Lymphatic Capillaries• Differ from blood capillaries in 4 ways:
–
–
–
–
start as pockets rather than tubes
have larger diameters
have thinner walls
flat or irregular in section
Lymphatic Capillaries
Endothelial cells loosely
bound together with
overlap
Overlap acts as one-way
valve:
allows fluids, solutes,
viruses, and bacteria
to enter
prevents return to
intercellular space
Figure 22–2
Lacteals
• Are special lymphatic capillaries in
small intestine
• Transport lipids from digestive tract
Lymphatic Vessels and Valves
Figure 22–3
Lymph Flow
• From lymphatic capillaries to larger
lymphatic vessels containing one-way
valves
• Lymphatic vessels travel with veins
Lymphatic Ducts and
the Venous System
Figure 22–4
The Lymphatic System
• Is divided into:
1) Superficial lymphatics - located in:
– skin
– mucus membranes
– serous membranes lining body
2) Deep lymphatics- Are larger vessels that
accompany deep arteries and veins
Superficial and Deep Lymphatics
• Join to form large lymphatic trunks
• Trunks empty into 2 major collecting
vessels:
– thoracic duct
– right lymphatic duct
The Inferior Thoracic Duct
• Collects lymph from:
– left bronchiomediastinal trunk
– left subclavian trunk
– left jugular trunk
• Empties into left subclavian vein
The Right Lymphatic Duct
• Collects lymph from:
– right jugular trunk
– right subclavian trunk
– right bronchiomediastinal trunk
• Empties into right subclavian vein
Lymphedema
• Blockage of lymph drainage from a
limb
• Causes severe swelling
• Interferes with immune system
function
Why are lymphocytes important,
and how are they distributed in
the body?
• Lymphocytes
• Make up 20–30% of circulating
leukocytes
• Most are stored, not circulating
3 Classes of
Circulating Lymphocytes
1. T cells: thymus-dependent
Make up 80% of circulating lymphocytes
2. B cells: bone–marrow derived
• Make up 10–15% of circulating lymphocytes
• Differentiate into plasma cells- Produce
and secrete antibodies (immunoglobin
proteins)
3. NK cells:
–
natural killer cells
3 Main Types of T Cells
1. Cytotoxic T cells-Attack cells infected by
viruses
Produce cell-mediated immunity
2. Helper T cells- Stimulate function of T
cells and B cells
3. Suppressor T cells-Inhibit function of T
cells and B cells
Regulatory T Cells
• Are helper and suppressor T cells
• Control sensitivity of immune response
Other T Cells
• Inflammatory T cells
• Suppressor and inducer T cells
Antigens
• Targets which identify any pathogen or
foreign compound
Immunoglobin Proteins (Ig’s)
Also called antibodies (Ab)
• The binding of a specific antibody to its
specific target antigen initiates antibodymediated immunity:
- A chain of events which destroys the
target compound or organism
Natural Killer (NK) Cells
• Also called large granular lymphocytes
• Make up 5–10% of circulating
lymphocytes
• Responsible for immunological
surveillance
• Attack:
– foreign cells
– virus-infected cells
– cancer cells
Lymphocyte Distribution
• Tissues maintain different T cell and B
cell populations
• Lymphocytes wander through tissues:
– enter blood vessels or lymphatics for
transport
– can survive many years
Production and Distribution
of Lymphocytes
Figure 22–5
Lymphopoiesis
• Lymphocyte production involves:
– bone marrow
– thymus
– peripheral lymphoid tissues
• Hemocytoblasts : In bone marrow,
divide into 2 types of lymphoid stem
cells
Lymphoid Stem Cells
• Group 1:
– remain in bone marrow
– produce B cells and natural killer cells
• Group 2:
– migrate to thymus
– produce T cells in environment isolated by
blood-thymus barrier
T Cells and B Cells
• Migrate throughout the body:
– to defend peripheral tissues
• Retain their ability to divide:
– is essential to immune system function
Differentiation
• B cells differentiate:
– with exposure to hormone interleukin-7
• T cells differentiate:
– with exposure to several thymic hormones
• Interleukin-7 - A cytokine produced by
stromal cells in bone marrow
What are the structures
and functions of lymphoid
tissues and organs?
Lymphoid Tissues :
Connective tissues dominated by
lymphocytes
Lymphoid Nodules
Figure 22–6
Lymphoid Nodule
• Areolar tissue with densely packed
lymphocytes
• Germinal center contains dividing
lymphocytes
Distribution of Lymphoid Nodules
•
•
•
•
Lymph nodes
Spleen
Respiratory tract (tonsils)
Along digestive and urinary tracts
Mucosa-Associated Lymphoid
Tissue (MALT)
• Lymphoid tissues associated with the
digestive system:
– aggregated lymphoid nodules:
• clustered deep to intestinal epithelial lining
• Appendix:
– mass of fused lymphoid nodules
The 5 Tonsils
• In wall of pharynx:
– left and right palatine tonsils
– pharyngeal tonsil (adenoid)
– 2 lingual tonsils
Lymphoid Organs
•
•
•
•
•
Lymph nodes
Thymus
Spleen
Are separated from surrounding tissues
By a fibrous connective-tissue capsule
Lymph Nodes
• Range from 1–25 mm diameter
Figure 22–7
Afferent Lymphatic Vessels
• Carry lymph:
– from peripheral tissues to lymph node
Efferent Lymphatic Vessels
Leave lymph node at hilus
• Carry lymph to venous circulation
Lymph from Afferent Lymphatics
• Flows through lymph node in a network of
sinuses:
• From subcapsular sinus:
– contains macrophages and dendritic cells
• Through outer cortex:
– contains B cells within germinal centers
• Through deep cortex:
– dominated by T cells
• Through the core (medulla):
– contains B cells and plasma cells
– organized into medullary cords
• Into hilus and efferent lymphatics
Lymph Node
• A filter:
– purifies lymph before return to venous
circulation
• Removes:
– debris
– pathogens
– 99% of antigens
Antigen Presentation
• First step in immune response
• Extracted antigens are “presented” to
lymphocytes:
– or attached to dendritic cells to stimulate
lymphocytes
Lymphoid Functions
• Lymphoid tissues and lymph nodes:
– distributed to monitor peripheral
infections
– respond before infections reach vital
organs of trunk
Lymph Nodes of Gut, Trachea,
Lungs, and Thoracic Duct
• Protect against pathogens in digestive
and respiratory systems
Lymph Glands
• Large lymph nodes at groin and base of
neck
• Swell in response to inflammation
Lymphadenopathy
• Chronic or excessive enlargement of
lymph nodes may indicate infections,
endocrine disorders, or cancer
The Thymus
Figure 22–8
The Thymus
• Located in mediastinum
• Deteriorates after puberty:
– diminishing effectiveness of immune
system
• Divisions of the Thymus Thymus is
divided into 2 thymic lobes
• Septa divide lobes into smaller lobules
A Thymic Lobule
• Contains a dense outer cortex
• And a pale central medulla
Thymus Hormones
• Thymosins
• Promote development of lymphocytes
Lymphocytes
• Divide in the cortex
• T cells migrate into medulla
• Mature T cells leave thymus by
medullary blood vessels
Reticular Epithelial
Cells in the Cortex
• Surround lymphocytes in cortex
• Maintain blood-thymus barrier
• Secrete thymic hormones that
stimulate:
– stem cell divisions
– T cell differentiation
Reticular Epithelial
Cells in the Medulla
• Form concentric layers (Hassall’s
corpuscles)
• The medulla has no blood–thymus
barrier:
– T cells can enter or leave bloodstream
The Spleen
Figure 22–9
3 Functions of the Spleen
1. Removal of abnormal blood cells and other
blood components by phagocytosis
2. Storage of iron recycled from red blood cells
3. Initiation of immune responses by B cells
and T cells:
–
in response to antigens in circulating blood
Structure of the Spleen
• Attached to stomach by gastrosplenic
ligament
• Contacts diaphragm and left kidney
• Splenic veins, arteries, and lymphatic
vessels:
– communicate with spleen at hilus
Structure of the Spleen
• Inside fibrous capsule:
– Red pulp: contains many red blood cells
Contains elements of circulating
blood plus fixed & free macrophages
– White pulp: resembles lymphoid
nodules
Trabecular Arteries
• Branch and radiate toward capsule
• Finer branches surrounded by white
pulp
• Capillaries discharge red blood cells
into red pulp
Splenic Circulation
• Blood passes through:
– network of reticular fibers
• Then enters large sinusoids (lined by
macrophages):
– which empty into trabecular veins
Spleen Function
• Phagocytes and other lymphocytes in
spleen:
– identify and attack damaged and infected
cells
– in circulating blood
Body Defenses
• Provide resistance to fight infection, illness,
and disease
• 2 categories of defenses:
• nonspecific defenses = Always work the same
way , against any type of invading agent
• specific defenses = Protect against specific
pathogens
• Depend on activities of lymphocytes
• Specific resistance (immunity):
– develops after exposure to environmental
hazards
7 Types of
Nonspecific Resistance
1.
2.
3.
4.
5.
6.
7.
Physical barriers
Phagocytic cells
Immunological surveillance
Interferons
Complement
Inflammation
Fever
Nonspecific and
Specific Defenses
• Operate together to provide resistance
to infection and disease
The 7 Nonspecific Defenses
Figure 22–10
The 7 Nonspecific Defenses
• Physical Barriers -Keep hazardous materials
outside the body
• Phagocytes -Attack and remove dangerous
microorganisms
• Immunological Surveillance -Constantly monitors
normal tissues:
– with natural killer cells (NK cells)
• Interferons -Trigger production of antiviral
proteins in normal cells
Antiviral proteins:
– do not kill viruses
– block replication in cell
The 7 Nonspecific Defenses
• Complement (C) Proteins -Form the
complement system
Complements action of antibodies
• Inflammation -Triggers a complex
inflammatory response
• Fever -A high body temperature:
– increases body metabolism
– accelerates defenses
– inhibits some viruses and bacteria
PLAY
Immunity: Complement
What are the components
and mechanisms of
each nonspecific defense?
Physical Barriers
•
•
•
•
Outer layer of skin
Hair
Epithelial layers of internal passageways
Secretions that flush away materials:
– sweat glands, mucus, and urine
• Secretions that kill or inhibit
microorganisms:
– enzymes, antibodies, and stomach acid
2 Classes of Phagocytes
• Microphages: neutrophils and eosinophils
• Leave the bloodstream
• Enter peripheral tissues to fight
infections
• Macrophages: large phagocytic cells
derived from monocytes
• Distributed throughout body
• Make up monocyte–macrophage system
(reticuloendothelial system)
Activated Macrophages
• Respond to pathogens in several
ways:
–
–
–
engulf pathogen and destroy it with
lysosomal enzymes
bind to pathogen so other cells can
destroy it
destroy pathogen by releasing toxic
chemicals into interstitial fluid
2 Types of Macrophages
• Fixed macrophages - also called histocytes:
Microglia:
– found in central nervous system
Kupffer cells:
– found in liver sinusoids
• Stay in specific tissues or organs:
– e.g., dermis and bone marrow
• Free macrophages -Travel through blood stream
• Special free macrophages:
– alveolar macrophages (phagocytic dust cells)
3 Functional Characteristics of Free
Macrophages and Microphages
• Move through capillary walls
(emigration)
• Are attracted or repelled by chemicals
in surrounding fluids (chemotaxis)
Phagocytosis begins:
– when phagocyte attaches to target
(adhesion)
– and surrounds it with a vesicle
Immunological Surveillance is carried out by
Natural killer (NK) cells
Natural Killer Cell Function
Figure 22–11
NK Cell Function
• Identifies and attaches to abnormal
cell (non-selective)
• Golgi apparatus in NK cell:
– forms perforin vesicles
• Vesicles release perforin (exocytosis)
• Perforin lyses abnormal cell membrane
NK Cells attack:
cancer cells and
cells infected with viruses
1) Cancer Cells -with tumor specific
antigens:
– are identified as abnormal by NK cells
– some cancer cells avoid NK cells
(immunological escape)
2) Viral Infections : Cells infected with
viruses:
– present abnormal proteins on cell membranes
– allow NK cells to identify and destroy them
Interferons
• Proteins (cytokines) released by
activated lymphocytes and
macrophages• Cytokines - Chemical messengers
released by tissue cells:
– to coordinate local activities
– to act as hormones to affect whole body
3 Types of Interferons
1. Alpha interferons:
–
–
produced by leukocytes
stimulate NK cells
2. Beta interferons:
–
–
secreted by fibroblasts
slow inflammation
3. Gamma interferons:
–
–
secreted by T cells and NK cells
stimulate macrophage activity
Complement Activation
Complement:
Plasma contains
11 special
complement (C)
proteins:
that
complement
antibody
action
Figure 22–12
Complement Activation
• Complements work together in
cascades
• 2 pathways activate the complement
system
– classical pathway
– alternative pathway
The Classical Pathway
• Fast method
• C1 binds to antibody molecule
attached to antigen (bacterium)
• Bound protein acts as enzyme:
– catalyzes chain reaction
The Alternative Pathway
• Slow method
• Exposed to antigen:
– factor P (properdin)
– factor B
– and factor D interact in plasma
• ** Both pathways end with:
– conversion of inactive complement protein
(C3)
– to active form (C3b)
4 Effects of
Complement Activation
1. Stimulation of inflammation
2. Attraction of phagocytes
3. Enhancement of phagocytosis by
opsonization:
–
complements working with antibodies
(opsonins)
4. Destruction of target cell membranes:
–
5 complement proteins join to form
membrane attack complex (MAC)
Inflammation
• Also called inflammatory response
• A localized response
• Triggered by any stimulus that kills
cells or injures tissue
Cardinal Signs and Symptoms
•
•
•
•
Swelling (tumor)
Redness (rubor)
Heat (calor)
Pain (dolor)
3 Effects of Inflammation
1. Temporary repair and barrier against
pathogens
2. Retards spread of pathogens into
surrounding areas
3. Mobilization of local and systemic
defenses:
–
and facilitation of repairs (regeneration)
Inflammation and Tissue Repair
Figure 22–13
Inflammation and Tissue Repair
• Injured cells release:
– prostaglandins
– proteins
– potassium ions
• Changes interstitial environment and
stimulates mast cells
• Mast cells release:
– histamine (increases capillary permeability)
– heparin (inhibits clotting
Inflammation and Tissue Repair
• Increased blood flow:
– raises local temperature
– causes area to swell, redden, and become
painful
• Blood clot forms around damaged area,
isolating it
• Complements:
– break down bacteria
– attract phagocytes
Inflammation and Tissue Repair
• Activated neutrophils attack debris and
bacteria
• Phagocytes and foreign proteins:
– activate body’s specific defense system
• Macrophages clean up pathogens and
cell debris
• Fibroblasts form scar tissue
Products of Inflammation
• Necrosis:
– local tissue destruction in area of injury
• Pus:
– mixture of debris and necrotic tissue
• Abscess:
– pus accumulated in an enclosed space
Fever - A maintained body
temperature above 37°C (99°F)
• Pyrogens - Any material that causes the
hypothalamus to raise body
temperature:
– circulating pathogens, toxins, or antibody
complexes
• Endogenous Pyrogens : Interleukin-1 (IL1)
– pyrogen released by active macrophages
– a cytokine
Forms of Immunity
Figure 22–14
Specific Defenses
• Specific resistance (immunity):
– responds to specific antigens
– with coordinated action of T cells and B
cells
T Cells
• Provide cell-mediated immunity
• Defends against abnormal cells and
pathogens inside cells
B Cells
• Provide antibody-mediated immunity
• Defends against antigens and
pathogens in body fluids
Forms of Immunity
• 1) Innate Immunity:
– present at birth
• 2) Acquired Immunity:
– after birth
Active:
– antibodies develop after exposure to antigen
Passive:
– antibodies are transferred from another
source
Active Immunity
• Naturally acquired:
– through environmental exposure to
pathogens
• Induced:
– through vaccines containing pathogens
Passive Immunity
• Naturally acquired:
– antibodies acquired from the mother
• Induced:
– by an injection of antibodies
4 Properties of Immunity
1. Specificity- Each T or B cell:
–
responds only to a specific antigen, ignores all others
2. Versatility-The body produces many types of
lymphocytes:
–
–
each fights a different type of antigen (Ag)
active lymphocyte clones itself to fight specific Ag
3. Memory-Some active lymphocytes (memory cells):
–
–
stay in circulation
provide immunity against new exposure
4. Tolerance- Immune system ignores “normal”
antigens
What are the differences
between cell-mediated
(cellular) immunity
and antibody-mediated
(humoral) immunity?
The Immune Response
Figure 22–15 (Navigator)
The Immune Response
• 2 main divisions:
– cell mediated immunity (T cells)
– antibody mediated immunity (B cells)
PLAY
Immunity: Cell-Mediated Immunity
What are the types of
T cells and their functions
in the immune response?
What are the types of
T cells and their functions
in the immune response?
1) Cytotoxic T Cells= also called Tc cells
• Attack cells infected by viruses
• Responsible for cell-mediated immunity
2) Helper T Cells= also called Th cells
• Stimulate function of T cells and B cells
3) Suppressor T Cells = also called Ts cells
• Inhibit function of T cells and B cells
Antigens and MHC Proteins
PLAY
Antigens and MHC Proteins
Figure 22–16a (Navigator)
Antigen Recognition
• T cells only recognize antigens that are
bound to glycoproteins in cell
membranes
Antigen Presentation
Figure 22–16b
MHC Proteins
• The membrane glycoproteins that bind
to antigens
• Genetically coded in chromosome 6:
– the major histocompatibility complex
(MHC)
– differs among individuals
2 Classes of MHC Proteins
• Class I: found in membranes of all nucleated cells
• Pick up small peptides in cell and carry them to
the surface:
– T cells ignore normal peptides
– abnormal peptides or viral proteins activate T cells to
destroy cell
• Class II: found in membranes of antigen-presenting
cells (APCs)
–
–
–
–
found in lymphocytes Antigenic fragments:
from antigenic processing of pathogens
bind to Class II proteins
inserted in cell membrane to stimulate T cells
Antigen-Presenting Cells (APCs)
• Responsible for activating T cells against
foreign cells and proteins
Phagocytic APCs :
• Free and fixed macrophages:
– in connective tissues
• Kupffer cells:
– of the liver
• Microglia:
– in the CNS
Pinocytic APCs
• Langerhans cells:
– in the skin
• Dendritic cells:
– in lymph nodes and spleen
What are the mechanisms
of T cell activation and the
differentiation of the major
classes of T cells?
An Overview of
the Immune Response
Figure 22–15 (Navigator)
Antigen Recognition
• Inactive T cell receptors:
– recognize Class I or Class II MHC proteins
– recognize a specific antigen
• Binding occurs when MHC protein
matches antigen
CD Markers
• Also called cluster of differentiation
markers:
– in T cell membranes
– molecular mechanism of antigen recognition
– more than 70 types:
• designated by an identifying number
CD3 Receptor Complex
• Found in all T cells
CD8 Markers
• Found on cytotoxic T cells and suppressor
T cells
• Respond to antigens on Class I MHC
proteins
CD4 Markers
• Found on helper T cells
• Respond to antigens on Class II MHC
proteins
• CD8 or CD4 Markers - Bind to CD3 receptor
complex
• Prepare cell for activation
Costimulation
• For T cell to be activated, it must be
costimulated:
– by binding to stimulating cell at second
site
– which confirms the first signal
2 Classes of CD8 T Cells
• Activated by exposure to antigens on
MHC proteins:
– one responds quickly:
• producing cytotoxic T cells and memory T cells
– the other responds slowly:
• producing suppressor T cells
Activation of Cytotoxic T Cells
Also called
killer T cells
Seek out and
immediately
destroy target
cells
Figure 22–17 (Navigator)
Actions of Cytotoxic T Cells
1. Release perforin:
–
to destroy antigenic cell membrane
2. Secrete poisonous lymphotoxin:
–
to destroy target cell
3. Activate genes in target cell:
–
that cause cell to die
Slow Response
• Can take up to 2 days from time of
first exposure to an antigen, for
cytotoxic T cells to reach effective
levels
Memory Tc Cells
• Produced with cytotoxic T cells
• Stay in circulation
• Immediately form cytotoxic T cells:
– if same antigen appears again
Suppressor T Cells
•
•
•
•
Secrete suppression factors
Inhibit responses of T and B cells
After initial immune response
Limit immune reaction to single
stimulus
Activation of Helper T Cells
Helper T Cells Activated CD4 T
cells divide into:
active helper T
cells:
secrete
cytokines
memory T cells:
remain in
Figure 22–18
4 Functions of Cytokines
1. Stimulate T cell divisions:
–
–
produce memory T cells
accelerate cytotoxic T cell maturation
2. Attract and stimulate macrophages
3. Attract and stimulate NK cells
4. Promote activation of B cells
Pathways of T Cell Activation
Figure 22–19
KEY CONCEPT
• Cell-mediated immunity involves close
physical contact between activated Tc cells
and foreign, abnormal or infected cells
• T cell activation usually involves:
– antigen presentation by phagocytic cell
– costimulation by cytokines from active
phagocytes
• Tc cells may destroy target cells through
local release of cytokines, lymphotoxins, or
perforin
What are the mechanisms
of B cell activation and the
differentiation of plasma
cells and memory B cells?
B Cells
• Responsible for antibody-mediated
immunity
• Attack antigens by producing specific
antibodies
• Millions of populations, each with
different antibody molecules
PLAY
Immunity: Antibody-Mediated Immunity
B Cell Sensitization
• Corresponding antigens in interstitial
fluids bind to B cell receptors
• B cell prepares for activation
• Preparation process is sensitization
B Cell Sensitization
and Activation During
PLAY
sensitization,
antigens are:
taken into the
B cell,
processed,
reappear on
surface, bound
to Class II
MHC protein
Figure 22–20 (Navigator)
Helper T Cells
• Sensitized B cell is prepared for
activation, but needs helper T cell
activated by same antigen
B Cell Activation
• Helper T cell binds to MHC complex:
– secretes cytokines that promote B cell
activation and division
B Cell Division
• Activated B cell divides into:
– plasma cells -Synthesize and secrete
antibodies into interstitial fluid
Memory B cells- Like memory T cells
remain in reserve to respond to next
infection
Antibody Structure
What is the
structure of
an antibody,
and what types
of antibodies
are found in
body fluids
and secretions
Figure 22–21a, b
Antibody Structure
• 2 parallel pairs of polypeptide chains:
– 1 pair of heavy chains
– 1 pair of light chains
• Each chain contains:
– constant segments
– variable segments-Determine specificity of
antibody molecule
5 Heavy-Chain
Constant Segments
• Determine 5 types of antibodies:
–
–
–
–
–
IgG
IgE
IgD
IgM
IgA
Binding Sites
• Free tips of 2 variable segments:
– form antigen binding sites of antibody
molecule
– which bind to antigenic determinant sites
of antigen molecule
Antibody Function
•Antigen–Antibody
Complex = An antibody
bound to an antigen
Figure 22–21c, d
A Complete Antigen
• Has 2 antigenic determinant sites
• Binds to both of antigen binding sites
of variable segments of antibody
• Exposure to a complete antigen leads
to:
– B cell sensitization
– immune response
A Hapten
• Also called partial antigen
• Must attach to a carrier molecule to
act as a complete antigen
Dangers of Haptens
• Antibodies produced attack both
hapten and carrier molecule
• If carrier is “normal”:
– antibody attacks normal cells
– e.g., penicillin allergy
5 Classes of Antibodies
Table 22–1
5 Classes of Antibodies
•
•
•
•
Also called immunoglobins (Igs)
Are found in body fluids
Are determined by constant segments
Have no effect on antibody specificity
7 Functions of
Antigen–Antibody Complexes
1. Neutralization of antigen binding sites
2. Precipitation and agglutination:
–
formation of immune complex
3. Activation of complement
4. Attraction of phagocytes
5. Opsonization:
–
increasing phagocyte efficiency
6. Stimulation of inflammation
7. Prevention of bacterial and viral adhesion
KEY CONCEPT
• Antibody-mediated immunity involves the
production of specific antibodies by plasma
cells derived from activated B cells
• B cell activation usually involves:
– antigen recognition, through binding to surface
antibodies, costimulation by a Th cell
• Antibodies produced by active plasma cells
bind to target antigen and:
– inhibit its activity or destroy it
– remove it from solution
– promote its phagocytosis by other defense cells
Primary and
Secondary Responses
• Occur in both cell-mediated and
antibody-mediated immunity
Figure 22–22
Primary and Secondary
Responses to Antigen Exposure
• First exposure:
– produces initial response (Primary)
• Next exposure:
– triggers secondary response
– more extensive and prolonged
– memory cells already primed
The Primary Response
•
•
•
•
•
Takes time to develop
Antigens activate B cells
Plasma cells differentiate
Antibody titer slowly rises
Peak response:
– can take 2 weeks to develop
– declines rapidly
• IgM:
– is produced faster than IgG
– is less effective
The Secondary Response
• Activates memory B cells:
– at lower antigen concentrations than original B
cells
– secrete antibodies in massive qualities
Effects of Memory B Cell Activation
• IgG:
– rises very high and very quickly
– can remain elevated for extended time
• IgM:
– production is also quicker
– slightly extended
KEY CONCEPT
• Immunization produces a primary
response to a specific antigen under
controlled conditions
• If the same antigen appears at a later
date, it triggers a powerful secondary
response that is usually sufficient to
prevent infection and disease
Summary of the
Immune Response
• Specific and nonspecific defenses
Figure 22–23
Body Responses to
Bacterial Infection
Figure 22–24
Combined Immune
System Responses
Figure 22–25
Combined Responses to
Bacterial Infection
• Neutrophils and NK cells begin killing
bacteria
• Cytokines draw phagocytes to area
• Antigen presentation activates:
– helper T cells
– cytotoxic T cells
• B cells activate and differentiate
• Plasma cells increase antibody levels
Combined Responses
to Viral Infection
• Similar to bacterial infection
• But cytotoxic T cells and NK cells are
activated by contact with virusinfected cells
Summary: Cells of
the Immune System
Table 22–2
KEY CONCEPT
• Viruses replicate inside cells, whereas
bacteria may live independently
• Antibodies (and administered antibiotics)
work outside cells, so are primarily
effective against bacteria rather than
viruses
• Antibiotics cannot fight the common cold
or flu
• T cells, NK cells, and interferons are the
primary defense against viral infection
What is the origin,
development, activation,
and regulation of normal
resistance to disease?
Immune System Development
• Fetus can produce immune response or
immunological competence:
– after exposure to antigen
– at about 3–4 months
Development of
Immunological Competence
• Fetal thymus cells migrate to tissues
that form T cells
• Liver and bone marrow produce B cells
• 4-month fetus produces IgM antibodies
Before Birth
• Maternal IgG antibodies:
– pass through placenta
– provide passive immunity to fetus
After Birth
• Mother’s milk provides IgA antibodies:
– while passive immunity is lost
Normal Resistance
• Infant produces IgG antibodies through
exposure to antigens
• Antibody, B-cell, and T-cell levels
slowly rise to adult levels:
– about age 12
Hormones of the Immune System
Table 22–3
6 Groups of Hormonal Cytokines
1.
2.
3.
4.
Interleukins
Interferons
Tumor necrosis factors
Chemicals that regulate phagocytic
activities
5. Colony stimulating factors
6. Miscellaneous cytokines
What are the origins
of autoimmune disorders,
immunodeficiency diseases,
and allergies, and what are
some examples of each?
Immune Disorders
• Autoimmune disorders- A malfunction of
system that recognizes and ignores “normal”
antigens
Activated B cells make autoantibodies against
body cells
• Immunodeficiency diseaseThyroiditis
Rheumatoid arthritis
Insulin-dependent diabetes mellitus
• Allergies -
Immunodeficiency Diseases
1. Problems with embryological
development of lymphoid tissues:
–
can result in severe combined
immunodeficiency disease (SCID)
2. Viral infections such as HIV:
–
can result in AIDS
3. Immunosuppressive drugs or radiation
treatments:
–
can lead to complete immunological failure
Allergies
• Inappropriate or excessive immune
responses to antigens
• Allergens:
– antigens that trigger allergic reactions
4 Categories of
Allergic Reactions
• Type I:
– immediate hypersensitivity
• Type II:
– cytotoxic reactions
• Type III:
– immune complex disorders
• Type IV:
– delayed hypersensitivity
Type I Allergy (1)
• Also called immediate hypersensitivity
• A rapid and severe response to the presence
of an antigen
• Most commonly recognized type of allergy
• Includes allergic rhinitis (environmental
allergies)
• Sensitization leads to:
– production of large quantities of IgE antibodies
– distributed throughout the body
• Second exposure leads to:
– massive inflammation of affected tissues
Type I Allergy (2)
• Severity of reaction depends on:
– individual sensitivity
– locations involved
• Allergens in blood stream may cause
anaphylaxis
Anaphylaxis
• Can be fatal
• Affects cells throughout body
• Changes capillary permeability:
– produce swelling (hives) on skin
• Smooth muscles of respiratory system
contract:
– make breathing difficult
• Peripheral vasodilatation:
– can cause circulatory collapse
(anaphylactic shock)
Antihistamine Drugs
• Block histamine released by MAST cells
• Can relive mild symptoms of
immediate hypersensitivity
Stress and the Immune Response
• Glucocorticoids:
– secreted to limit immune response
– long-term secretion (chronic stress):
• inhibits immune response
• lowers resistance to disease
Functions of Glucocorticoids
• Depression of the inflammatory
response
• Reduction in abundance and activity of
phagocytes
• Inhibition of interleukin secretion
Aging and the Immune Response
• Immune system deteriorates with age,
increasing vulnerability to infections
and cancer
4 Effects of Aging
on Immune Response
1. Thymic hormone production:
–
greatly reduced
2. T cells:
–
become less responsive to antigens
3. Fewer T cells reduce responsiveness of
B cells
4. Immune surveillance against tumor
cells declines
Integration with Other Systems
Nervous and
Endocrine
Systems
Interact with
thymic
hormones
Adjust
sensitivity of
immune
Figure 22–27
Disorders of the
Lymphatic System
• 3 categories affect immune response:
– disorders resulting from:
• an insufficient immune response
• an inappropriate immune response
• an excessive immune response
SUMMARY (1)
• Divisions of the lymphatic system:
– lymphatic vessels (lymphatics)
– lymph
– lymphoid tissues and organs
• Types of lymphocytes:
– T cells
– B cells
– NK cells
• Lymphoid tissues and organs:
– Nodules
– MALT
– spleen
nodes
thymus
SUMMARY (2)
• 7 nonspecific defenses:
–
–
–
–
–
–
–
physical barriers
phagocytes
immunological surveillance
interferons
complement
inflammation
fever
SUMMARY (3)
• Specific defenses:
– cell-mediated immunity
– antibody mediated immunity
• Forms of immunity:
– innate or acquired
– active or passive
• Properties of immunity:
– specificity, versatility, memory,
andtolerance
SUMMARY (4)
• T cells and cell-mediated immunity:
–
–
–
–
–
antigen presentation
MHCs and APCs
antigen recognition
CD8 T cell activation
CD4 T cell activation
SUMMARY (5)
• B cells and antibody-mediated
immunity:
–
–
–
–
–
sensitization
plasma cells and memory B cells
antibody structure
antigen–antibody complex
5 classes of immunoglobins
SUMMARY (6)
• Primary and secondary responses to
antigen exposure
• Hormones and the immune system:
– interleukins, interferons, TNFs, and CSFs
• Immune disorders
• Effects of aging on the immune
response