Identify the precapilary sphinters and the thoroughfare channels. Which
side
of the bed has higher hydrostatic pressure? See p. 774, 7th ed.; p. 753, 8th
ed.
LYMPHATIC CIRCULATION - See p. 774-779, 7 th ed.; p. 753-755, 8th ed..
Lymph or Interstitial or Extra-Cellular
Fluids (ICFs) are formed by pressure
filtration from the high pressure
(closest to arterioles) side of capillary beds.
Interstitial fluid carries amino acids,
glucose and other nutrients, blood gases like
Oxygen, and immune substances to combat
bacteria or viruses in tissues. Lymph
returns to the blood in two ways: (1)
most lymph returns by diffusion into the low
pressure side of the blood capillary
bed from the tissue spaces, returning lymph
carries wastes like CO2;
(2) Large antibody-bound substances, viruses,
bacteria,
cancer cells, and debris from dead/broken
cells flow through blind-ended lymphatic
system ducts which have valves (similar
to venous valves) and lymph nodes
along
the route.
Identify the precapilary sphinters and the thoroughfare channels. Which
side
of the bed has higher hydrostatic pressure? See p. 774, 7th ed.; p. 753, 8th
ed.
Muscle contractions and breathing movements
help push the lymph throughthe system.
The lymph nodes contains thousands
of lymphocytes (White Blood
Cells) some of which
can make antibodies against
viruses and bacteria in the fluid
as well as macrophages. The
lymphatic system drains back into the
blood through the subclavian veins.
The Spleen and Liver are organs
which assist in blood cleansing. They are lined
with fixed position macrophages that
eat cell debris and antibody-bound material as
they pass by in the blood. The spleen
also serves as a reservoir of blood, containing
about 350 ml, that it can add to the
circulation. See p. 783, 7th ed.; p. 758, 8th ed.
The Thymus serves
as a processor of
T-Lymphocytes
-- the "Killer Cells" of the immune system that
can lyse cancer cells
or cells containing many viruses by secreting perforin enzymes
that break the cell
membrane of the cancer cell. T-cells appear to burrow right through
them, cannon
ball-like. The thymus is large in the infant. It grows in size to
age 12,
then decreases in adulthood; but, it still functions to help in T cell
maturation by secreting
thymosin hormones.
Lymph vessels have thin walls lined with squamous endothelial cells.
Lymph vessels
have valves like veins do therefore muscle contraction and breathing
movements
help move lymph through these vessels back into the blood via the subclavian
veins.
TONSILS
These are bodies of lymphocytic nodules. The pharyngeal tonsils
or
adenoids
are
embedded in the posterior nasopharynx. The paired palatine tonsils
are
further
anterior and removed by tonsillectomy if they restrict breathing. Lingual
tonsils
are located at the base of the tongue.
RESISTANCE TO DISEASE - Chapter 21
(This will be covered more thoroughly in your Microbiology course.)
MECHANICAL & CHEMICAL - see p. 789, 7th ed.; p. 767, 8th ed.
Antibodies released by B cells can do the following when antigens bind
to the variable
region of the antibody.
5. Immobilization of motile (flagellated) bacteria.
6. Precipitation of soluble antigens.
7. Inflammation - Mast cells release histamines when their imbedded
IgE antibodies bind to
an antigen or allergen. Produced by the liver,
blood C reactive protein levels increase during inflammations.
8. Complement Fixation - complement reactions cascade to promote opsonization.
Antibody Types - Review
Secreted by B lymphocytes, the most common IgG's
are circulating antibodies
included in the gamma globulins, they protect against viruses
and bacteria and are
passes from mother to baby through the placenta. Dimeric IgA's
occur in mother's
milk and mucus secretions. IgE's bond
allergens on mast cells which release histamines.
The five antibodies in one, pentameric IgM's
are released by plasma cells
in the primary immune response and are the blood agglutinins for blood
types A and B
cross reactions. IgD's activate B cells.
Antigen Types
Proteins, nucleic acids, lipoproteins, glycoproteins, and large polysaccharides
(particularly those with Nitrogen atoms) can serve to bind with antibodies.
Haptens
are partial antigens, which when bound to a larger self molecule, will
bind to
antibodies. Penicillin, poison ivy, toxins, and some viral antigens
are haptens. The
latter, when bound to host cell proteins, can cause autoimmune reactions
as
in
Multiple Sclerosis where antibodies attack myelin sheaths.
Antigen Processing - See p.789, 7th ed.; p. 776, 8th ed.
Bacteria, virus and other materials are phagocytized by macrophages
and displayed
of their surface as well as the surface of B cells and dendritic cells
in the skin
(macrophage-like with branch-like projections), B cells and T helper
cells are found
crowded around macrophages, probably picking up displayed antigens,
"sniffing them
out" so to speak. This can be called "immune surveillance."
Your own cell membranes display major histocompatibility complex
antigens
which identify those cells as "self." .
Class I Major Histocompatibility antigens (MHCs) occur on the surfaces
of (self)
cells. Class II MHC's are displayed on the surface of T and B cells
and macrophages
along with antigens derived from a foreign cell or virus that has been
phagocytized.
B cells are activated after being presented a foreign antigen and MHC-II
antigen
(together), by a macrophage or dendritic cell. The B cell then, according
to one theory,
rearranges its genes to produce the appropriate antibody. If the antigen
has been
"seen before," the activation process is quick because this B Memory
Cell can begin
to multiply rapidly after being stimulated by Interleukin-2,
Il-4,
or Il-5, secreted by
THelper cells. These rapid mitoses occur in lymph
nodes to produce plasma cells
which are prolific producers of antibodies. Also Memory cells are produced.
See p. 811, 7th ed.; p. 782, 8th ed.
Primary and Secondary Immune Responses
A first response to a foreign antigen produces a moderate increase in
antibody of IgG
and IgM. Think of vaccinations with live/weakened killed
viruses. Look at what
happens when the antigen is encountered a second time. The IgG
secretion increases
dramatically to counteract the infection. Why do you get mumps only
once?
-
Day 1 Day 60
Cell-Mediated or Cytotoxic Immunity - See p. 810-821, 7th ed.; p. 786-795, 8th ed..
An antigen presenting cell, usually a macrophage or dendritic cell,
phagocytizes or is
penetrated by a virus or other parasite. An antigen is presented on
its surface and
the macrophage secretes Il-1 which stimulates T and B cells
reproduction and helps
to cause fever. A T-Helper cell (CD4+) brings its
receptors and CD4-MHC antigens
to recognize the nonself foreign antigen presented. The activated T
Helper cell then
makes more T Helper cells which secrete Il-2 which stimulate
mitosis and
maturation of T killer cells and B cells. T Helper Memory cells
are also produced.
T Killer or cytotoxic cells (CD8+) bind
to a viral antigen on the surface of a self cell
to become activated. The activated T K cells then
attack foreign or parasitized host
cells by directly lysing their membranes with perforin enzymes.
T
Natural Killer
cells attack cancer cells. See 
How does transplant rejection occur? What do cyclosporin, cortisones
and cytotoxic
drugs do? Drugs are given which decrease T and B cell numbers by limiting
their
production or killing them outright, or by decreasing IL-2 secretion
by T Helpers. The
effects would be what? T Suppressor cells cause reductions in
B cells when an
infection is "conquered."
Gamma Interferons or macrophage activitating factor is secreted by THelper and
TKiller cells to greatly increase the "Garfield cell's" appetite
for phagocytizing
bacterial "lasagna," virus, antigen/antibody complexes,and other cell
debris.
Recognition and Tolerance of Self Antigens
It is thought that during embryonic and fetal development that CD4+
and CD8+ cells
which cannot recognize self MHCs either die or are inactivated. Those
that cannot
bind and react to self MHCs survive.
AIDS - See p. 820, 7th ed.; p. 796, 8th ed..
The Acquired Immune Deficiency Syndrome or AIDS is caused by
the HIV virus
after many years of incubation. One can be HIV+ without symptoms -
a few
individuals never develop symptoms. The total lymphocyte count is low;
but, in
particular, if the CD4+ THelper count is below
200/mm 3 , the person has AIDS.
| CD4/Helper cell count | Weeks/years post infection | Symptoms/Infections |
| 1000 | 0 | None |
| 500 | 4 | Fever |
| 650 | 10 | None |
| 500 | 4-6 years | Weight loss, bacterial infections of the skin |
| 400 | 7 years | Shingles (eruption of chicken pox virus) |
| 300 | 8 years | Yeast infections of mouth, anus |
| <200 | 9-10 years | Pneumocystis pneumonia, Herpes eruptions, Cryptococcus,
Toxoplasma, dementia etc |
The fragile AIDS-HIV virus is a retrovirus - meaning that RNA is its
core. RNA
serves to make a DNA copy in the host cell; then, more RNA cores, reverse
transcriptase enzyme (for RNA ---> DNA step), and protein coats
are manufactured
by the infected cell.
See
The drug AZT interferes with the action of the core reverse transcriptase
enzyme to make
DNA from RNA. The dug is substituted for thymidine in replication of
DNA. A membranous
covering is derived when the virus erupts from the host cell.
Protease inhibitors prevent the synthesis of capsid protein. A three
drug "cocktail" is used to
treat AIDS, but it cant cure it.
The virus enters any host cell displaying CD4+ MHC protein,
which serves as a portal of entry
by binding with the virus' GP 120 glycoprotein.HIV can be transmitted
by free virus
coming into contact with an uninfected cell or by touch, as happens
when THelper
cells crowd around macrophages or dendritic cells - the "Trojan
horse" effect.
See
HIV can be transmitted by (1) blood which has infected monocytes and
T Helper cells
(about 20% of babies born to AIDS+ mothers, get AIDS), (2) seminal
fluid which also
has these immune cells, (3) similarly, vaginal secretions, and (4)
mother's milk.
Transmission by kissing or bites would be rare because of the small
numbers of
infected cells present in salivary secretions and the presence of a
slpi
protein that
covers the virus, preventing entry into cells. Tears and sweat
also have very small
numbers of infected cells. However, blood in saliva is dangerous.Witness
the dentist
Acer in Florida.
Because cells harbor the virus and the virus can be transmitted by cell
contact, the
condom is an effective method to prevent infection. So, even though
the virus is small
enough to go through condom pores, the condom works for people not
showing
symptoms. Why? Macrophages can cross the blood/brain barrier, turn
into microglial
cells and infect the brain, causing AIDS -related dementia.
HIV is tricky in several ways. First, large numbers inhabit macrophages
and dendritic
cells without killing them. They serve as a reservoir to pass to THelper
(CD4+) cells.
Secondly, the virus mutates readily and changes its antigenic coats.
The immune
system time can't keep up with the changes. Third, the virus can make
a DNA copy
that is inserted into THelper cell chromosomes as a provirus,
waiting to be activated at
a future time. In other words, killing all cells making virus would
not get rid of HIV. So
they die of opportunistic infections like pneumocystis pneumonia or
cancers caused by a
Herpes virus.Fourth, the virus can apparently pentrate helper cells
even when it coated by
the naturally occurring antibodies that the infected person makes to
fight the infection.
Recent evidence suggests cells. The basis of the AIDS test is the occurence
of antibodies.
The virus is not assayed directly.
If one had sex with an infected individual, why would an AIDS test be
useless until
three months had passed?
Alpha interferon is effective in the treatment of Kaposi's
Sarcoma (form of cancer
caused by herpes virus).Chronic fatigue syndrome has recently
linked to
Epstein-Barr virus infection.
The track record for developing vaccines against parasites of immune
cells is very
poor. Nevertheless, work continues.
ALLERGY or HYPERSENSITIVITY - See p. 823, 7th ed.; p. 798, 8th ed.
TYPE IV or Delayed hypersensitivity
12-72 hours after exposure to an allergen, macrophages and T cells cause
inflammation in the skin.
REVIEW OF WBC FUNCTION - INFLAMMATIONS
See
If you have an infection, the immune system organizes a response. Bacteria
start
growing in the wound and histamines are released by mast cells after
stimulation by
hormone-like bradykinins released by damaged cells. Bradykinins
are all thought to
stimulate pain neurons in the area. The histamines cause the blood
vessels
(arterioles and capillaries) to become leaky releasing more interstitial
fluid into the
tissues. Neutrophils, monocytes and lymphocytes migrate right through
blood vessel
walls. If this bacterium has been experienced before, antibodies may
already be
present in the bloodstream and B memory cells in the lymph nodes. Therefore,
interstitial fluid including antibodies and complement enzymes and
WBCs leak out
into the tissues. These antibodies attach to the bacteria and the bacteria
are
"narfed" by macrophages and neutrophils. The macrophage and neutrophils
will eat
anything labeled with antibodies. B-Cells will make additional antibodies
after they
turn into plasma cells. Also B memory cells will be formed. Some antigens
will travel
to a lymph node and there signal the node to make more B-cells, active
and Memory,
which can make antibodies against the antigen of the bacterium. T killer
cells will
attack a foreign cell by punching holes through it's membrane. T memory
cells will be
formed. After the infection has been cleaned up, antibody (influenced
by
T Suppressor Cells) and histamine secretions decrease and
the swelling goes down. Pain
ceases when the swelling stops putting pressure on certain pressure
sensitive nerve
endings.
Fever is a resetting of the hypothalamic thermostat by Il-1 and prostaglandins.
Remember what tylenol and ibuprofen do?
Higher body temperature kills many bacteria, speeds up body defenses
and repair
mechanisms, and enhances the effects of interferons that inhibit
virus reproduction.
Study Questions
john.aliff
@ gpc.edu