Transcript The Immune System

Primary Function
 To
Protect the body from invaders.
 Specific and Non Specific Mechanisms
 Cellular as well as chemical attacks are
mounted against the pathogens!
 Antigen – the identified enemy.
 Specific cellular soldiers include the B
cells and T cells.
 Non-specific cellular soldiers include
Macrophages
Perks if the Immune System
 The
immune system Ha s the ability to
recognize self from non-self.
 Small number of genes used to make a
vast array of recognition structures.
 Responds to pathogens and not
pollen(usually)
 Has memory.
Horse
Lining of the Trachea
Mucus secreting cells( orange ) trap microbes
Cilia( yellow ) sweep microbes into mucous
First Line of Defense
 Skin
provides a physical as well as a
chemical barrier.
 Mucous containing enzymes like lysozyme
trap and kill organisms.
 Acidic environment of the stomach kills
bacteria.
 However Hepatitis A can survive the gut
and can spread through this means.
Second Line of Defense
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If the invader makes it past the skin then non
specific cellular recruits are brought in.
 Inflammation ensues.
 The primary function of the inflammatory
response is to provide a means for these cellular
recruits to get to the damaged area.
 The response is initiated by chemicals released
by damaged cells.
Second Line Players
 Macrophages
 Natural
Killer Cells
 Eosinophils
 Neutrophils-first to arrive and are also
phagocytic but tend to self destruct and
only last a few days.
 Basophils
 Mast Cells
Macrophages
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Phagocytic
Differentiate from monocytes.
Secret super oxides and nitrous oxide to kill
bacteria.
Secrete lysozymes and work as a clean up
crew for cellular debris.
Are strategically placed in the body(spleen,
lymph nodes and connective tissue)
Tuberculosis can live and reproduce in
macrophages.
Macrophage
Phagocytosis of Bacteria by a
Macrophage
Notice that macrophages have
psuedopodia
Where Macrophages Hang Out in
the Body
Eosinophils
 Kill
larger parasites like the blood
fluke(Schistosoma mansoni).
 Limited phagocytic abilities.
 Shoot cytoplasmic toxic granules at the
parasite and cause it to lyse.
Natural Killer Cells
 Do
not directly attack microorganisms.
 Kill virally infected cells and abnormal cells
like cancer cells.
 Destruction of a virally infected cell causes
interferon to be released and protect
neighboring cells from viral infection.
Chemical Fighters of the First Line
of Defense
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Chemokines attract the cells of the non-specific
response. (Chemotaxis)
 Pyrogens induce fever to kill pathogen.
 Septic shock is a systemic non specific response
and can kill the patient in 24 hours.
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Septic shock can result in high fevers and a drastice
potentially lethal drop in blood pressure.
Complement System: a group of proteins that
lyse microbes.
The Inflammatory Response
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Primary function is to increase the local
blood supply to the affected areas.
– Precappilary atrioles dilate to increase blood
supply coming from the heart.
– Post capillary venioles constrict to keep the
blood in the damaged area. This causes
swelling(edema) and redness.
– Interstitial fluid (fluid between cells) also
moves into the area because macrophages
reside there.
Signals That Initiate the
Inflammotory response
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Basophils and Mast cells produce
histamine.
Histamine causes blood vessels to dilate
 Prostaglandins are also produced by
damaged tissue. Iniates pain.
 Clotting is a sign of repair and platelets
are involed.
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The Inflammatory Response
Neutrophil
Third Line of Defense
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Specific response
 Cellular components that recognize and destroy
specific antigens.
 The specific attack is launched by:
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B Cells
T cells
Antigenic receptors are proteins embedded in
the plasma membrane of B cells and T cells that
recognize specific antigens
 B cells may produce antibodies.
Genetic Basis for Specificity
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B and T lymphocytes bear about 100,000
receptors for antigen with the exact same
specificity.
 As undifferentiated T and B cells gain specificity
they link together several segments of antibody
genes to create unique peptides that make up
the antigen receptors.
 This occurs before the effector cell has seen the
antigen.
 This allows the immune system to respond to an
enormous variety of antigens.
Selective Response
Humoral response
B Cells
Cell mediated Response
Free Floating anitgens
Antibodies
T Cells
Infected Cells
Activate other cells
Memory Cells
i
Clonal Selection
Clonal Selection
Clonal Selection
Primary Immune Response
 Occurs
the first time the body is exposed
to the antigen.
 Takes 10-17 days after antigen exposure
to create the maximum effector response.
 Specific B cells and T cells generate
plasma cells that produce antibodies.
 These cells clear antigen from the body.
Secondary Immune Response
 On
the second exposure to the same
antigen a more rapid response occurs(2-7
days) due to memory.
 The response is greater and lasts longer.
 Antibodies have a higher affinity for the
antigen.
 Known as immunological memory.
Where do Lymphocytes Develop?
 Lymphocytes
develop from pluripotent
stem cells.
 Lymphocytes that migrate from the bone
marrow to the Thymus become T cells.
 Lymphocytes that remain in the bone
marrow become B cells.
Primary Verses Secondary
Response
How Lymphocytes Distinguish
“Self” From “Non-self”
 Newly
differentiated lymphocytes that
react with receptors on body cells are
made non-functional or programmed for
cell death (apoptosis).
 Failure of these to recognize self from
non-self leas to auto immune diseases like
Multiple Sclerosis.
Major Histocampatibility
Proteins(MHC)
 MHC
proteins are present on body cells
that distinguish the cell as “self”.
 T cells react with these proteins to
facilitate a specific response.
 There are two main classes of MHC
proteins.
B lymphocyte
MHC Proteins
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Class I MHC proteins are found on almost all
nucleated cells.
 Class II MHC proteins are found on specialized
B cells activated by T cells, some macrophages
and cells that make up the interior of the thymus.
 MHC proteins are polymorphic and there are
many alleles for MHC proteins.
 It is highly unlikely (with the exception of
identical twins) that any two individuals have the
same MHC proteins.
Two Main Types of Cells that
respond to MHC Proteins
Antigen Presentation
MHC I
Cytotoxic T Cells
MHC II
T Helper Cells
Attack infected cells
Involve antigen presenting cells
 Cell
Mediated Response and Cytotoxic T
Cells
More on MHC II and Helper T Cells
 Antigen
presenting cells (APC) ingest the
antigen, break it down and present pieces
of the antigen on its surface in the context
of MHC II proteins.
 An additional protein called CD-4
enhances the binding of the helper T cells
to the APC.
 APC Cells may be specialized
macrophages or B cells
MHC II and Helper T Cells
 When
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Helper T cells bind to the APC:
Clones of activated helper T cells proliferate.
Activated T helper cells secrete Interleukin II.
• Causes B cells that have seen the antigen to
differentiate into plasma cells.
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APC also secrete Interleukin I that stimulated
T cells to secrete interleukin II.
Action of Cytotoxic T Cells
Cell Mediated response
T Dependent Verses T Independent
Anitgens
T
Dependent antigens are antigens that
stimulate cause T cells to stimulate B cells.
 T Independent anitgens are antigens that
that do not involve T cells and stimulate
the production of plasma cells.
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Usually polysacharrides form bacterial
capsules, parts of the flagella or toxins.
Elicits a weaker response with no memory
cells.
T Dependent Antigens
Antibody Structure and Function
 Epitopes
( antigenic determinates) are
accessilble parts of the antigen that bind to
the antibody.
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One bacterial cell can be bound to as many
as 4 million antibodies.
There may be many different epitopes present
on a single pathogen.
 Antibodies
are known as serum proteins
called Immunoglobulins.
Antigens Can Have Many Epitopes
Immunoglobulins
 Consists
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of 4 polypeptide chains.
Two constant heavy chains and two variable
light chains.
• The variable region binds to the epitope.
• The constant region determines what type of
antibody it is.
Monoclonal antibodies are manufactured in
the lab for clinical use and research
studies.
Antibody Structure
Types of Immunoglobulins
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IgM - Largest and cannot cross the placenta with
many sites. Involved in agglutination.
IgG - Most abundant and small enough to cross
the placenta. Usually the first to arrive.
IgA - Found on mucous membranes and are
found in breast milk. Protect abaies from
gastrointestinal infection.
IgD - Found on the surface of B cells and most
like initiate plasma cell production.
IgE – Tails attach to basophils and mast cells
and trigger the release of histamine.
Antibody Mediated Disposal of the Antigen
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Neutralization - Antibody binds and blocks the
activity of the antigen.
Opsonization – Antibody attaches to antigen and
facilitates phagocytosis by macrophages.
Agglutination – Antibody clumps antigen
together and precipitates it out of body fluids and
facilitaes phagocytosis by macrophages.
Complement System – antibodies bind to
complement proteins and chemicals are release
to put holes in the pathogen membrane.
Immune Adherence- Antigen coated with
antibodies and complement proteins adhere to
the walls of blood vessels immobilizing than for
phagocytosis.
Complement System
Allergies Activated Histamine Release
T Cell With HIV
Active Verses Passive Immunity
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Active immunity individuals make their own
antibodies due to exposure to the antigen.
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Lasting immunity
Can be induced by vaccination.
Passive immunity occurs when antibodies are
passed from one individual to another.
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Temporary and an immediate fix (rabies).
Occurs naturally from mother to infant (IgG and IgA)
Blood Transfusions
The immune reaction of patients receiving the wrong blood
type will agglutinate surface antigens present on red
blood cells. The result is lethal.
Mothers and Rh factors. If the Mother is Rh negative and the baby is
Rh positive, during delivery when fetal and maternal blood is
exchanged the mother will produce antibodies against the Rh
antigen.
The problem occurs during the second pregnancy with an Rh positive
fetus.
Remedy – the mother is injected with antibodies against Rh antibodies
Allergies
Allergies - exaggerated response to
environmental antigens.
- Usually involves IgE.
- Some of the IgE antibodies will attach themselves
to mast cells instead of pollen and on subsequent
exposures to pollen stimulate the release of
histamine.
Anaphylactic Shock – a massive release of
histamine causes a lethal drop in blood pressure
-Individuals at risk carry epinephrine.
Transplanted tissues
verses Host Disease – Rejection of
transplanted tissues due to incompatible
MHC proteins.
 May remedied by the regeneration of the
patients tissues in cell culture.
 Currently close MHC matches are sought
out.
 Graft
HIV Budding
Immunodeficiency Diseases
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Scid(severe combined immunodeficiency).
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Hodgkins Lymphoma
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Genetic
Missing the functional enzyme called adenosine
deaminase(ADA)
Both branches of the immune system fail.
Usually requires bone marrow transplant.
Gene therapy is being tried to replace the ADA gene
but the results are unequivocal.
A type of cancer
Damages lymphatic system.
Acquired Immunodeficiency Disease(AIDS)
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viral
AIDS
 Caused
by a retrovirus called Human
immunodeficiency virus.
 Patients
with AIDS are highly susceptible
to opportunistic infections.
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Typically die of pneumocystitis
• Pneumocystis carinii (protozoan)
HIV Mode of Infection
Two major strains- HIV-1 and HIV-2
 Infects T helper (CD-4) cells.
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CD-4 along with a coreceptor called fusin
is its mode of entry.
Fusin is usually a receptor for chemokines.
Chemokines can suppress HIV-1 infection
because they compete with the virus for the
receptor.
Some individuals are have defective receptors
and are resistant to HIV infection.
HIV Replication in the Host
 HIV
makes DNA from RNA using reverse
transcriptase and integrates itself into the
host chromosome.
 As a provirus it continues to replicate its
viral proteins for the life of the host cell.
 Evades the host cell in this way.
HIV Budding
HIV Infection Stages
Arthritis