Transcript Chapter 22 The Lymphatic System, Nonspecific Resistance to Disease

Chapter 22
The Lymphatic and
Immune Systems
The Lymphatic System
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Basic organization
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Lymph fluid in lymph vessels
Structures, organs w/ lymph tissue, red bone
marrow
Functions
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drain interstitial fluid and proteins
transport dietary fats
protect against invasion
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resistance - fight off disease
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nonspecific resistance - general protection against disease
immunity - specific protection
susceptibility - lack of resistance
Lymphatic Vessels
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Lymphatic capillaries
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Blind ended vessels between cells, larger than blood
capillaries
Not in avascular tissues, CNS, splenic pulp, bone marrow
Lymphatic Capillaries
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Structure/Function regulates fluid flow
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Anchoring filaments - from lymphatic endothelium attach
to surrounding tissues
Endothelial cells overlap
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high hydrostatic fluid pressure separates cells, fluid into caps
hydrostatic fluid pressure in cap prevents fluid movement out
The Lymphatic System
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Lymph flow follows
venous circulation
Lymph vessels have
same organization as
vascular tree
Smaller vessels drain
into larger vessels
The Lymphatic System (cont.)
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Lymph returns to
venous blood
through R,L
lymphatic ducts
Enter at internal
jugular and
subclavian veins
The Lymphatic System
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Lymph ducts
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Right lymphatic
duct
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about ½ inch long
drains lymph from
upper right side of
body
Thoracic (left)
duct
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main collecting duct
of lymph system
38-45 cm long
drains 75% of body
begins as a dilation
known as cisterna
chyli located
anterior to lumbar
disk #2
The Lymphatic System
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Flow of Lymph
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More fluid out of blood capillaries by filtration than
returns by absorption - Starling’s Law
 3Ll day of lymph fluid
Proteins from blood returned by lymphatics
Lymph flow by muscle pump, respiratory pump,
valves
Lymphatic Tissue - General
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1º lymphatic organs - site of B and T
cell production
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bone marrow - produces B cells, pre-T
cells
thymus gland - migrate to thymus gland
2 º lymphatic organs
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site of most immune responses
lymph nodes, spleen – surrounded by
connective tissue capsule
lymphatic nodules – not surrounded by
capsule
Thymus Gland
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Thymus Gland
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Between sternum, heart
2 lobes
Atrophies w/ age
Structure/Function
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Outer cortex
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pre-T cells migrate to
thymus
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proliferation
Maturation
dendritic cells
macrophages
Inner medulla – more of
the same
Lymph Nodes
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Lymph Node Structure
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oval, bean shaped
structures along lymph
vessels
may be deep or
superficial scattered
throughout body
concentrated in
mammary glands, axillae,
groin
filter lymph fluid
Lymph Nodes
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Connective tissue
capsule w/ trabeculae
extending into cortex
Stroma -supportive
network of reticular
fibers, fibroblasts
Lymph Nodes
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Parenchyma
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Outer cortex lymphatic nodules
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inner germinal
center site of B-cell
proliferation
Site of B-cell
maturation and
plasma cell
formation
Inner medulla medullary cords of
lymphycytes,
macrophages,
plasma cells
Cortex
Medulla
Lymphatic Tissue - Specific
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Node fluid flow
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Enter cortex through
afferent vessels
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Filter, remove damaged
cells, microorganisms,
foreign substances by
reticular fibers
macrophages phagocytize
some, lymphocytes
destroy others
exit medulla from hilus
by efferent vessels
Metastasis
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cancer cells from tumor
trapped in lymph nodes
Lymph Nodes
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Histology
Lymphatic Tissue - Specific
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Spleen
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largest mass of lymphoid tissue in body
Left side of body between
stomach/diaphragm
thick fibrous capsule w/ artery, vein,
efferent lymph vessel
organ function:
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immune function
removal of worn
out, damaged
RBC’s
storage of
platelets
production of
RBC’s during fetal
life
Lymphatic Tissue - Specific
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Lymphatic nodules (tonsils)
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oval-shaped nonencapsulated groups of
lymphatic tissue
scattered in mucous
membranes, GI tract,
respiratory tract, urinary
tract, reproductive tract
protect against invasion of
inhaled or ingested foreign
substances
Nonspecific Resistance to Disease
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Summarized in Table 22.1
Surface Barrier – Skin and mucosa
Internal Defenses
1)
2)
3)
4)
Antimicrobial proteins
Natural killer cells and Phagocytosis
Inflammation
Fever
Nonspecific Resistance to Disease
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Surface Barrier – Skin and mucosa
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Mechanical protection
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intact epidermis
mucous membranes
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line body cavities, mucus prevents drying, traps foreign
bodies
nose hairs, respiratory tract cilia
lacrimal apparatus
saliva - dilute microbes, wash them from teeth
surface
urine flow, vaginal secretions – flow and pH help kill
microorganisms
defecation and vomiting - expel microbes
Nonspecific Resistance to Disease
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Surface Barrier – Skin and mucosa
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Chemical protection
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Skin
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sebum (unsaturated FA’s) forms layer, prevents bacterial
growth
perspiration has fatty acids, lo pH
lysozyme - enzyme breaks down bacterial walls
gastric juice - stomach nearly sterile due to lo pH,
2ish
Nonspecific Resistance to Disease
1) Antimicrobial substances produced against
pathogens that penetrate 1º defense
A. Interferons
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Released from infected cells
Stimulate production of antiviral proteins from
neighboring cells
B. Complement system
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20 plasma and cell membrane proteins
Function to complement (enhance) certain immune,
allergic and inflammatory systems
C. Transferrins – inhabit bacterial growth by
binding iron
Nonspecific Resistance to Disease
2) Natural killer (NK) cells and phagocytosis
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NK
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nonspecific killers that respond before immune
system is activated
ability to kill virus infected body cells and some
tumor cells by poking holes in cells and stimulating
cell death
Nonspecific Resistance to Disease
2)
Natural killer (NK) cells and phagocytosis
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Phagocytosis
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ingestion of microbes or foreign material by phagocytes
2 kinds of phagocytosis - neutrophils and macrophages
steps
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chemotaxis
adherence
ingestion
digestion
killing
Nonspecific Resistance to Disease
3) Inflammation
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4 symptoms:
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Redness
Pain
Heat
Swelling
3 steps in process
1. Vasodilation/increased
vessel permeability
2. Phagocyte migration
3. Tissue repair
Nonspecific Resistance to Disease
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Step 1. Vasodilation and
increased vessel
permeability
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Release of factors from
leukocytes stimulate
vascular changes
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Histamine, kinins,
prostaglandins, leukotrienes
Vasodilate, increase
permeability, stimulate
emigration and chemotaxis
Cause heat, redness and
swelling
Nonspecific Resistance to Disease
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Step 2. Phagocyte
migration
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leukocytosis-inducing
factors
chemotaxis
Emigration
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neutrophils - rapid
monocytes - slower
Nonspecific Resistance to Disease
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Step 3. Tissue repair
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Tissue regrowth and
repair of damage
Pus
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dead phagocytes, damaged
tissue
if too numerous for easy
removal may form abscess
Nonspecific Resistance to Disease
4) Fever
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increase effects of antimicrobial substances
inhibits some microbes
increase rate of body repair
Nonspecific Resistance to Disease
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Surface Barrier – Skin and mucosa
Internal Defenses
1)
2)
3)
4)
Antimicrobial proteins
Natural killer cells and Phagocytosis
Inflammation
Fever
Immunity
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Immunity
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ability of body to defend itself against specific
invaders
specificity and memory differentiate this from
non-specific system
two types
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Humoral (antibody mediated) immunity
Cellular (cell mediated) immunity
Antigens
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Antigen - substances that
provoke immune response
Epitope
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antigen part that triggers
immune response
most antigens have many
epitopes
Antigens (cont.)
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Chemical nature of
antigens
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large, complex molecules mostly proteins, nucleo-,
lipo-, glycosmaller substances may be
incomplete antigens hapten
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react with antibodies but not
cause immune response
poison ivy toxin
usually foreign substances
Antigens (cont.)
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Antigen receptor diversity
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>1 billion different epitopes
recognized by body
diversity - genetic recombination,
shuffle, reorganize different
genes
Major Histocompatibility
Complex antigens (MHC)
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unique to each individuals cells,
help in identifying foreign bodies
2 classes of MHC antigens
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class I MHC - all body cells but
RBC's
class II MHC - only on antigen
presenting cells (APC’s), thymus
cells, activated T cells
Pathways of Antigen Processing
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For immune response to occur, B and T cells
must recognize foreign antigen
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B cells can recognize, bind to antigens in ECF,
blood, lymph
T cells only recognize antigen protein fragments
presented w/ MHC self-antigens - good/bad
proteins
Pathways of Antigen Processing
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During protein digestion and production in cell,
small peptides used to stabilize MHC proteins
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if peptides from normal body cells, no response
if peptides from antigens
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T cells recognize them
immune response!
preparation of foreign antigen for cell surface known as
processing and presenting of antigen
Antigen Presenting Cell's (APC’s)
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macrophages, activated B cells, dendritic cells
process exogenous antigens present them w/ MHC class
II molecules to T cells
Pathways of Antigen Processing
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Processing of exogenous antigen – produced outside cell
1)
2)
3)
4)
5)
phagocytosis/endocytosis
digestion
vesicles fuse, peptide fragments bind to MHC-II’s
exocytosis to membrane
move to lymphatic tissue, present antigen to T-cells
Pathways of Antigen Processing
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Processing of endogenous antigen –
produced within body cells
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viral proteins from viral infection of cell
produced, incorporated into MHC-I molecules
during normal cell growth
put on surface of cell
identifies cell as infected, signals that cell
needs help
T and B cell formation
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Both B and T cells
produced from stem
cells in bone marrow
Development of
immunocompetence
occurs in different
sites
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B cells complete
maturation in Bone
marrow
Pre-T cells move to
Thymus - complete
maturation in thymus
Immunity - General
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Before mature
cells leave home:
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both types
acquire surface
proteins - antigen
receptors
T cells exit as
CD4+ or CD8+
cells w/ different
functions
CD4+ cells
become helper T
cells
Immunity - General
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2 Types of immune
responses
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Cell-mediated
immunity
Antibodymediated immunity
General
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Initial activation
of Helper T cells
Helper T cells aid
both types of
immune responses
Pathogens often
activate both
types of responses
Immunity - General
1) Cell-mediated
immune (CMI)
responses
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CD8+ cells change
into killer T cells
with aid from
Helper T cells
directly attack
infecting antigen
Effective against:
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intracellular
pathogens
some cancer cells
foreign tissue
transplants
Immunity - General
2) Antibodymediated immune
(AMI) responses
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B cells transform
into plasma cells
with aid of Helper
T cells
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synthesize,
secrete specific
proteins
(antibodies or
immunoglobulins)
antibodies bind
and inactivate
antigens
Effective against:
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antigens in body
fluids
EC pathogens
(bacteria)
Cell -Mediated Immunity
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Basic steps
1. Recognition of APC antigen by T cell receptors
(TCR’s) – first signal
2. Costimulation for activation
3. Proliferation and differentiation
4. Clone effector cells capable of recognizing
initial activator (antigen)
5. Elimination of intruder
Cell-Mediated Immunity (cont.)
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T cell recognition,
proliferation,
differentiation
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APC presents antigen
TC’s recognize, bind
foreign antigen millions of T cells each
specific for 1 antigen
Need co-stimulator
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20 known, cytokines,
interleukins, needed
for full immune
response
prevent false
activation?
Cell-Mediated Immunity (cont.)
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T cell enlarges, makes
clones capable of
recognizing antigen
Cell-Mediated Immunity (cont.)
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Clones
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Helper T (TH)
cells - CD4+
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after costimulation
helpers secrete
co-stimulators
co-stimulates
helper T cells,
cytotoxic T
cells, B cells
Cytotoxic T (TC) cells - CD8+
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recognize antigen fragments associated w/ MHC-I molecules,
some tumor cells and tissue transplant cells
become cytolytic need stimulators from helper T cells
Cell-Mediated Immunity (cont.)
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Tc elimination of
invaders
1. Migrate from lymph to
infection site
2. Recognize, attach to
target antigen/cell
3. Kill invaders
4. Detach, seek out
another invader w/
proper antigen
Cell-Mediated Immunity (cont.)
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More Clones
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Suppressor T
(TS) cells
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produced
with other
clones
downregulate
immune
system by
producing
other
cytokines
Memory T (TM) cells
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recognize original invading antigen
second response rapid due to large numbers of TM cells
present
Antibody-Mediated Immunity
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Body contains millions
of B cells
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located in lymphoid
tissue
each responds to
specific antigen
Become activated in
presence of foreign
antigen
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unprocessed antigen
weak response
need to process
antigen for stronger
response
Antibody-Mediated Immunity
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Unprocessed antigen
taken into cell
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incorporated into
MHC-II self-antigen
activates helper T
cells
Costimulation production of
cytokines
Antibody-Mediated Immunity
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Some B cells change into plasma
cells
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secrete specific antibodies, at high
rate for 4-5 days
antibodies circulate in lymph and
blood to site of invasion
Circulating antibodies combine w/
antigens
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neutralizes antigen
immobilizes bacteria
agglutinating (clumping) antigens
activates complement system
enhances chance antigen will be
phagocytized
Antibody-Mediated Immunity
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Activated B cells
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some turn into memory B
cells
respond more rapidly,
forcefully if antigen
appears again
Antibodies
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Antibodies (Abs)
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Globulins (proteins) specific for antigenic determinant of
antigen that triggered its production
5 different classes - IgG, IgA, IgM, IgD, IgE
Immunological Memory
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Long lived
antibodies and
lymphocytes arise
during activation of
antigen-stimulated
B, T cells
Immunization possible because memory B cells and
memory T cells remain after 1º response
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w/ secondary exposure system responds more quickly,
forcefully
secondary response - antibodies produced during second
exposure have a higher attraction for antigen
Acquired Immunity
Self-recognition and Self-tolerance
The Immune System - Pathologies
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Immunology and cancer
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With development of cancer cell surface proteins (tumor
antigens) appear that rarely appear
If body recognizes surface proteins as non-self will
destroy them
most effective in eliminating viral tumor cells
Hypersensitivities - allergies
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first exposure sensitizes to allergen - IgE production
next exposure anaphylaxis - massive histamine release
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local - surface exposure
systemic - body
The Immune System - Pathologies
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Autoimmune diseases
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multiple sclerosis - white matter destruction
myasthenia gravis - effects nerve/muscle
communication
Graves disease - excessive thyroid hormone
production
Type I diabetes - destruction of pancreatic islet
cells
glomerulonephritis - impaired renal function
rheumatoid arthritis - destruction of the joints
Acquired Immunodeficiency Syndrome
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Human Immunodeficiency Virus
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Enters cells through receptor
mediated endocytosis
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A retrovirus
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infects mainly helper T cells
uses the CD4 protein on cell surface
carries genetic material as RNA
inserts genetic material into host DNA w/
enzyme reverse transcriptase
cell makes copies of the virus, releases
them for further infection
May be carried unknowingly in cells
for years, being passed on during
cloning
Activation will destroy Helper T’s
Poor immune response to simple
things
Applied Immunity and HIV
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Enter the body?
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Spread?
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Effect of infection?
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Cause of death?