2. To protect the body against pathogens, the
immune system relies on a multilevel network of
physical barriers, immunologically active cells,
and a variety of chemicals.
first line of defense – any barrier that blocks invasion
at the portal of entry – nonspecific
second line of defense – protective cells and fluids;
inflammation and phagocytosis – nonspecific
third line of defense – acquired with exposure to
foreign substance; produces protective antibodies and
creates memory cells – specific
2
5. Skin and mucous membranes of respiratory,
urogenital, eyes and digestive tracts
outermost layer of skin is composed of epithelial cells
compacted, cemented together and impregnated with
keratin; few pathogens can penetrate if intact
flushing effect of sweat glands
damaged cells are rapidly replaced
mucous coat impedes attachment and entry of bacteria
blinking and tear production
stomach acid
nasal hair traps larger particles
5
6. Sebaceous secretions
Lysozyme, an enzyme that hydrolyzes the cell wall
of bacteria, in tears
High lactic acid and electrolyte concentration in
sweat
Skin’s acidic pH
Hydrochloric acid in stomach
Digestive juices and bile of intestines
Semen contains antimicrobial chemical.
Vagina has acidic pH.
6
8. Some hosts are genetically immune to the
diseases of other hosts.
Some pathogens have great specificity.
Some genetic differences exist in
susceptibility.
8
9. The study of the body’s second and third
lines of defense is called immunology.
Functions of a healthy immune system:
1. Constant surveillance of the body
2. Recognition of foreign material
3. Destruction of entities deemed to be foreign
9
11. Large, complex, and diffuse network of
cells and fluids that penetrate into every
organ and tissue
Four major subdivisions of immune
system are:
1. Reticuloendothelial system (RES)
2. Extracellular fluid (ECF)
3. Bloodstream
4. Lymphatic system
11
13. Network of connective tissue fibers that
interconnects other cells and meshes with the
connective tissue network surrounding organs
Inhabited by phagocytic cells – mononuclear
phagocyte system – macrophages ready to
attack and ingest microbes that passed the
first line of defense
13
14. Whole blood consists of plasma and blood
cells – red blood cells and white blood
cells.
Serum is the liquid portion of the blood after a
clot has formed-minus clotting factors.
Plasma – 92% water, metabolic proteins,
globulins, clotting factors, hormones and
all other chemicals and gases to support
normal physiological functions
14
15. Neutrophils- 55-90% - lobed nuclei with lavender
granules; phagocytes
Eosinophils – 1-3% - orange granules and bilobed
nucleus; destroy eucaryotic pathogens
Basophils, mast cells – 0.5% - constricted nuclei,
dark blue granules; release potent chemical
mediators
Lymphocytes – 20-35% - large nucleus B (humoral
immunity) and T cells (cell-mediated immunity)
involved in the specific immune response
Monocytes, macrophages – 3-7%- large nucleus;
phagocytic
15
18. 1. Provides an auxiliary route for return of
extracellular fluid to the circulatory
system
2. Acts as a drain-off system for the
inflammatory response
3. Renders surveillance, recognition, and
protection against foreign material
18
20. Lymph is a plasma-like liquid carried by
lymphatic circulation
Formed when blood components move
out of blood vessels into extracellular
spaces
Made up of water, dissolved salts, 2-5%
proteins
Transports white blood cells, fats, cellular
debris and infectious agents
20
21. Lymphatic capillaries permeate all parts of
the body except the CNS.
Thin walls easily permeated by
extracellular fluid which is then moved
through contraction of skeletal muscles
Functions to return lymph to circulation;
flow is one-direction-toward the heart-
eventually returning to blood stream
21
22. Classified as primary and secondary
Primary lymphoid organs – sites of lymphocytic
origin and maturation – thymus and bone
marrow
Secondary lymphoid organs and tissues –
circulatory-based locations such as spleen and
lymph nodes; collections of cells distributed
throughout body tissues – skin and mucous
membranes – SALT, GALT, MALT
22
24. Thymus – high rate of growth and activity
until puberty, then begins to shrink; site of T-
cell maturation
Lymph nodes - small, encapsulated, bean-
shaped organs stationed along lymphatic
channels and large blood vessels of the
thoracic and abdominal cavities
Spleen – structurally similar to lymph node;
filters circulating blood to remove worn out
RBCs and pathogens
24
27. Classic signs and symptoms characterized by:
Redness – increased circulation and vasodilation in
injured tissue in response to chemical mediators
and cytokines
Warmth – heat given off by the increased blood
flow
Swelling – increased fluid escaping into the tissue
as blood vessels dilate-edema; WBC’s, microbes,
debris and fluid collect to form pus; helping prevent
spread of infection
Pain – stimulation of nerve endings
Possible loss of function
27
28. pain (dolor)
heat (calor)
redness (rubor)
swelling (tumor)
loss of function
(functio laesa).
30. Diapedesis – migration of cells out of
blood vessels into the tissues
Chemotaxis – migration in response to
specific chemicals at the site of injury or
infection
30
34. Initiated by circulating pyrogens which reset the
hypothalamus to increase body temperature;
signals muscles to increase heat production and
vasoconstriction
exogenous pyrogens – products of infectious agents
endogenous pyrogens – liberated by monocytes,
neutrophils, and macrophages during phagcytosis;
interleukin-1 (IL-1) and tumor necrosis factor (TNF)
Benefits of fever:
inhibits multiplication of temperature-sensitive
microorganisms
impedes nutrition of bacteria by reducing the available
iron
increases metabolism and stimulates immune reactions
and protective physiological processes
34
35. 3 main types of phagocytes:
1. Neutrophils – general-purpose; react early to
bacteria and other foreign materials, and to
damaged tissue
2. Eosinophils – attracted to sites of parasitic
infections and antigen-antibody reactions
35
36. 3. Monocytes
called wandering cells until they enter a tissue where
they become fixed and turn into macrophages
Macrophages
scavenge and process foreign substances to prepare
them for reactions with B and T lymphocytes
▪ destroy old, damaged and dead cells in the body
▪ macrophages are found in the liver, spleen, lungs,
lymph nodes, skin and intestine
38. General activities of phagocytes:
1. To survey tissue compartments and
discover microbes, particulate matter and
dead or injured cells
2. To ingest and eliminate these materials
3. To extract immunogenic information
from foreign matter
38
40. Small protein produced by certain white blood
cells and tissue cells
alpha interferon- lymphocytes and macrophages
beta interferon – fibroblasts and epithelial cells
gamma interferon – T cells
Produced in response to viruses, RNA, immune
products, and various antigens
Bind to cell surfaces and induce expression of
antiviral proteins
Inhibit expression of cancer genes
40
42. Consists of 26 blood proteins that work in concert
to destroy bacteria and viruses
there are only a handful of proteins in the
complement system, and they are floating freely
in your blood.
manufactured in the liver.
activated by and work with (complement) the
antibodies, hence the name.
they cause lysing (bursting) of cells and signal to
phagocytes that a cell needs to be removed
42
47. Third line of defense – acquired
Production of specific antibodies by dual system of
B and T lymphocytes in response to an encounter
with a foreign molecule, called an antigen
Two features that characterize specific immunity:
specificity – antibodies produced, function only against
the antigen that they were produced in response to
memory – lymphocytes are programmed to “recall” their
first encounter with an antigen and respond rapidly to
subsequent encounters
47
48. Nonspecific and Specific responses of the
Immune System
T cells B cells
http://images.google.com/imgres?imgurl=http://www.vacadsci.org/jsr/imuneR.jpg&imgrefurl=http://www.vacadsci.org/jsr/tlist2.htm&h=663&w=1009&sz=460&tbnid=w5XN6XPgUBEJ:&tb
nh=97&tbnw=149&hl=en&start=9&prev=/images%3Fq%3Dimmune%2Bresponse%26svnum%3D10%26hl%3Den%26lr%3D%26sa%3DG
49. Made up of two cellular systems (lymphocytes)
1. humoral or circulating antiBody system - B cells
2. cell mediaTed immunity - T cells
50. B cells make
antibodies
T cells mount
direct attack on
foreign/infected
cell
http://www.people.virginia.edu/~rjh9u/gif/irsum.gif
52. Aka: humoral immunity
Involves antigen-antibody interactions to
neutralize, eliminate, or destroy foreign
proteins.
Purpose:
Main function of B-cells: to become sensitized to a
specific protein (antigens) and to produce
antibodies directed specifically against that
protein
53. B-cells
Macrophages
T-lymphocytes
All these work with B-cells to start and
complete antigen-antibody interactions
Therefore: for optimal AMI, the entire
immune system must function adequately
54. Start in bone marrow
Released in the blood
Then migrate into secondary lymphoid
tissues where maturation is completed
Spleen
Parts of lymph nodes
Tonsils
Peyer’s patches of GIT
56. Two main functions:
1) Return tissue fluid
to circulation
2) Fights infection
- both specific and
non-specific
resistance.
Lymph- fluid carried by
lymphatic vessels
57. - fluid enters lymphatic system by diffusing into dead-
end lymphatic capillaries
- infection-fighting activities occur in the lymph nodes
58. Lymphocytes (25-35% of WBCs)
T-cells: 70% of lymphocytes
▪ Cell mediated immunity
B-cells: 20-25% of lymphocytes
▪ Humoral immunity
59. Body learns to make enough of any specific
antibody to provide long-lasting immunity
against specific organisms or toxins
7 Steps needed to make a specific antibody
against an antigen
61. B cell activation occurs in response to
exposure to a specific foreign antigen
Invasion must occur in large #s that some
may evade detection by other lines of
defense
62. Helper T cells secrete a chemical called
interleukins
Interleukin 6 – induces maturation of B cells and
proliferation of T cells
67. Virgin B-cell can be sensitized only once
Therefore each B-cell can be sensitized to
only one type of antigen
Immediately after it is sensitized –it divides
and form two types of B-lymphocytes
68. B cells divide:
1. Plasma cells = synthesize and secrete large
numbers of antibodies with the same antigen
target
▪ Can make as much as as 300 molecules of antibody
/sec
2. Memory B cells = remain in reserve for future
attacks by the same antigen
69. When an antibody binds to the outer coat of a
virus particle or the cell wall of a bacterium it
can stop their movement through cell walls.
Or a large number of antibodies can bind to
an invader and signal to the complement
system that the invader needs to be
removed.
71. Antibody molecules are released in blood and
other body fluids as free antibody
Each remain in the blood for 3 to 30 days
Note: circulating antibodies can be
transferred from one person to another to
provide the receiving person with immediate
immunity of short duration
73. When a pathogen enters the
body it stimulates specific
lymphocytes to make
antibodies
These antibodies are
proteins of a very specific
shape and they will attach to
the specific antigens on the
surface of the pathogen
Binding of the antibody to
the pathogen targets the
pathogen for destruction by
macrophages
74. http://www.biology.arizona.edu/immunology/
tutorials/antibody/graphics/antibody.gif
http://www.blc.arizona.edu/courses/181summer/graphics/gr
aphics%20lect16/Life7e-Fig-18-10-
2%20structure%20of%20antibody%20p2.jpg
Antibodies are protein complexes made of 2 heavy chain and 2 light chain peptides
•Constant region (shown dark blue and dark red) = same in all antibodies
•Variable region (shown light blue and light red)= unique in each antibody
77. Type Number of Site of action Functions
ag binding
sites
IgG 2 •Blood •Increase
•Tissue fluid macrophage activity
•CAN CROSS •Antitoxins
PLACENTA •Agglutination
IgM 10 •Blood Agglutination
•Tissue fluid
IgA 2 or 4 •Secretions (saliva, •Stop bacteria
tears, small intestine, adhering to host
vaginal, prostate, cells
nasal, breast milk) •Prevents bacteria
forming colonies on
mucous membranes
IgE 2 Tissues •Activate mast cells
HISTAMINE
•Worm response
78. IgG (75% of Total Immunoglobulin)
• Appears in serum and tissues (interstitial fluid)
• Assumes a major role in bloodborne and tissue infections
• Activates the complement system
• Enhances phagocytosis
• Crosses the placenta
IgA (15% of Total Immunoglobulin)
• Appears in body fluids (blood, saliva, tears, breast milk, and
pulmonary, gastrointestinal, prostatic, and vaginal secretions)
• Protects against respiratory, gastrointestinal, and genitourinary
infections
• Prevents absorption of antigens from food
• Passes to neonate in breast milk for protection
79. IgM (10% of Total Immunoglobulin)
• Appears mostly in intravascular serum
• Appears as the first immunoglobulin produced in response
to bacterial and viral infections
• Activates the complement system
IgD (0.2% of Total Immunoglobulin)
• Appears in small amounts in serum
• Possibly influences B-lymphocyte differentiation, but role
is unclear
IgE (0.004% of Total Immunoglobulin)
• Appears in serum
• Takes part in allergic and some hypersensitivity reactions
• Combats parasitic infections
82. Actual binding of antibody to antigen is
usually not lethal to the antigen
Instead it starts other actions that neutralize,
eliminate, or destroy antigen
87. The first exposure to a
pathogen gives only a
slow and small immune
response
Levels of antibodies in the blood build up slowly when you are first exposed to
a particular pathogen.
•It takes over 5 days for the antibodies to reach a level that will fight off the
infection.
•During this time, you will feel the symptoms of the infection and damage will
be caused to your body tissues.
•In serious diseases, this can be fatal.
88. •The first exposure to a pathogen gives only a slow and small immune response.
•Repeated exposure to the same pathogen gives a much stronger and quicker memory response.
89. When your body is first infected with a pathogen, the
main task of the immune system is to combat the
infection. However, it also produces lymphocytes that
remain in your body for many years and remember
the pathogen in case it returns.
Immune memory
If you get infected a second time, your immune system is
already prepared for the pathogen and can quickly make
enough antibodies to kill the infection before any symptoms
are felt.
Vaccination takes advantage of this feature of the immune
system.
91. Once a T cell is activated by the presentation of the
combined MHC/Ag, it will clone (by mitosis) &
differentiate into:
cytotoxic T cells
helper T cells
memory T cells
suppressor T cells
93. 1. Cytotoxic T cells
attack foreign cells
seek out the specific pathogen/infected cell that
contains the targeted Ag & destroys it by secreting
various chemicals
Killer cell Target cell
94. 2. Memory T-cells
remain in reserve
When body sees the same antigen again, these cells
produce a rapid, specific response
these cells can immediately differentiate into cytotoxic &
helper T cells, causing a swift secondary response to the
invasion
95. 3. Suppressor T-cells
depress the response of T and B cells
are slow to activate but effectively “put on the brakes” or
end the immune response
activated more slowly than the other T cells
inhibit the response of the immune cells to prevent
potential “autoimmune” response
96. 4. Helper T cells
orchestrate immune response
necessary for coordination of both specific & non-specific
defenses, as well as for stimulating both cell-mediated &
antibody-mediated immunity.
In cell-mediated immunity they release chemicals
(cytokines) that strengthen the activity of cytotoxic T cells.
In antibody-mediated immunity they release cytokines
that stimulate activated B cell division & differentiation
into plasma cells
97. Helper T cells
release a variety of compounds called cytokines
cytokines
1. coordinate both specific and non-specific defenses
2. stimulate production of more t cells
3. stimulate production of antibodies by B cells
98. T lymphocytes (T cells) – they mature in the thymus and
are responsible for cell-mediated immunity
a) Helper T cells – direct the rest of the immune system by
releasing cytokines
b) Cytotoxic T cells – release chemicals that break open
and kill invading organisms
c) Memory T cells – remain afterwards to help the immune
system respond more quickly if the same organism is
encountered again
d) Suppressor T cells – suppress the immune response so
that it does not get out of control and destroy normal cells
once the immune response is no longer needed
99. Activated T cells clone &
differentiate into:
stimulate
Direct physical & Cytotoxic T cells
Helper T cells B cell
activation
chemical attack
Memory T cells
Suppressor T cells
Prevent
autoimmune
Antigens Remain in
response
reserve CELL MEDIATED IMMUNITY
ANTIGENS
bacteria
SPECIFIC APC’s phagocytize Ag & activate T
bacteria DEFENSES cells
viruses (Immune
response)
viruses
103. Immunization raises host resistance,
defenses, and immunity
104. Immunity is the resistance to injuries/disease caused by specific pathogens
Types of immunity:
http://faculty.ircc.edu/faculty/tfischer/images/t
ypes%20of%20immunity.jpg
106. present at birth
independent of previous exposure to Ag
genetically determined
species dependent
107. arises throughout life by active or passive
means
108. Active immunity
Lymphocytes are activated by antigens on
the surface of pathogens
Takes time for enough B and T cells to be
produced to mount an effective response.
109. Natural active immunity
naturally acquired active immunity
acquired due to infection
natural exposure results in immune response &
development of long term immunity
Artificial active immunity
Vaccination
induced (artificial) active immunity – deliberate “artificial”
exposure to Ag (i.e. vaccine/immunization)
110. Passive immunity – development of immunity
due to transfer of “pre-made” antibodies
naturally acquired passive immunity – Ab’s
transferred from mom baby across placenta or in
breast-milk
induced (artificial) passive immunity – administration
of Ab’s to fight disease after exposure to pathogen
111. Passive immunity
B and T cells are not activated and plasma
cells have not produced antibodies.
The antigen doesn’t have to be encountered
for the body to make the antibodies.
Antibodies appear immediately in blood but
protection is only temporary.
112. Used when a very rapid immune response
is needed
e.g. after infection with tetanus. Human
antibodies are injected. In the case of tetanus
these are antitoxin antibodies.
Antibodies come from blood donors who have
recently had the tetanus vaccination.
Only provides short term protection as abs
destroyed by phagocytes in spleen and liver.
113. A mother’s antibodies pass across the
placenta to the foetus and remain for several
months.
Colostrum (the first breast milk) contains lots
of IgA which remain on surface of the baby’s
gut wall and pass into blood
115. A preparation containing antigenic
material:
Whole live microorganism
Dead microorganism
Attenuated (harmless) microorganism
Toxoid (harmless form of toxin)
Preparation of harmless ags
118. Why aren’t they always effective?
Natural infections persist within the body for a
long time so the immune system has time to
develop an effective response, vaccinations from
dead m-os do not do this.
Less effective vaccines need booster injections
to stimulate secondary responses
Some people don’t respond well/at all to
vaccinations
Defective immune systems
Malnutrition particularly protein
119. Antigenic variation caused by mutation
Antigenic drift – small changes (still recognised by
memory cells)
Antigenic shift – large changes (no longer recognised)
No vaccines against protoctists (malaria and sleeping
sickness)
Many stages to Plamodium life cycle with many
antigens so vaccinations would have to be effective
against all stages (or be effective just against infective
stage but given in very small time period).
120. Sleeping sickness – Trypanosoma has a
thousand different ags and changes them
every 4-5 days
Antigenic concealment parasites live inside
body cells
Plasmodium – liver and blood cells
Parasitic worms – cover themselves in host
proteins
HIV – live inside T-helper cells
121. Review of the immune response
Non-
specific
response
Specific
response
NOTE: key role played by Helper T cells!!!
http://www.vacadsci.org/jsr/imuneR.jpg
125. Who should not get the vaccine or should wait?
1. people who have had a life threatening allergic reaction to
gelatin, neomycin, or a previous dose of the vaccine
2. people who are moderately or severely ill should wait
3. pregnant women should wait until after birth, women should
not get pregnant for 1 month after getting the vaccine
4. people with HIV/AIDS, immune system problems, taking any
drugs that affect the immune system, have cancer, or taking
chemotherapy or x-ray therapy for cancer should check with
their doctor before receiving the vaccine
5. people who recently had a blood transfusion should check
with their doctor
126. Live-microbial vaccines should not be given
simultaneously with blood, plasma, or immune globulin,
which can interfere with development of desired
antibodies; ideally, such vaccines should be given 2 wk
before or 6 to 12 wk after the immune globulins.
Immunocompromised patients should not receive live-
virus vaccines, which could provoke severe or fatal
infections.
In patients receiving short-term (ie, < 14 days)
immunosuppressive therapy (eg, corticosteroids,
antimetabolites, alkylating compounds, radiation), live-
virus vaccines should be withheld until after treatment.
127. Immunity may or may not be life-long with
vaccines.
To help keep the antibody levels high enough
to keep you protected you sometimes need
to have “booster shots”.
128. Nutrition and the immune system
Malnutrition impairs immune function
Fish oil: anti inflam
Stress and the immune system
Chronic stress has detrimental effects on immune
system
Ageing and the immune system
Vaccination