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Transcript
Module C-9
Immunology
Immune System Components:
Non-specific Immunity
1. “First line” of defense
Physical and chemical barriers:
a. Unbroken skin/mucus membranes. Most important defense is skin.
All body openings are lined with mucus membranes
Skin is an excellent barrier
b. Skin is a very hostile environment for bacteria
1. Skin is hypertonic to most microorganisms due to high salt concentration in sweat; fatty
acid breakdown also leaves lipids on the skin.
2. Lactic acid left from decayed sugars
c. Mucus lines internal surfaces as well.
1. Lungs, trachea, alveoli, etc.
2. Bacterial presence in the internal mucus membranes causes increase production of mucus
3. Membranes is made up of ciliated cells, lining the surface of the membrane, are used to
move the mucus coated bacteria out of the internal areas
4. This is called the mucociliary escalator
d. Digestive Tract (stomach and intestines)
1. The function of the mucus membrane is to lubricate the intestinal tract, helping to
eliminate the bacteria from the system.
2. Mucus membranes are used together with peristalsis, which is a very important
mechanism. It is present in the ureters, fallopian tubes, intestinal tract, etc. Keeping
things moving is important.
e. Tears; saliva
1. Contain lysozymes, an enzyme that attacks bacterial cell walls
f. Eyelashes, eyebrows, earwax
2. “Second line” of defense
1. Phagocytosis
a. Accomplished by white blood cells
b. Activated by chemicals given off by invaded or dead tissue,
2. Complement system
a. Proteins that are triggered and work in what is called a cascade effect; the end result of this
system is always cell destruction
b. Can be triggered by non-specific and specific immunities
3. Interferon
a. Non-specific because it works against all viruses
b. Inhibits viruses
c. When activated, causes you to have malaise, fever, weakness, etc.
4. Fever
a. Causes interferon to work better
5. Inflammation:
a. Redness, swelling, heat, pain, vasodilation
b. Increased permeability of blood vessel walls
c. Fluid leaks out of blood vessels into injured tissue. In the fluid are polymorphonuclear
leukocytes (PMH).
d. Chemotaxis is attracted to the chymen released for the damaged cells
e. Release of histamines by mast cells
1. Mast cells are cells that contain granules of histamine, and are located throughout the
body
f. Release of prostaglandins
Specific Immunity - Acquired, not genetic. Our bodies’ ability to recognize and defend itself against specific
invaders and their products. Body creates a memory for invaders.
1. Antibodies
1. Also called immunoglobulins (“Ig”)
2. There are no “all-purpose” antibodies – they can only do one specific thing.
3. All have the same basic structure created from proteins:
a. Two heavy chains and two light chains
1. Two heavy chains are forming a Y, with the light chains parallel to the top part of the Y
b. All immunoglobulins of the same class (there are 5 classes – see next page) have the same
amino acid sequence except for the tips of the Y
c. These differences of the tips provide for the selection of a specific antigen.
4. How the antibodies work:
a. Antitoxin (antibodies against toxins)
b. Agglutinins
1. Clumping insoluble antigens
2. Will include whole cells and particles (particulate, cellular)
3. These are very useful in the lab to do tests,
1. Serology, the study of antibodies, using agglutinins for lab test to determine blood
typing. Two drops of blood are placed on a slide; agglutinins are applied to each drop
(Anti-A and Anti-B). Whichever clumps determines blood type – A, B, AB if both
clump, and type O if neither clump.
c. Precipitins
1. Causes dissolved fractions of the blood and cause the foreign bodies to precipitate
2. Works against molecules
3. Soluble particles (soluble antigens – toxins, etc – are molecular)
4. Very useful in forensics to determine poisoning.
1. Toxicology will take blood and apply precipitins. If the blood is positive for the
presence of a specific toxin, it will precipitate and fall to the bottom of the vial.
d. Lysins
1. Kills foreign cells directly and immediately
e. Complement-fixing
1. Attaches to antigen and forms antigen/antibody complex
2. Can be triggered in non-specific immunities and specific immunities
3. Triggers compliment system resulting in cell destruction
f. Opsonins
1. Stimulate and enhance phagocytosis
2. They attach to the surface of the antigen and completely coat the surface. Increases the
ability of the phagocytes to see the antigen. Are ingested by the phagocytes.
g. Neutralizing antibodies
1. Neutralizes the pathogen by attaching to the attachment sites on the pathogen, so that the
pathogen cannot bind to other surfaces (binding to the pili of bacteria, tails and spikes of
a virus, etc.)
Classes of antibodies (chart 16.1):
Immunoglobulin = “Ig”
1. IgG antibodies,
a. Make up 85% of the antibodies in the blood stream. Migrate outside of the bloodstream to work.
b. The only antibodies that can cross the placenta
2. IgM antibodies
a. Major defense against bacteremia (bacteria in the bloodstream)
3. IgA antibodies
a. Mostly found in exocrine secretions (secreted into ducts, such as sweat, etc)
b. Often found in mucus in gut
4. IgD antibodies
a. Experts theorize that they are precursors to other antibodies
5. IgE antibodies
a. Responsible for allergy response
b. Form a connection with mast cells and tissues
c. Are part of the production of histamine
d. Correspond w/ parasitic infestations
Active vs. Passive immunity
1. Active (long-term)
a. Whenever your body is challenged to make its own antibodies
b. Can have both natural and artificial immunities
c. Natural active would be when you are exposed to the disease your body produces the antibodies for
the disease, you recover for the disease and now have long term immunities to the disease
d. Artificial active would be when you get vaccinated, your body makes its own immunities, but the
body did not actually get the disease, but still has long term immunities to the disease
2. Passive (short-term, 6 mo. or less)
a. When the antibodies come from another source
b. These antibodies are not long term antibodies
c. Can have both natural and artificial immunities
d. Natural passive immunities are immunities that are passed through the placenta to the baby and ones
that are passed through the breast milk
e. Artificial passive, mostly refers to antitoxins (i.e. tetanus antitoxin) or antivenins (i.e. snake bite), If
exposed to a disease, they give you a readymade antibody from another source, will not give you
long term immunity
Antigens - Anything that elicits a response from the immune system
1. Generally are a portion of the object that the immune system recognizes, not generally the whole object
a. May be the pili, the flagella, or the tails on a virus, etc
2. Not all antigens are equally good at eliciting a response from the immune system. This is referred to as
immunogenic (“Immuno”- immune response, “-genic” – generating)
3. Order of severity of response:
1. Proteins
a. Flagella
b. Exotoxins
c. Toxoids
2. Glycoproteins
a. Proteins that have a carbohydrate chain attached to them
3. Complex carbohydrates (large molecules)
a. Cell wall
4. Lipids
Immune cells responsible for specific immunities:
1. Leukocytes (all are lymphocytes)
a. White blood cells form in the bone marrow
b. Two types:
1. B Cells
2. T Cells
2. B Cells
a. Antibody producing cells.
b. Mature in the bone marrow itself
c. Called B-Cells because they were first discovered in the Bursa of Fabricius in chickens (lymph
organ in chickens)
d. Once matured they migrate to three places
1. Lymph nodes
2. Malt cells
1. “Mucosa associated lymphoid tissue;” also known as “Galt cells”
2. Galt cells - “Gut associated lymphoid tissues”
a. Gall bladder
b. Spleen
c. Appendix
d. Tonsils
e. They are also transported in the blood
f. The main function of the B-Cells are to manufacture antibodies
g. They respond best to “free antigens”
h. Only targets antigens that are not associated with the bodies’ own cells - exogenous
1. Bacteria
2. Toxins
3. Viral re-infections
i. Have sensors on their surface to sense the antigen; any type of antigen that we could possibly be
exposed to.
j. We have a B-Cell for every possible antigen in our system already; it just has to be exposed to the
antigen to trigger them.
k. When they are exposed to an antigen, they cause the release of a specific antibody. When that
specific B-cell is activated is begins to make copies of itself.
3. T Cells
a. Do not produce antibodies
b. Migrate from the bone marrow to the thymus gland where they mature
c. Act directly on the antigen
d. Comprise 90% of lymphocytes in the blood
e. Respond to systemic fungal, initial virus infections, tissue rejections, abnormal or infected body cells
f. Also responds to antigens associated with the bodies’ own cells (such as virally infected endogenous
cells)
g. Will only recognize an antigen if it is on a cell that has your MHC proteins on it (Major
Histocompatibility Proteins - identity markers for our own cells)
h. Works against cancer cells
i. Four different types:
1. Cytotoxic, “killer” T-Cells (Tc) – these do the killing. Cellular assassins
2. Helper T-Cells, (Th)
1. Help to keep the Killer T-cells at bay (H1 cells)
2. Help to control the B-cells (H2 cells)
3. Memory T-Cells (Tm) – remember the abnormal cell so it can identify it the next time it is
encountered
4. Suppressor T-cells (Ts) – controls entire immune response. Shuts down immune response to
keep body from exhausting itself.
4. APC - “Antigen Presenting Cells” (possibly a dendritic cell)
a. The first cell to recognize the presence of an antigen because they constantly patrol bloodstream.
b. Usually a macrophage or phagocyte
c. Consume and phagocytize the antigen, and then place the fragments on their surface to “present”
them to the B and T Cells. These fragments are ID molecules such as spikes, tails, etc.
d. 1st step in process of immune response
How the components work together:
1. B-Cell Mediation, (AMI)
AMI = Antibody mediated immunity/Humoral immunities
1. First Exposure
a. The first component that recognizes the antigen is the APC, which phagocytes the antigen and
places components on its surface
b. The APC then places these parts on display for the T and B cells
c. The helper T-Cell is going to trigger the correct B-Cell to multiply
d. These B-Cells are produced in two forms, Memory Cells and Plasma Cells
e. The Plasma cells mature and form antibodies, Ab, (The antibody is specific to the antigen that
the APC was exposed to), This process may take anywhere from a couple of days to a month
2. Second Exposure
a. The APC stimulates the memory B-cells which form more memory and plasma cells
2. T-Cell mediated immunities (CMI)
a. CMI = cell mediated immunities
b. The APC stimulates the Killer T-Cells which multiply and form memory and Killer T-Cells
c. The Helper T-Cells limit the extent which the Killer T-Cells can function
Hypersensitivity (allergies)
a. We typically refer to the antigen as an allergen because they are typically harmless
b. There are four types of responses to the allergen
1. The first three are mediated by the Ab (antibodies – B-cell responses)
2. The last one is mediated by CMI (cell-mediated responses)
1. Type one is mediated by IgE antibodies and cause anaphylaxis, asthma, and atopic allergies (hay
fever, urticaria, food intolerance). “Classic” allergies; most common. Immediate reaction.
a. Mucus secretions
b. Histamine release
c. Blood vessel dilation
d. Bronchial constriction
e. Localized reaction typically
f. Anaphylactic reactions are “systemic hypersensitivity” (system-wide)
2. Type two is referred to as cytotoxic hypersensitivity.
a. Compliment fixing enzymes trigger the compliment system
b. Two examples
a. Rh factors –Rh negative mother carrying an Rh positive baby.
b. ABO blood group – transfusion reaction
c. Results in lysis of the cells (cellular destruction)
3. Type three is immune complex mediated
a. Whenever you have an antigen attached to an antibody it triggers the Antigen/Antibody
complex (Ag/Ab)
a. Typically the body clears them out of the body but if this is not done, they are deposited
in the joints of your body and cause arthritis, glomerulitis in the kidneys, or “arthus
reaction” due to rupture of the blood vessel, causing hemorrhaging
b. Rheumatoid arthritis
c. Farmers lung from hay bacteria
4. Type four is referred to as delayed hypersensitivity
a. No antibodies involved - CMI involved (cell-mediated). Involves T-memory cells (Tm)
b. Exaggeration of cellular response
c. Any type of contact dermatitis
a. Poison ivy
b. Poison oak
c. Makeup, detergents, etc.
d. TB Montoux test
1. The bump that you get is called an induration. This positive response only confirms
exposure, not presence of disease.
d. Graft rejection
HIV interferes with helper T-Cells, therefore interfering with the AMI response, and inhibit the regulation of
Killer T-Cells. This limits and hinders the complete immune system.
The predominant local flora for the skin is Staphylococci, which is able to tolerate the hypertonic environment.
There are pathogenic Staphylococci that also cause infections of the skin.
Specific immunities are immunities that are acquired, not genetic.
Antigen – any substance that triggers an antibody.
Antibody – immune system response to an antigen.
Immunoglobulins - The tips are variable because the mRNA as it leaves the nucleus is “scrambled” which give
the variableness to the tips.
MHC – Major histocompatibility proteins, allow the body to recognize the cell by the marker that the cell wall
contains, and allows the body to differentiate your cells from a foreign cell.
AMI – Antibody mediated immunity/Humoral immunities are immunities that are mediated by the B-cells.
CMI – Cell mediated immunities. Involves T-Cells that are mediating immunities.
Cytokines / lymphokines– A group of chemicals that allow cells to communicate between themselves. These are
also known as “interleukins.”