The Lymphatic System and Immunity: Chpt. 22
Pathogen:
Fungus:
Bacteria
Virus
Immunity:
Consists of:
1. network of lymphatic vessels
2. lymph:
similar to interstitial fluid
3. lymphatic tissues & organs
4. Lymphocytes, phagocytes &
Functions of Lymphatic System:
1. Production, maintenance, and distribution of lymphocytes
2. Return of fluid and solutes from interstitial fluid
3. Transport of hormones, nutrients
Distribution & Structure of Lymph Vessels - form a 1-way system
1. Lymphatic Capillaries (lacteal):
similar to systemic blood capillaries except lymphatic capillaries are more
lacteals also have thinner walls
are found near systemic capillaries
endothelial cells overlap and leave “flaps” which open when fluid P> in interstitial space allowing
interstitial fluid to enter lymph. cap
Proteins and large debris (including bacteria, viruses and cancer cells) easily enter lymph vessels
However, lymph takes detours through lymph nodes
2. Small Lymphatic Vessels
collect lymph from lymphatic capillaries transport to larger lymphatic vessels
larger lymphatic vessels have valves to prevent backflow of lymph
often found near arteries and veins
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superficial and deep lymphatics
superficial in subcutaneous layer
deep near deep arteries/veins of skeletal muscles
lymphangitis:
3. Lymphatic Trunks: collect lymph from the lymphatics
major trunks – Lumbar
Intestinal
Bronchomediastinal
R,L Subclavian
R,L Jugular
Trunks drain lymph into 1 of 2 ducts:
1. Right Lymphatic Duct: collects lymph from the
, and
trunks
,
2. Thoracic Duct: largest
begins as an enlarged sac termed the Cisterna Chyli located at L1 which collects lymph from
the
and
trunks.
As thoracic duct runs superiorly, accepts lymph from the
, and
,
trunks.
Each duct empties lymph into the subclavian veins (R and L)
lymphangitis: inflamed lymphatic vessels
Lymph Transport:
∙ low pressure
∙ lymph moves one-way
∙skeletal muscle contractions, pressure changes thorax during breathing
∙ valves
∙ arterial pulses
∙ lymphedema: lymph cannot drain due to blockage in limb
limb becomes swollen – higher risk of infection in area
Lymphoid Cells:
• account for 20-30% of all circulating leukocytes (WBCs)
• 3 types of lymphocytes:
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1. T cells (thymus-dependent) – 80% of circulating lymphocytes
provide cell-mediated immunity or cellular immunity
cytotoxic T cells – attack foreign cells & virus infected cells
hand-to hand combat
helper T cells – stimulate T & B cells
suppressor T cells –
2. B cells (bone marrow-derived) – 10-15% of circulating lymphocytes
provide antibody-mediated immunity or humoral immunity
when encounter antigen become activated & form 2 types of clones (sensitive to the antigen)
plasma cells and memory cells
plasma cells make antibodies (immunoglobulins) to attack the antigen
memory cells:
3. NK cells (natural killer or large granular) – 5-10% of circulating lymphocytes
provide immunological surveillance – “police”
Note: lymphocytes circulate in blood, bone marrow, spleen, thymus and lymph tissue.
Lymphocyte lifespan 4 - 20 years – new lymphocytes made in bone marrow and lymph tissue
4. Macrophages:
5. Dendritic cells: “Antigen Presenting Cells”
Lymphopoiesis: occurs in bone marrow, thymus and peripheral lymph tissue
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Hemocytoblast generates 2 main types
of lymph stem cells –
1.) One group remains in bone marrow:
produces immature B cells & NK cells
B cells migrate into lymph nodes,
spleen & lymph tissue
NK cells circulate through peripheral
Tissues
2.) The other migrates to the thymus
gland to form T cells
T cells develop in the thymus gland
and then are released to the blood
travel to bone marrow, peripheral
Lymph Tissues
tissues, lymph tissues & lymph
• connective tissue with lymphocytes
organs
• lymphoid or lymphatic nodules densely packed in connective tissue of respiratory, digestive and urinary
tracts
• examples include
MALT (mucosa-associated lymphatic tissue): Peyer's patches and appendix
Tonsils
ring of lymph. tissue around entrance to pharynx (throat)
pharyngeal tonsil or adenoid:
palatine tonsils: throat
lingual tonsils: back of tongue
Lymph Organs
1. Lymph nodes: bean shaped
filter and purify lymph before it enters blood (removes
99% of antigens)
Each node has a fibrous capsule, a cortex, & a medulla
Cortex contains dendritic cells, macrophages and T cells
Medulla mostly contains B cells and plasma cells
Lymph enters lymph nodes via afferent lymph vessels &
exits via efferent vessels.
There are fewer efferent vessels than afferent which
Largest lymph nodes found in the inguinal, axillary,
submandibular & cervical regions of body
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Sometimes the nodes are overwhelmed and become painful/swollen
Tonsillitis:
Lymphadenopathy: chronic or excessive enlargement of lymph nodes
Lymph nodes can also become secondary cancer sites (lymphoma)
2. Thymus Gland
located in mediastinum
grows throughout childhood and is largest at puberty then atrophies
secretes hormones (thymosins) cause T lymphocytes to become immunocompetent
3. Spleen
soft, blood rich organ on lateral border of stomach (9-11th rib)
largest lymphatic organ
Functions of the spleen:
1. spleen cleanses blood: phagocytosis
2. Stores some iron from breakdown of RBCs
3. Initiates the immune response (immune surveillance) of B & T cells
4. Stores platelets
spleen surrounded by fibrous capsule
inside of spleen contains red pulp: regions containing macrophages & dendritic cells
white pulp: contains lymphocytes
Injury to spleen: impact on left abdomen can tear capsule
Splenectomy:
Immunity:
Defenses: Nonspecific vs. Specific
Nonspecific: same response to any threat
Specific: lymphocytes respond to antigens
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Nonspecific: (p. 776 figure 22-10): prevent entrance and/or limit spread of pathogens
1. Physical Barriers: keep organisms out of body
skin: first line of defense
keratin and hair
sweat, sebaceous glands: secretions contain lysozyme and antibodies
mucus membranes in respiratory, digestive, urinary and reproductive tracts
HCl in stomach
2. Phagocytes:
first line of cellular defense
attack & remove microorganisms before lymphocytes detect their presence
microphages: neutrophils and eosinophils normally in blood
leave blood and travel to injured/infected tissue
respond quickly
neutrophils become activated which increases metabolic rate (respiratory burst)
and they produce nitric oxide & H2O2 to destroy engulfed pathogens.
also release cytokines to attract other neutrophils and macrophages to area
macrophages: larger, derived from monocytes (leukocyte)
Activated Macrophages:
1. Adhere to pathogen & engulf it to destroy it in lysosome
Opsonization: complement or antibodies coat pathogen
2. bind to pathogen to "hold" it for other cells to help destroy it
3. release toxic chemicals (cytokines) to destroy pathogen (tumor necrosis factor, defensins)
fixed vs. free:
fixed include Langherhans cells, microglia and kupffer cells
free or mobile: dust cells and those that circulate in blood
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Movement of microphages & free macrophages:
• diapedesis – move through capillary walls out of blood
• chemotaxis
• adhesion: phagocyte must first attach to target
3. Immunological surveillance: cell (pg. 778 figure 22-11)
natural killer (NK) cells: recognize and destroy abnormal cells (via antigens) in peripheral tissues
can destroy many types of cells
recognizes abnormal cell, adheres to it, produces and releases perforins (exocytosis) which
destroys cell membrane of abnormal cell
(rotates golgi apparatus to “aim” at cell and then releases perforin proteins)
4. Interferons (cytokines): alpha (), beta() and gamma () interferons
•small proteins released from activated lymphocytes, macrophages and cells infected with virus
•releases antiviral proteins to healthy cells – inhibit viral replication
•also stimulate NK cells and macrophages
5. Complement:
• 11 plasma proteins
• once activated this system causes a complement cascade which eventually:
1. forms MAC
2. release of histamine
3. attracts neutrophils and macrophages to area
4. facilitates phagocytosis – coating of complement proteins & antibodies makes it easier for
phagocyte to adhere/engulf
Assist with opsonization
6. Inflammatory Response:
4 signs of inflammation:
vasodilation of blood vessels:
mast cells release histamine - increased permeability of blood vessels:
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leukotrienes & prostaglandins also released for inflammation
why beneficial? (see tissue notes)
7. Fever: temperature >37.2o C or 99o F
pyrogens: circulating proteins, toxins, antibody complexes cause hypothalamus to reset
temperature –
Endogenous pyrogens = interleukin-1 (IL-1) pyrogen released by active macrophages
a cytokine
beneficial because: increases metabolism,
accelerates defenses
inhibits some viruses and bacteria
Immunity (specific resistance)
Responds to specific antigens – with coordinated action of T and B cells
Cellular Immunity:
T cells (lymphocytes) : provide cell-mediated immunity
directly kill cells
indirectly by releasing cytokines
Humoral Immunity:
B cells (lymphocytes): provide antibody-mediated immunity
Antigens:
Proteins, polysaccharides, lipids, nucleic acids
Mobilize immune system
Complete Antigens:
Immunogenicity: Stimulate antibody formation
Reactivity: react with activated lymphocytes & antibodies
Antigenic determinants:
Hapten: incomplete antigen
Usually doesn’t trigger immune response unless attached to protein
Poison ivy & animal dander
Self-Antigens: MHC Proteins: glycoproteins
MHC Class I: proteins in cell membranes of all nucleated cells
-peptide displayed is synthesized within the cell (endogenous)
-displays peptides from cellular protein recycling (T cells ignore
normal peptides)
- if cell is infected it will display the protein and T cell will
recognize it and be activated – abnormal peptides activate T
cell
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also occurs during organ rejection
Tolerance: immune system doesn’t respond to some antigens –
ignores self-antigens and nonharmful antigens
Forms of Immunity:
Innate:
Acquired: Active vs. Passive
Passive Immunity:
• naturally acquired
• artificially acquired (induced)
Active Immunity:
• naturally acquired
• artificially acquired (induced)
Specific Defenses and Immunity: T and B cells
T Cells: Cell-Mediated Immunity
protect against abnormal cells or pathogens inside of our cells
3 Types of T cells:
1.) Cytotoxic: TC or CD8
2.) Helper T: TH or CD4
3.) Suppressor T: TS
1.
Cytotoxic: TC or CD8
directly attack foreign cells or cells infected with viruses
use physical and chemical methods
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BUT: must be activated first (this is done by antigen presentation through MHC proteins or HLAs)
Note: must be costimulated to be activated
T cells respond to either class I or class II antigens (page 789 figure 22-19)
CD8 cells activated by class I antigens
CD4 respond to class II antigens
Once activated form killer T cells and memory T cells
Killer T cells release chemicals to destroy cell
perforins
lymphotoxin
activate genes to stimulate cell to die (apoptosis)
slow response time
Memory T cells:
Produced with cytotoxic T cells
immediately form cytotoxic T cells if exposed to same antigen again
2.
Suppressor TS
release suppression factors to limit the immune response
inhibit responses of T and B cells
Act after initial immune response
3.
Helper: TH or CD4
once activated divide to form: active helper T cells & memory helper T cells
Activated helper T cells release cytokines which:
1. stimulate production & maturation of killer T cells
2. attract macrophages to area
3. stimulate and attract NK cells
4. stimulate B cell to make antibodies
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B Cells: antibody-mediated or humoral immunity
B cells attack antigen by producing specific antibodies
B cell must first be activated or sensitized (usually in lymph node) - Requires helper T cell
Once sensitized produces clones that will become:
1. plasma cells: make and secrete antibodies against the antigen
(2000 molecules/second)
Antibodies released into interstitial fluid & circulate in blood or lymph
2. memory cells: remain for second exposure to antigen
Immunoglobulins: antibodies
Structure: 2 heavy parallel polypeptide chains: heavy & light
Each chain has constant (stem) and variable region
Constant region determines antibody class
Antigen-antibody complex
5 classes: IgG, IgE, IgD, IgM and IgA
IgG: most numerous in plasma (accounts for aprx. 80%)
protects against viruses, bacteria & toxins
Main antibody of secondary response
Only one to cross the placenta
IgE: triggers release of histamine & inflammatory chemccals from mast cells
allergic reactions, asthma
chronic parasitic infections in GI tract
IgM: first antibody secreted during primary response
IgA: found in saliva, mucus, tears
Complete antigen vs. hapten:
Complete antigen binds to both antigen binding sites
Hapten: Small molecule that triggers immune response by linking to other protein (carrier)
Dangers of Haptens
 Antibodies produced will attack both hapten and its linked protein
 If carrier is “normal”
 Antibody attacks normal cells
 For example, penicillin allergy, poison ivy, detergents, etc.
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Antibody Effects:
1. Neutralization: bind to pathogen site so pathogen cannot bind to other cells
effective at preventing viral and toxin binding to host cells
2. Agglutination and precipitation: binds to several antigens and clumps them together
3. Activate complement
4. Attract phagocytes
5. Opsonization: antibodies surround/coat pathogen so phagocytes can grab and ingest it more easily
6. Stimulate inflammation: via mast cells
7. Prevent bacteria and viruses from adhering to cells
mainly IgA in saliva etc. prevents binding/entrance of pathogens
Primary vs. Secondary Responses to Antigen Exposure
Immunological competence: the ability to produce an immune response after exposure to an antigen
Form antibodies (antibody titer)
Note: monoclonal antibodies used in research, clinical testing, treatment
Important Cytokines (pg. 799 table 22-3)
1. Interleukins (IL-2 etc)
produces by leukocytes and macrophages
stimulate T and B cell activity
increase antibody production
trigger fever and inflammation
2. Interferons
resistance to viral infections
stimulate NK cells and macrophages
3. Tumor necrosis factors (TNFs)
slow tumor growth, can kill tumor cells
cause fever, increase neutrophil production
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stimulate T cells activation
4. Perforin
5. Lymphotoxins
6. Leukotrienes
stimulate inflammation
Response to Bacterial Infection
Defense Against Bacterial and Viral Pathogens
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Summary of Immune Response
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Clinical Aspects of the Immune System
1.
Immunodeficiency diseases:
Severe combined immunodeficiency disease (SCID)
AIDS: - HIV infection
Immunosuppressive Drugs:
2. Autoimmune Disorders:
B cells produce autoantibodies
Can be due to decreases suppressor T cells
Increased stimulation of helper T cells
Tissue damage
Examples: thyroiditis, rheumatoid arthritis, insulin-dependent diabetes mellitus, multiple sclerosis, lupus
3.
Allergies
excessive immune response to antigen (allergens)
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usually IgE antibody response
may be genetic
response releases histamine, heparin, cytokines etc.
4 categories of allergic reactions:
1.) Type I: immediate hypersensitivity
Rapid & severe response to antigen (allergen)
IgE binds to mast cells & triggers release of histamine
increased capillary permeability cause swelling (hives)
smooth muscles contract in respiratory passageways - difficulty breathing
Can be local or systemic
Local: histamine: runny nose, watery eyes, itchy, hives
If allergen inhaled: bronchoconstriction
Tx: antihistamine, benedryl, corticosteroids
Systemic
anaphylaxis: (pg. 801 figure 22-26) allergen activates mast cells throughout the
body – when allergen is in the blood
vasodilation can be so great as to drop BP and cause anaphylactic shock
bronchoconstriction restricts air flow
Tx: Epi
2.) Type II (subacute hypersensitivity): cytotoxic reactions
Caused by IgG and IgM
Slower onset (1-3 hours, longer duration)
Blood transfusion reaction
3.) Type III: immune complex disorders
Antigens widely distributed throughout the body
Results in numerous antibody-antigen complexes, can’t be removed
Causes inflammation and cell lysis by neutrophils
Glomerulonephritis, systemic lupus erythematosus, and rheumatoid arthritis.
4.) Type IV: delayed hypersensitivity
Slowest to appear (1-3 days)
Caused by cytokines (antihistamines don’t work), corticosteroids help
Allergic contact dermatitis (caused by haptens: poison ivy, detergents, etc)
Tine test for tuberculosis
Stress and the Immune System: caused by CRH and ACTH: glucocorticoids
secreted to limit response- chronic secretion interferes with immune function
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1. depression of inflammatory response:
2. decreased number and activity of phagocytes:
3. inhibition of interleukin secretion:
4. decreased production of antibodies
Aging and the Immune System
 Immune system diminishes with age, increasing vulnerability to infections and cancer
 Thymic hormone production is greatly reduced
 T cells become less responsive to antigens
 Fewer T cells reduces responsiveness of B cells
 Immune surveillance against tumor cells declines
Nervous & Endocrine System adjust sensitivity of Immune System
How to have a healthy immune system:
Don’t be too clean!! The “hygiene hypothesis”
Rest/De-stress
Diet
Supplements
Laugh
↑ number & activity of cytotoxic T cells that attack viral infected cells, cancer & tumor cells
↑ number of NK cells
↑ activated T cells
↑ IgA
↑ gamma interferon
↑antibody formation
↓ cortisol
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