Download Chapter 21: Blood Vessels and Circulation

Chapter 22: The Lymphatic System
and Immunity
BIO 211 Lecture
Instructor: Dr. Gollwitzer
1
• Today in class we will discuss:
– Body defenses and the components, mechanisms and
functions of:
• Nonspecific defenses
–
–
–
–
–
–
–
Physical Barriers
Phagocytes
Immunological surveillance
Interferons
Complement system
Inflammatory response
Fever
• Specific defenses
– Immune response
» T cells
» B cells
» Types of immunity
» Properties of immunity
2
Immune System
• A physiological system that includes several
organ systems
– Primary = lymphatic system
– Plus components of integumentary,
cardiovascular, respiratory, digestive, and other
anatomic systems
– e.g., interactions between lymphocytes and
Langerhans cells of skin important in defenses
against skin infections
3
Immune System
• Specialized sensory “megaorgan”
• Enables us to detect things that are foreign
or cannot be seen with the naked eye
(microbes, allergens…)
• Allows us to fight (defend against)
pathogenic microbes while normal flora left
alone
4
Body Defenses
• Physical and chemical barriers that prevent or
slow entry/progress of infectious organisms
• 2 Types of defenses
– Nonspecific defenses
– Specific defenses
5
Body Defenses
• Nonspecific defenses
– NOT unique
– Against any invading agent
– Many different threats elicit same response
– Present from birth (innate)
– e.g., physical barriers, phagocytic cells,
immunological surveillance, interferons,
complement, inflammation, fever
6
Body Defenses
• Specific defenses (AKA: Adaptive defenses)
– Protect against specific threats (e.g., one type of
bacterium or virus)
– Develop after birth as a result of exposure
– Depend on activities of lymphocytes
– Result in specific resistance or immunity = ability
to resist infection and disease through activation
of specific defenses
7
Nonspecific Defenses
Figure 22-11
8
Nonspecific Defenses:
Physical Barriers
• Keep pathogens from entering body
– Epithelial linings
• Skin surface layers with keratin and desmosomes water
resistant, impregnable wall
– Epithelial accessory structures (e.g., hair, cilia)
• Protect against mechanical abrasion
• Prevent hazardous contact with skin
– Epithelial secretions
• Mechanical barrier, e.g., mucous in respiratory tract, stomach
• Antibacterial, e.g. sebum (oily secretion from sebaceous gland),
lysozyme enzyme in tears
• Flushing action (tears, urine, mucus in respiratory tract)
9
Nonspecific Defenses:
Phagocytes
• Perform “police,” “first-responder,” “janitorial”
services in peripheral tissues
• First line of cellular defense
– Roving cells on look-out for foreign invaders
– Remove pathogens and cell debris (cell eaters)
– Often attack and remove invaders before lymphocytes
aware of them
• Attracted to chemicals (chemotaxis)
– Chemicals released:
• From damaged body cells
• By pathogens into surrounding fluids, e.g., cytokines
• Move out of bloodstream by squeezing between
endothelial cells (diapedesis)
10
Nonspecific Defenses:
Phagocytes
• Must be activated
• Respond to invasion by foreign compounds or
pathogens in several ways
– Engulf pathogen or foreign object and destroy with
lysozymes
– Bind or remove pathogen from interstitial fluid but not
able to destroy without assistance from other cells
– Destroy pathogen by releasing:
• TNF (tumor necrosis factor), NO (nitric oxide), or H2O2 (hydrogen
peroxide)
• Brief lifespan for active phagocytes
(30 min – 1 hr)
11
Nonspecific Defenses:
Phagocytes
• 2 Classes of phagocytes
– Microphages (“small eaters”)
– Macrophages (“big eaters”)
12
Nonspecific Defenses:
Microphages
• Circulating neutrophils and eosinophils that
leave bloodstream and enter injured or
infected tissues
• Neutrophils
– Abundant, quick, mobile
– Engulf pathogens or cellular debris
• Eosinophils
– Much rarer cells
– Target foreign compounds or pathogens (antigens)
coated with antibodies, e.g., allergens
13
Nonspecific Defenses:
Macrophages
• Large, actively phagocytic cells derived from
monocytes
• Spend very little time in blood
• 2 Types
– Fixed/resident macrophages
• Permanent cells in certain tissues, e.g.,
– Microglia in CNS, Kupffer cells in liver, alveolar macrophages in
lungs
– Free macrophages
• Mobile; travel throughout body through tissues or
blood
14
Nonspecific Defenses:
Immunological Surveillance
• Immune system programmed to ignore cells of
own body (e.g., intestinal bacteria) unless they
become abnormal
• Normal tissues constantly monitored by natural
killer (NK) cells looking for:
– Abnormal cells (cancer cells with tumor-specific
antigens)
– Cells infected with viruses
15
Nonspecific Defenses:
Immunological Surveillance
• NK cells
– Lymphocyte “spy system” in peripheral tissue
– Recognize/respond to wide variety of proteins on
cell membranes
• vs. T cells or B cells that can be activated only by
exposure to a specific antigen at a specific site on a cell
membrane
– Respond immediately on contact with abnormal
cell
• Much more rapidly than T or B cells whose activation is
complex and time consuming
16
Nonspecific Defenses:
Immunological Surveillance
• NK cell
– Attaches to abnormal cell
– Producess protein (perforin) that creates large
pores in cell membrane  lyses cell
– Especially important opponent for cancer cells
17
How NK Cells Kill Cellular Targets
Fig. 22-12
18
Nonspecific Defenses:
Interferons
• Small protein chemical messengers (type of cytokine)
produced by:
– Macrophages
– Cells infected with viruses
– Activated lymphocytes
• Interfere with spread of disease
– Coordinate local defenses against viral infection
– Stimulate macrophages and NK cells
– Signal WBCs and lymphatic system (“tattle tales”)
• Increase resistance of cells to viral infections
– Trigger production of antiviral proteins that inhibit
replication within cells
19
Nonspecific Defenses:
Complement System
• System of 11 blood proteins that interact in a
chain reaction (cascade)
• Assists (complements, supplements)
antibodies in destroying pathogens
– Begins when first complement protein (C1) binds
to antibody (Ab) attached to its specific antigen
– Ends with pore formation and lysis of target cell
membrane
20
Complement System
Figure 22–12, 7th edition
21
Nonspecific Defenses:
Complement System
• Attracts phagocytes to injury or infection (via
chemotaxis)
• Enhances phagocytosis of antibody-antigen
(pathogen) complex
• Stimulates inflammation
– Enhances histamine release by mast cells
(basophils in tissues)
• Increases local inflammation and accelerates blood flow
22
Nonspecific Defenses:
Inflammation
• Local tissue response to injury or infection
• Stimulus
– Anything that changes cell and alters chemical
composition of interstitial fluid
– Anything that kills cells, damages CT fibers, or
injures tissue
– e.g., impact, abrasion, chemical irritation, infection
by pathogens, extreme temperatures
23
Nonspecific Defenses:
Inflammation
• Stimulus causes mast cells 
– Histamine
– Heparin
• 
– Local vasodilation  increased blood flow 
redness and heat
– Increased capillary permeability  blood proteins
into injured tissue  local swelling
– Stimulation of pain receptors  pain
24
Nonspecific Defenses:
Inflammation
• Inflammatory response
– Walls off region, slows spread of injury/ pathogens
from site
– Combats infection by activating:
• Phagocytes
• Complement
• Specific defenses
– Performs temporary repair and prevents access of
other pathogens
– Mobilizes regeneration (permanent repair)
25
Figure 22-15
26
Nonspecific Defenses:
Fever
• High body temperature (>99 F)
• Caused by pyrogens
– = Proteins released by macrophages that can raise body
temperature
– Affect temperature-regulating center in hypothalamus
• Stimuli for pyrogens
– Pathogens
– Bacterial toxins
– Antigen-antibody complexes
• Act directly as pyrogens
• Stimulate release of pyrogens by macrophages
27
Nonspecific Defenses:
Fever
• Beneficial phenomenon
– Increases body’s metabolic rate so more enzyme
made to fight infection
– Inhibits pathogenic enzymes
– Stimulates cell repair
28
Specific/Adaptive Defenses:
The Immune Response
• Immunity
– Specific resistance to injury and disease caused by
foreign compounds, toxins, or pathogens
• Provided by coordinated effort of 2 types of
lymphocytes: T and B cells
• Lymphocytes
– Respond to presence of specific antigens
– “Organize” the defense
29
Figure 22-17
30
Specific Defenses:
The Immune Response
• T cells (thymus-dependent)
– Initiate, maintain, control the immune response
– Responsible for cell-mediated immunity
– Defend against abnormal cells and pathogens inside
cells (do not respond to pathogens in body fluids)
– 3 Major types of T cells
• Cytotoxic
• Helper
• Suppressor
31
Specific Defenses:
The Immune Response
• B cells (bone marrow-derived)
– Responsible for antibody-mediated (humoral)
immunity
– Differentiate into plasma cells that produce
antibodies
– Defend against antigens and pathogens in body
fluids (antibodies can’t cross cell membranes)
32
Specific Defenses:
The Immune Response
• Types of immunity
– Innate immunity
• Present at birth (genetically determined)
• Does not require exposure to antigen or antibody
production
•  Diseases that are species specific
– Acquired/Adaptive immunity
• Not present at birth
• Produced by prior exposure to specific antigen or
antibody production
• 4 types
33
Figure 22-14, 7th edition
34
Specific Defenses: Acquired Immunity
• Active immunity
– Appears after exposure to an antigen
– Requires active response by body, i.e., antibody
production (immune response)
– Two types
• Naturally acquired (active) immunity
– Through environmental exposure to pathogens
• Induced (active) immunity
– Through vaccines containing dead/inactive pathogens or antigens
– Antibody production stimulated before possible future exposure
35
Specific Defenses: Acquired Immunity
• Passive immunity
– Requires no response by body
– Produced by transfer of antibodies from one
individual to another
– Two types
• Natural passive immunity
– Antibodies acquired from mother during development (across
placenta) or in early infancy (through breast milk)
• Induced passive immunity
– Antibodies (developed in another body) administered via injection
– e.g., IG injected into Rh- mother after first Rh+ baby; antirabies
virus antibodies injected into person bitten by rabid animal,
antivenom…snake bite
36
Specific Defenses:
The Immune Response
• Properties of immunity that enable body to
respond with a specific defense
– Specificity
– Versatility
– Memory
– Tolerance
37
Specific Defenses:
4 Properties of Immunity
• Specificity
– Specific defenses activated by one specific antigen
• Immune response targets that antigen ONLY
– Each T and B lymphocyte has receptors that bind to
only one specific antigen and ignore all others
– T or B cells will destroy or inactivate that antigen
without affecting other antigens or normal tissues
38
Specific Defenses:
4 Properties of Immunity
• Versatility
– Ability of immune system to confront any antigen any time
– Results from large diversity of lymphocytes in body
• During development, cell differentiation in lymphatic system
produces millions of different lymphocyte populations (each has
several 1000 identical cells)
• Each lymphocyte population responds to a different antigen
– Several 1000 lymphocytes not enough to overcome
pathogenic invasion, but begin dividing when activated in
presence of appropriate antigen
– Produce more lymphocytes with same specificity  clone
39
Specific Defenses:
4 Properties of Immunity
• Memory
– Lymphocytes remember antigens they’ve
encountered before
– During initial response to antigen, lymphocytes
undergo repeated cycles of cell division
– Produce 2 types of cells
• Activated lymphocytes that attack antigen invader
• Memory cells that remain inactive until exposed to same
antigen again at a later time
– After second exposure, response is faster, stronger,
and lasts longer than first time
40
Specific Defenses:
4 Properties of Immunity
• Tolerance
– Immune system
• Ignores “normal” (self) antigens
• Attacks foreign (nonself) antigens
– Can also develop in response to chronic (long-term)
exposure to antigen in environment; lasts only as
long as exposure continues
– Failure  autoimmune diseases
41
• Today in class we will discuss:
– The immune process
•
•
•
•
Antigens
T cells
B cells
Types of immune responses
– Cell-mediated immunity
•
•
•
•
Antigen presentation
Antigen recognition
T cell activation
Destruction/elimination of target cell/antigen
42
Immune Response Process
• Antigen
– = Foreign substance capable of inducing antibody
production
– Triggers immune response
– Activates
• Phagocytes  activation of T cells
• B cells
43
Immune Response Process
• T cells
– Initiate, maintain, control immune response
– Carry out direct physical/chemical attack on
antigen
– Stimulate activation of B cells
• B cells
– Mature into plasma cells that produce antibodies
– Antibodies in bloodstream bind to/attack antigen
 antigen-antibody complex that is eliminated
from system
44
Figure 22-17
45
Immune Responses
• 2 types
– Cell-mediated immunity
(T cells)
– Antibody-mediated (humoral) immunity
(B cells)
46
Immune Responses
• Cell-mediated immunity
– Involves T cells
– Process
•
•
•
•
Antigen presentation
Antigen recognition
T cell activation
Destruction/elimination of target cell/antigen
(cytotoxic T cells)
47
T Cells and Cell-mediated Immunity
• Antigen presentation
– = Process whereby foreign antigen is displayed
(“presented”) on cell membrane
– Requires combining foreign antigen + glycoprotein
(e.g., MHC protein)
Antigen = foreign peptide that has potential to
induce antibody formation
48
T Cells and Cell-mediated Immunity
• MHC proteins
– Membrane glycoproteins
– Synthesis controlled by group of genes called the
major histocompatability complex (MHC)
– Bind antigens
– Differ among individuals
– Two classes of MHC proteins
• MHC I
• MHC II
49
T Cells and Cell-mediated Immunity
• MHC I proteins
– Continuously being formed in all normal, healthy
cells that have a nucleus
• MHC II proteins
– In:
• Antigen-presenting cells (APCs)
– Present only when cell actively processing foreign antigen
• Lymphocytes (B cells and helper T cells)
NOTE: these cells also have MHC I proteins
50
T Cells and Cell-mediated Immunity
• Antigen-presenting cells (APCs)
– Phagocytic APCs
• Free and fixed macrophages in CT
– Engulf and break down foreign cells (bacteria or cancer) and
viruses
–  Foreign antigens
– e.g., microglia in CNS, Kuppfer cells in liver
– Nonphagocytic APCs
• Remove foreign antigens from their surroundings by
pinocytosis
• e.g., Langerhans cells of skin, dendritic cells of lymph
nodes and spleen
51
T Cells and Cell-mediated Immunity
• Antigen presentation (continued)
– As MHC proteins are formed they pick up small
peptides/antigens from cytoplasm
– Carry them to cell membrane
– Peptide/antigen-MHC protein complex inserted into
cell membrane
– Peptide/antigen “presented” to circulating T cells
52
Figure 22-18a
53
Figure 22-18b
54
T Cells and Cell-mediated Immunity
• Antigen recognition
– Circulating T cells (inactive) have receptors for:
• A specific antigen-MHC I or MHC II protein complex
– If membrane-bound peptide normal, ignored by
circulating T cells
– If peptide abnormal (from cancer cell) or foreign
(from bacteria or virus that infected cell) and
circulating T cell contains appropriate antigen-MHC
protein complex, membrane-bound complex will be
noticed (“recognized”) by T cell
55
T Cells and Cell-mediated Immunity
• Antigen recognition (continued)
– MHC I protein with foreign antigen
• Recognized by cytotoxic T cells and suppressor T cells
• Tells immune system “I’m an abnormal/infected cell – kill
me!” (= cytotoxicity)
– MHC II protein with foreign antigen
• Recognized by helper T cells
• Tells immune system “I’m an active APC. This antigen is
dangerous – get rid of it.”
• T cell will bind to antigen-MHC protein receptor
on cell membrane
56
Antigen Recognition by and Activation of
Cytotoxic T Cells
Figure 22-19, (Steps 1-3)
57
Antigen Recognition by and Activation of
Cytotoxic T Cells
Figure 22-19, (Steps 4)
58
T Cells and Cell-mediated Immunity
• T cell activation
– Must occur before immune response can begin
– When T cell released from antigen-MHC protein
receptor on cell membrane it is “activated”
– Activated T cell divides to produce:
• Active cells (cytotoxic, helper T cells)
• Memory cells
– Reserve (“sleeper”) cells
– Immediately become active T cells when antigen appears a
second time
59
Antigen Recognition and Activation of Helper T Cells
Antigen Recognition by CD4 T Cell
Foreign antigen
Antigen-presenting
cell (APC)
Class II MHC
Antigen
APC
Costimulation
CD4 protein
Inactive
CD4 (TH)
cell
T cell receptor
TH cell
Figure 22-20, (Part 1 of 2)
60
Antigen Recognition and Activation of Helper T Cells
CD4 T Cell Activation and Cell Division
Memory TH cells
(inactive)
Active
TH cells
Cytokines
Cytokines
Active helper T cells secrete
cytokines that stimulate both
cell-mediated and
antibody-mediated immunity.
Figure 22-20, (Part 2 of 2)
Cytokines
61
T Cells and Cell-mediated Immunity
• End result
– Activated cytotoxic T cells (Fig 22-19)
• Destroy abnormal or infected cells that “display” its target
antigen and MHC I protein (cytotoxicity)
– Activated helper T cells (Fig 22-20)
• Secrete cytokines when exposed to cells that “display” its
target antigen and MHC II protein
• Cytokines interact with sensitized B cells (see Fig 22-22)
• Summary of T cell activation (Fig 22-21)
62
Pathways of T Cell Activation
Figure 22–21
63
• Today in class we will discuss:
– Antibody-mediated immunity
•
•
•
•
•
T cells
B cell activation
Antibodies and their classification
Primary response in antibody-mediated immunity
Secondary response in antibody-mediated immunity
– Body responses to
• Bacterial infection
• Viral infection
– Immune disorders
– Aging and the immune response
64
Immune Responses
• Antibody-mediated (humoral) immunity
– Involves B cells
– Process
•
•
•
•
B cell sensitivation
B cell activation (by helper T cells)
Antibody production (by plasma cells)
Destruction/elimination of target antigen-antibody
complex
65
B Cells and Antibody-mediated
Immunity
• B cell sensitization
– Each B cell carries its own antibody molecules on its
cell membrane
– As it migrates through tissues, it finds appropriate
antigen that binds to its antibodies = “sensitization”
(like antigen presentation in T cells)
• Usually occurs in lymph node nearest site of
infection/injury
– Antigens brought into B cell and appear on cell
membrane bound to MHC II proteins
66
The Sensitization and Activation of B Cells
Figure 22-22
67
B Cells and Antibody-mediated
Immunity
• B cell activation
– Sensitized B cell on “standby” until it meets
appropriate, activated helper T cell
– T cell
• Recognizes antigen-MHC protein complex
• Binds to it
• Secretes cytokines
– Cytokines stimulate B cell activation
68
B Cells and Antibody-mediated
Immunity
• B cell activation (continued)
– B cell divides to form:
• Activated B cells
– Become plasma cells
» Produce antibodies specific for that antigen
• Memory B cells
– Remain in reserve to deal with subsequent injuries/infections
that involve same antigen
69
B Cells and Antibody-mediated
Immunity
• Antibodies (immunoglobulins, Igs)
– Found in body fluids, not cells
– Y-shaped, 2 parallel pairs of polypeptide chains
– 5 classes determined by structural differences
• IgG = largest, most common; only one that crosses the
placenta
• IgE = important in allergic responses
• IgD = helps B cells
• IgM = first Ab produced during immune response, then
declines when IgG increases
• IgA = found in glandular secretions (mucus, tears, saliva)
70
Figure 22-23
71
5 Classes of Antibodies
Table 22–1
72
B Cells and Antibody-mediated
Immunity
• Immune response
– Occurs after exposure to an antigen
– 2 types of responses
• Primary
• Secondary
73
B Cells and Antibody-mediated
Immunity
• Primary response
– Initial response
– Develops slowly, takes 1-2 weeks to peak after exposure
• Antigen must activate appropriate B cells, which then differentiate
into plasma cells
– IgM is first antibody to appear
• Provides immediate, limited defense that fights infection until IgG can
be produced
– Concentrations of IgM and IgG relatively low and do not
remain elevated
• Plasma cells have short life spans
• Production of new cells inhibited by suppressor T cells
– May not prevent an infection
74
Figure 22-24, 7th edition
75
B Cells and Antibody-mediated
Immunity
• Secondary response
– Response after second exposure
– More extensive and prolonged; more effective defense
– Due to large numbers of memory B cells primed for arrival of
antigen (may last > 20 years!)
– When same antigen appears a second time, memory B cells
differentiate into plasma cells that secrete huge quantities of
IgG antibodies
– IgG antibody activity stays elevated for extended period
– Response very adequate for preventing infection
– Effectiveness of secondary response is basic principle behind
use of immunization to prevent disease
76
Figure 22-24b, 7th edition
77
B Cells and Antibody-mediated
Immunity
• Antibody molecule binds to corresponding
antigen molecule  antigen-antibody complex
• Elimination of antigen-antibody complex
– Destroyed by phagocytes
– Destroyed by complement system
– Complexes may be insoluble and precipitate
– Form large complexes through agglutination
78
Overall Summary of Defense Mechanisms
Figure 22-26
79
Body Responses to Bacterial Infection
Figure 22–24
80
Responses to Bacteria & Viruses
Figure 22-27
81
Key Concepts
• Viruses replicate inside cells
• Bacteria may live independently
• Antibodies (and antibiotics) work outside cells,
so are primarily effective against bacteria rather
than viruses
• Antibiotics can’t fight common cold or flu
(caused by viruses)
• Primary defense against viral infection
– NK cells, interferon, T cells
82
Immune Disorders
• Allergies – over-reaction of immune system;
anaphylaxis = most extreme form
• Autoimmune diseases – produce (auto)antibodies
against own tissues
– Rheumatoid arthritis (connective tissue and joints)
– Thyroiditis (anti-thyroglobulin)
– Insulin-dependent diabetes mellitus (pancreas)
• Immunodeficiency diseases – problems with:
– Development of lymphoid tissues (genetic)
– Viral infection (AIDS – interferes with helper T cells)
– Treatment with immunosuppressive drugs (steroids,
antineoplastics) or radiation
83
Aging and the Immune Response
• Immune system less effective
• Some effects may be related to involution of thymus
and decreased thymic hormones
• T cells less responsive to antigens so fewer cells
respond to infection
• B cells less responsive so Ab levels don’t increase as
quickly  increased susceptibility to viral and bacterial
infections (Note: reason vaccinations for flu,
pneumonia recommended for elderly persons)
• Decreased immune surveillance (NK cells)  tumor
cells aren’t eliminated as effectively  increased
cancer rate
84