Download The Immune System

Overview of the Immune
System
YOU MUST KNOW:
*Elements of INNATE immune response.
*Differences between B & T cells (how
activated & actions of each)
*How antigens are recognized by immune
system cells.
*Differences in humoral and cell-mediated
immunity.
*Why Helper T cells are central to immune
response.
What is its function?
• PROTECTION FROM INVADERS!
• Three Lines of Defense:
• Innate Immunity- born with it!
• 1. Barrier Defenses – NONSPECIFIC
• 2. Internal Cellular Defenses - NONSPECIFIC
• 3. Acquired Immunity –develops only after
exposure to a SPECIFIC pathogen!
Barrier Defenses / 1st line of defense
• The Skin and Mucous Membranes
• Physical barriers; trap microbes
• Secrete substances (oil, sweat, etc.) that makes
the skin too acidic (pH= 3-5) for microbes to live
there
• Also secrete lysozyme, an enzyme that can
destroy bacterial cell walls (in saliva, mucous
secretions, & tears.)
• INNATE=you’re born with it!
Internal Cellular Defenses
• If an invader gets inside the body, the
internal defenses (2nd line of defense!)
take over
• Phagocytes (“to eat”/”cell”)
• White blood cells that “eat”/engulf
invaders
• NEUTROPHILS
•
•
•
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most numerous phagocyte (60-70%)
Attracted to infected tissue
Tend to destroy self with pathogen
Short-lived
• MONOCYTES
• Become macrophages
• Long-lived
Internal Cellular Defenses
• MACROPHAGES
• Can patrol lymphatic system/ spleen, lymph
nodes for pathogens
• Only about 5% of phagocytes
• Does not self-destruct after destroying
pathogen
• EOSINOPHILS
• Phagocytize parasitic invaders
• They do not engulf parasites, but instead
release destructive enzymes
• DENDRITIC CELLS
• Still act as phagocytic cell, but also
• Activates acquired immune system
• Invaders (bacteria/virus/etc) are then digested by
lysosomes.
Internal Cellular Defenses
• Antimicrobial Proteins
• Complement System- 30 serum
proteins w/ variety of functions.
Many lyse invaders.
• Interferon = “Warning Protein”
sent out by virus infected cells.
• Other body cells then make other
substances to inhibit viral
replication.
Internal Cellular Defenses
• Inflammatory Response
• Damage to tissue (from physical injury or the entry of
pathogens) leads to inflammation
• Histamine (signal molecule) is released by
basophyls & mast cells (leukocytes).
• This causes increased vasodilation & increased
permeability of capillaries.
• Increases blood flow to site of injury
• Carries clotting factors, platelets, phagocytes,
etc.
• Diffuse into interstitial fluid to help REPAIR
• Causes redness, edema (swelling caused by
fluid), & increased temperature occur.
• The purpose is to limit infection and repair damaged
tissue
Internal Cellular Defenses
• Example of how to activate the
inflammatory response
Internal Cellular Defenses
• Natural Killer (NK) Cells- Patrol the body and attack
virus-infected cells and cancer cells
• Surface receptors (“nametags”) identify these
infected/damaged cells
• NK cells release chemicals that cause cells to kill
themselves, apoptosis (programmed cell death)
• Indiscriminate . . . can damage surrounding healthy
cells
• All 4 of these internal defenses (phagocytes, interferons,
inflammatory response, and natural killer cells) occur
INNATELY.
Acquired Immunity
• Acquired immunity is the third line of
defense.
• Acquired immunity only comes after
EXPOSURE to a specific pathogen.
• Receptor proteins in cell membrane
provide pathogen-specific recognition.
• Acquired immunity occurs more slowly
than innate immunity.
Acquired Immunity
• Acquired immunity is
performed by
lymphocytes
• Made from stem cells in
the bone marrow
• B-cells:
• mature in the bone
marrow
• T-cells:
• mature in the thymus
Acquired Immunity
• Antigen = foreign molecule that is
recognized by lymphocytes and
causes them to respond
• Other phagocytic cells release
cytokines (chemical proteins) that
activate acquired immunity
• An antigen is usually a surface
marker (“nametag”) that is
“presented” by another
phagocyte
• Lymphocytes
• Have antigen receptors (100,000
on each cell!) that recognize a
SPECIFIC portion of the antigen
(epitope) by shape
• VERY SPECIFIC!!!
Acquired Immunity
• B-lymphocytes are
responsible for the humoral
immune response
• They are responsible for
pathogens OUTSIDE of cells
(in body fluids, etc.)
• B-lymphocyte is “activated”
when specific antigen binds
to its receptors.
• Activated B-lymphocytes
reproduce using clonal
selection in order to destroy
the invader (the clones are
able to specifically bind to
antigens)
Acquired Immunity
• These B-lymphocytes produce
two types of cloned cells:
• Effector cells (Plasma Cells)
• Make antibodies!
• Special proteins that bind onto
the ANTIGENS of the “invaders,”
which flags them for destruction
(usually by macrophages)
• Memory cells
• These cells live a long time, and
can respond quickly if this same
antigen is seen again
Types of Antibodies
• IgM
• First of the antibodies produced
• Responsible for agglutination of antigens
• Activates complement
• IgG
• Most abundant antibody
• This is the only antibody that can cross placenta to fetus (discuss
later)
• Agglutinates and neutralizes antigens
• IgA
• Found in tears, saliva, mucus, and breast milk
• Gives localized defense of mucous membranes by antigen
agglutination
• Gives passive immunity to nursing infants through breast milk
Types of Antibodies
• IgE
• Triggered release form mast cells and basophils
• Responsible for agglutination of parasites
• Also responsible for allergic reactions
• IgD
• Present on surface of non-differentiated B cells
• Acts as an antigen receptor and stimulates the differentiation of
and proliferation of B cells (clonal selection)
Primary vs. Secondary Response
• Primary Immune
Response
• When an individual is
first exposed to an
antigen, it takes time to
activate the immune
system
• Must do a series of
recombinant changes in
protein synthesis to
create the correct
antibody that binds to a
specific epitope
• Secondary Immune Response
• After an initial exposure, the
memory cells that remain are
able to recognize the SAME
antigen
• Subsequent exposures allow
the immune system to
RAPIDLY respond to the
antigen and create the
necessary immune cells
• Individual doesn’t fell
symptoms and is considered
immune
Acquired Immunity
• T-lymphocytes are responsible for the
cell-mediated immune response
• Guard against invaders hiding out inside infected cells
• Cytotoxic T cells
• They are the effectors (“hit men”) of the cell-mediated immune
response by lysing infected cells or “punching holes” in the
membrane
• They kill infected body cells (present foreign antigens on major
histocompatability complex (MHC) or other cells that don’t belong
(like tumors) at the cell membrane
• Class I MHCs = on almost all body cells except RBCs.
• Class II MHCs= made by dendritic cells, macrophages, & B cells.
• Some of these cells will become memory cells, so they can be
reactivated if the pathogen “strikes again.”
Acquired Immunity
•
•
•
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Helper T Cells
When activated by binding to MHC protein of an
antigen presenting cell, Helper T-cells secrete
cytokines (like interleukin) which stimulate &
activate B cells & Cytotoxic-T cells.
“Master Switch of acquired immunity”
HIV destroys Helper T cells, and shuts down both
humoral & cell-mediated immunity!
Cytotoxic T Cells & MHC
The Immune System
• Key Features of the Immune System
• Specificity
• Recognizes SPECIFIC invaders – species of
bacteria, for example
• Due to ANTIGENS displayed on the MHC
(Major Histocompatibility Complex)
• Diversity
• The immune system can respond to millions
of different invaders because it has so many
different lymphocytes “on reserve”
The Immune System
• Key Features of the Immune System
• Memory
• The immune system can “remember” antigens it’s
seen before and react more quickly the second,
third, etc. time it sees them
• Acquired immunity
• Because of memory cells (B & T cells)!
• Self/Nonself Recognition
• The immune system can distinguish between the
body’s own molecules from foreign molecules
• Autoimmune disorders (example: lupus, MS,
rheumatoid arthritis) means that this part of the
immune system is not working – the immune system
destroys the body’s own tissues
Passive vs. Active Immunity
• Passive Immunity
• Transferring antibodies from one person to
another, without the B-lymphocytes having to
make them!
• The person will already have the memory cells
and antibodies, so the next response will be
quicker!
• Example:
• Pregnant mother passes antibodies to her fetus through
the placenta
• Antibodies in breast milk
• Immunoglobulins (antibodies) may be given to a person
who is exposed to a disease to prevent them from
getting the disease.
Passive vs. Active Immunity
• Active Immunity
• Immunity to a specific pathogen that
comes after having come in contact
with the pathogen.
• Can come naturally
• Been sick with the pathogen before
• Example: had measles before, 2nd
time won’t take as long to respond
• Can come artificially
• Immunization (weakened or dead
form of the pathogen is used to
induce immune response.)
• Edward Jenner - smallpox
• Stimulates B-lymphocytes to make
antibodies AND memory cells
Problems associated
with the immune
system
Blood Groups and Transfusions
• When we discussed Genetics, we discussed blood groups (A,B,O)
• The A and B represent different protein markers on the surface
of blood cells
• If you have an A protein on your blood cell, you have Type A
blood
• If you have a B protein on your blood cell, you have Type B
blood
• If you have an A protein and a B protein on your blood cell, you
have Type AB blood
• If you have neither an A protein or a B protein on your blood
cell, you have Type O blood
• There is also a factor called the Rh factor
• If you have the Rh factor, you are considered “+”
• If you don’t have the Rh factor, you are considered “-”
Blood Groups and Transfusions
• Your bodies’ immune system is able to “recognize” your
blood type
• If you get a transfusion that has a surface protein your
blood cells are lacking, your immune system will
mount a reaction
• Example: You have type A blood. If you get a
transfusion of type B or type AB, your immune
system will attack the blood as a foreign antigen
• This is why type O blood is the universal donor, it
doesn’t have any surface proteins to activate the
immune system
Rh Factor and a Fetus
• The Rh Factor can cause some problems for
pregnant mother
• Take the following scenario:
• Rh Factor is dominant to no Rh Factor
• Mother is homozygous recessive for Rh
factor
• Father is homozygous dominant for Rh
Factor
• Do a Punnett square to determine the Rh
Factor phenotype for the infant
Erythroblastosis Fetalis
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•
•
Blood does transfer from mother to fetus (through placenta)
During child birth, the mother is exposed to blood of child
After 1st child, mother has been exposed to Rh factor
For all other fetuses that are Rh+ (does have the Rh factor), the
mother, who is Rh- (does not have the Rh factor), has produced
antibodies against the Rh factor
• REMINDER: IgG antibodies can pass through the placenta
• End result, the antibodies produced by the mother will attack the
blood of infant
• This is called Erythroblastosis Fetalis
• NOWADAYS: There are ways to prevent death of fetus through
transfusions
• Also, the mother can be given a shot of anti-Rh antibodies to destroy
any baby blood cells that the mother becomes exposed to . . .
prevents the mother form developing memory cells
Organ and Tissue Transplants
• MHC markers on cells are unique to everyone
(except identical twins)
• Therefore when looking for donors, they must
have a majority of these markers that “match”
• Otherwise, body will recognize the
transplant/graft as a foreign antigen and the
organ/tissue will be destroyed
• Many individuals that have transplants must take
immunosuppressive drugs to prevent a “graft vs.
host reaction” . . . rejection of the
transplant/graft
Allergies
• Allergies are hypersensitivies of the immune system to an
environmental molecule because of its ANTIGENS
• Allergic reactions are caused by the release of IgE antibodies .
. . an over-reaction to nonharmful stimuli
• Anaphylactic shock
• Life-threatening allergic reactions to ingested or injected
allergens
• Peanuts, shellfish, bee stings, etc.
Autoimmune Diseases
• Sometimes a body loses the ability to recognize
“self” cells
• As a result, the immune system attacks these self
cells
• Rheumatoid arthritis: immune system attacks
cartilage and bone of joints
• Insulin-dependent diabetes mellitus: Cytotoxic
T cells attack the insulin-producing beta cells in
the pancreas
HIV/AIDS
• We have already discussed the action of HIV (human
immunodeficiency virus) and how it affects cells (retroviruses)
• What makes HIV so dangerous is that is targets and eventually
destroys the T helper cells
• Since the T helper cells are key to activating both cellmediated and humoral immune responses (through the
release of cytokines), the acquired immune system is
effectively shut down
• HIV does not kill the individual, it is subsequent diseases
• Since the host doesn’t have an immune system, they cannot fight
off the infection
• The condition of a compromised immune system is given the
name of the disease, AIDS (acquired immunodeficiency
syndrome)