Chapter 9: Immunology: A fight for your life
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Objectives
·
List
the bodies Three Lines of Defense and know how they
work.
·
Why do
we have Inflammation.
·
What are the roles of Macrophages
and their like
·
The
Immune system: Define how specificity and
memory occur?
·
Antibody-Mediated
Responses B cells (plasma cells)
produce antibodies, how do antibodies and antigens
interact?
·
Describe
Abnormal or Deficient Immune Responses: Allergies, Aids, and Rheumatoid arthritis.
·
You are
exposed to an organism that can cause a disease and it is also resistant to antibiotics.
Describe the process of your infection and how your body would
eventually overcome the bacterial infection.
·
Differentiate
between nonspecific and specific
immunity.
Important
figures 9.2 pathogens, 9.3 the lymphatic system, 9.7 inflammation, 9.9 antibody
production, 9.10 how antibodies work, 9.12 antigen presenting cells. 9.15 how
immunity works.
Be able to
discuss the Health watch topic on Antibiotic Resistance.
1.
Humans and the discovery
of immunity
A. 1796 Dr. Jenner discovers immunization with cowpox protects humans form smallpox.
B. A century later Pasteur develops the procedure to discover other vaccines (Rabies).
C. At this same time Robert Koch determines the link between pathogens (bacteria) and disease.
2. The three Lines of Defense: your body has 3 ways to prevent/fight infection .
A. Pathogen: is a virus, bacteria, fungi, protozoan or parasite that can cause disease.
B. The 3 points of defense
1) Surface Barriers to Invasion (a strong outer coat that physically prevents invasion).
a) Intact skin and mucous membranes are important barriers to invasion of pathogens.
b) Resident bacteria of mucous membranes, such as in the gut and vagina, keep pathogens in check by growing faster and using all the available resources. (competition prevents one species from overgrowing all others)
c) Lysozymes, in the mucous membranes attack bacteria and degrade their cell walls.
d) Enzymes in tears, saliva and gastric fluid also degrade pathogen cell walls.
e) Even urine with its low pH helps prevent invasion of the bladder and kidneys.
a) Phagocytosis by white blood cells (macrophage or agranulocytes) (WBC's).
b) Attachment and neutralization by plasma globulin proteins.
c) Inflammation (swelling, redness, heat).
a) Mounted by lymphocytes that recognize unique molecular configurations on invading pathogens (remember you only get sick by one type of pathogen once, then you are immune).
Some circulating proteins that provide protection:
3. Complement Proteins
A. 20 different proteins (make up the protective complement system) circulate in the blood in an inactive form. Too much complement can cause damage to tissues, so it is only activated 2 ways.
1) A complement protein (C1) can bind to a complex consisting of antibody and antigen.
2) Complement protein can interact with carbohydrate molecules on the surfaces of microorganisms (lipopolysaccharides and peptidoglycan make this stuff go wild).
B. These proteins are activated in a domino effect (1 activates 2 which activates 3 and so on) with these results:
1) Membrane attack complexes become inserted into the plasma membranes of pathogens causing cell death .
2) Chemical gradients of proteins attract phagocytes to the scene.
3) Complement proteins coat the surface of invading cells-attracting phagocytes.
A. The role of Macrophages and their like.
1) White blood cells arise from stem cells in bone marrow and either circulate in the blood or reside in tissues.
2) Three types of white blood cells act swiftly but are not adapted for sustained battles.
(1) Neutrophils ingest and digest bacteria.
(2) Eosinophils secrete enzymes that damage parasitic worms: they also phagocytize foreign proteins and help to control allergic responses.
(3) Basophils secrete histamine, which alters blood vessel permeability.
3) Macrophages immature form is called monocyte engulf many foreign agents and do so repeatedly with a big appetite.
B. The Inflammatory Response.
1) Acute inflammation in a besieged tissue allows phagocytes, complement proteins, and plasma proteins to escape from the blood.
2) Physical signs include redness, swelling, heat and pain.
3) The progression of inflammation is as follows.
a) Tissue irritation causes mast cells (type of basophile) to release histamine and other substances which cause the blood vessels to become engorged and capillary walls to become leaky, fluids and proteins leak from the capillary bed into the surrounding tissues.
b) Within a few hours, Neutrophils and macrophages leave the blood vessels to begin engulfing foreign materials.
c) Macrophages release interleukin01, which signals other white blood cells, allows body temperature to rise further (enhancing defense mechanisms) and causes conservation of body energy due to drowsiness.
d) Clotting mechanisms help wall of the pathogen and promote repair of tissues.
5. The Immune system
A. Defining Features
1) Sometimes physical barriers and inflammation are not sufficient to contain an infectious pathogen.
a) The vertebrate immune system (your resistance to infection) is due to the interaction of white blood cells called B and T lymphocytes and the infectious agent (virus, bacteria, worms ect).
b) This system displays both specificity and memory.
2) Each kind of cell, virus or substance is coated with a number of unique molecules that gives every particle/cell a unique identity.
a) Your own cells(“self”) have surface proteins, which your lymphocytes ignore.
b) However, ”nonself” markers form viruses, bacteria, bee venom, organ transplants, and all other particles have antigens that trigger an immune responses.
c) When B and T lymphocytes encounter a nonself marker, they begin to divide repeatedly.
(1) Some subpopulations become effector cells, which will engage and destroy the pathogen.
(2) Others become memory cells that will be called later if the body is infected again.
3) Immunological memory and specificity involve three events
a) recognition of a specific invader (you were exposed once to this pathogen).
b) repeated cell divisions to form huge populations of lymphocytes.
c) differentiation into subpopulations of specialized effector and memory cells (you produce more memory cells and more cells that will kill the pathogen).
B. Antigen-Presenting Cells--The triggers for Immune Responses
1) Any nonself marker that triggers the formation of lymphocytes is an antigen; the antigen binding receptors are antibodies secreted by B cells. (also called plasma cells).
2) MHC (Mass Histocompatibility Complex) markers reside in the plasma membranes of body cells: some are unique to your lymphocytes and macrophages.
3) Macrophages can digest bacterial invaders , pieces of the pathogen are attached to Macrophage MHC molecules to form antigen-MHC complexes.
4) Any cell that displays the complex is an antigen-presenting cell.
5) When antigen fragments and a certain MHC marker are displayed together at the cell’s surface, T helper lymphocytes signal B lymphocytes, that can recognize the antigen to divide many times.
C. Key Players in Immune Responses
1) Helper T cells produce and secrete chemicals that promote formation of large populations of effector and memory cells.
2) Cytotoxic T cells kill body cells that have either become infected with intracellular parasites or are identified as tumor cells (i.e. cell-mediated immune responses).
3) B cells are lymphocytes that produce antibodies. (i.e. antibody mediated responses).
D. Control of Immune Responses.
1) When antibodies have “saturated” the binding sites on pathogens, fewer exposed antigens translate into less production of antibodies.
2) Inhibitory signals form cells with suppresser functions shut down the immune response.
6. Lymphocyte Battlegrounds
A. The antigen-presenting cells and lymphocytes interact in lymphoid organs (tonsils, adenoids), lymph vessels and lymph nodes.
B. In lymph nodes, cells are organized for maximum effectiveness with antigen presenting cells in the front line engulfing invaders.
7. Cell mediated Responses
A. T cell formation and Activation.
1) T cells arise form stem cells (totipotent blood cells that make the blood) in the bone marrow, then travel to the thymus gland where they differentiate into helper T and Cytotoxic T cells and acquire receptors for MHC markers and antigen specific receptors.
2) Virgin
T cells ignore both unadorned MHC markers and free antigen but do bind antigen
MHC complexes on presenting cells, which stimulates division of T cells to form
clones.
B. Functions of effector T cells
1) Some clones, effector Helper T cells, secrete interleukins that stimulate cell divisions of virgin T cells and virgin B cells.
2) Effector cytotoxic T cells recognize MHC markers on viral infected cells and tumors and kill the cells by secreting performs that punch holes in the cell membranes.
C. Natural Killer Cells
1) Other Cytotoxic cells such a natural Killer (NK) cells also kill tumor and infected cells.
2) They
do not require an antigen MHC encounter.
8. Antibody-Mediated Responses
A. B cells and Targets of Antibodies
1) B cells also arise form stem cells and
eventually produce copies of specific antibody.
a) Antibodies
are proteins with binding sites for a single antigen
b) The
Y shaped antibody is embedded in the B cell membrane with the two arms
extending as antigen receptors.
2) When its receptors lock onto an antigen, the
B cell will undergo repeated cell divisions if their are also present
secretions form a helper T cell already activated by the same antigen.
3) The
clonal B cells differentiate into effector (formerly known as plasma) cells and
memory cells: effector cells produce antibodies that recognize antigens and
mark their possessors for destruction by phagocytes.
4) The
main targets of antibody-mediated responses are extracellular pathogens and
toxins.
B. Immunoglobulins
1) All
five classes of antibodies have binding sites for antigen but the ones in each
class have special sites for specific functions.
2) The different classes are the protein
products of gene shuffling
a) IgM
antibodies set the complement cascade in motion and bind invaders into clumps.
b) IgG
antibodies neutralize toxins, are long lasting, can cross the placenta, and are
found in mother’s milk.
c) IgA
antibodies are present in the mucus of respiratory, digestive, and reproductive
tracts.
d) IgE
antibodies bind to Basophils and mast cells where they act as raps for antigen.
e) IgD
are antibodies on B cells that probably participate in the differentiation of
sensitized B cells into effector and memory b cells.
9. Immune specificity and Memory
A. Formation
of antigen-specific Receptors
1) Immunological specificity lies in DNA
recombination’s
a) All
T and B cells have the same genes coding for the polypeptides in each arm of
the antibody molecule.
b) Many
different polypeptides can be made by shuffling the genes into millions
of combinations to produce antibodies against numerous agents.
2) The clonal selection theory proposes
that a lymphocyte activated by a specific antigen will divide and give rise to
a clone of cells that are specific only to that antigen.
B. Immunological memory of a primary immune
response is explained by the clonal selection theory.
1) some B and T memory cells will continue to
circulate for years and make a secondary response to any subsequent encounter
of the same antigen.
2) this
later response will be more rapid, greater, and of longer duration than was the
primary immune response.
10. Immunization
and Other Practical Applications of Immunology.
1) Immunization
involves a deliberate production of an immune response and memory cells.
a) In
active immunization, the first dose of vaccine elicits a primary immune
response: a second dose (“booster”) elicits a secondary, and more long lasting
response.
b) Passive
immunization involves injections of antibodies to persons already infected
with pathogens.
c) A
vaccine can be made form killed or weakened pathogens, inactivated toxins, or
genetically engineered viruses.
B. Monoclonal antibodies.
1) Monoclonal antibodies are obtained by
techniques that produce large quantities of antibody form B cells.
a) A
mouse is immunized with a specific antigen: B cells are extracted and fused
with cancerous cells known as myeloma cells to produce a hybridoma cells.
b) The
hybridoma cells produce the desired antibody indefinitely.
2) monoclonal
antibodies are being used commercially in home pregnancy tests, screening for
prostate cancer, and passive immunity.
C. Cytokines.
1) Signaling
molecules produced by lymphocytes are called Cytokines.
2) Tumor
necrosis factor secreted by cytotoxic T cells has been used experimentally to
treat malignant melanoma of the skin.
3) Interferon’s
have been used to suppress viral diseases.
11. Abnormal or
Deficient Immune Responses
1) An
allergy is a secondary immune response to a normally harmless substance.
2) Exposure
to an allergen triggers production of IgE antibodies, which cause the release
of histamines and prostaglandin’s from
mast cells.
3) In
a few individuals explosive
inflammatory responses trigger life threatening anaphylactic shock in which air
passages constrict and fluid rushes out of the capillaries.
4) Antihistamines
are often used to relieve the short term symptoms of allergies.
B. Autoimmune disorders
1) In an autoimmune response, lymphocytes turn against the body’s own cells.
2) Consider some examples:
a) Rheumatoid arthritis is an inflammation of the joints caused by antibody that treats the body’s own IgG molecules as if they were antigens
b) In systemic lupus erythematosus, patients develop antibodies to their own DNA
C.
Deficient Immune Responses
1) When
the body has inadequate numbers of lymphocytes, infections that would normally
not be serious become life threatening.
2) In acquired immune deficiency syndrome(Aids) the cause is the HIV
virus
12. Immunity Defied: Infectious Disease
A. Modes of
Transmission
1) Pathogens
can be transferred by direct contact (contagion) of body parts.
2) Indirect
contact with food and inanimate objects that have previously been in contact
with an infected person can spread pathogens.
3) Pathogens
can be inhaled after being put into the air by a cough or sneeze.
4) biological
vectors, such as arthropods(insects), can carry disease organisms form one
victim to another.
B. Patterns
of Occurrence
1) Sporadic
diseases break out irregularly and affect few people (e.g. whooping cough).
2) Endemic
diseases occur continuously in rather localized populations (e.g. Leprosy).
3) In
an epidemic a disease abruptly spreads through large portions of a
population for a limited time (cholera in Peru in 1991).
4) When
epidemic spread around the world, a pandemic is declared (e.g. influenza
in 1918).
C. Virulence
1) Virulence
refers to the damage that a pathogen can do to a susceptible host.
2) It
depends o n how easily the pathogen can avoid detection and destruction within
the body.
D. What
antibiotics Can and Cannot Do
1) Antibiotics
can destroy or inhibit the growth of bacteria.
2) Antibiotics
are not effective against viruses, although some antiviral drugs can ease
symptoms.
1) Bacterial
resistance is a major problem due to overuse, which selects for the most
resistant strains.
2) Infectious
disease specialists have proposed a worldwide surveillance system to identify
new resistant strains before they can become established.
F. Case
Study: The Resurgence of tuberculosis
1) Globally,
tuberculosis kills more people that any other single infectious disease.
2) It
is easily transmitted in airborne droplets produced by coughing or sneezing.
3) The
problem is exacerbated in persons with weakened immune systems e.g. aids
victims.
4) As
little as 30 years ago this disease could have been destroyed like small pox,
now?????
Possible assignments:
things to think about
1.
Follow the paths of resistance that an organism would
have to overcome to produce infection.
2.
Differentiate between nonspecific and specific
immunity.
3.
How does immunization work?
4.
Describe the
antigen presenting process. Which of
the lymphocytes determines that an antigen is worth responding against?
5.
Define and antibody and an antigen. What cells make these products. How are they related?
Example Multiple choice questions. Choose the best answers. More than one answer is possible top
1.
A pathogen can be a:
2.
Which of the following are responsible for immune
specificity
3. Immunity memory is due to
4. If you are vaccinated for the flue this year, how come you can get the flu next year?
5. Too little and too much immune response can be harmful to your body. Which of the following are correct examples of immune disorders.
Answers to quiz: 1) all are correct, 2) B, 3) B, 4) D, 5) B, C
Some interesting web sites:
http://www.cdc.gov/ This is the beginning site for the Center for Disease Control (CDC) they are the governmental watchdogs that are looking out for our health. If you are interested in diseases and where they are located, this is the site for you.
The American Share foundation. This is a very large site that describes the process of organ donation. It does not go into the science of it, but hey, it is fun cruzing around.
http://www.lupus.org/lupus/info/general.html
A lupus information home page.
Sorry I could not find a page that describes the antigen antibody interaction a little better.
nkko