Download Ch. 22 – The Lymphatic System and Immunity The lymphatic system

Ch. 22 – The Lymphatic System
and Immunity
Above: macrophage (gray), T lymphocyte (pink), and bacteria (orange)
The lymphatic system
General functions:
•
•
•
It acts with other organ systems to
help provide immunity (= the ability to
prevent and fight disease)
It returns “lost” plasma (= interstitial
fluid) to the blood
It transports dietary lipids from the
digestive tract to the blood (more in
Ch. 24)
Components:
•
•
•
•
Lymph = interstitial fluid that gets
absorbed and transported by…
Lymphatic vessels (lymphatics) =
low pressure tubes that ultimately
return lymph to the blood
Lymphoid tissues and organs
Lymphocytes and supporting cells
Fig. 22-1, p. 783
1
Lymphatic
capillaries
• Are different than typical
blood capillaries, in part
because they:
–
–
–
–
Have larger diameters
Have thinner walls
Are more permeable
Are composed of loosely bound,
overlapping endothelial cells…
• Which act as one-way valves
for entry
Fig. 22-2, p. 784
Lymphatic vessels
• Are a.k.a.
lymphatics
• Are similar in
structure to veins,
but they have even
thinner walls
• The larger ones have
valves to prevent the
backflow of lymph
Fig. 22-3, p. 785
2
Lymphatic trunks and ducts
•
Lymphatic vessels merge to form lymphatic trunks, which drain into either the…
– Thoracic duct – which empties into the left subclavian vein, or the…
– Right lymphatic duct – which empties into the right subclavian vein
Fig. 22-4, p. 786
Types of lymphocytes
Total in the body:
~ 1 trillion = 1 kg = 2.2 pounds!
Fig. 22-5, p. 787
3
Lymphocyte production
Fig. 22-6, p. 789
Lymphocytes – NK and T cells
• NK cells (natural killer cells)
– Are responsible for “immune surveillance”
– Function: nonspecifically attack foreign,
virus-infected, and cancerous cells
• T cells (thymus-dependent cells)
– Are responsible for cell-mediated immunity
– The main types of T cells include:
• Cytotoxic T cells (TC cells)
– Function: specifically attack foreign, virusinfected, and cancerous cells
• Helper T cells (TH cells)
– Function: stimulate T and B cells; coordinate
cell- and antibody-mediated immunity
• Suppressor T cells (TS cells)
– Function: inhibit T and B cells
Fig. 22-6, p. 789
4
Lymphocytes – B cells
• B cells (bone marrow-derived
cells)
– Are responsible for antibodymediated (humoral) immunity
• Function: when stimulated, they
differentiate into plasma cells which
secrete specific antibodies
(immunoglobulins)
– Effects of antibodies include:
•
•
•
•
•
Neutralizing toxins
Agglutinating and precipitating antigens
Activating complement proteins
Attracting phagocytes
Opsonizing antigens (making them
easier to hang onto) to enhance
phagocytosis
• Promoting inflammation…
Fig. 22-6, p. 789
– By stimulating basophils and mast cells
• Interfering with bacterial/viral adhesion to
body surfaces
= connective tissues (CTs)
dominated by
lymphocytes
•
•
Lymphoid tissues
No external fibrous
CT capsule is present (as
opposed to lymphoid
organs – see the next
slide)
If the lymphocytes are
densely
packed, it’s
called a
lymphoid
nodule
Examples:
• MALT (mucosaassociated
lymphoid tissue)
Fig. 22-7, p. 791
– E.g. aggregated
lymphoid nodules
(Peyer’s patches)
in the digestive
tract
•
Tonsils = large lymphoid
nodules in the walls of the
pharynx
– E.g. the palatine tonsils (2),
pharyngeal tonsil (1, a.k.a.
the adenoid), and lingual
tonsils (2)
5
Lymphoid organs
• Have an external
fibrous CT
capsule
separating the
organ from other
tissues (as
opposed to
lymphoid tissues
– see the
previous slide)
• Include the:
– Lymph nodes
– Thymus
– Spleen
Fig. 22-1, p. 783
Functions:
•
1. They filter (purify) lymph before its
return to the bloodstream
Lymph nodes
– They remove > 99% of the antigens
in the lymph
– Antigen presentation is performed
by macrophages and dendritic cells
(which are examples of antigenpresenting cells, or APCs)
• This is the 1st step
in the activation
of an
immune
response
• Reminder:
antigens =
substances
that trigger
an immune
response
•
2. They serve as
an “early warning
system”, monitoring
the condition of
peripheral tissues via
the interstitial fluid/lymph
•
3. They are strategically located in
the axillae, groin, neck, and torso
Fig. 22-8, p. 792
6
The thymus
•
•
•
•
Is where lymphoid stem cells mature (differentiate) into T cells
Is located in the mediastinum above the heart
Reaches its maximum relative size (% of body weight) in the first 1–2
years of life
Reaches its maximum absolute size just before puberty
– It gradually involutes (deteriorates into CT and shrinks) from then on
Fig. 22-9a, p. 793
Fig. 22-9, p. 793
The thymus
• Is filled with lymphocytes that are
surrounded by thymic epithelial cells
(TECs), which…
– Maintain the blood-thymus barrier
– Secrete thymic hormones (thymosins) that
promote the division and maturation of T cells
7
The spleen
•
Note the non-intuitive
orientation here!
Is the
largest
lymphoid
organ
Fig. 22-10, p. 795
• Functions:
The spleen
– Its macrophages remove (via phagocytosis) abnormal or worn out
blood cells
– It stores iron (recycled from RBCs)
– It initiates immune responses (via APCs) to antigens that are present in
the blood
• The spleen is sort of like a lymph node for the blood!
Fig. 22-10c, p. 795
8
Body defenses
• Function: provide resistance
(= the ability to maintain
immunity; i.e., the ability to fight
infection, illness, and disease)
• The main types of body
defenses:
– 1. Innate (nonspecific) defenses – provide nonspecific
resistance to disease; a.k.a. innate (nonspecific) immunity
• They provide general protection against a wide range of pathogens
• The response is the same regardless of the type of invader
• They are present at birth
– 2. Adaptive (specific) defenses – provide specific
resistance to disease; a.k.a. adaptive (specific) immunity or
the immune response
• They provide specific protection against a particular pathogen
• An immune response is specific to the particular antigen(s)
associated with a particular pathogen
• They require functioning specific lymphocytes (T and B cells) and
exposure to the pathogen
Innate (nonspecific) defenses
• 1. Physical barriers = epithelium and its accessory
structures and secretions, which keep hazardous
organisms and materials outside the body
• 2. Phagocytes consume debris, foreign objects, and
pathogens in peripheral tissues
• 3. Immune surveillance (by NK cells) destroys
abnormal (foreign, bacterial, virus-infected, and
cancerous) cells in peripheral tissues
• 4. Interferons cause the production of anti-viral proteins
• 5. The complement system = circulating proteins that
enhance the action of antibodies
• 6. Inflammation = a localized tissue response to limit
the spread of an injury/damage and/or infection
• 7. Fever = a higher-than-normal body temperature that
accelerates tissue metabolism and the activity of
defenses
9
1. Physical barriers (and their accessory
structures and secretions)
• Epithelial coverings
–
–
–
–
Are often thick and/or keratinized, and sometimes hairy
Are held together by desmosomes or tight junctions
Have a dense, fibrous basement membrane
Have an acidic pH in the skin, stomach, and vagina
• This inhibits pathogen growth, but is OK for “friendly” resident bacteria
– Tears and saliva are antimicrobial and may contain antibodies
• Mucous membranes and cilia
– Mucus traps pathogens, and can be swept away by cilia for removal
• Tears, saliva, and urine – wash away pathogens
Fig. 22-11, p. 797
•
•
Microphages include neutrophils and
eosinophils
Macrophages (most are derived from
monocytes from the blood) include:
2. Phagocytes
– Fixed macrophages – permanently reside in
specific tissues
• E.g. microglia in the CNS, Kupffer cells in the liver
– Free (wandering) macrophages – travel
throughout various tissues
•
Phagocyte movement and phagocytosis
– Emigration (diapedesis) – they exit the
bloodstream through the capillary walls
– Chemotaxis – they are attracted to (or repelled
by) chemical signals released by other body
cells and pathogens
– Adhesion – surface membrane receptors allow
the attachment to a target
– Phagocytosis is followed by the fusion of the
vesicle that contains the target with a lysosome
or peroxisome for digestion/destruction
Fig. 22-11, p. 797
10
3. Immune surveillance
Fig. 22-12, p. 781
•
Is carried out by NK cells, which…
– Recognize a variety of abnormal antigens
on bacteria, cancerous cells (tumorspecific antigens), and virus-infected cells
– When activated, release perforins, which
cause the abnormal cell’s membrane to
rupture (lyse)
Fig. 22-11, p. 797
4. Interferons
• Are examples of cytokines (chemical messenger
proteins released by tissue cells that can act locally
or system-wide as hormones)
• Are released by:
– Activated lymphocytes
– Macrophages
– Virus-infected cells
• Main effects of interferons:
– They cause the production of antiviral proteins that
interfere with viral reproduction in nearby cells, slowing the
spread of infection
– They stimulate NK cells and macrophages
Fig. 22-11, p. 797
11
•
•
5. The complement system
= a group of over 30 special plasma proteins that complement the action of
antibodies
Is involved in both specific (the classical pathway) and nonspecific (the
alternative pathway) defenses (see the next slide for a figure that depicts
these pathways):
– The classical pathway (which is faster, and specific):
• C1 binds to antibodies that are already bound to the invader’s membrane antigens
• A cascade is initiated, and eventually C3b forms and attaches to the invader
– The alternative (properdin) pathway (which is slower, and nonspecific):
• Factors P (properdin), B and D interact directly with the invader’s membrane
• C3b forms and attaches to the invader
•
Some effects of activated and bound complement (C3b):
– Membrane attack complexes (MACs) are formed, causing lysis (similar to
how perforins work)
– Inflammation is stimulated (due to ↑ histamine release)
– Phagocytes are attracted (chemotaxis)
– Phagocytosis is enhanced (opsonization)
Fig. 22-11, p. 797
(antibodies are NOT involved)
Complement
activation
(antibodies are involved)
Fig. 22-14, p. 800
12
Fig. 22-15, p. 801
6. Inflammation
•
•
•
•
= a localized tissue response to injury/damage
Examples of damaging stimuli: impact,
abrasion, chemical irritation, infection by
pathogens, extreme temperatures
Signs and symptoms: swelling (edema),
redness, heat, pain
Overall effects:
– It temporarily repairs the damage
– It “walls off” the damaged area to prevent or
slow the spread and additional entry of
pathogens
– It activates nonspecific and specific defenses to
kill pathogens
– It initiates permanent tissue repair (regeneration)
Fig. 22-11, p. 797
7. Fever
• = a regulated elevation of body temperature above 37.2°C
(99°F)
• Pyrogen = a circulating protein that can cause a fever
– Stimuli that either act as pyrogens themselves or stimulate
macrophages to release pyrogens include:
• Pathogens, bacterial toxins, and antibody-antigen complexes
• The benefits of a fever (as long as it’s “mild”):
– It leads to an overall increase in metabolic rate, so there is increased
activity of WBCs and other body defenses
– It inhibits some viruses and bacteria
Fig. 22-11, p. 797
13
Adaptive (specific) defenses
• Adaptive defenses = specific defenses = specific
resistance = adaptive immunity = the immune
response
• Are provided by the activities of T cells and B cells
• Some properties of adaptive immunity:
– 1. Specificity – the response is targeted to an antigen of a
specific molecular size and shape
– 2. Versatility – millions of different lymphocyte
populations exist, each sensitive to a specific antigen
– 3. Memory – activated lymphocytes divide to produce
many clones:
• Some clones are active cells that respond to a specific antigen
immediately
• Other clones are memory cells = inactive reserve cells that
recognize the same specific antigen if exposed to it at a later date
– 4. Tolerance – normally, self-antigens do not stimulate an
immune response
Forms of immunity
(“get sick”)
(vaccine)
Fig. 22-16, p. 803
14
An overview of the immune response
• 1. Cell-mediated (cellular) immunity
– Is directed against specific cellular and intracellular
pathogens, such as…
• Abnormal cells (e.g. cancerous cells)
• Foreign cells (e.g. bacteria, protozoa, and tissue graft cells)
• Pathogen-containing cells (e.g. virus-infected cells)
– Is carried out by…
• TC cells that directly attack target (“bad”) cells
• TH cells that secrete cytokines, stimulating:
– Macrophages and NK cells to attack target (“bad”) cells
– The division and maturation of other T cells
– The activation of B cells (see below)
• 2. Antibody-mediated (humoral) immunity
– Is directed against specific antigens (both free and on the
surface of pathogens) that are found in body fluids
– Is carried out by antibodies that attack these antigens
• Activated B cells differentiate into plasma cells, which then secrete
antibodies
An overview of the immune response
Fig. 22-17, p. 805
15
T cells and antigen presentation
• T cells need to be exposed to an antigen in order to be
activated
– This most often occurs due to an antigen being presented on the
surface of a cell’s membrane in combination with a MHC (major
histocompatibility complex) protein
• There are 2 types of MHC proteins:
– Class I MHC proteins are found on all nucleated cells
• Antigens bound to Class I MHC proteins stimulate TC cells (quickly, and in
larger numbers) and TS cells (slowly, and in smaller numbers) [both of
which have CD8 markers]; the message = “I’m abnormal—kill me!”
– Class II MHC proteins are found on APCs (e.g. macrophages and
dendritic cells) and lymphocytes only
• They are present on an APC only when it has engulfed and is processing
an antigen
• Antigens bound to Class II MHC proteins stimulate TH cells [which have
CD4 markers]; the message = “This antigen is dangerous—help me get rid
of whatever it came from!”
• The first binding of a T cell to an antigen-MHC complex (on a
stimulating/presenting cell) prepares the T cell for activation
– Costimulation (= the binding of a T cell to the stimulating/presenting
cell at a 2nd site, OR additional chemical stimulation from the
stimulating/presenting cell or other activated lymphocytes) is needed for
complete activation
Class I MHC antigen presentation
(which can be any nucleated cell)
Fig. 22-18a, p. 807
16
Class II MHC antigen presentation
(remember, only APCs and lymphocytes
can express Class II MHCs)
Fig. 22-18b, p. 807
TC (cytotoxic T) cell activation
Fig. 22-19, p. 808
17
Fig. 22-20, p. 809
TH (helper T) cell
activation
• Some effects of cytokines
secreted by TH cells:
– 1. ↑ Memory TH cell production
and TC cell maturation
– 2. Attract macrophages and ↑
their activity
– 3. Attract TC cells and ↑ their
activity
– 4. Activate B cells, and ↑ their
division, maturation (into plasma
cells), and antibody production;
see Fig. 22-22
A summary of the pathways of T cell activation
These processes can take a few days…
(found on any nucleated cell)
In which case, they will
immediately respond!
(found on APCs and lymphocytes only)
In which case, they will
immediately respond!
Fig. 22-21, p. 810
18
B cell sensitization and activation
Up to 100 million
antibodies per
plasma cell per hour!
Fig. 22-22, p. 811
Antibody structure and function
Fig. 22-23, p. 812
19
The classes and effects of
antibodies (immunoglobulins)
• There are 5 classes (*denotes the biggest players):
– *IgG – make up 80% of all antibodies; they are
versatile and effective; they can cross the placenta
– IgE – are found on basophils/mast cells
– IgD – are found on B cells
– *IgM – are secreted first (soonest) following
antigen exposure; they are potent agglutinators
– IgA – are found in secretions (e.g. mucus, tears,
and saliva)
• Effects (repeated from earlier in the Ch. 22 notes):
–
–
–
–
–
Neutralize toxins
Agglutinate and precipitate antigens
Activate complement proteins
Attract phagocytes
Opsonize antigens (making them easier to hang
onto) to enhance phagocytosis
– Promote inflammation…
• By stimulating basophils and mast cells
– Interfere with bacterial/viral adhesion to body
surfaces
Table 22-1, p. 813
Primary and secondary responses by
B/plasma cells to antigen exposure
•
•
•
A primary response will occur upon the initial (first) exposure to a specific antigen
Thanks to memory cells, a secondary response will occur upon subsequent
exposure to the same specific antigen as before
There is a dropoff in antibody titer (= level of antibodies in the blood plasma) with
time because:
– Plasma cells are short lived (they have a very high metabolic rate)
– Suppressor T cells eventually inhibit antibody production by plasma cells
Fig. 22-24, p. 814
20
A summary
of the
immune
response
Fig. 22-26, p. 816
The time course of an immune
response to a bacterial infection
Fig. 22-25, p. 815
21
Defenses
against
bacteria
and
viruses
Fig. 22-27, p. 817
A summary table of the cells that
participate in tissue defenses
Table 22-2, p. 815
22