Transcript Ch 22 Student Revised

22
The Lymphatic System
and Immunity
PowerPoint® Lecture Presentations prepared by
Jason LaPres
Lone Star College—North Harris
© 2012 Pearson Education, Inc.
Functions of the Lymphatic System
1. Defense
• Lymphocytes residing in the lymphatic tissues protect the body
against microorganisms and foreign substances. Such as
viruses, bacteria, parasites, and fungi.
• Immune system – not an organ system, but a population of
cells that inhabit all of our organs and defend the
body from agents of disease
• The body harbors about 10,000 times as
many bacterial cells as human cells
• some beneficial; some potentially disease causing
2. Fluid balance
• Excess interstitial fluid enters lymphatic capillaries and
becomes lymph; drains into the circulatory system.
3. Fat Absorption
• absorbs fat and other substances from the intestines using
specialized vessels called lacteals
© 2012 Pearson Education, Inc.
Components of the Lymphatic System
 Lymph is fluid drained from interstitial spaces in all tissues. It is
essential for fluid balance.
 Main source of lymphocytes is from lymph leaving lymph nodes
 Consistency of lymph determined by location. ex: after heavy
fat absorption-milky color
 No lymph present in CNS (brain /spinal cord), cartilage,
cornea, bone marrow, bone, or teeth
• Lymphatic capillaries and vessels transport the lymph
– Lymph  Lymphatic Capillaries  Lymphatic collecting vessels
 Lymph nodes  6 lymphatic trunks  2 Lymphatic ducts 
Drain into large veins of the body.
• Lymphatic tissues composed of aggregates of lymphocytes and
macrophages that populate many organs in the body
• Lymphatic organs
– defense cells are especially concentrated in these organs
– separated from other organs by connective tissue capsules
Lymphatic CAPILLARY Structures
Similar to blood capillaries; penetrate most
tissues of the body. Increased permeability is
due to: larger diameters and thinner walls
1) Endothelial cells are loosely attached.
Edges overlap one another forming
flap-like mini-valves
– Larger gaps allow bacteria and cells to
entrance lymphatic capillary
– Increases in interstitial fluid pressure
separates the flaps.
• Flaps push inward - fluid enters
• Flaps push outward –fluid remains in
vessel
2) Filaments anchor endothelial cells to
surrounding structures - prevents sac from collapsing
3) Lacteals - special lymphatic capillaries in small
intestine -Transport lipids from digestive tract
Higher pressure
outside in interstitial
fluid pushes flap open
Lower pressure inside vessel
http://antranik.org/wpcontent/uploads/2011/12/lymphat
ic-capillaries-minivalves.jpg
Lymphatic
Vessels
Lymph capillaries merge to form lymphatic
vessels similar to veins with tunica
interna (endothelial and valves), media
(elastic and smooth muscle), externa (very
thin) travel alongside veins/ arteries - share
common connective tissue sheath
 one way valves prevent backflow
• Lymph moves through vessels by the
“milking action” of the skeletal muscles
and pressure changes created by the
respiration similar to action of veins.
– Lymph from upper regions of the
body flows through the help of gravity.
– Lymph flows at lower pressures and
speed than venous blood vessels
– exercise significantly increases
lymphatic return
Vessels flow through lymph nodes: bean shaped clusters of B
and T cells found along the length of the vessels; lymph fluid moves
slowly thru nodes to increase filtration of microorganisms
Lymph
Trunks
1.
2.
3.
4.
5.
6.
Jugular
Subclavian
Bronchiomediastinal
Intercostal
Intestinal
Lumbar
• Lymph is drained from major portions of body into six (6)
lymphatic trunks: As lymphatic vessels exit from lymph nodes,
they merge to form the 6 lymph trunks
• Each lymphatic trunk drains fluid from a certain area of the body.
• e.g. jugular trunks drain from the head and neck, subclavian
trunks drain from the upper arms and superficial thoracic wall.
Lymphatic trunks
drain into two
lymphatic ducts
Thoracic duct: Main
collecting duct of the
lymphatic system.
Receives lymph from
the left side of the head,
neck, and chest, the left
upper extremity, and the
entire body below the
ribs.
Immune Cells of Lymphatic System
1. Macrophages- large, phagocytic cells of the connective tissue
– Formed from monocyte WBCs. Phagocytize tissue debris, dead
neutrophils, bacteria, and other foreign matter
– antigen presenting cells (APCs)-process foreign; display antigenic
fragments alerting the immune system to the pathogens
2. Neutrophils, basophils, eosinophils (WBCs)
3. LYMPHOCYTES: (WBC)
I. Natural killer LYMPHOCYTE (NK) cells –non-specific-INNATE
• large lymphocytes that attack and destroy bacteria, transplanted
tissue, host cells infected with viruses or have turned cancerous
• responsible for immune surveillance
II. T LYMPHOCYTES (T cells) specific - mature in thymus
III.B LYMPHOCYTES (B cells) specific - differentiation into plasma cells
that produce antibodies; mature in bone marrow
4. Dendritic cells - APCs found in epidermis, mucous membranes, and
lymphatic organs. Alert T cells to presences of pathogens
5. Antimicrobial proteins - destroy bacteria
6. Reticular cells- branched stationary cells contribute to the connective
tissue framework of a lymphatic organ; act as APCs in the thymus
macrophage
Reticular cells
Dendritic celll
Red Bone
Marrow
soft loosely
organized highly
vascular
material
involved in hemopoiesis (blood formation) and immunity
– as lymphocyte blood cells mature, they push their
way through the reticular and endothelial cells to
enter the sinus and flow away in the blood stream
Lymphocytes
80%
Lymphatic (lymphoid) “TISSUE”
Aggregations of lymphocytes (WBCs) in the connective tissues of
mucous membranes and various organs not surrounded by a capsule.
1. Diffuse lymphatic tissue – SCATTERED lymphocytes rather than
densely clustered
• Prevalent in body passages OPEN TO THE EXTERIOR
• respiratory, digestive, urinary, and reproductive tract
• Mucosa-associated lymphoid tissue (MALT) small concentrations
of lymphoid tissue in various sites of the body- such as:
–BALT - bronchus associated lymphoid tissue
–LALT - larynx-associated lymphoid tissue
–SALT - skin-associated lymphoid tissue under epidermis
–GALT - Gut-associated lymphoid tissue
»Peyer patches –dense clusters of digestive system; found in
the ileum, the distal portion of the small intestine, the
appendix
2.Lymphatic nodules (follicles) DENSE MASSES of lymphocytes &
macrophages; form in regions of frequent exposure to microorganisms
• Nodules unlike lymph nodes are much smaller and do not have a
well-defined connective-tissue boundary capsule.
• Tonsils regions where nodules have merged together
Clusters of both
Diffuse and Dense
(nodules) aggregations
of lymphocytes
(WBCs) in connective
tissues
http://www.dartmouth.edu/~anatomy/Histo/lab_5/GI/DMS137A/44.gif
Peyer patches –dense clusters of GALT in the digestive system;
found in the ileum, the distal portion of the small intestine
Tonsils
Large groups of NODULES
in the mucosa of the
pharynx. Protection
against bacteria entering
the body through the
mouth or nasal cavities.
– Pharyngeal tonsil
(adenoids) single
tonsil on wall of
nasopharynx
– Palatine tonsils on
each side wall; most
often infected
– Lingual tonsil in the
back of the tongue
Lymphatic ORGANS
• Areas where lymphatic tissue is concentrated
– Separated from other organs by a connective tissue
CAPSULE
• Primary Lymphatic organs:
• where IMMUNE cells (lymphocytes, macrophages)
are produced and mature to the point where they
can produce a normal immune response.
(immunocompetent)
– e.g. red bone marrow and thymus gland
• Secondary Lymphatic organs:
• are the sites where the MATURE lymphocytes
RESIDE and carry out immune response.
• e.g. spleen, lymph nodes
Thymus Gland
• Large organ in infants but atrophied as adult.
• 2 lobed organ located in mediastinum
• Site of maturation of T cells
Thymus Gland
Surrounded by a connective
tissue fibrous capsule with
trabeculae divide the gland into
several lobules
Each lobule has cortex and
medulla
• Cortex (numerous
lymphocytes)
• Medulla (fewer lymphocytes)
• Reticular cells separate cortex
from medulla and reinforce the
blood-thymus barrier
– barrier prevents immature
T cells from coming into
contact with foreign antigens
in the blood; contact with
antigens at this stage would
destroy T cells
Lymph Nodes
1. Located along lymphatic vessels;
most numerous
2. Concentrated near mammary glands,
axilla, groin, thoracic cavity, throat
3. Filter lymph through a network of
sinuses
4. Dense CT capsule surrounds outer
structure and extends inwardly as
trabeculae.
5. Outer cortex contains lymphatic
nodules filled with T-lymphocytes
and macrophages
6. Inner medulla lymphatic tissue
called medullary cords consist of
B-lymphocytes, macrophages,
plasma cells, reticular cells
7. Lymph enters the nodes via the
afferent lymphatic vessel and leaves
via the efferent lymphatic vessel
.
http://www.bing.com/images/search?q=lymp
h+nodes+locations&FORM=HDRSC2#view=
detail&id=14023092BB8EF106AEA273AF09
ABCD39B51B7CBA&selectedIndex=0
T- lymphocytes
B- Lymphocytes
Lymphatic System
• Metastasis – when cancerous cells break free from the original,
primary tumor, travel to other sites in the body, and establish new
tumors. Characteristic of malignant tumors
– PRIMARY SITE where cancer cells travel via blood or lymphatic
system and establish new tumors where they lodge
• tend to lodge in the first lymph node they encounter
– SECONDARY TUMOR sites can be predicted by direction of
lymphatic flow from primary site; prevention of metastasis by
removing nodes “downstream” from originate site.
• Lymphoma - cancer of lymph cells that usually originate in the
lymph nodes. There are multiple systems used to classify
lymphoma based on cell type, prognosis, etc.
• Lymphedema Blockage of lymph
drainage from a limb
• Causes severe swelling; often a
consequence of surgically removing
the lymph nodes in the armpit (axilla)
or groin, or their damage caused by
radiotherapy.
• Interferes with immune system function
http://drugster.info/img/ail/2624_2643_1.jpg
Spleen
Largest lymphatic organ. Similar to
a large lymph node - blood filter.
• CT Capsule; trabeculae, divide spleen into compartments
Each compartment filled with:
– White pulp – lymphocytes and macrophages Monitors blood
for pathogens
– Red pulp is lymphatic tissue filled with RBCs. (76%-79%).
• Old and deformed cells deposited, RBC “graveyard”
– Metabolizes (breaks down) hemoglobin recycling iron
components
• Transfers excess plasma from blood to lymphatic system –
controls blood volume. Fluid flows into spleen out into interstitial
fluid. Acts as blood reserve in event of hemorrhagic shock
• The spleen often damaged by trauma/injury. Rupture can lead to
bleeding, shock, death. Removal (splenectomy) may be required
to prevent excessive bleeding.
The hilum depression for
splenic blood
vessels
Resistance
• Ability to protect damage or disease from foreign substances
such as microorganisms and harmful chemicals.
• Susceptibility: lack of resistance.
• Categories of resistance:
 INNATE or NONSPECIFIC resistance- guards equally
against a broad range of pathogens
 ADAPTIVE or SPECIFIC immunity specific defense due to
prior exposure to a pathogen.
• Three lines/categories of defense (resistance)
1. first line of defense – nonspecific / INNATE defense
EXTERNAL barriers, skin and mucous membranes; chemical
antimicrobial barriers
2. second line of defense – several nonspecific / INNATE
defense mechanisms. Activated when pathogens reach
INTERNAL areas of the body. Generalized responses to
pathogen infection – do not target a specific cell type
3. third line of defense – specific / ADAPTIVE resistance
DEFENSE
How does the immune system know to
engage or react with a foreign substance?
• The immune system protects the body like a
guardian from harmful influences found in the
environment. It can be activated by many “nonself” substances or receptors called antigens.
ALL CELLS HAVE ANTIGENS!!
• Antigen : Collectively any molecular substance
located ON/IN a bacteria, virus, fungi, protozoa,
pollen, or transplanted tissue cell CAPABLE
OF TRIGGERING AN IMMUNE RESPONSE
– Self-antigens: molecules on cells within the body that
usually do NOT trigger an immune response unless the cell
is infected or the immune system is not operating properly:
Ex: autoimmune diseases.
– Foreign antigens are present on cells produced
OUTSIDE the body
EPITOPES- REGION where a molecular fraction of a self or foreign
protein is displayed on the surface of an antigen capable of initiating
immune response. A single antigen can have SEVERAL effective
epitopes (receptors) [Such as the A or B antigens on RBCs]
ANIMATION:
http://highered.mheducation.com/sites/
0072507470/student_view0/chapter22/a
nimation__antigenic_determinants__ep
itopes_.html
http://cnx.org/content/m44821/l
atest/Figure_42_02_03.png
This is the antigen; an antigen
receptor inside a foreign cell
is displayed on the cell’s
surface. Our immune system
recognizes that it is not part of
our own body components and
initiates an immune response
http://classes.midlandstech.edu/carterp/Courses/bio225/cha
p17/Slide1.jpg
NS Resistance 1st line- Physical Barriers
Prevents entry of microbes
SKIN (epidermis) closely packed,
tough keratinized cells prevents
penetration of microbes; shedding
helps remove microbes
• Defensins- antimicrobial
chemicals found in almost all
epithelial cells. Bind to microbial
cell membranes and form pores
that allow the outflow of essential
ions and nutrients
• Perspiration- Lactic acid (acid
mantle) in sweat prevents
bacterial growth
• Sebum (oil) inhibits growth of
bacteria & fungus
• Hyaluronic acid- forms in plasma
membrane and produces a
viscous consistency that makes
it difficult for microbes to navigate
NS Resistance 1st line- Physical Barriers
1. Mucous membrane secretes viscous mucous
2. Cilia & mucus trap & move microbes toward throat
• Coughing and sneezing speed up the process
3. Nose hairs trap and filter microbes and dust
4. The washing action and flow of tears, urine, saliva
and vaginal secretions prevent microbe colonization
– Ex: tears dilute and drain away microorganisms that
enter the eye
5. Lysozymes- enzyme that destroys bacteria by
dissolving their cell walls.
6. Acidic pH of gastric juice and vaginal secretions
destroys bacteria
NON-SPECIFIC (NS) / Innate Defenses
2ND LINE: INTERNAL DEFENSES
I.
Leukocytes 4 of the 5 types involved in NS immunity
– Leukocytes Phagocytic
• Monocytes - Macrophages fixed and free (wandering)
• Neutrophils
– Leukocytes Non-phagocytic
 Basophils
 Eosinophils
II. Antimicrobial proteins
– Cytokines = Interferons
– Complement
III. Immunological surveillance - (Natural killer cells)
IV. Inflammatory response
V. Fever
Phases of phagocytosis
Phagocytosis
1. Chemotaxis:
macrophages attracted
to chemicals from
damaged tissues,
2. Adherence: pathogen
attaches to plasma
membrane of
phagocyte
3. Ingestion: engulf by
pseudopods to form
“phagosome”
4. Digestion: merge
with lysosome
enzymes forming the
phagolysosome.
5. Killing: microbe
destroyed. Digested
contents are
Animation:
eliminated from the
http://www.youtube.com/watch?v=7VQU28itVVw
cell via exocytosis.
“NS” 2nd Line – I. Leucocytes PHAGOCYTIC
MONOCYTES:- 5% of WBC. Leave blood, migrate to tissues
and develop into macrophages.
• Fixed macrophages types - stay in specific tissues or
organs
• Microglia in CNS (brain and spinal cord)
• Alveolar dust cells (lungs)
• Kupffer cells found in liver sinusoids
• Free macrophages
• Travel throughout body
Animation:
http://www.youtube.com/
watch?v=KiLJl3NwmpU
“NS” 2nd Line - I. Leucocytes PHAGOCYTIC
NEUTROPHILS: stay primarily in connective tissue (CT). During
periods of pathogen exposure they migrate to infected area
• Attracted to the chemicals released by damaged cells.
Methods of defense:
1. Phagocytosis
2. Release defensins (drillers)peptides drilling holes in their
membranes (same as epidermis
process)
3. Respiratory burst
• When neutrophils comes into contact with microbe initiates
release of lysosome enzymes into (interstitial) fluid.
• Enzymes produce toxic combination of superoxide, hydrogen
peroxide and hypochlorite (similar to bleach) which establishes
a “Killing Zone”.
• Chemicals kill larger numbers of the microbes than neutrophils
would be unable to “disarm” using normal phagocytosis.
Unfortunately, the neutrophils exposed to the chemicals are
also destroyed.
“NS” 2nd Line
I. Leucocytes
“NONPHAGOCYTIC”
IgE
• BASOPHILS –Involved in allergic response; inflammatory action
– contain GRANULES of toxic chemicals that can digest foreign
microorganisms. Produce Mast cells that:
1. release toxic chemicals when alerted by antibodies
2. release histamine-increases permeability of capillaries
3. cause blood vessels near wound to constrict- inhibiting
pathogen entrance to the body.
• EOSINOPHILS- found in mucus membranes
• Parasites, allergens
• Chemical release similar to neutrophils
• Limited phagocytic ability; plays limited role in bacterial infections
Non-specific (NS) / Innate Defenses
2ND LINE: INTERNAL DEFENSES
I.
Leukocytes 4 of the 5 types involved in NS immunity
– Leukocytes Phagocytic
• Monocytes - Macrophages fixed and free (wandering)
• Neutrophils
– Leukocytes Non-phagocytic
 Basophils
 Eosinophils
II. “ANTIMICROBIAL PROTEINS”
– Cytokines = Interferons
– Complement
III. Immunological surveillance - (Natural killer cells)
IV. Inflammatory response
V. Fever
“NS” 2nd Line – II. ANTIMICROBIAL PROTEINS
Proteins on the INSIDE of the body that kill microbes by attacking
directly or impeding microbial reproduction.
Target cytoplasmic membrane; may also interfere with DNA
and protein synthesis; may penetrate into the cell to bind
intracellular molecules which are crucial to cell living of microbe
1: Cytokines “SIGNALING” proteins - released by macrophages,
also by B and T lymphocytes
– Similar in function to hormones but are present in much
higher quantities in the blood than hormones
1. Stimulate an increase in macrophage activity
2. Coordinate local cellular activities such as inflammation
 Interferons (type of cytokine) Cells infected by viruses
• Using a 2nd messenger interferons stimulates the
neighboring cell to produce antiviral proteins TO INHIBIT
REPLICATION. (interferons “interfere” with viral production)
• The infected cell cannot survive but provides warning for
neighboring cells; “last dying act”
• Release of interferons also attracts the attention of NK cells
and macrophages from the interstitial fluid signaling them to
destroy the infected cell.
Body cell
infected by
virus will
release
interferons to
stimulate
neighboring
cells to
produce
antiviral
proteins
http://classes.midlandstech.edu/carterp/Courses/bio211/chap21/Slide11.JPG
“NS” 2nd Line
II. ANTIMICROBIAL PROTEINS
2. Complement proteins Utilized in both NS and Specific immunity
• The complement system is comprised of a large number of distinct
plasma proteins that react with one another to fight infection. Set of
approx. 30 “INACTIVE” individual BLOOD PROTEINS
synthesized by LIVER hepatocytes. “Complements” activity of
antibodies/phagocytosis
• Proteases (protein enzymes) cleave specific proteins to release
cytokines; initiates an amplifying cascade resulting in the activation
of cell-killing membrane attack complex proteins C3a, C3b, C35
which produce various defensive actions against pathogens.
– Non-specific immunity: ALTERNATIVE action binds directly to
target cells and work independent of antibodies
• SLOW able to distinguish self from non-self on the basis of the
surface expression of complement regulatory proteins
– Specific immunity: CLASSICAL action requires an antibody to
activate
• FAST - antibody binds to microbe, antibody’s shape is changed
revealing binding site for complement proteins. Binding initiates
activation of complement actions
Complement
System
“NS” 2nd Line
II. Antimicrobial PROTEINS
Actions of complement proteins against foreign substances:
1. Cytolysis Pore formation -– ring forms to penetrate
membrane- electrolytes “leak-out”.
2. Phagocytosis: C3b protein binds to surface of pathogen
producing OPSONIZATION; enhances the uptake of the particle
by a phagocyte, coats pathogen decreasing repulsion effect.
3. Inflammation- C5a recruits and activates inflammatory
leucocytes such as basophils and neutrophils
4. Immune clearance- C3b complement protein binds with
Ag-Ab complex that then binds to RBCs. Immune complexes are
antibody and antigens bound together; must be broken down and
eliminated to prevent tissue damage. The RBCs move to the
liver or spleen where macrophages strip the Ag-Ab complex
from RBC leaving them unharmed. Primary means of clearing
foreign antigens from the body
Complement is the principal means of pathogen destruction
used by ANTIBODIES!
** Opsonization
macrophage
complement
antibodies
Foreign bacteria enters body;
macrophages begin to attack and
destroy as many bacteria as
possible to decrease or eliminate
the infection.
Repulsion force between the
bacterial cell membrane (-VE
negative charge) and body
macrophage membranes (-VE
negative charge) hinders binding
process.
Antibodies and complement
proteins NEUTRALIZE the negative
repulsion using opsonization
coating the negative membrane
surface enabling macrophages to
adhere to bacterium membranes.
http://www.phartoonz.com/wp-content/uploads/2010/12/Opsonizationmacrophages_complement-system_immunoglobulins1.jpg
Opsonization enables
the macrophage to bind
to the microbe more
readily
Cytolysis
Animation:
http://www.youtub
e.com/watch?v=aN
h5A0gtuLE
(2.55 min- 1.49)
http://image.slidesharecdn.com/complementitsbiologicalrole-110703093215-phpapp02/95/complement-its-biological-role-8728.jpg?cb=1309685650
Non-specific (NS) / Innate Defenses
2ND LINE: INTERNAL DEFENSES
I.
Leukocytes 4 of the 5 types involved in NS immunity
– Leukocytes Phagocytic
• Monocytes - Macrophages fixed and free (wandering)
• Neutrophils
– Leukocytes Non-phagocytic
 Basophils
 Eosinophils
II. Antimicrobial proteins
– Cytokines = Interferons
– Complement
III. IMMUNOLOGICAL SURVEILLANCE-NATURAL KILLER CELLS
IV. Inflammatory response
V. Fever
NS 2nd Line –III. Immune Surveillance–Natural Killer Cells
Immune surveillance – performed by lymphocytes called Natural
killer (NK) cells that patrol the body for pathogens and diseased
host cells. Virus infected cells and tumor cells display abnormal
MHC (identity) markers; activated in response to interferons or
macrophage-derived cytokines
• NK Cells- MORE RAPID than T or B lymphocytes
– Have the ability to identify and attach to abnormal cell
even without antibody alert or MHC (specific) designation.
• Golgi apparatus in NK cell
1. forms vesicles that release proteins (perforins) that “drill” a
hole in the membrane - allows rapid inflow of fluid, salts
2. vesicles containing granzymes (degrading enzymes) also
enter and destroy the cell’s enzymes causing apoptosis
(programmed cell death).
• Cancer cells are sometimes able to avoid detection by NK cells
(immunological escape) and can continue to proliferate
throughout the body
• Function in “NS” similar to cytotoxic T- cells for specific immunity
Natural Killer Cells
Animation: http://www.youtube.com/watch?v=HNP1EAYLhOs
Non-specific (NS) / Innate Defenses
2ND LINE: INTERNAL DEFENSES
I.
Leukocytes 4 of the 5 types involved in NS immunity
– Leukocytes Phagocytic
• Monocytes - Macrophages fixed and free (wandering)
• Neutrophils
– Leukocytes Non-phagocytic
 Basophils
 Eosinophils
II. Antimicrobial proteins
– Cytokines = Interferons
– Complement
III. Immunological surveillance - (Natural killer cells)
IV. INFLAMMATORY RESPONSE
V. FEVER
“NS”
2nd line of defense – IV. Inflammation
• LOCALIZED - Triggered by injury
chemical irritation, microbes,
temperature, distortion WBCs (basophils
& mast cells) release of histamine which
initiates vasodilation/vasoconstriction.
• Cytokines –regulate inflammation
act at short range, neighboring cells
(paracrines) or the same cell that
secretes them (autocrines)- ALERT
system to presence of foreign substance
• Small vessels near injury dilate,
increase blood supply (causing
redness, heat). Fluids from dilated
vessels move into neighboring tissues,
causing swelling (edema).
• Migration of phagocytes from the blood
into the infected tissues, eliminates the
pathogens by phagocytosis.
Increased blood flow
brings antibodies; clot
formation to isolate
bacteria, tissue clear
up and repair
“NS”
2nd line of defense V. FEVER
• Circulating proteins (pyrogens) raise and reset body
temperature. Initiation of fever usually by “EXOGENOUS
PYROGENS” = fever producing agents ON SURFACE OF
BACTERIA AND VIRUSES
• Neutrophils and macrophages attack pathogens and release
“ENDOGENOUS PYROGENS” (cytokine- interleukins-1)
Pyrogens cause a release of prostaglandin E2 (PGE2) that
stimulate the hypothalamus to raise the set point for body
temperature - causing fever
– Methods - retaining heat: vasoconstriction; shivering
(chills) increase muscle heat production
• An abnormal elevation of body temperature inhibits
reproduction of bacteria and viruses
• Elevated temperature stimulates the liver to hold back
important nutrients necessary for microbe reproduction
• Neutrophil activation increases; rate of T cell proliferation
Increases
• Antipyretic – fever-reducing medications such as aspirin and
ibuprofen “INHIBIT” PGE2
21-49
Specific Resistance
• Requires time to react unlike the innate immune system that is always
present and ready to engage foreign organisms.
• Provides ability to recognize and remember specific pathogens and
reacts more rapidly on subsequent exposure to the same organism.
– Recognize foreign antigens via plasma membrane antigen
receptors. REACTS ONLY with the organism that induced the response.
– B and T cells MUST recognize a foreign antigen before beginning
their immune response!
1. HUMORAL (B lymphocytes) - stem cells form and mature in red bone
marrow ---> divide and differentiate into B- lymphocyte cells; migrate to
the various lymphatic tissues in the body.
– B cells bind to antigen in extracellular fluid OUTSIDE CELLS –
they cannot cross cell membrane! Capable of Phagocytosis and
antigen presentation to other immune cells.
2. CELL-MEDIATED (T-lymphocytes) - stem cells divide and differentiate
into T- lymphocyte cells which exit bone marrow migrate to thymus gland
and upon maturity travel to the various lymphatic tissues.
– T cells can ONLY recognize fragments of foreign antigens that have
been processed and displayed/presented to them as part of a cell’s
MHC molecule. T cells defend against microbes that have ENTERED
(INSIDE) cells. Do not resond to antigens outside of cells
Self vs. Non-self Antigens
• B cells and T cells must recognize non-self from self antigens.
• CELL SURFACE glycoprotein molecule called Major
histocompatability complex (MHC) displays a small piece of
one of the body cell’s proteins (epitope); acts as an
“identification tag.”
• MHC is found on ALL body cells with the exception of RBC.
UNIQUE for each genetically different individual. MHC molecules
are coded by genes on chromosome 6.
• B and T-cells do not elicit immune response against the body's
OWN MHC unless body cell has been infected by a pathogen.
• Two classes of MHC proteins:
– Class I (MHCI): on surface of ALL NUCLEATED cells both
self and non-self (EXCEPTION RBCs)
• Foreign pathogens/substances also display MHC markers.
A foreign antigen’s MHC will triggers an immune response.
– Class II (MHCII): produced and appear on the surface of
SPECIALIZED CELLS called antigen-presenting cells
(APCs), mature B-cells, macrophages, dendritic cells, Kupffer
cells, APC cells activate T-cell defenses.
MHC II
APC
http://www.hindawi.com/journals/jtrans/2012/842
141.fig.001.jpg
MHC I
Good animation:
http://wps.pearsoned.com/fahimhalimkh
an/155/39695/10162084.cw//10162145/index.html
MHC I
Foreign pathogens are
consumed by phagocytosis.
Protein fragment of foreign cell
is displayed on MHCII and
draws attention of T-helper cells
which activate or warn other
cells of the immune system.
MHC I
T-cytotoxic cell destroy
diseased or compromised
body cells. Protein fragment
of disease cell is displayed on
the MHCI to draw attention of
Tc cells.
MHCII
T Lymphocytes
1. Cytotoxic T (TC) cells: KILL INFECTED BODY CELLS bind to
MHC-I molecules; Also known as the Killer cells
2. Helper T (TH) cells: recognize antigen fragments associated
with MHC-II molecules (APC)
– When a TH cell binds to a MHC-II molecule it initiates the
release of cytokines, most important, interleukin-2, which act
as a co-stimulators or confirmation for other helper T cells,
cytotoxic T cells, and B cells.
Function of T-helper and cytotoxic T-cells is very different.
3. Memory T cells help to recognize the antigen which invades for
the second time. Stay in circulation - immediately forms
cytotoxic T cells if same antigen appears again
4. Suppressor T cells (also called TS cells) Inhibit T and B cells
– Act after initial immune response; prevent overstimulation
of the immune system; maintain immune system
homeostasis and tolerance to self-antigens preventing the
immune system from destroying normal, healthy tissue.
– The lack of cytokine stimulation produces inhibition
Cell-Mediated Immunity (T- cell): PROCESS
1. Activation occurs when TC or TH cell BINDS to a MHC1=TC or
MHCII=TH displaying a foreign antigen or infected cell epitope that
the T cell is programmed to recognize. The CD4 or CD8 coreceptors tighten the binding capacity of immune cell to antigen.
2. Co-Stimulation: T cells require two (2) signals to fully activate.
– First signal, antigen-specific, is provided through binding of the
T cell receptor with MHC molecules.
– Second signal, the co-stimulatory signal, is antigen nonspecific
and is provided by the interaction between co-stimulatory
molecules (cytokines, CD28 etc.) expressed on the membrane of
APC and the T cell. This insures the immune system does not
launch an attack against self. Once confirmation is achieved, cell
is activated and will attack any cell with the same MCH
designation as the stimulating cell.
3. Proliferation: TH cell releases interleukin-2 which stimulates
repeated T cell mitosis producing a large number of identical (clone)
T cells programmed against the same foreign substance epitope.
4. Differentiate identical cells then differentiate into 3 types of T cell
effectors: helper T cells, cytotoxic T cells, and memory T cells
Co-stimulator, Binding Enhancing CD Markers
• T cells respond to antigens of MHC-1 or MHC-11 based on a
special type of PROTEIN in the T cells’ own plasma membrane.”
These membrane glycoproteins are part of a group of proteins called
cluster of differentiation (CD) markers. All body cells have one or
more of them.
• CD Markers assist with the recognition and binding of an antigen to
the specific immune receptors found on T- cells.
• Important CD Markers: CD4 and CD8
1. CD8 Protein Markers
• Found on cytotoxic T cells and suppressor T cells
• Respond to antigens on Class I MHC proteins
2. CD4 Proteins Markers
• Expressed / Found on helper T cells
• Respond to antigens on Class II MHC proteins
3. One of the best CO-STIMULATORY molecules expressed by T
cells is CD28, which interacts with CD80 (B7-1) and CD86 (B7-2)
on the membrane of APC or in some cases infected body cells.
• Other co-stimulators are Interleukins 1 and 2
© 2012 Pearson Education, Inc.
Activation animation of T-cells
http://www.sbs.utexas.edu/psaxena/MicrobiologyAnimations/Animations/CellMediatedImmunity/micro_cell-mediated.swf
Action of Antigen Presenting Cells - MHCII
Response to foreign substance OUTSIDE the cell
1. APCs ingest antigens by phagocytosis.
2. Inside the APCs, the antigen is digested into shorter pieces.
3. APCs synthesize MHC-II molecules in the endoplasmic
reticulum.
4. The antigen pieces bind to MHC-II molecule; CD4 co-receptor
5. MHC-II-antigen complex is then inserted in the
plasma membrane of the APC.
6. The APC then migrates to
lymphatic tissue to present the
antigen to the T cells
7. Display of MHC-II with foreign
antigen activates other immune
cells such as B Lymphocytes,
macrophages, neutrophils, and
NK cells.
CD4 Proteins
Markers
CD4 is a co-receptor that assists the T cell receptor (TCR) on
the membrane of the T cell in communicating with an antigenpresenting cell. CD4 amplifies the signal generated by the
TCR. Also interacts directly with MHC class II molecules on the
surface of the antigen-presenting cell by increasing the binding
power of the T-helper cell.
Role of Helper T (TH) Cells
Coordinate non specific and specific immunity
1) APC cells present foreign
substance on cell membrane MCH-11
2) APC cells release chemical
messenger, cytokine interleukin I.
•IL-1 draws attention of helper T cells.
T cells have cytokine interleukin I
receptors and when successful binding
occurs between the T cells and cytokine
receptors the TH cells release
interleukin 2. (co-stimulator)
1. IL-2 alerts T-cytotoxic cells
which multiply (proliferate) and
terminate foreign cells.
2. IL-2 also stimulate the actions and
proliferation of B lymphocytes to
produce antibodies
3. Stimulates non-specific neutrophils, NK cells and
macrophages. Prevents macrophages from leaving the
area of infection.
Good Animation:
Overview
https://www.youtube.co
m/watch?v=Bf2t8n1ibwQ
Animation:
http://www.youtube.co
m/watch?v=1tBOmG0Q
MbA
Animation:
http://bcs.whfreeman.c
om/thelifewire/content/
chp18/1802003.html
CYTOTOXIC T CELLS Class I MHC Proteins
• activated when they are alerted to the presence of an antigen
when a fragment of the antigen is displayed on the MHC-1 of a
diseased cell
• Cytotoxic T cells ignore normal peptides
• Abnormal peptides or viral proteins activate T cells to destroy cell
http://bio1152.nicerweb.com/Locked/me
dia/ch43/43_09TcellsAndMHC_L.jpg
CD8 is a trans-membrane
glycoprotein that serves as a
CO-RECEPTOR for the T cell
receptor (TCR). Like the TCR,
CD8 binds to a major
histocompatibility complex
(MHC) molecule, but is specific
for the class I MHC protein
The CD8 on the T-cytotoxic cell
interacts with the Class I MHC
molecule. This affinity keeps
the T cell receptor of the
cytotoxic T cell and the target
cell bound closely together
during antigen-specific
activation
CD 8 Proteins
Markers
http://apbrwww5.apsu.edu/tho
mpsonj/Anatomy%20&%20Ph
ysiology/2020/2020%20Exam
%20Reviews/Exam%202/Agpresentation.fig.22.15.jpg
ACTIONS
 Migrate to site of infection
or tumor formation
 Recognize, attach & attack
1. secrete perforin and
granzymes that punch
holes in target celldegrades enzymes and
induces apoptosis
2. Interferons that inhibit
viral replication and
recruit macrophages
3. Secretes poisonous
lymphotoxin that disrupts
cellular metabolism
Animation: T-cell MHC1
http://bcs.whfreeman.com/thel
ifewire/content/chp18/1802003
.html
Cytotoxic T cells (Tc)
Animation actions of cytotoxic T cells
http://highered.mcgrawhill.com/sites/0072507470/student_view0/chapter2
2/animation__cytotoxic_tcell_activity_against_target_cells__quiz_2_.html
Cytotoxic T Cell Function
T cell
T cell
Cancer cell
Dying cancer cell
(a)
10 µm
(b)
• Cytotoxic T cell binding to cancer cell
21-70
Training of Lymphocytes:
Self Recognition and Self Tolerance
T- Lymphocyte training in the thymus before activation occurs
• Self-recognition: ability to recognize self (MHC) proteins
If T cell does not recognize MHC, then cell dies (apoptosis)
If cell does recognize MHC, positive selection- cell survives.
• Self-tolerance: “LACKS” reactivity to peptide fragments of self
proteins; can tolerate ‘self”
• T-cells that bind to self-peptides are eliminated= negative selection
• Clonal selection: the T-cell dies
• Anergy –cell is inactivated; survives but is unresponsive. Anergic
cells will not respond to any antigen in the future and are believed
to circulate
© 2012 Pearson
Education, Inc. throughout the body with no value until they undergo
Humoral or Antibody-mediated response
1) B cell exposed to antigen; binds to receptor; B cell prepares for
activation.
– Antigen engulfed by B cell, broken down into peptide fragments,
combines with MHCII, moves to the B cell surface.
– Helper T cells binds to MHCII complex and secrete cytokines
(interleukins 2) for co-stimulation necessary to finish B cells
activation; proliferation and differentiation are initiated
2) Macrophage binds to antigen; presents fragment on MHCII complex.
TH cells binds to complex; becomes activated to the antigen; TH
cells secretes cytokines (interleukins 2) for co-stimulation; Activated
TH cells then bind to B cells specific for that antigen which become
fully activated and begin proliferation and differentiation
• Activated B cells divide and differentiate to form two types of cells
through the process of sensitization
– a) effector cells (plasma cells): secrete antibodies into the
interstitial fluid that destroy the antigen
• Plasma cells synthesize and secrete antibody to employ
various methods (neutralization, agglutination, precipitation,
complement fixation) to render antigen harmless)
– b) memory cells: long lived cells containing receptors specific to
the antigen.
T CELLS and
B CELLS
bind to
specific
epitopes
they are
programmed
to recognize
****
Animation: http://highered.mcgrawhill.com/sites/0072507470/student_view
0/chapter22/animation__tcell_dependent_antigens__quiz_2_.html
http://faculty.ccbcmd.edu/~gkaiser/SoftChalk%20BIOL%20230/Adaptive%20Immunity/Bcells/Bcell_BCR.jpg
Animation:
http://www.you
tube.com/watc
h?v=hQmaPwP
0KRI
http://bio1151b.nicerweb.net/Locked/media/ch43/43_17HelperTCentralRole-L.jpg
Antibodies class of proteins called
Immunoglobulins (Igs ).
• Four polypeptide chains: two
heavy and two light. Each light
is held to a heavy by a disulfide
bond.
• Each chain has two regions; a
constant region (C) which is
the same within a class of
antibody and a variable region
(V) which varies from one
antibody to the other.
• V region from each chain has
the antigen binding site to
recognize and specifically
attach to a particular antigen.
• Sites for complement-bindingconstant area of heavy chain
Antibodies
Antibodies
 Based on chemistry and
structure, antibodies are
grouped into five principal
classes each with specific
biological roles (IgG, IgA,
IgM, IgD, and IgE).
Five Classes of Antibodies
Named for the structure of their C region
• IgA – plasma, mucus, saliva, tears, milk, and intestinal secretions;
attack pathogens before they gain access to internal tissues;
mother’s milk provides IgA antibodies to infant after birth; prevents
pathogen colonization
• IgD - B cell transmembrane antigen receptor to increase B cell
activation; also known to activate basophils and mast cells
• IgE - transmembrane protein on basophils and mast cells
– Binds to mast cells and stimulates release of histamine inflammation and allergy
• IgG - constitutes 80% of circulating antibodies
– resistance against many viruses, bacteria, and bacterial toxins;
crosses placenta to fetus, COMPLEMENT FIXATION; Anti-Rh
antibodies produced by Rh-negative mothers
• IgM – in plasma and lymph - first class of antibody secreted after an
antigen is encountered; eliminates pathogens before there is
sufficient IgG available; produces anti-A and anti-B antibodies
responsible for the agglutination of RBC; COMPLEMENT FIXATION.
1.Neutralization antibodies bind to
receptor site of antigen effectively
blocking it from adhering to target cell;
preventing attachment of viruses to body
Animation:
https://www.youtube.com/watch?v=lrYlZJiuf18
2.Immobilize bacteria by attacking
cilia/flagella
3.Agglutinate and precipitate antigens
cross-links antigens causing clumping
and precipitation. If bind enough
antigens together they are unable to
remain in solution. Insolubility diminishes
or stops antigen.
4.Complement activation (primary)
5.Enhancing phagocytosis through
precipitation, complement activation or
opsonization (coating with special
substance to neutralize charge
differentiations)
Actions of
Antibodies
https://strangerz1989.files.wordpress.com/2014/07/bad_boys_bad_boys__by_velica.jpg
Immunological Memory
Primary immune response
First exposure to antigen
response is steady, slow
resulting in proliferation of
lymphocytes to form clones
of plasma cells and memory
cells.
Secondary immune response
with second exposure to the
same antigen
Memory cells proliferate and
differentiate into plasma cells
Faster and stronger
than the primary
immune response.
Antibody (level) = TITER
• Hapten- partial antigen: small molecules that bind to “normal”
molecules such as proteins creating a unique complex
recognized as a foreign by immune system. Usually only
large molecules can illicit an immune response. So haptens
will go unnoticed by immune system until they bind to a larger
molecule. Ex: penicillin allergy, poison ivy toxins. Poison
ivy toxin reacts with skin proteins forming complex
Types of Immunity
Active immunity: body's immune system is stimulated to make
antibodies and other immune cells (killer cells).
• Active immunity can be NATURALLY or ARTIFICIALLY acquired.
– NATURALLY acquired ACTIVE immunity is seen when the
individual is EXPOSED to the antigen in a natural manner.
– Body responds to antigen; activates B and/or T cells, and memory
cells are made.
– ARTIFICIALLY acquired ACTIVE immunity weak or dead antigen
INJECTED into the individual.
– Body responds to antigen; activates B and/or T cells, and memory
cells are made. This immunity forms the basis for vaccination.
Passive immunity: prepared antibodies received from outside source
• immediate protection lasts for a short term
• Body's immune system is NOT involved in this immunity NO
MEMORY CELLS ARE PRODUCED.
– NATURALLY acquired PASSIVE immunity: Ex: IgG crosses the
placenta to go from the mother's blood to fetus blood; infant receives
IgA through the breast milk.
– ARTIFICIALLY acquired PASSIVE immunity: given shots of
PREPARED antibodies or serum to treat or prevent infections. Ex:
gamma globulins given to hospital patients / travelers for temporary
protection against hepatitis.
Antibiotics
• Antibiotics, also known as ANTIBACTERIALS, are types of
medications that destroy or slow down the growth of
BACTERIA. The Greek word anti means "against", and the
Greek word bios means "life" (bacteria are life forms). They are
NOT “ANTIBODIES”
• In order to be useful in treating human infections, antibiotics
must selectively target bacteria for eradication and not the cells
of its human host.
• Most bacteria produce a cell wall composed partly of a
macromolecule called peptidoglycan. Penicillin, one of the first
widely used antibiotics, prevents assembly of this
macromolecule. The result is a very fragile cell wall that
bursts, killing the bacterium. No harm comes to the human
host because penicillin does not inhibit any biochemical process
that goes on within us.
• A different antibiotic, tetracycline, inhibits bacterial growth by
stopping protein synthesis
Disorders
HIV is a form of retrovirus (produces DNA from RNA) with a protein coat
wrapped by an envelope of glycoproteins.
• Host cell for HIV are the HELPER T CELLS.
• New HIV DNA is produced in the helper T cell along with new protein
coats and then released. TH cells are destroyed.
• Progression to Acquired Immunodeficiency Syndrome (AIDS) due to
reduced numbers of helper T cells and resulting immunodeficiency.
• Treat with reverse transcriptase inhibitors
Autoimmune Diseases- Immune system initiates immune response
against body’s own cells
– Rheumatoid arthritis leads to damage and painful inflammation of the
cartilage and bone of joints.
– Lupus-results in inflammation and tissue damage; effects any part of
the body
– Insulin-dependent diabetes mellitus, pancreatic insulin-producing
beta cells are the targets of autoimmune cell-mediated responses.
– Multiple sclerosis (MS) is the most common chronic neurological
disease. Body attacks the myelin sheath surrounding the axon fiber of
the neuron.
Hypersensitivity Reactions: Allergies
• Allergens: antigens that induce an allergic reaction in some
people but are tolerated by most people.
– dust, mold, pollen, vaccines, bee and wasp venom, poison ivy
and other plants, foods such as nuts, milk, eggs, and shellfish,
drugs such as penicillin, tetracycline, and insulin
• Allergic (hypersensitive) people respond to allergens.
– EX: asthma - triggers intense airway inflammation
– Severe hypersensitivity can cause anaphylactic shock- the
significant drop in blood pressure leading to circulatory
collapse.
• Antihistamines
• Drugs that block histamine
released by mast cells
• Benadryl
Animation: http://highered.mcgrawhill.com/sites/0072507470/student_view0/ch
apter22/animation__ige_mediated__type_1
__hypersensitivity__quiz_1_.html
http://www.umm.edu/careguides/000006.htm