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CH 14

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Chapter 14
The Lymphatic System and Immunity
Lymphatic System
Primary functions
1. Production, maintenance, and distribution of lymphocytes
2. Return of fluid and solutes from peripheral tissues to bloodstream
3. Distribution of hormones, nutrients, and waste products from tissues to general circulation
Functions
- Defends against infection and disease
- Returns tissue fluids to the bloodstream
- Lymph - Fluid transported by lymphatic vessels
- Monitored for signs of injury/infection
- Homeostasis- Recirculation of this fluid essential to maintain
-
Pathogens and the Lymphatic System
Pathogens
- disease-causing organisms
- Include viruses, bacteria, fungi, and parasites
- Each has different mode of life
- Viruses
o Exist within cell
o Lack cellular structure
o Only have nucleic acid and protein
o Replication only within living cell
- Bacteria
o Multiply in interstitial fluid
o Roundworms burrow through internal organs
- Renegade cells produce lethal cancers
Lymphatic system
- Includes cells, tissues, and organs that defend the body
- Lymphocytes
o Primary cells of this system
o Essential to body’s ability to resist/overcome infection or disease
Forms of Immunity
Immunity
- Ability to resist infection and disease
- Two forms of defense systems work independently and together
1. Innate (nonspecific) defenses
2. Adaptive (specific) defenses
Innate/nonspecific
- Anatomical barriers and defense mechanisms
- Prevent or slow entry of infectious organisms
- Attack infections if gain entry
- Innate means we are born with them
- Nonspecific means they do not distinguish one threat from another
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Adaptive/Specific Defense
- Lymphocytes
○ respond to specific threats
○ organize a defense against that type of bacterium
○ Immune response- defense against specific antigens
The Immune System
- All cells and tissues involved in production of immunity
Includes:
- Integumentary
- Skeletal
- Lymphatic
- Cardiovascular
- Respiratory
- Digestive
4 Components of Lymphatic System
1. Lymphatic vessels/lymphatics
- Carry fluid from peripheral tissues to veins
2. Lymph
- Fluid flows through lymphatic vessels
- Resembles plasma
- Contains much lower concentration of proteins
3.Lymphocytes
- Specialized cells that function in defending body
4. Lymphoid tissues and lymphoid organs
- Lymphoid tissues
o Collections of loose connective tissue and lymphocytes
o In structures called lymphoid nodules
o Example: tonsils
- Lymphoid organs
o More complex structures
o Contain large numbers of lymphocytes
o Connected to lymphatic vessels
o Examples: lymph nodes, spleen, thymus
Primary Lymphoid Tissues and Organs
-
Sites where lymphocytes are formed and mature
Include:
-
red bone marrow- where other defense cells, monocytes and macrophages are formed
thymus gland
Secondary lymphoid tissues and organs
-
Sites where lymphocytes are activated and cloned
Produced in large numbers of identical copies
Include:
-
Appendix
Spleen
lymph nodes
tonsils
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MALT (Mucosa-Associated Lymphoid Tissue) in digestive, respiratory, urinary and reproductive
tracts
Lymphatic System
Primary functions
1. Production, maintenance, and distribution of lymphocytes
2. Return of fluid and solutes from peripheral tissues to bloodstream
3. Distribution of hormones, nutrients, and waste products from tissues to general circulation
1. Production, maintenance, and distribution of Lymphocytes
- Functions: Work to eliminate threats or render them harmless by physical and chemical actions
- Produced: in red bone marrow and thymus
- Stored/located: lymphoid organs (such as spleen)
- Respond to:
o Presence of invading pathogens (example: bacteria or viruses)
o Abnormal body cells (example: virus-infected cells, cancer cells)
o Foreign proteins (example: toxins produced by bacteria)
2. Return of fluid and solutes from peripheral tissues to bloodstream
- maintains normal blood volume
- Eliminates local variations in composition of the interstitial fluid
- Volume = 3.6 L/0.95 gal per day
- Break in vessel > rapid fatal decline in blood volume
3. Distribution of hormones, nutrients, and waste products from tissues to general circulation
- Substances unable to enter bloodstream directly may do so by vessels
- Ex: lipids absorbed by digestive tract enter bloodstream after travel along lymphatic vessels
Lymphatic Capillaries
-
-
Smallest lymphatic vessels
Begin as blind pockets in tissues
Lined by overlapping endothelial simple squamous epithelium cells with basement membrane
absent or incomplete
Region of overlap:
o acts as one-way valve
o Allows fluid and solutes to enter ((large proteins, viruses, bacteria and cell debris)
o Prevents fluid and solutes (large proteins, viruses, bacteria and cell debris) from returning
back to intercellular spaces
One-way flow into larger lymphatic vessels
Vessels/lymphatics carry lymph from peripheral tissue to venous system
Flow of lymph
- Capillaries > larger lymphatic vessels (that lead to trunk of body) > lymphatic ducts/collecting
structures (thoracic duct and right lymphatic duct)
Layers of capillaries
- Walls contain similar layers like veins
- Skeletal muscle contractions aid flow of lymph
- Contain valves
o Essential to maintaining normal lymph flow due to pressures in lymphatic system being
low
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Thoracic Duct
-
Collects lymph from:
o Lower abdomen
o Lower pelvis
o Lower limbs (inferior to diaphragm)
o Left side of head
o Neck
o Chest
-
Empties collected lymph
o into venous system near left internal jugular vein
o and into left subclavian vein
Cisterna chyli- Base of thoracic duct is an expanded saclike chamber
-
Right Lymphatic Duct
-
Ends on right side
Collects:
o lymph from right side of upper body above diaphragm
Empties:
o into right subclavian vein
Lymphedema
- Swelling of a limb as a result of blocked lymphatic drainage
- Interstitial fluid accumulates
- Limb becomes swollen and grossly distended
Lymphocytes
-
Account for 20%-40% circulating WBC
Circulating lymphocytes make up only small fraction of total lymphocyte population
1 trillion /1012 (approximately) lymphocytes with combined weight of 2.2lb / 1kg are located within
lymphoid organs and tissues
Bloodstream function > rapid transport system for lymphocytes moving from one site to another
Lymphocytes in blood, bone marrow, spleen, thymus and peripheral lymphatic tissues = VISITORS
not residents
Life span = long, 80% survive for 4 years, some last 20 + years
Normal lymphatic populations maintained through divisions of stem cells in red bone marrow and
lymphoid tissues
3 Classes of circulating lymphocytes:
1. T cells- About 80 percent of circulating lymphocytes
2. B cells- About 10–15 percent of circulating lymphocytes
3. NK cells- About 5–10 percent of circulating lymphocytes
- ALL 3 cell types (T, B, NK) enter bloodstream and migrate to peripheral tissues (lymphoid tissues,
organs, spleen)
- B cells and T cells that migrate from their sites of origin retain ability to divide and produce daughter
cells of the same type
-
Dividing B cell produces other B cells NOT T cells or NK cells
Increase lymphocyte number = success of immune response
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T cells/ T (thymus-dependent)
- Cytotoxic T cells
o Directly attack foreign cells or virus-infected cells
o Provide cell-mediated, or cellular immunity
- Helper T cells/ Regulatory T cells
o Stimulate activities of both T and B cells
o Help establish and control sensitivity of immune response
- Suppressor T cells/ Regulatory T cells
o Inhibit T and B cells
o Help establish and control sensitivity of immune response
B cells
- B (bone marrow–derived) cells
- Differentiate into plasma cells under proper stimulation > Secrete antibodies that are soluble
proteins/ immunoglobulins
- Responsible for antibody-mediated immunity, or humoral immunity
- Antibodies:
o occur in body fluids
o bind to specific targets called antigens
- Antigens are made of
o pathogens
o parts/products of pathogens
o foreign compounds
- Antigen-antibody compound
o Starts a chain of events leading to destructions of target compound or organism
NK cells
-
NK (natural killer) cells
Provide innate (nonspecific) immunity
Attack foreign cells, normal cells infected with viruses, and cancer cells that appear in normal
tissues
Immune surveillance- continual monitoring of peripheral tissues
Lymphocyte Production
-
Lymphopoiesis
o Production and development of lymphocytes
o Involves: red bone marrow, thymus, peripheral lymphoid tissues
B cells and T cells develop/mature > gain ability to respond to specific antigen
NK cells gain ability to respond to abnormal antigens and recognize abnormal cells
Hematopoietic stem cells (hemocytoblasts) in red bone marrow produce lymphoid stem cells with
2 different fates
o One group stays in red bone marrow and generates B cells and NK cells
o Second group migrates to thymus > influenced by thymic hormones called thymosins>
cell divides to form T cells
o T cells- undergo selection process to make sure they will not react to body’s own healthy
cells and cellular products
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Lymphoid Tissues
-
Loose connective tissues dominated by lymphocytes
Lymphoid Nodules
- Form large clusters
- Lymphocytes are densely packed in area of areolar tissue
- Each nodule contains a pale center region (germinal center) where lymphocyte division occurs
- Nodule diameter = 1mm but can increase or decrease depending on number of lymphocytes present
- Doesn’t have capsule surrounding it
- MALT(mucosa-associated lymphoid tissue/collection lymphoid tissue) is epithelia that
protects the digestive, respiratory, urinary and reproductive tract are open to the external
environment
- Infections possible: tonsillitis, appendicitis
MALT
-
-
Defends body against foreign proteins and bacteria from food we eat
Example: Tonsils
o large clusters of nodules in walls of pharynx
o guard entrance to digestive and respiratory tract
o 5 tonsils present: Pharyngeal tonsil or adenoid (x1), Palatine tonsils (x2), Lingual tonsils
(x2)
o Peyer patches in lining of small intestines
Example: Appendix/vermiform
o Vermiform appendix near junction of small and large intestines
o Walls contain mass of fused lymphoid nodules
Lymphoid Organs
-
Separated from surrounding tissue by fibrous connective tissue capsule
Include:
-
Lymph nodes
Thymus
Spleen
Lymph Nodes
Characteristics
- Small, oval lymphoid organs covered by fibrous capsule
- Diameter 1-25 mm up to 1 in
Function
-
purifies lymph before it reaches veins
filters pathogens from lymph
Location
-
Greatest number in neck, armpits, and groin where they defend against bacteria and other invaders
2 Types vessels are connected to each lymph node
- Afferent lymphatics - bring lymph to the lymph node from peripheral tissues
- Efferent lymphatics – drain node and carry lymph away towards venous system
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Lymph Flow
- Subscapular space > cortex > medullary sinuses
- 99% of antigens in lymph are removed by fixed macrophages and branched dendritic cells destroy
pathogens
- T and B cells are stimulated and initiate immune response
The Thymus
Function
-
Site of T cell production and maturation
Location
-
mediastinum, posterior to sternum
-
Greatest size reached 1st-2nd year after birth
Maximum size reached during puberty and weighs 30-40 grams/ 1.06-1.41oz
Then gradually decreases in size
Size
Lobes
-
2 lobes made of lobules ( by fibrous partitions)
Divided by septum/septa wall
Each lobe has outer cortex containing clusters of lymphocytes that secrete thymosin hormones
Thymosins stimulate > lymphocyte stem cell division > T cell maturation > T cell migrate to
medulla > leave thymus in one of the blood vessels in that region
Central medulla has capillaries where T cells enter circulation
The Spleen
-
Contains largest collection of lymphoid tissue in the body
Size = 12 cm/5 in. long
Weight = 160g/5.6 oz
Function
-
Filters blood instead of lymph
removing abnormal blood cells and components
initiates responses of B cells and T cells to antigens in circulating blood
Stores iron from recycled red blood cells
Location
-
between stomach, left kidney, and muscular diaphragm
attached to lateral boarder of stomach by mesentery
Blood vessels
- splenic artery- after enters spleen > branches outward toward capsule into smaller arteries that are
surrounded by white pulp
- splenic vein
- lymphatic vessels
- all connect spleen at hilum (groove at boarder between gastric and renal areas)
- blood from red pulp enters venous sinusoids ( small vessels lined by macrophages> flows into small
veins > splenic veins
Cellular components
- red pulp : contain large numbers of RBC
- white pulp : resemble lymphoid nodules
- capillaries : discharge blood into network of reticular fibers that make up red pulp
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Macrophages engulf damaged or infected cells
- presence of lymphocytes > microorganism or abnormal antigen > immune response stimulated
Body Defenses
Functions
- Both defenses work together to provide adequate resistance to infections/diseases
- The natural or acquired ability to maintain immunity
2 Categories
1. Innate (nonspecific)/natural immunity
- Does not distinguish between on threat and another
- Response is the same regardless of invader type
- Defenses that are present at birth
o Physical barriers
o Phagocytic cells
o Immune surveillance
o Interferons
o Complement
o Inflammation
o Fever
- All above defenses provide body with nonspecific resistance
2. Adaptive (specific)/acquired immunity (humoral immunity B cells and Cellular immunity T cells )
- protects against threat
- fight infection by one type of bacterium but ignore other bacteria/viruses
- defenses develop after birth as result of exposure to environmental hazards and infectious agents
- defenses depend on activities of specific lymphocytes
- B cells and T cells are apart of adaptive defenses
- These defenses provide specific resistance
Physical Barriers
-
Keep hazardous organisms and materials outside the body
Skin
-
Keratin coating, layers of cells, and desmosome junctions that lock adjacent cells together
Provide protection for underlying tissues
Hair
-
Protects against mechanical abrasions on body and scalp
acts as barrier to hazardous material and insects
Epidermal layer
- receives secretions from sebaceous glands and sweat glands
- secretions flush surface washing away microorganisms and chemical agents
- secretions contain microbe-killing chemicals, destructive enzymes (lysozymes) and antibodies
Mucous membranes
- Epithelia lining digestive, respiratory, urinary and reproductive tract more delicate but equally
defended
Digestive tract
- Mucous bathes most surfaces of digestive tract
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Stomach
- Contains powerful acid that can destroy pathogens
Respiratory tract
- Mucous swept across tract
Urine
- Flushes the urinary passageways
Reproductive tract
- Glandular secretions flush structures in tract
Secretions effectiveness
- Aided by special enzymes, antibodies, and acidic pH
Phagocytes
-
Cells that can surround and engulf solid objects
Functions:
- “First line of cellular defense”
- Remove cellular debris and microorganisms before lymphocytes become aware
- Respond to invasion by foreign compounds/pathogens
- All cells function in same way but targets are different from one cell to another
2 Classes
1.
Microphages
o Neutrophils- abundant, mobile, quick to phagocytize cellular debris or invading bacteria
o Eosinophils- less abundant, target foreign compounds or pathogens that have been coated
with antibodies
o Both circulate blood
 Functions: leave bloodstream and enter peripheral tissues subject to
injury/infection
2.
Macrophages
- Large actively phagocytic cells derived from circulating monocytes
- All body tissue shelters resident/fixed or visiting/free macrophages
- Monocyte-macrophage system/ reticuloendothelial system = defused collection of
phagocytes
 Kupffer cells- found in and around blood channels in liver
 Microglia- found in CNS
Both classes
- Share phagocytosis
- All can move through capillary walls by squeezing between adjacent endothelial cells known as
diapedesis
- Attracted or repelled by chemicals in the surrounding fluids a process called chemotaxis
- Both are sensitive to chemicals released by other body cells or pathogens
Immune Surveillance
-
Constant monitoring of normal tissues
Functions
- Primarily involves NK (natural killer) cells
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Plasma membrane of abnormal cells have “non-self,” or foreign antigens
NK cells
o recognize abnormal cell by its foreign antigens
o less selective of targets
o Respond to variety if abnormal antigens that appear on plasma membrane
o Secrete perforins that create holes in the target cell’s plasma membrane, killing the cell
when it encounters antigens from bacterium, cancer cell, virus cell
o Respond more rapidly thank T cells and B cells
o Killing abnormal cells slow spread of bacteria/viral infection
o Eliminates cancer cells before they spread, but some cancer cells avoid detection from NK
cells called immunological escape
o Immunological escape = once this happens cancer cells multiply and spread without NK
interference
Interferons
-
Small proteins called cytokines released by activated lymphocytes, macrophages, and tissue cells
infected with viruses
- Interferons are examples of cytokines- chemical messengers that tissue cells release to coordinate
local activities
o Cytokines- act only within one tissue
o However, if released by cellular defenders cytokines act as hormones and affect activities
of cells and tissues throughout body
Functions
- Normal cell response to interferons by producing antiviral proteins that interfere with viral
replication inside of cell
- Slow spread of viral infections and DNA of viruses
- Stimulate macrophages and NK cells
The Complement System
-
Plasma contains over 30 plasma complement proteins that form complement system
“Complement” > Adds to, completes the action of antibodies
Proteins interact with one another in chain reactions similar to the clotting system
Functions in chain reaction
1. Complement protein binds to either a pair of antibody molecules already attached to a bacterial cells
wall or attach directly to bacterial cell wall
2. Bond complement protein then interacts with a series of other complement proteins
3. Complement activation is known to 1 attract phagocytes, 2 stimulate phagocytosis, 3destroy plasma
membranes, 4 promote inflammation
Inflammation
-
Also called the inflammatory response
Localized tissue response to injury
Produces local swelling, redness, heat, and pain
Any stimulus that kills cells or damages loose connective tissue can produce inflammation
Effects
-
Temporarily repairing damaged tissue
Pathogens are prevented from entering the wound
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The spread of pathogens away from the injury is slowed
Wide range of defenses are mobilized to overcome the pathogens and aid permanent repairs by
regeneration
Mast cells
- play role in inflammation
- are small mobile connective tissue cells
- found near blood vessels
- release histamine and heparin chemicals into interstitial fluid when stimulated by mechanical
stress or chemical environmental changes
- histamine and heparin begin the inflammation process
Histamine
- Make capillaries more permeable
- Speeds up blood flow through area
- When stimulated and released histamine stimulates and activates specific defenses and pave way for
the repaired of injured tissue
Pain sensation
- Caused by combination of abnormal tissue conditions
- Caused by chemicals released by mast cells stimulates local sensory neurons producing pain
sensation
Temperature
- Caused by increased blood flow that reddens the area and raises local temperature
- Increases rate of enzymatic reactions
- Speed up activity of phagocytes
- Denature foreign proteins or enzymes of invading microorganisms
Clotting
- Increased vessel permeability allows clotting factors and complement proteins to leave the
bloodstream and enter injured area
- Clotting does not take place at actual site of injury, due to heparin being present
- Clot forms around the damaged area
- Clot isolates the region and slows the spread of chemical or pathogen into healthy tissues
After injury
- Tissue conditions become more abnormal before improvement
- Necrosis occurs- tissue destruction that takes place after cells have been injured or destroyed
o Begins several hours after the original injury and is due to lysosomal enzymes
- Lysosomes
o Break down by autolysis > releases digestive enzymes that first destroy
- The injured cells > then attack surrounding tissues
Inflammation continues
- Debris and dead/dying cells collect at injury site
- They form thick fluid mixture called pus
- A build up of pus in an enclosed tissue space = abscess
Fever
Defined as body temperature >37.2ºC (99ºF)
Temperature controlled by hypothalamus
Advantages
- Inhibit some bacteria/viruses
- Increase in rate of metabolism
- Cells can move faster enhancing phagocytosis
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- Enzymatic reactions proceed more quickly
Disadvantages
- Temperature over 40C/104F can damage physiological systems
- Can cause CNS problems
- Nausea
- Disorientation
- Hallucinations
- Convulsions
Pyrogens
o circulating proteins
o reset temperature center in hypothalamus
o raise body temperature
o Examples that act as pyrogens: pathogens, bacterial toxins, antigen–antibody complexes
 Can stimulate the release of pyrogens by macrophages
Adaptive (Specific) Defenses
-
Coordinated activities of T cells and B cells provide adaptive/specific defenses
These cells respond to presence of specific antigens
T cells
-
Cell-mediated immunity, or cellular immunity
Result of T cell defense specifically against pathogens inside living cells
B cells
-
Antibody-mediated immunity, or humoral immunity
Result of B cell defense specifically against pathogens in body fluids
Both Cells/ Immunities
- Activated T cells do not respond to antigens in solution
- Antibodies produced by activated B cells can not cross plasma membranes to enter cells
- Immunity categorized into several forms according to when and how it arises in the body
Immunity
Types
1. Innate (nonspecific) immunity
- Genetically determined
- Present at birth
- Includes nonspecific defenses
2. Adaptive (specific) immunity
- Not present at birth
- Develops only when person has been exposed to a specific antigen
- Can be active or passive
- Acquired either naturally or artificially
Active Immunity
-
Immune system capable of defending against enormous number of antigens
Appropriate defenses are mobilized only after encounter of a particular antigen
Body responds to antigens by making its own antibody
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-
Naturally acquired active immunity
o Develops after natural exposure to an antigen in environment
o Not fully functional at birth
o Begins to develop after birth
o Continues to build as person encounters new pathogens or antigens
o Example: child’s vocabulary, child begins with few basic common words and learns new
ones as needed
Artificially induced active immunity
o deliberate exposure to antigen result of immune response
o stimulates body to produce antibodies under controlled conditions so person will be able to
overcome natural exposure to the same pathogen in future
o basic principle behind immunizations, vaccinations to prevent diseases
o vaccine preparation designed to induce an immune response
 contains either dead or inactive pathogen or antigens derived from that pathogen
 given orally, IM, Sub Q injections
Passive Immunity
-
Produced by transferring antibodies to a person from another source
Naturally acquired passive immunity
- Antibodies provided to baby before birth through placental transfer
- Early infancy through breast milk
Artificially induced passive immunity
- Person receives antibodies that are injected to fight infection or prevent disease after exposure to
pathogen
- Example: person bitten by a rabid animal receives an injection of antibodies that attack the rabies
virus
Properties of Adaptive Immunity
1.
-
2.
3.
-
Specificity
Specific defense is activated by specific antigen
Immune response targets that particular antigen and no others
Occurs: the plasma membrane of each T cell and B cell has receptors that will bind only to one
specific antigen, ignoring all other antigens
o either lymphocyte will inactivate or destroy only that specific antigen, without affecting
other antigens or normal tissues
Versatility
Millions of different antigens in environment can pose threat to our health
Humans will encounter tens of thousands antigens in lifetime
Immune system can not anticipate which antigens it will encounter
Immune system must be ready to confront any antigen at any time
Occurs: by producing millions of different lymphocytes populations each with different antigen
receptors
Variability in the structure of synthesized antibodies
Immune system ready to produce specific responses to each antigen when exposure occurs
Memory
Immune system remembers antigens it encounters
Occurs:
o First exposure lymphocytes sensitive to its presence divide repeatedly 2 cells are produced
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
4.
-
Memory cells- inactive cells that enable immune system to remember an antigen
it has previously encountered and launch a faster stronger longer lasting response
if antigen ever appears again
 Active cells- attack antigen
o Second exposure to an antigen triggers faster, stronger, longer-lasting immune response
than first exposure
Tolerance
Immune system does not respond to all antigens
Immune response targets foreign cells and compounds but it generally ignores normal tissues and
their antigens
Occurs:
o
Exists when immune system does not respond to normal (or self) antigens
o We have tolerance because T cells and B cells undergoing differentiation (in the red bone
marrow and thymus) are destroyed if they react to normal body antigens
o Normal B cells and T cells will ignore normal/self antigens and will attack foreign/nonself
antigens
Overview of Immune Response
Purpose
-
Defense against specific antigen
Inactivate or destroy pathogens
Destroy abnormal cells
Destroy foreign molecules/toxins
Pathway
1. Antigen triggers immune response
2. Activates both T cells and B cells
3. T cells activated first only after phagocytes have been exposed to antigen
4. T cells attack antigen and stimulate B cell activation
5. Activated B cells mature into cells that produce antibodies
6. Antibodies in blood stream bind to and attack antigen
T cell
role in starting immune response
role in controlling immune response
-
Before immune response can begin T cells must be activated by antigen exposure
This activation seldom results from direct interaction between T ells and antigen
Foreign substances or pathogens entering a tissue rarely stimulate and immediate immune response
Antigen Presentation
Occurs:
-
T cells are activated by antigens bound to glycoprotein receptors in the plasma membrane of other
cells
o Plasma membrane: of cell contains lipids, proteins and carbs
o Membrane proteins: function as receptors, channels, carriers, enzymes, anchors and
identifiers
o Identifiers/recognition proteins: identify a cell as self or nonself, normal or abnormal to
the immune system
o Carbohydrates: form complex molecules with lipids or proteins on the outer surface of a
plasma membrane.
 Glycoproteins: act as receptor for extracellular compounds like antigens
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Structure
- antigen binding receptors is genetically determined and dofferes among individuals
Membrane receptors
- MHC (major histocompatibility complex) proteins
o Has 2 classes:
 Class 1 MHC protein- antigen that is bound to this protein acts like a red flag that
in effect tells the immune system its an abnormal cell kill me
 Class 2 MHC protein- tells immune system this is a dangerous antigen get rid of it
Class 1 MHC proteins
-
Located: in plasma membrane of all nucleated cells
Bind and display small peptide molecules and chains of amino acids that are continuously produced
in the cell and exported to the plasma membrane
If cell is healthy and peptides are normal self T cells ignore them
If cell contain abnormal nonself, viral or bacterial peptides, their appearance in plasma membrane
will activate T cells > leading to destruction of abnormal cell
Organ donations- rejected due to recognition of nonself peptides in transplanted tissue and rejected by
recipient body
Viruses/bacteria
- T cells activated by contact with viral/bacteria antigens bound to Class 1 MHC proteins on surface
of infected cells
- Activation of T cells by these antigens > lead to infected cell destruction
Class 2 MHC proteins
Location
- Membranes of lymphocytes and APC’s (Antigen-presenting cells)
APC’s
Function
Specialized for activating T cells to attack foreign cells, bacteria and foreign proteins
Cell types
- monocyte macrophage group
- Free and fixed macrophages in connective tissues
- Kupffer cells in liver
- Microglia in the CNS
- Dendritic cells
o Location: skin, lymph nodes and spleen
o Function: remove antigenic materials from their surroundings by phagocytosis and
pinocytosis
o Their plasma membrane also present antigens bound to Class 2 MHC proteins
o These cells travel with their foreign antigens to lymphocyte-packed lymph nodes which
makes them different from macrophages who do not migrate far from an infection site
Phagocytic APC
- Function
o engulf and break down pathogens or foreign antigens
- Fragments of foreign antigens are then bound to Class 2 MHC proteins and displayed on their cell
surfaces
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T cells that are exposed to an APC membrane containing such antigen become activated > initiating
and immune response
T cell Activation
-
-
Inactive T cells have receptors that can bind either Class 1 or Class 2 MHC proteins
The receptors also have binding sites for specific target antigen
T cell must bind to stimulating cell at second site for costimulation before being activated
o This binding occurs between other membrane proteins, each specific to their cell type APC
or T cell
o Costimulation confirms that antigen recognition has occurred
 prevents T cells from mistakenly attacking normal self tissues
 determines whether T cell will become activated
upon activation T cells divide and differentiate into cells with specific functions in the immune
response
4 Major T cell types
1. Cytotoxic T cells
2. Helper T cells
3. Memory T cells
4. Suppressor T cells
Binding/ Antigen recognition
- Occurs when MHC protein contains specific antigen that the T cell is programmed to detect
- T cell recognizes it has found appropriate target
- Binding of T cells depends on type of protein in the T cell’s own plasma membrane
- Antigen-binding receptors on cells called major histocompatibility complex (MHC) proteins
Membrane proteins
- T cells have membrane proteins called CD (cluster of differentiation) markers
- Type of CD marker determines response to MHCs
- Two key CD markers
o CD8 T cells
 respond to antigens on Class I MHC proteins
o CD4 T cells
 respond to antigens on Class II MHC proteins
Cytotoxic T Cells
- TC/ Killer T cells
Function
- CD8 cells responsible for cell-mediated immunity
Activated
- by exposure to antigens bound to Class 1 MHC proteins
- activated cells undergo cell divisions that produce more active cytotoxic cells and memory TC cells
- activated cytotoxic T cells track down and attack the bacteria, fungi, transplanted that contain the
target antigen.
Ways Cytotoxic T cells destroy targets
- Releasing perforin that ruptures target cell’s membrane
- Secreting cytokines that activate genes in the targets cell’s nucleus that tell cell to die
o Apoptosis- process of genetically programmed cell death
- Secreting poisonous lymphotoxins which kills target by disrupting target cell metabolism
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Helper T Cells
-
Also called TH cells
Function
-
Have CD4 markers that are activated by exposure to antigens bound to Class 2 MHC proteins p
antigen-presenting cells
- Cells divide to produce both active helper T cells and memory T H cells
Activated
- Activated by exposure to antigens bound to Class II MHC proteins
- Active helper T cells secrete various cytokines that coordinate specific and nonspecific defenses
- Activated helper T cells stimulate both cell-mediated and antibody-mediated immunity
Memory T Cells
-
Cells produced following the activation of cytotoxic T cells and helper T cells develop into memory
T cells
Memory TC and TH remain “in reserve”
With second exposure to same antigen, will rapidly differentiate into cytotoxic and helper T cells
enhancing the speed and effectiveness of the immune response
Suppressor T Cells
-
Have CD8 markers
Function
- Activated suppressor T cells suppress the responses of other T cells and of B cells by secreting
cytokines called suppression factors
Activated
- Slowly by exposure to antigens bound to Class 1 MHC proteins
Suppression
- does not take place immediately
- Suppressor T cells
o are activated more slowly than other types of T cells
o they act after the initial immune response
o these cells put on the breaks limiting the degree of the immune response to a single
stimulus
B cells
respond to antigens exposure
by producing specific antibodies
Function:
- responsible for launching a chemical attack on antigens in body fluids
- produce specific antibodies that target specific antigens
Antigen exposure
- do not immediately produce antibodies in response to antigen exposure
o Sensitization
o Activation
o Division
o Differentiation into antibody- producing cells
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B Cell antigen Exposure response Process
Pg 490 figure 14-14
-
Each B cell carries its own antibody molecule in its plasma membrane
Corresponding antigens appear in interstitial fluid the interact with these antibodies
Antigen-antibody binding
B cells prepares for activation by sensitization
Sensitization Process
1. Antigens enter B cell by endocytosis
2. Then become displayed on surface of b cell and bound to Class 2 MHC proteins
3. Sanitization B cell on stand by and doesn’t become activated until Helper T cell says OK and the
Helper T cell has become activated to the same antigen
○ Helper T cell acts like a safety to prevent inappropriate B cell activation
Activation Process
1. Activator Helper T cell attaches to the MHC protein-antigen complex of the sensitized B cell and
cytokine costimulation takes place
Cell Division and Differentiation Process
1. Secretion/stimulation of cytokines begins
○ Cytokines- promote B cell activation, stimulate B cell division and accelerate B cell
development into plasma cells
2. Activated B cells divides repeatedly producing daughter cells that differentiate into plasma cells
and memory B cells
3. Plasma cells synthesize and secrete large quantities of antibodies with the same target as the
antibodies on the surface of the sensitized B cell
4. Memory B cells remain in reserve to respond to future exposure to same antigen
5. Plasma cells respond by differentiating into antibody-secreting plasma cells
Antibody Structure
-
Molecule has Y-shaped protein
2 parallel pairs of polypeptide chains
o 1 pair of long heavy chains
o 1 pair of shorter light chains
- each chain has constant and variable segments
- approximately 10 trillion B cells of a normal adult can produce 100 million different antibodies
Constant segment
- heavy chains provide base for antibody
- B cells produce 5 types of constant segments
- Specificity of an antibody molecule depends on the structure of the variable segments of the light
and heavy chains
Antigen binding sites
- Free tips of variable segments
- Shape is determined by the specificity of antibody
- Small differences in the amino acid sequence of the variable segments affect the precise shape of the
antigen binding sites
- Different shapes of these sites account for the specific differences among the antibodies produced
by different B cells
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Antigen–Antibody Complex
-
Antibody molecule binds to its specific antigen
Antibodies do not bind to the entire antigen as a whole
Antibodies bind to certain portions of its exposed surface regions called antigenic determinant
sites
o Most environmental antigens have multiple antigenic determinant sites
o Entire microorganisms have thousands
- Specificity of that binding depends on the 3D fit between the variable segments of the antibody
molecule and the corresponding sites of the antigen
- Complete antigen has at least two antigenic determinant sites
o One for each arm of the antibody molecule
Exposure
- Exposure to a complete antigen can lead to B cell sensitization
- Exposure can lead B cell to immune response
Five Classes of Antibodies
Table 14-1 pg 492
-
Antibodies also called immunoglobulins (Igs)
1.
IgG
Largest and most diverse class (80%)
Responsible for resistance against viruses, bacteria and bacterial toxins
Can cross the placenta and provide passive immunity to fetus
2.
3.
4.
5.
IgM
Circulating IgM Attack bacteria
Responsible for cross-reactions between incompatible blood types
IgA
Found in exocrine secretions like mucous, tears and saliva
Attack antigens/pathogens before they can cross epithelial surfaces and enter the body
IgE
Stimulate basophils and mast cells to release histamine, chemicals that stimulate inflammation
Involved in allergic responses and inflammation responses
-
IgD
Attached to B cells
aid in B cell sensitization
-
eliminate antigens
formation of an antigen-antibody complex may cause the elimination of antigens in many ways
Six Functions of Antibodies
1. Neutralization
- Antigen–antibody complex bind to viruses or bacterial toxins making them incapable of attaching to
cell
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2. Precipitation and agglutination
- When large number of antigens are close together, one antibody molecule can bind to antigenic sites
on two different antigens
- Antibodies can link antigens together and create large complexes
- Antigen is a soluble molecule like bacterial toxin the complex may be too large to stay in solution
Precipitation
- occurs when large antigen–antibody complexes settle out of body fluids
Agglutination
- target antigen is on surface of cell, the formation of large complexes
Example: clumping red blood cells from mixing incompatible blood types
3. Activation of complement
- Binding with an antigen changes antibody molecule shape, exposing segments that bind with
complement proteins
- The bound complete molecules then activate the complete system destroying the antigen
4. Attraction of phagocytes
- Antigen–antibody complex attracts eosinophils, neutrophils, and macrophages
- These cells engulf pathogens
- Destroy cells with foreign or abnormal plasma membranes
5. Enhancement of phagocytosis
- Coating of antibodies and complement proteins makes pathogens with slick plasma membrane or
capsule easier to phagocytize/engulf this is called opsonization
6. Stimulation of inflammation
- Antibodies promotes inflammation by stimulating basophils and mast cells
- This causes mobilizing nonspecific defenses
- Slows the spread of the infection to other tissues
Primary and Secondary Responses
Primary response
- Initial response to an antigen
- Takes time to develop
- Slow and less effective at preventing diseases
- Antigen must activate B cells
- B cells must respond by differentiating into plasma cells
- Plasma cells begins secreting antibodies
- Concentration of circulating antibodies undergoes gradual sustained rise
- Antibody levels in blood takes 1–2 weeks to peak after initial exposure
- IgM molecules are the first to appear in blood stream > followed by slow rise in IgG
o If person no longer exposed to antigen the antibody concentration decline
Secondary response
- Rapid and intense response
- Prevents diseases
- Reflects presence of large numbers of memory cells that are already primed for arrival of antigen
- Immunizations are effective because it stimulates memory B cells under controlled conditions
- Memory B cells differentiate into plasma cells when exposed to the same antigen a second time
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o
-
Memory B cells respond right away and stronger during 2 nd exposure because numerous
memory cells are activated by low levels of antigen
o Memory B cells give rise to plasma cells that secrete massive quantities of antibodies
o This antibody secretion is the secondary response to antigen exposure
Increase in IgG concentrations is immediate and higher than first response
Secondary response can appear years after first exposure due to memory cells surviving for 20 +
years or more
Cells that Participate in Tissue Defenses
Look at page 494 > table 14-2
Hormones of the Immune System
Example of physical interaction
- is the display of antigens by antigen-presenting macrophages
Example of chemical messenger release
- is the secretion of cytokines by activated helper T cells and other cells involved in the immune
response
Cytokines
- are chemical coordinators of defenses
- classified according to sources
o Sources (common):
 Lymphokines- secreted by lymphocytes
 Monokines- released by active macrophages and other antigen-presenting cells
 Lymphocytes and macrophages secrete the same chemical messenger. Cells
involved with nonspecific defenses and tissue repair may do the same
o Groups (5 common):
1. Interleukins
2. Interferons
3. Tumors necrosis factors
4. Phagocyte regulators
5. Colony stimulating factors
Interleukins (IL)
-
are most diverse and important chemical messengers in immune system
20 types have been identified
Primary sources are lymphocytes and macrophages
Endothelial cells, fibroblasts and astrocytes produce interleukins like IL-1
Effects
-
Increase T cell sensitivity to antigens presented by APC’s
Stimulate B cell activity and antibody production
Enhance nonspecific defenses like inflammation and fever
Some suppress immune function
Shorten duration of an immune response
Interferons
-
make cells resistant to viral infection
make the cell synthesizing
slowing spread of virus
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-
antiviral activity
Attract and stimulate NK cells and macrophages
Interferons are used to treat some cancers
Tumor Necrosis Factors
TNFs
-
Slow tumor growth
Kill sensitive tumor cells
Stimulate production of neutrophils, eosinophils, and basophils
Promote eosinophil activity
Cause fever
Increase T cell sensitivity to interleukins
Phagocytic regulators
-
Coordinate specific and nonspecific defenses by adjusting phagocyte cell activity
Include cytokines
Cytokine factors attract free macrophages and microphages to an area
Prevent macrophages and microphages from premature departure
-
Produced by wide variety of cells
Cells include: Active T cells, cells of monocyte–macrophage group, endothelial cells, fibroblasts
CSF stimulate production of blood cells in red bone marrow
CSF stimulate production of lymphocytes in lymphoid tissues and organs
Colony-stimulating Factors (CSFs)
Abnormal Immune Responses & Immune Disorders
Immunological competence
- Ability to produce normal immune response after exposure to antigen
Disorders of abnormal immune function
1.
2.
3.
Autoimmune disorders
o Relatively rare conditions
o Clear evidence of the effectiveness of the immune system’s control process
Immunodeficiency diseases
○ Relatively rare conditions
○ Clear evidence of the effectiveness of the immune system’s control process
Allergies
o More common
o Usually less dangerous
Autoimmune Disorders
Occur
-
When immune system response mistakenly targets normal body cells and tissues
Risks increases for people with unusual types of MHC proteins
50 clinical conditions linked to specific variations in MHC structure
o Examples: psoriasis, rheumatoid arthritis, myasthenia gravis, narcolepsy, Graves diseases,
Addison’s, pernicious anemia, systemic lupus erythematosus, chronic hepatitis
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-
Activated B cells begin to develop autoantibodies (misguided antibodies against normal body cells
and tissues)
- Autoantibodies attack normal cells and tissues
- Result condition depends on which antigen is attacked
Example
- rheumatoid arthritis
o antibodies attack connective tissue around joints
- type 1 diabetes mellitus
o autoantibodies attack cells in the pancreatic islets
Mistaken identity disorders
Example:
- proteins associated with measles
- Epstein-Barr
- Influenza
- viruses containing amino acid sequences resembling myelin proteins
Antibodies that target these viruses also attack myelin sheaths
o Explains neurological damage after vaccine or viral infection/virus
o Responsible for Multiple Sclerosis- demyelinating disorder that may affect the optic
nerve, brain and spinal cord
Immunodeficiency Diseases
Causes
-
Immune system fails to develop normally
Immune response is blocked in some way
Infants
-
Severe combined immunodeficiency disease (SCID)
o Infants fail to develop either cell- or antibody-mediated immunity
o Treated by bone marrow transplants and gene-splicing techniques
Can not produce an immune response so even mild infections can be fatal
Total isolation offers protection
Requires severe lifestyle restrictions
AIDS
-
is result of viral destruction of helper T cells
as number of helper T cells declines the normal immune response breaks down
Allergies
-
Inappropriate or excessive immune responses to antigens
Sudden increase in cellular activity or antibody levels can have several unpleasant side effects
Examples
- Neutrophils or cytotoxic T cells may destroy normal cells while attacking the antigen
- Antigen- antibody complex may trigger a massive inflammatory response
Allergens- Antigens that set off allergic reaction
4 categories
1.
Immediate hypersensitivity (Type I)
o MOST common type
o Rapid and strong response to an antigen
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o
o
o
Example: allergic rhinitis, hay fever, environmental allergies
Affect 15% of US population
Sensitization to an allergen during initial exposure leads to production of large quantities
of IgE antibodies
o First exposure to allergen does not produce antibody due to lag time needed to activate B
cells, produce plasma cells and make antibodies
o After sensitization, IgE antibodies become attached to the plasma membranes of basophils
and mast cells throughout the body
o Second exposure to same allergen cells are stimulated to release histamine, heparin,
several cytokines, prostaglandins and other chemicals into surrounding tissues and affected
tissues become inflamed
- Severity of immediate hypersensitivity allergic reaction depends on person’s sensitivity and the
location involved
Exposure area
- If allergen exposure takes place at body surface > response may be restricted to that area
- If allergen encounters blood stream the response can be lethal
Anaphylaxis
- circulating allergen affecting mast cells throughout body
- S/S:
o Develop in minutes
o Changes in capillary permeability produces swelling and edema in the dermis
o Raised hives, welts on skin
o Smooth muscles in respiratory passageways contract
o Narrowed passageways make breathing difficult
o Anaphylactic shock - Peripheral vasodilation (severe cases) > drop in BP >circulatory
collapse
o Shock is treated with antihistamines > block action of histamine, can prevent S/S of
hypersensitivity
2. Cytotoxic reactions (Type II)
o Example: cross-reactions in incompatible blood type transfusions
3. Immune complex disorders (Type III)
o Example Result if phagocytes are not able to rapidly move circulating antigen-antibody
complexes.
o The presence of these complexes leads to > inflammation and tissue damage within blood
vessels and kidneys
4. Delayed hypersensitivity (Type IV)
o Example: itchy rash with poison ivy
o inflammatory response that occurs 2-3 days after exposure to an antigen
Stress and the Immune Response
-
1st cytokines produced as part of immune response is interleukin-1 (IL-1)
Stress promotes inflammation
Stimulates production of adrenocorticotropic hormone (ACTH) by anterior pituitary
ACTH > leads to secretions of glucocorticoids by adrenal cortex
Short term
- Anti-inflammatory effects of glucocorticoids may help control extent of the immune response not
dangerous
Long term/Chronic release of Glucocorticoids
- Chronic stress causes long-term secretion of glucocorticoids > depressing of immune system >
serious health threat
- Inhibit immune response
- Depressing inflammation
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-
Reducing phagocyte numbers and activity
Inhibiting interleukin production
Result is a lowering of a person’s resistance to disease
Immunity and Aging
-
Immune system becomes less effective at fighting disease
T cells become less responsive to antigens
Fewer cytotoxic T cells to respond to infection
May be due to shrinkage of thymus and reduction in thymic hormones
Fewer helper T cells = B cells become less responsive
Slower production of antibodies after antigen exposure
Increase in susceptibility to viral and bacterial infections
Vaccinations for acute viral diseases (flu, pneumococcal pneumonia recommended for elderly
Increase in incidence of cancer due to immune surveillance declines > less effective tumor cell
destruction
-
Endocrine system
Thymic hormones and cytokines stimulate TRH production
Leads to increased cell and tissue metabolism with immune response
Nervous system
Can adjust sensitivity of immune response
PNS innervates dendritic cells in lymph nodes, spleen, skin, and other APCs
Neurotransmitter release increases local immune response
Emotional stress can decrease immune response
Lymphatic Integration with Other Systems
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