8

Internal Defense

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 Vertebrates launch both nonspecific and specific

immune responses.
A specialized lymphatic system allows more complicated
immunological responses.

Vertebrate nonspecific defense mechanisms include

mechanical and chemical barriers.
The skin is the first defense againts pathogen.
Sweat and sebum contain antibacterial chemicals.
Lysozyme in tears and other fluids is a defense againts grampositive bacteria.
Enzymes and stomach mucos trap inhaled pathogens which are
then phagotized.

Inflammation is a protective mechanism.

Injured cells and basophils release histamines that dilate blood
vessel.
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 Increased blood flow increases the temperature of the affected area, bring
increased number of phagocytes and causes redness.
Histamines make the capillaries more permeable and phagocytes leave the blood
vessel.
The leaky blood vessels also release plasma, causing edema and accompanying
pain.
The damage tissues swell and as the inflammation develops, the effects of
histamine are enhanced by other chemical mediators, including kinins and
complement protein, formed in blood plasma.
These chemicals attract neutrophils by a process called chemotaxis.The
neutrophils first stick to the walls of damaged blood vessels and then penetrate
into the tissues by squeezing between the endothelial cells lining the vessel
walls.
In the tissue they attack both bacteria and damaged tissue cells, engulfing them
in cytoplasmic vacuoles. Inside the vacuoles, bacteria are normally killed and
digested by lysosomal enzymes. Dead bacteria, tissue cells and neutrophils may
accumulate to form pus at the site of injury.
Inflammation is often simply a local response, but fever is a widespread
inflammatory response.
Macrophages and other cells release compounds such as IL-1 which cause fever.
Prostaglandins are also involves in causing fever.
Fever interferes with the growth of some bacteria by decreasing the free
ion required for growth, and increases the activity of some other cells
involved in the defense mechanism.
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 Fever
An infected area often fells warm to the touch because heat is one of
the bodys way of fighting pathogen. Normally the brain keeps the
human body at about 37oC (98.5oF). However when the body is
infected, some white blood cells (normally neutrophils) respond by
releasing hormone that act as pyrogen (fire-producers). If enough
pyrogen reach the brain the body thermostat is reset to a higher
temperature, allowing the body temperature to rise, producing fever.

Phagocytes destroy pathogens.

Inflammation leads to phagocytosis, particularly by
neutrophils and macrophages, which can engulf large numbers
of bacteria before being inactivated.

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 First line of defence:

Intact skin
Mucous membrane
Infection fighting chemical in tears, saliva etc.

Second line
Inflammation (WBC, macrophages, blood
clotting)
Organ with pathogen killing function (lymph
nodes).
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Describe the mechanism of inflammatory responses due to tissue damage?

While jogging barefoot along a seashore, your feet accidentally land on a
jellyfish. Soon the toes and foot are swollen, red and warm to the the touch.
Describe the events that result in these signs of inflammation.
Bacteria invade a tissue and directly kill cells or release metabolic
products that damage tissue.
Mast cells in tissue release histamine, which then trigger arteriolar
vasolidation (hence redness and warmth) as well as increased
capillary permeability.
Fluid and plasma proteins leak out of capillaries; localized edema
(tissue swelling) and pain result complement proteins attack
bacteria clotting factors wall off inflammed area neutrophils and
other phagocytes engulf invaders and debris macrophages
secretions attracts even more phagocytes, directly kill ivaders and
call for fever and for B and T cell proliferation.

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INVASION BY PATHOGEN

NON-SPECIFIC DEFENSE
MECHANISMS

Barrier

Inflammation

Acid secretion and

enzymes

SPECIFIC DEFENSE
MECHANISMS
Cell mediated
immunity

Antibody
mediated
immunity

Cytokines (e.g.
interleukins), interferon
Phagocytes; Phagocytosis

Interleukins: a diverse group of regulatory proteins (cytokines) produced mainly by macrophages and
lymphocytes
Interferons: A proteins (cytokines) produced by animal cells when challenged by a virus. Important in
immune responses, it prevent viral reproduction and enables cells to resist a variety of viruses.
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WHITE BLOOD CELL

GRANULAR
LEUKOCYTES

AGRANULAR
LEUKOCYTES
Monocyte

Neutrophil
Lymphocyte
Eosinophil
Basophil

Mast Cell: A type of cell found in connective tissue, contains histamines and is important
in allergic reactions.

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The effector cells of the immune system include granulocytes that is

neutrophils, eosinophils and basophils and agranulocytes comprising
lymphocytes and monocytes.
All of these cells are involved in the defence of body against disease but they
have different roles.
Granulocytes and monocytes are involved in non-specific immune responses.
This means that they react to general stimuli such as release of chemicals from
damaged tissue, rather than to individual types of disease organism.
Lymphocytes on the other hand mediate specific immune responses, including
the production of antibodies.

Interferon:
Viral infections cause several different types of body cells to produce
interferon. This substance is released into the circulation and then acts on
other cells making them immune to viral attack.
Interferon stimulates cells to produce antiviral proteins which interfere with
viral DNA and RNA replication.

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 Specific defence mechanisms in vertebrates include

antibody-mediated immunity and cell mediated
immunity.
The specific defense mechanism may take days to active,
but are very effective.
Specific mechanism rely on the lymphatic system; including organ
such as bone marrow, the thymus glands, spleen and lymph nodes.
Specific immunity include antibody-mediated immunity
(involving B cells) and cell-mediated immunity (involving T
cells).

Cells of the immune system include lymphocytes and

phagocytes
The three types of lymphocytes are T lymphocytes (T cells), B
lymphocytes (B cells) and natural killer (NK cells).

T cells are responseible for cellular immunity.

T cells originate from stem cells in the bone marrow and become
immunocompetent in the thymus gland.
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 Their generalized function is to attack tumor cells and cells

infected by pathogens.
CD8 cells include cytotoxic T and suppressor T cells.
Cytotoxic T cells (Tc) are also called killer T cells recognize and
destroy cells with foreign antibodies.
Their targets are virus-infected cells, tumor cells and foreign
tissue.
Their action via release of cytokines and various enzymes.

Suppressor T cells (Ts) release cytokines that may inhibit the

action of other T and B cells.

Helper T cells are called CD4 cells because of CD4

marker molecule.
Helper T cells enhance the action of other cells.
Helper 1 (Th1) cells promote cell-mediated responses.
Helper 2 (Th2) cells stimulate antibody production.

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 B cells are responsible for antibody-mediated

immunity.
B cells are produced in the bone marrow, and become
immunocompetent there as well.
B cells are produced with specific antigen receptors
When a B cell contacts a specific antigen, it bind to it and
divides rapidly, forming a clone of identical cells.
B cells mature into plasma cells which produced
antibodies
Plasma cells can produce more than 10 million
molecules of antibodies per hour.

Natural killer cells attack cancer cells.

NK cells are large, granular lymphocytes closely related to
T cells.
NK cells attack a wide variety of infected cells and tumor
cells.
NK cells function without prior exposure and do not
require presentation of antigens.
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 NK cells produce cytokines and various enzymes.

Macrophages are important in both nonspecific and

specific defense responses.
Macrophages are phagocytes which digest bacteria, but
retain some of the antigens and present them on their own
surface.
These antigen-presenting cells (SPCs) active helper T
cells.
Macrophages also secrete about 100 different compounds,
including interferons, interleukins and various enzymes.

The thymus instruck T cells and produces

hormones.
T cells develop in the thymus, dividing and developing
specific receptor sites in a form of positive selection.

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 Antibody-mediated (humoral) immunity is a chemical warfare

mechanism.
B cells produce a specific antibody that can combine with a specific
antigen.
The binding activates the B cell in a complex process that involves
macrophages (presenting antigens) and helper T cells
A macrophages displaying a foreign antigen-MHC complex secretes
interleukins, which activates helper T cells.
The B cell binds with the complementary antigen and displays it with a
class II MHC protein.
The B cells grows, divides and forms a clone; known as clonal selection.
Some of the clone mature into plasma cells which produce an antibody
specific to that antigen.
The B cells remain in the lymph nodes, but the antibodies pass out into the
lymph and ultimately the blood.
Some activated B cells become memory cells and avoid the programmed
death.
These memory cells produce small amount of antibody which
becomes part of the gamma globulin fraction of the blood.
Memory cells can become plasma cells if re-exposed to the same
antigen at a latter time.
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 Antibodies are group in five classes.

Antibodies are immunoglobulins (IG) and are classified in 5
groups.
IgG makes up about 75% of human immunologlobulins and are
part of the gamma globulin fraction of the blood.
IgG and IgM defend againts various pathogens.
IgA is present in other body fluids such as mucus, tears, saliva
and milk and prevents pathogens from attaching to epithelia.
IgD is present in low concentrations and with IgM and is
important in the function of B cells.
IgE is important in immunity to worms and release of
histamines.

The binding of antibody to antigen activates other defense

mechanism.
Antibodies typically bind to several antigens forming antibodyantigens complexes.
This complex may inactivate the pathogen or toxin.
It may stimulate phagocytosis of the pathogen.
It may work with the complement to destroy the pathogen.
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 Cell mediated immunity provide cellular warriors.

The T cells and macrophages destroy cells attacked by pathogens or
tumor cells.
T cells which are activated give rise to cytotoxic and memory T cells.
Cytotoxic cells leave the lymph nodes and move to the site of
infection.
Cytotoxic T cells secrete granules of enzymes which destroy the
target cell as well as lymphotoxins which target cancer cells.
Suppressor T cells are not well known and thought to inhibit T cells,
B cells and macrophages.

A secondary immune response is more rapid than a primary

response.
The primary response results in antibodies produced within 3-14
days after exposure.
IgM is the primary antibody produced during the primary
response, peaking during the logarithmic phase.
The antibody production declines after the infection is
suppressed.
The secondary response occurs after the second exposure to the
same antigen, as memory cells may last through out the entire
life of a person.
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 The seconsary response is a rapid effective response.

A second cold ar flu is due to exposure to a slightly
different strain of the bacterium or virus to which there are
no specific memory cells or antibodies.

Active immunity follows exposure to antigen.

Activate immunity can be induced artificially by immunization.
A vaccination causes production of the appropriate
antibodies and memory cells.
Viruses may be attenuated so that they do not cause
diseases after administration of a vaccine.
Some vaccines are killed pathogens or are derived from
bacterial toxins.

Passive immunity is borrowed immunity.

Passive immunity is the acquisition of antibodies produced by
the immune systems of another organism.
The effects are less long lasting.

Normally the body effectively defends itself againts cancer.

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 Graft rejection is an immune response againts

transplanted tissue
Tissues and organs from a donor have different MHC
antigens, which provokes graft rejection by the T cells.
Tissue typing allows close mathes of MHC antigens.
If close matching is not possible, immunosuppressive
drugs are administered.

Allergic reactions are abnormal immune responses.

Allergens are mild antigens that only trigger immune res
in some individuals.
Allergic asthma or hayfever is seen in about 20% of the
US population.

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 The first step is sensitization; macrophages degrade the allergen

and display it to the T cells.
T cells become activated and stimulate B cells to become plasma
cells and produce IgE.
Mast cells are activated by the allergen binding to the IgE on the
mast cells.
Mast cells release histamine and seratonin that result in
inflammation.
The mast cells attract white blood cells to the inflamed area
which further damage tissue and the allergic response.
Systemic anaphylaxis occurs after development of an allergy
which results in widespread vasolidation and may lead to death.
Allergic reactions are often treated with antihistamines which
block the histamines.

AIDS is an immune disease cause by retrovirus.

AIDS is caused by HIV the human immunodeficiency virus.
Immunosuppression is caused by HIV destruction of helper T
cells by attaching to the CD4 membrane protein.
AIDS is transmitted by semen, blood and other body fluids.

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Blood Group
Phenotype

Genotype

Antibodies present in
blood serum

Reacts (clumps) when red blood cells from groups below

are added to serum from group at left?
O

AB

ii

Anti A,
Anti B

No

Yes

Yes

Yes

IAIA or IAi

Anti B

No

No

Yes

Yes

IBIB or IBi

Anti A

No

Yes

No

Yes

AB

IAIB

No

No

No

No

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Antigen: Substance that can stimulate immune system or any non-self molecular configurations
which when recognized by certain lymphocytes, trigger immune responses.
Antibody: Protein produce by the immune system that combine with the specific antigen.
Vaccination
Vaccine: Commercially produced weakened or killed antigen of a particular disease that stimulates
the body to make antibodies.
Immunization:
Immune response: The production of antibodies or T cells in response to foreingn antigens.
Attenuation: The loss of virulence of a pathogenic microorganism after several generations of culture
in vitro. Attenuated microorganisms are commonly used in vaccines.
AIDS Aquired Immune Deficiency Syndrome.
HIV Human Immunodeficiency Syndrome.
Antibiotic:
One of a group of organic compounds, varying in structure, that are produced
by microorganisms and can be kill or inhibit the activities of other microorganism. One of the best
known example is penicillin, which was discovered by Sir Alexander Fleming, Streptomyxin etc.
Effector cells: are differentiated cells of lymphocytes subpopulation that immediately engages and
destroy an antigen-bearing agent during an immune response.
Memory cells: B or T cells that forms during an immune response but that does not act at once. It
enters a resting phase, from which it is released for a secondary immune response.

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