Transcript Slide 1

Saladin Ch. 21
Lymphatic & Immune Systems
Lymphatic System General
• Lymphatic System - composed of lymph, lymphatic
vessels, and lymphatic tissue
• Functions of Lymphatic system functions
– Draining of interstitial fluid
– Transporting dietary lipids/lipid soluble vitamins
from GI to blood.
– Facilitating the Immune Response - by B and T
lymphocytes.
Lymph & Lymphatic Vessels
Lymph
– Usually clear, colorless, derived from blood
plasma but with less protein
– Lacteals - specialized capillaries along the small
intestine - pick up lipids - gives fluid white,
opaque look = chyle
– Contains large numbers of lymphocytes, etc.
Lymph & Lymphatic Vessels
Lymphatic capillaries
– Closed ends; One way flow - wall cells overlap;
fluid pushes in & can separate the cells.
– Anchoring filaments - hold capillaries in place &
help open gaps when interstitial fluid builds up.
– Location - not in cartilage, epidermis, CNS, parts
of spleen or red marrow.
Lymph & Lymphatic Vessels
Lymph trunk and ducts
• In embryo form from buds from veins - similar
structure.
• Flow - capillaries into vessels into nodes. After
passing through a string of nodes - goes into
"trunks“
Lymph & Lymphatic Vessels
– [Trunks: Lumbar, intestinal, subclavian
bronchomediastinal, & juglar]
– From trunks, lymph flows into either the thoracic
duct or the right lymphatic duct
– From the ducts, flow is into venous blood
Lymph & Lymphatic Vessels
• Right lymphatic duct
– Drains from upper R side
– Drains into R. subclavian vein
– Trunk feeders - R juglar from R head and neck, R
subclavian from R upper limb, R
bronchmediastinal from R thorax.
Lymph & Lymphatic Vessels
• Thoracic Duct - begins as cisterna chyli anterior to L2 vertebra
– Receives from left of head & neck, chest, left
upper limb, & all of the body below the ribs.
– Drains into the left subclavian vein
– Feeder trunks - lower body -R & L lumbar,
intestinal
Lymph & Lymphatic Vessels
– Lumbars drain from lower limbs, pelvis, kidneys,
adrenals & abdominal wall.
– Intestinal drains from intestines, pancreas, spleen
& liver
– From the neck, the thoracic duct gets lymph from
the l. juglar, l. subclavian, l. bronchomediastinal
trunks
Lymphatic Cells
• Lymphocytes - stem cells divide to produce B
& T cells
– Produced in red marrow
– B cells may become plasma cells that produce
antibody
– Pluripotent cells in red marrow  pre-T cells 
thymus to mature.
Lymphatic Cells
– Macrophages [Phago. & APC's]
– Dendritic Cells [activate T cells - APC's]
– Reticular cells – fibroblasts that produce reticular
fibers for tissue “stroma”
Lymphatic Tissue
• Aggregations of lymphocytes in connective
tissues of mucus membranes
• MALT, Galt, nodules, Peyer's patches
Malt – Peyer’s Patches
Lymphoid Organs
• Include marrow, thymus, lymph nodes, spleen,
tonsils
• Red Bone Marrow --> lymphocytes [review
blood chapter]
Lymphoid Organs
• Thymus Gland
– Functions in T cell maturation – Reticular
epithelial cells produce thymic hormones that aid
in maturation of T cells
– Below sternum - large in infants, shrinks with age
from puberty on.
– 2 lobes – have capsule with trabeculae
Lymphoid Organs
– Lobules - 2 regions - cortex and medulla
• Cortex - deep staining - lymphocytes & reticular
epithelial cells
• Medulla - paler - mostly reticular epithelium fewer lymphocytes -Has thymic corpuscles
[Hassall's] - concentric whorls of flattened
reticular epithelium
Thymus
Lymphoid Organs
• Lymph Nodes - about 600 bean-shaped organs
– Concentrated in axillae, groin & near mammaries.
– Function:
• Trap material on reticular fibers,
• Clear out foreign & damaged materials through
phagocytosis,
• Immune processes
Lymphoid Organs
• Structure - stroma & parenchyma
– Stroma - capsule - dense connective tissue
covering - has trabeculae.Supports & holds
vessels. Also has network of reticular fibers &
fibroblasts.
Lymphoid Organs
– Parenchyma - 2 regions - cortex and medulla
• Cortex - outer and inner
–Outer - lymphatic nodules of B cells.
Germinal centers - where B cells proliferate
into plasma cells. Dendritic cells - APC's initiate immune response. Also have
macrophages.
–Inner - T-cells
Lymph Node
Lymphoid Organs
• Medulla – B & T cells, plasma cells tightly
packed in "medullary cords“
– Lymph nodes have unidirectional flow - enters
through afferent vessels  sinuses  efferent
lymphatic vessels. [Hilus - place where efferent
vessels emerge.]
– Lymph flows through a series of nodes --> quite
clean at the end.
Lymphoid Organs
• Metastasis - spread of cancer.
– Sites for metastasis are predictable based on
lymphatic flow patterns.
– Conversely, when a secondary tumor is found, the
primary can usually be located by going in reverse
back the flow paths.
Lymphoid Organs
• Tonsils
– Pharyngeal = adenoid, palatine =at base of
palatine bones, lingual = base of tongue, tubal =
around auditory tube openings
– No capsule – “crypts” that trap bacteria &
particulate material
Tonsils
Lymphoid Organs
• Spleen - largest lymphatic structure - between
stomach & diaphragm.
– Function:
• Immunologic – precipitate, kill antigens
• Clean up old rbc’s,
• Store platelets,
• Stabilize blood volume
Lymphoid Organs
• Parenchyma
– White pulp - Lymphocytes & macrophages
– Red pulp – venous sinuses filled with blood &
Billroth’s [splenic] cords [rbc’s, macrophages,
lymphocytes, B cells, granulocytes pressed
together]
Lymphoid Organs
• Stroma
– Capsule with trabeculae covered, with serous
visceral peritoneum.
– Interior reticular tissue.
Non-specific Disease Resistance
• Non-specific Resistance to Disease –> immediate
protection against a wide variety of pathogens &
foreign substances
– NO memory – always the same
– Pathogen = a disease-causing agent
Non-specific Disease Resistance
– Lines of Defense:
1 - external barriers - non-specific
2 - non-specific internal responses
3 - immune system - specific
Non-specific Disease Resistance
• External Barriers Skin & Mucous Membranes
– Mechanical factors – physical barriers – intact
skin, tight junctions
– Mucous membranes – physical barriers also –
mucous catches dirt, etc.; hairs filter out material,
cilia sweeps out invaders
Non-specific Disease Resistance
• Chemical Factors:
– Defensins
– pH of skin [3-5] antimicrobial
– Sweat – flushes, contains lactic acid = acid mantle
Non-specific Disease Resistance
– Tears – dilute agents. Also some lysozyme antibiotic properties
– Saliva – same Urine / vaginal secretions
– Dermal hyaluronic acid - viscous - hard to traverse
Some organisms have hyaluronidase to dissolve it.
Non-specific Disease Resistance
• Internal Defenses - Leukocytes & Macrophages
Phagocytes – eat foreign matter
– Neutrophils – in most body tissues. In addition to
phagocytosis, use respiratory burst - series of
reactions/agents that create H2O2, HClO &
superoxide ions that destroy bacteria
Non-specific Disease Resistance
– Eosinophils – can attack parasitic worms, promote
basophil action, reduce inflammatory response
– Basophils - secrete histamine - vasodilator and
Heparin - anticoagulant [both also released by
mast cells].
Non-specific Disease Resistance
– Lymphocytes - 3 classes [specific and non] 80% T,
15% B, 5% NK
– Monocytes
– Special "macrophages" - dendritic cells, microglia,
alveolar, hepatic
Non-specific Disease Resistance
• Internal Defenses - Antimicrobial Proteins
– Interferons – produced by virally infected
lymphocytes, macrophages, & fibroblasts
• Attach to uninfected cells & induce synthesis of
proteins that interfere with viral replication
• Protects these cells from infection
• Also activate NK cells
Non-specific Disease Resistance
– Complement – a group of 30+ proteins that are
synthesized by the liver & in the blood normally
inactivated
• When activated – enhance all parts of the
immune response as well as allergic responses
• Activated 3 ways - complement fixation [Ab],
alternative path [ spontaneous - no Ab], Lectin
path - attach to sugars on microbes
Non-specific Disease Resistance
– 4 methods.
• Inflammation - C3a stimulates mast and
basophils to release histamine and initiate the
IR, activates & attracts neutrophils
• Immune Clearance - C3b - binds Ab-Ag
complexes to rbc's - collected by macrophages
in liver & spleen
Non-specific Disease Resistance
• Phagocytosis - opsonization by C3b
• Cytolysis - C3b initiated.--> cascade -->makes a
hole in membrane of target cell
Non-specific Disease Resistance
• Immune Surveillance
– NK cells patrol for foreign
agents and diseased host
cells - destroy them
– Use perforins +
granzymes
Non-specific Disease Resistance
• Inflammation – tumor, rubror, calor and pain
– 3 stages – mobilization = vasodilation and
increased permeability, emigration, containments
& destruction, tissue repair [see table 21.1 for
cells and chemicals]
Non-specific Disease Resistance
• Sequence of inflammation events
– Vasodilation
• Causes – normal or damaged cells release
histamine & other vasoactive chemicals -->
• Dilation & increased permeability --> redness,
heat & swelling
Non-specific Disease Resistance
– Emigration - Neutrophils, then macrophages come
into clean up - Attracted by cytokines
• Margination – neutrophils in vessels adhere to
walls of vessel near injury due to selectins
• Diapedesis – neutrophils leave vessels
Non-specific Disease Resistance
• Chemotaxis – neutrophils outside vessels
attracted to site of injury
• Pain is produced from damaged sensors or
irritation by toxic substances & bradykinin.
Prostaglandins also increase pain
Non-specific Disease Resistance
– Containment
• Blood clotting factors reach site and form clot –
walls off injured area
• Anticoagulants prevent clot at immediate entry
area - enhances clearance by leukocytes
• Chemotaxis brings neutrophils, then and other
macrophages --> rapid increase in neutrophils
Non-specific Disease Resistance
– Tissue Cleanup & Repair
• Monocytes do phagocytosis & are Agpresenting cells
• Pus forms [dead material] – Ulcer – open edge,
abscess – all enclosed
• Platelet-derived growth factor stimulates
fibroblasts --> collagen --> scaffold for new cells
Non-specific Disease Resistance
• Fever – increase in body temperature produced by
the hypothalamus
– In response to pyrogens secreted by leukocytes
and macrophages
– Accompanies infection and inflammation
– Promotes interferon production, inhibits bacterial
growth, speeds up metabolism --> faster repair
Non-specific Disease Resistance
– Reye Syndrome
• Children less than 15yo - with acute viral
infection - brain swelling, etc.
• Can be triggered by use of aspirin.
Specific Immunity
• General Aspects of Specific Immunity
– Immunity is systemic – body-wide
– Immunity is specific - ability of the body to
defend itself against specific invading agents such
as bacteria, toxins, viruses & alien tissues.
Specific Immunity
– Requires initial exposure before can develop
"memory" of the agent remains after infection-->
continued defense.
– Antigens [Ag] are substances that provoke such an
immune response [usually “foreign”]
Specific Immunity
• Forms of Immunity
– 2 classes of response:
• Cell-mediated – cells [lymphocytes] attack
other cells.
–Intracellular agents
• Humoral Response – antibody-mediated. Ab
usually in body fluids. Extracellular agents &
molecular pathogens
Specific Immunity
– Active versus Passive Immunity
• Active – make our own Ab/T cells
–Natural – infection/exposure to fully active
Ag  B and T cell memory
–Artificial – vaccination [mostly B cell
responses – not T]
Specific Immunity
• Passive – get Ab from elsewhere
–Natural – maternal – placenta & milk
–Artificial – pooled gamma globulin
Specific Immunity
Ag’s - trigger immune responses
• Immunogenicity – ability to provoke either a T or B
cell response
• Reactivity – ability of Ag to react with Ab or cells
provoked
• If an Ag does both it is “complete Ag”
Specific Immunity
• Ag’s include whole or parts of microbes, bacterial
toxins, pollen, egg white, blood cells, tissues
• Large molecules made of small repeating units
usually evoke no response
• Hapten – a substance that cannot evoke a response
by itself, but can if bound to something else [e.g., a
cell receptor].
Specific Immunity
• Antigenic Determinants = epitopes – specific regions
of Ag molecules that trigger a response
– Many / Ag – thus for a given invader – get a
variety of Ab’s per Ag
Specific Immunity
Lymphocytes - Cells of the Immune System
• Develop from pluripotent red marrow cells
• 3 populations of lymphocytes – NK, B’s and T’s
• T’s cells leave marrow and go to the thymus for final
processing by thymic hormones
Specific Immunity
– Becoming immunocompetent means being able to
recognize a foreign antigen & not responding to
self-antigens.Tested for self-recognition
• 1) must be able to bind MHC molecules
bearing Ag presented for recognition, &
• 2) must NOT react with “self” Ag. If they do,
they are eliminated. Those that pass --> clones
Specific Immunity
• B’s mature into “immunocompetent” cells in the
marrow throughout life  humoral responses
[Develop receptors for 1 AG – receptors are AB’s.]
– B cells that recognize self-antigens are either
inactivated in the marrow, or killed
• Each individual B or T cell is genetically programmed
to recognize only one antigenic determinant
Specific Immunity
Antigen-Presenting Cells - Pathway of Ag processing
for response
• T cells usually need help recognizing Ag, they require
APC's - B cells, or macrophages, or reticular cells, or
dendritic cells.
Specific Immunity
• Self-Ag’s - Major Histocompatibility Complex = MHC
– On membrane surfaces – glycoproteins
– Also called HLA Ag’s – first found on wbc’s
– Unique - usually recognize them before birth &
don't attack
Specific Immunity
• APC’s engulf foreign particles & then present
fragments on their own cell surfaces, “signal flags.”
– Strategically located so as to ensure coverage of all
body parts & tissues
– Secrete proteins interleukins that activate T cells &
stimulate killer cells
• T-cells circulate [enhances chances of encountering
the AG]
Specific Immunity
Cell-Mediated Immunity – Targets body cells infected
with viruses or bacteria, abnormal or cancerous cells,
& foreign transplants
• T cells classed by type of “cell differentiation”
glycoprotein on their surfaces
– CD4 - helper T cells
– CD8 - cytotoxic T cells
Specific Immunity
Recognition:
• T cells only “recognize” processed fragments of
protein Ag’s displayed on cell surfaces
• Antigen Recognition and MHC Restriction
– 2 types of MHC’s are important to T cell activation
• MHCI are found on all self cells except red
blood cells
Specific Immunity
–Pick up endogenous materials on way to
surface - display them. If Ag is foreign
material from inside cells [e.g., viral
protein], it is recognized
–T cells [Tc]kill the cell showing it
MHCII – on
mature B, T &
APC’s – have
exogenous
engulfed &
digested Ag [not
self] - Th respond
Specific Immunity
T-Cell Activation
• Activation [clonal selection] – 2 steps
– Recognition & binding to presented complex by a
specific T-cell receptor
– Co-stimulation – required second signal – from
cytokines, & plasma membrane molecules on
APC’s
Specific Immunity
– Proliferation and Differentiation
• After activation – T cell enlarges & divides
several times
• Forms more highly specialized T-cells in clones
• Activation and proliferation etc. occurs in
secondary lymphatic organs & tissues – tonsils,
lymph nodes, etc.
Specific Immunity
Attack
• Helper = TH or T4 – essential to specific immunity.
– Interact with both T & B cells & macrophages.
• Recognize MHCII presented Ag. Activated by
APC’s
– When activated, secrete interleukins which attract
neutrophils & NK's, stimulate phagocytosis, &
stimulate clone formation
Specific Immunity
• Cytotoxic = TC or T8 = Killer T cells
– Recognize MHCI bound Ag [viral, tumor,
transplant]
– TC – attach to invader – use Perforin – pokes holes
in target cell’s membrane => lysis, interferons, &
tumor necrosis factor [kills cancer cells]
Specific Immunity
Memory
• T Cells– left over after cell-mediated response
is done can initiate a new response if the Ag
reappears
Specific Immunity
Humoral Immunity
Recognition
• B Cells - each has receptors to only one Ag
• B cell Ag receptors bind to Ag – several pieces
link together & are then endocytosed through
receptor mediated process
Specific Immunity
• The activation response is stronger if neighboring
dendritic cells also process &present the Ag
• Ag taken in by B cell, broken down, & moved to the B
cell membrane
• This results in co-stimulation by helper T's to
proliferate & form clones
Specific Immunity
• Activated B cells from the clone enlarge & become
plasma cells – secrete Ab at rate of 2000 molecules
per second per cell for 4 to 5 days
• Some activated B cells become memory cells instead
of plasma cells
Specific Immunity
Attack
• Ab’s – match antigenic determinants that stimulate
their production
• Also called immunoglobulins = gamma globulin
fraction of blood
Specific Immunity
• Ab structure – glycoproteins = carbohydrate &
protein
– 2 heavy chains
– 2 light chains
– Disulfide bridges hold L to H and H to H
Specific Immunity
– 2 regions per H & L chain pair
• Variable – Ag binding site – recognizes
determinant
• Constant – same for most Ab of a given class –
different among classes [especially the H
chains]
Ab Structure
Specific Immunity
Ab classes – 5 groups classed by their constant
regions [Table 21.3].
• IgG – 80% - antibacterial, antiviral, opsonizing,
neutralizing, complement trigger. Monomer.
Can cross placenta
• IgA – 1-15% - sweat, tears, saliva, mucus, milk,
GI. Monomer & dimer
Specific Immunity
• IgM – 5-10% Activates complement,
agglutinates, anti-ABO Ab’s in plasma.
Pentamer.[Can fix complement.]
• IgD – 0.2% Monomer. Ag receptors on B cells
• IgE – Bound to basophils and mast cells.
Allergic & hypersensitivity reaction. Protects
from worms. Monomer.
Specific Immunity
Mechanisms of Ab Diversity
• Humans can produce from 10 billion to a trillion
different Ab's
• Have about 100,000 genes to code for Ab proteins
• Composed of “bits” put together in different
combinations by “somatic recombination”
• H & L chain exons on same chromosome
Specific Immunity
Ab Actions – inactivate and tag for destruction
• Neutralization – bind to & block antigen/toxin
• Agglutination/ precipitation –clumping
• Complement Fixation
• Complement also stimulates inflammatory response
in region, Opsonization – coat & make sticky to
phagocytes
Agglutination
Neutralization
Specific Immunity
Memory
• Both long lasting Ab & memory cells
• Primary response [first exposure] – takes a few days
to see Ab
• Ab levels increase, then drop but memory cells
remain
• Second response produces more & more effective Ab
Specific Immunity
Immune System Disorders
• Allergy – hypersensitivity. One system has 4 types:
– Type I = immediate [acute] - hay fever, etc.
Anaphylactic shock can occur.
– Type II - antibody-dependent cytotoxic [Ab
opsonizes or complement fixation] Transfusion
reactions, some drug reactions
Specific Immunity
– Type III - Immune complex - precipitate in tissue,
then activate complement, leading to tissue
damage. Autoimmune SLE & Glomerulonephritis
– Type IV - Delayed – cell-mediated. Poison ivy, graft
rejection
Specific Immunity
Autoimmune Diseases
• Failures of self-tolerance
• 3 causes - cross-reactivity [e.g., strep], abnormal
exposure to occult Ag [usually sequestered]Hashimoto's thyroiditis], Change in self-Ag structure [type I diabetes]
Specific Immunity
• Immunodeficiency
Diseases
– SCID - "boy in
bubble“
– AIDS - review on
own