Transcript Lecture 12 - Immunology

Immunology
The Lymphatic System
Lymphatic System

Lymphatic System: Provides the body
with a defense mechanism against foreign
invaders.
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Most interstitial fluid surrounding the capillary
beds is reabsorbed into the capillaries - the
lymphatic ducts picks up the remaining
interstitial.
Pathogens are filtered out through the lymph
nodes.
Lymph nodes contain concentrations of
lymphocytes & macrophages to respond with
to the pathogens.
Lymphatic System
Lymph: The clear fluid in the lymphatic
vessels.
 Subclavian Veins return the lymph into
the heart.
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The Lymphatic System
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Major Functions of the Lymphatic System:
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Draining excess fluid from tissues to be
returned to the bloodstream.
Transporting lipids & vitamins reabsorbed in
the gastrointestinal tract to the bloodstream.
Activating the body’s immune response to
pathogens.
Lymphatic Anatomy
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Lymph: Clear fluid within the lymphatic vessels
that has been reabsorbed from the interstitial
fluid.
Lymphatic Vessels: The vessel system that
provides transportation for the lymph.
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Lymphatic Capillaries: The start of the lymphatic
system – endothelial cells that are closed at one end &
have flaps that work as valves.
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These allow fluid & large proteins & foreign bodies to enter.
Lacteals: Lymphatic capillaries in the small intestine that
specialize in transporting lipids.
Lymphatic Vessels: Structured in the same 3 layers as
the blood vessels, but with thinner walls & more valves.
Lymph Nodes: Bean-shaped structures positioned at
regular intervals along the lymphatic vessel routes.
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Approximately 600 total in the lymphatic system.
Lymphatic Path
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Lymphatic
capillaries 
collecting
lymphatic vessels
 lymph nodes 
more collecting
vessels  six
lymphatic trunks 
two final collecting
ducts  subclavian
veins.
Lymphatic Trunks
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Lymph Trunks: Larger lymphatic vessels
that occur when vessels merge/unite. 5
major trunks!
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Lumbar Trunk
Intestinal Trunk
Broncho-Mediastinal Trunk
Subclavian Trunk
Jugular Trunk
Lymphatic
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Lymphatic Ducts: Trunks drain into one
of two main ducts..
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Thoracic Duct aka Left Lymphatic Duct:
Drains all parts of the body below the
diaphragm and on the left side of the body
(left arm, left side of head, etc) & empties into
the left subclavian vein.
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Cisterna Chyli: The prominent sac in the abdominal
cavity that begins the thoracic duct.
Right Thoracic Duct: Drains the right upper
extremity, the right part of the head & neck,
and the right area of the thoracic region &
empties into the right subclavian vein.
Lymphatic Nodes
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Lymph Nodes: Bean-shaped structures
positioned at regular intervals along the
lymphatic vessel routes. Designed to filter
the lymph fluid.
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The most prolific & important organ in the
lymphatic system.
Embedded in the connective tissue throughout
the body.
Most concentrated in the cervical, axillary,
abdominal, pelvic & thoracic regions.
Lymphatic Nodes
Capsule: Layers of connective tissue that
cover the lymph node.
 Trabeculae: Extensions that divide the
node into compartments & provide
support & a network for blood vessels to
travel along.
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Lymphatic Nodes
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Cortex: Outer layer of the lymph node.
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The outer area is responsible for collecting the
B-lymphocytes or B-cells.
The inner area is responsible for collecting Tcells.
Medulla: The inner part of the lymph
node that holds a concentration of
macrophages, in addition to B cells &
plasma cells.
Lymphatic Nodes
Afferent Lymphatic Vessels: Structure
that lymph enters the node through and
directs the lymph inward toward the
sinuses.
 Sinuses: The portion of the lymph node
where most of the filtering takes place.
 Efferent Lymphatic Vessels: Structures
that leave the node at the hilum.
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Hilum: A small depression where the efferent
lymphatic vessels leave the lymph node.
Lymphatic Nodes
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Lymphatic Nodules: Masses of lymphatic
tissue that lack the capsule.
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Found in mucous membranes of the
gastrointestinal, urinary, & reproductive tracts.
Found in the respiratory airways.
Tonsils: The lymphatic nodules located at the
entrance to the pharynx that are placed to deal
with ingested & inhaled foreign particles &
pathogens. Palatine, lingual, & pharyngeal
tonsils located in that area.
Thymus
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Thymus: A two lobed lymph organ
located between the lungs in front of the
aorta.
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Most often active in childhood & has both a
lymphatic & endocrine function.
Secretes hormones critical for maturation of
the T-cells.
Lobules: The divisions of the thymus,
each made up of a cortex & medulla.
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Cortex: The outer layer of the lobules that has
a high T-cell concentration, some dendritic
cells, & a few epithelial cells.
Meduulla: The inner layer that contains
epithelial cells, T-cells, dendritic cells, and
macrophages.
Spleen
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Spleen: The largest mass of lymphatic
tissue in the body, located in the
hypochondriac region of the abdomen.
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Composed of a capsule & extending trabiculae.
Two kinds of tissue in the spleen:
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White Pulp: Composed mostly of lymphocytes
& macrophages.
Red Pulp: Composed of blood-filled sinuses &
Billroth’s cords or splenic cords (cords of
splenic tissue).
Spleen
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Primary functions of the Spleen:
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Reservoir for blood
Place for destroying old red blood cells
Filter for the blood
Creation of blood cells during fetal
development
Ruptured Spleen: A common physical
injury that typically results in hemorrhage
& can put the patient at risk for sepsis
(blood infection).
Immune Response
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Immune Responses: The defensive
actions our body takes to respond to
foreign invaders.
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Nonspecific or Innate Defenses: Defenses
that are innate & not geared toward specific
pathogens. A generic response!
Immunity: The defense system where
lymphocytes target & destroy specific
pathogens. A learned response!
Immune Response
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First Line of Defense: The first steps our
body takes to defend against foreign
invaders.
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Epidermis: Keratinized cells form many layers
that very few pathogens can infiltrate.
Mucous Membranes: Epithelial layers lining
body cavities secrete mucus to trap microbes
& contains protective chemicals.
Immune Response
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Mucous membranes in the nose have hairs that
filter microbes from the air.
Mucous membranes of the upper respiratory
tract contain cilia to trap microbes & propel
them back up the airway & out of the body.
Lacrimal apparatus of the eye contains
lysozyme which clears the eyes of pollutants &
microbes.
Saliva can wash microbes from the teeth &
mouth.
Immune Response
Sebum created by the sebaceous glands
of the skin prevent the growth of some
bacteria.
 Stomach acid, lysozome enzymes in
perspiration, and avid in the vagina deter
pathogens.
 Hyaluronic acid, found in connective
tissue, inhibits the spred of pathogens in
that tissue.
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Immune Response
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Second Line of Defense: The body’s
internal defenses that take over if a
pathogen gets through the first line of
defense.
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Leukocytes
Macrophages
Antimicrobial Proteins
Immune Response
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Leukocytes: 5 major categories.
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Neutrophils: Phagocytic cells that wander
throughout the connective tissue destroying
bacterias.
Eosinophils: Phagocytic cells that destroy
allergens, antigen & anti-body complexes, &
some inflammatory chemicals.
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Surround larger parasites & attack them with
enzymes to weaken or destroy them.
Defend against allergies & parasitic worm infections.
Basophils: Helper cells that secrete
vasodilators & anticoagulants in order to speed
other leukocytes to the infected zone.
Immune Response
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Lymphocytes: A variety of cells active in the
immune response.
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Natural Killer Cells (NK Cells): Attack any cell with
an unusual plasma membrane, such as cells that are
infected by a virus or have become cancerous.
 Cytolysis: Perforin protein is injected into the cell
to cause it to “explode”.
 Granzymes: Cause the cell to self-destruct.
 Found in the spleen, red bone marrow, & lymph
nodes.
Monocytes: Wandering cells that eventually
turn into macrophages.
Immune Response
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Phagocytosis: The process of an immune
response cell “eating” a foreign invader. 5
steps:
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Chemotaxis: Phagocytic cells are attracted to
the site of damage via a chemical response.
Adherence: Occurs when the phagocytic cells
attach to the microbe.
Ingestion: Extends the pseudopods to engulf
the microbe.
Digestion: The microbe is dissolved through
toxic chemicals (including hydrogen peroxide!)
in an oxidative burst.
Killing: The microbe is destroyed & the
phagocytic cell typically dies as well.
Apoptosis: The normal death of a cell.
Immune Response
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Macrophages: Two categories of cells
that “eat: foreign invaders or damaged
cells.
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Fixed Macrophages: Non-motile cells that
are found in a particular tissue where they
permanently stand guard.
Wandering Macrophages: Motile cells that
roam through the body looking for foreign
invaders.
Include histiocytes in connective tissue,
reticular cells in the liver, microglia in the
nervous system, and the alveolar microphages
in the lungs.
Immune Response
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Antimicrobial Proteins: Found in the blood and
intestinal fluid to prevent infection. 3 types
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Interferons (IFNs): Polypeptides secreted by cells that
have been invaded by a virus.
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Travel to adjacent cells & stimulate the production of antiviral proteins.
Activate natural killer cells & macrophages & aid in the
destruction of cancerous cells.
Transferrins: Can bind to & reduce the amount of iron
available in bacteria, which can inhibit the spread of
certain bacteria.
Complement System: Group of twenty plus beta
gobulins (proteins in the blood plasma) that enhance the
immune, allergic, & inflammatory reactions.
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Optimization: Where the complement system chemically
coats the surface of bacteria which in tern makes them
Inflammation
Inflammation: One of the body’s most
common responses to tissue damage.
Occurs in roughly the same way in any
tissue.
 Four Cardinal signs of Inflammation:
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Redness
Swelling
Heat
Pain
Inflammation
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3 Stages of Inflammation:
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Vasodilation of Blood Vessels: Increases
blood flow & increases the permeability of
capillaries.
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Emigration (Movement) of Phagocytes:
Phagocytes move to effected areas to remove
dead cells & toxins.
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Prompted by histamines & kinins.
Capillary dilation is the cause of redness.
Basophils secrete leukotrienes to increase this
reaction.
Leukocytosis: The sudden increase of white blood
cells migrating to the area.
Repair of Damaged Tissues: The tissues
repaire itself.
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Platelet Derived Growth Factor (PDGF): Prompts
fibroblasts to multiply faster & speed up tissue repair.
Fever
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Fever: An increase in body temperature
often due to the interaction of bacteria &
macrophages.
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Interleukin-1: Released by macrophages,
which triggers prostaglandin E to be secreted
by the hypothalamus, which increases the
body’s internal thermostat.
Positive Effects: Promotes interferon
activity, speeds up metabolism & other
processes that aid in repair, slows down
the growth of some bacteria & viruses.
 Negative Effects: Cellular dysfunction &
brain damage possible if the fever gets too
high.
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Immune System
Immune System: A combination of cells
designed to recognize specific foreign
substances & neutralize or destroy them.
 Specific Immune Defenses: The cells
are specifically geared toward fighting
certain invaders, and remembers previous
foreign invaders so that they can be
rapidly eliminated in the future.
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Immune System
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Two Divisions of the Immune System:
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Humoral Immunity aka AntibodyMediated Immunity: Involves antibodies
which bind to foreign substances like toxins &
bacteria to “tag” or mark them for destruction.
Driven by T cells & B cells.
Cellular Immunity: Cell-mediated immunity
which includes the actions of lymphocytes that
attack foreign cells or cells infected with
cancer, viruses, or parasites. Driven by T cells.
Antigens
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Antigen (Ag): Any substance recognized
as foreign to the body & triggering an
immune response.
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Typically large molecules, often proteins.
Two defining characteristics:
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Immunogenicity: Stimulate the immune
system to produce specific antibodies.
Reactivity: An antigen will react with the
appropriate antibody once it is produced.
Antigens
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Epitope: The part of a molecule that
initiates an immune response.
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The antigen could be an entire microbe.
Typically it is just a portion of the microbe or a
specific chemical or toxin component.
Antigens can include blood cells of a different
type, pollen, egg whites, etc.
Antigens
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Haptens: Smaller substances that can
cause reactivity, but not full
immunogenicity.
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Stimulate an immune response only if attached
to a larger carrier molecule.
Example: Toxin in poison ivy, which only
triggers a response when bound to particular
proteins in the body.
Antigen Processing
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Antigen Processing: The means by
which the body recognizes that a foreign
antigen is present.
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Differs depending on whether the antigen is
inside or outside the body cell, which
determines if the body engages in cellular or
humoral immunity responses.
Antigen Processing
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Major Histocompatability Complex
(MHC): “Self-antigens” that are unique to
all of your body cells except red blood
cells.
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Help T-cells recognize which cells are foreign.
MHC-1s: Cells that posses MHC and are
labeled “you” by the T-cells.
Antigen Processing
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Two types of antigens:
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Exogenous Antigens: Those found outside of
the body cells that include bacteria, parasitic
worms, pollens & viruses that have not yet
infected body cells.
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Antigen-Presenting Cells (APCs): Macrophages &
B-cells that phagocytize the antigen, then display the
resulting peptide fragments on the plasma
membrane to trigger T-cells (called MCH-2’s).
Endogenous Antigens: Those found inside
the body cells and are either viral proteins
produced by a virus-infected cell or a
cancerous cell.
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Most cells with endogenous antigens process them &
display them on their cell membranes to signal the
immune system for help.
Cellular Immunity
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Cellular Immunity: Lymphocytes directly
attack & destroy foreign cells & infected
host cells.
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Begins with activation of T-Cells or Tlymphocytes by a specific antigen.
Millions of T-cells, each with its own T-cell
receptor to recognize a specific antigen.
Roughly 75% of the lymphocytes in the body.
Cellular Immunity
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Types of T-Cells involved in Cell-mediated
Response:
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Cytotoxic T-Cells: Responsible for actual
attacking of the foreign body or infected cell.
Helper T-Cells: Stimulate other helper T-cells,
cytotoxic T-cells, and B cells.
Suppressor T-Cells: Help regulate the attack
& prevent tissue destruction.
Memory T-Cells: Remain as an immune
response and stimulate faster responses if the
same antigen invades again.
Cellular Immunity
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Three stages of the Cell Mediated
Response:
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Recognition
Attack
Memory
Cellular Immunity
– Recognition
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Recognition: Helper and cytotoxic T-cells
patrol the body, examining the MHC of
other cells.
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T-cell receptors recognize & bind to the antigen – the
first signal.
Costimulation: The need for a second signal of
cytokines (Interleukin-2) provided by the helper Tcells.
Cloning: Activated T-Cell then proliferates &
differentiates to create a population of clones.
Cellular Immunity
– Attack
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Attack: Helper t-cells secrete
lymphokines to prompt inflammation &
attract neutrophils.
Cellular Immunity
– Attack
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Cytotoxic T-cells actually attach to the foreign
or diseased cell to destroy it.
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Apoptosis: Cytotoxic t-cells bind to the target cell & digest
it – granzymes digest the protein of the cell & cause it to
break apart. Released microbes are then phagocytized.
Cytolysis: Cytotoxic T-cells bind to the infected cell,
release perforin to create holes in the plasma membrane,
which causes the cell to burst. Granulysis released by the
t-cells destroy the microbes.
Lymphotoxin: Toxic molecules released by the T-cells
which cause the DNA of target cells to fragment,
destroying the cell.
Suppressor T-cells release lymphokines to inhibit T & B
cell activity & prevent damage to healthy tissue.
Cellular Immunity
– Memory
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Memory: After the first exposure &
resulting response, some T-cells become
memory cells and “memorize” the foreign
invader.
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T-Cell Recall Response: The second
exposure to the same antigen triggers a faster
& more effective response thanks to the
memory T-cells.
Humoral Immunity
Humoral Immunity aka AntibodyMediated Immunity: Depends on B cells
(B-lymphocytes) to produce antibodies
(Ab) to engage in a complex purging
process.
 Immunoglobulins (Igs): Antibodies
made up of glycoproteins called globulins.
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Two heavy (H) chains & two light (L) chains of
polypeptides.
Antigen-Binding Site: Tips of each chain are
called variable (V) regions & are areas where
the antibody attaches to the antigen.
Humoral Immunity
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5 classes of antibodies:
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IgG: Protect against viruses & bacteria - 80% of
antibodies. The only class that can cross the placenta to
react the fetus & provide immunity.
IgA (Secretory antibody): Found in sweat, saliva,
mucous, tears, breast milk, & the GI secretions to
provide local protection against viruses & bacteria –
15% of antibodies.
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Known to decrease in times of stress, which lowers the
body’s resistance.
IgM: Found in the blood & lymph 0 cause agglutination
& lysis of microbes, serves as an antigen receptor on the
surface of B cells – 5% of antibodies.
IgD: Acts as an antigen receptor for and activates B
cells – 0.2% of antibodies.
IgE: Protects against allergies & parasitic worms,
located on most cells & basophils – less than 1% of
antibodies.
Humoral Immunity
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Complement System: Plasma proteins
produced by the liver that help destroy microbes
through cytolysis – activated by the antigenantibody complexes. Effects:
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Activation of Inflammation: Some Complement
proteins activate blood flow & histamines, some combat
infection & allergies, some chemotactic agents to attract
phagocytes.
Opsonization: Makes microbes more susceptible to
phagocytosis by C3b binding to the surface of the
microbe & then reacting with receptors on the
phagocytes.
Cytolysis: Complement proteins combine to form
membrane attack complex (MAC) that forms large holes
in the microbe’s plasma membrane, resulting in the
microbe to uptake fluid too fast and lysing (bursting).
Humoral Immunity
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Humoral Immunity Follows 3 General
Steps:
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Recognition
Attack
Memory
Humoral Immunity
– Recognition
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Recognition: B-cells bind to antigen &
engage in endocytosis of the antigen Bcell receptor complex.
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Antigen is digested & broken into gragments.
Fragments are displayed on the B-cell membrane,
which causes t-cell activation.
Helper factors cause B-cells to begin dividing &
differentiating, creating plasma cell clones, which
produce & release antibodies.
Humoral Immunity
– Attack
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Attack: Antibodies neutralize antigens,
immobilize bacteria, activate complement,
enhance phagocytosis of other cells, and
causes agglutination & precipitation of
antigens.
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Causes antigens to cluster together and allows them
to be phagocytized easier.
Humoral Immunity
– Memory
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Memory: After the primary immunity
response several cloned cells become
memory cells that remain for future
attacks.
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Anamnestic Response: A secondary
response within the humoral immunity to a
second invasion of the same invader. Typically
much faster, more powerful, & more effective.
Humoral Immunity
– Memory
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Antigen Titer: Measure of memory based on
the amount of antigen serum present.
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Primary Response: Antigen titer should be zero for the
first several days, but will slowly rise through IgM first then
IgG followed by a gradual decline as the pathogen dies off.
Secondary Response: Antigen titer consists of mainly
IgG antibodies during the primary response, and is more
intense.
Types of Immunity
Active Immunity: You encountered the
pathogen yourself and developed your
own antibodies to it.
 Passive Immunity: You received
antibodies directly introduced into the
body.
 Naturally Acquired: Antibodies are
received through natural means.
 Artificially Aquired: Antibodies are
received through artificial (scientific)
methods.
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Types of Immunity
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Naturally Acquired Passive Immunity: IgG
antibodies are transferred from mother to fetus
through the placenta or through breast feeding.
Naturally Acquired Active Immunity: The
pathogen is encountered, T-cells and B-cells
recognize the antigen, and antibodies are formed
through cell-mediated immunity.
Artificially Acquired Passive Immunity:
Antibodies are acquired through direct injection
into the system.
Artificially Acquired Active Immunity:
Antigens are introduced through vaccines that
stimulate the immune system to create memory
cells.
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Vaccines are immunogenic, not pathogenic – unless it is
a partially-killed (still alive!) virus, you cannot get sick
from the vaccine itself!
Immune System Disorders
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Hypersensitivity: When the immune
system reacts to a substance that is
normally not reacted to.
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Allergens: The substance being reacted to.
Immune System Disorders
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4 Types of Hypersensitivity:
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Type 1: Acute or Anaphylactic Reactions:
The most common reaction – caused by mast
cells and basophiles reacting to allergens.
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Common Symptoms: Inflammation, edema, mucus
production, congestion, cramps, vometing, diarrhea.
Can cause… airway constrictions, weakened
contractions of the heart muscles.
Treatment: Epinephrine injections, Benadryl,
respiratory support.
Common Causes: Bee stings, latex, antibiotics,
certain chemicals, etc.
Immune System Disorders
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Type 2: Cytotoxic Reactions: caused by
antibodies attacking a person’s own blood or
tissue cells.
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Symptoms: Destruction of the cells via cytolysis.
Common cause: Incompatible blood transfusions.
Immune System Disorders
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Type 3: Immunne-Complex Reactions:
Caused when immune complexes avoid
phagocytosis & become trapped in the
endothelium of blood vessels.
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Symptoms: Inglammation.
Common Example: Rheumatoid Arthritis
Immune System Disorders
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Type 4: Delayed Hypersensitive Reaction:
Occur when the antigen presenting cells travel
from lymph node to lymph node & display the
allergen to helper T cells, which then migrate
to the site of allergen entry to cause
inflammation.
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Symptoms: Inflammation & rashes
Common Cause: Poison ivy, poison oak,
Tuberculosis titer test.
Immune System Disorders
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Autoimmune Disease: Marked by failure
of the immune system to properly
distinguish the body’s own cells from
foreign antigens.
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Results: Immune system produces antibodies
that attack antigens & the body’s own tissues.
5% of adults in the US have autoimmune
disease.
Immune System Disorders
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T-cells: Must have TWO traits to function
properly….
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Self-Recognition: The ability to recognize the
body’s own major histocompatability complex
(MHC) proteins – you must recognize your own
cells!
Self-Tollerance: Lack of reactivity to peptide
fragments from your own proteins – don’t
attack your own cells!
Immune System Disorders
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Severe Combined Immunodeficiency
Disease (SCID): Congenital disorder
where B & T cells are deficient.
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Leaves children highly susceptible to infections
so they must live in protective enclosures.
Can be cured via red bone marrow cells with
very similar MCH antigens.
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Can provide normal stem cells to give rise to normal
B & T cells.
Can also be treated with gene therapy of
good copies of the defective cells with
treatments every few months for life.
Fortunately VERY rare!
Immune System Disorders
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Acquired Immune Deficiency Syndrome
(AIDS): Immunodificiency disease caused by the
Human Immunodeficiency Virus (HIV).
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HIV is a retrovirus that carries genetic information on
its RNA instead of DN.
Infects cells, replicates via RNA, & causes the infected
cell to reproduce viral cells through cell division.
Primarily targets helper T-cells.
Transmitted through exchange of blood & some bodily
fluids.
HIV & AIDS are typically the cause of immune
compromization that leads to death from
opportunistic infections.
HIV has reached epidemic proportions & has
claimed over 20,000,000 lives so far.