Immune System - Action Overview
Lecture 15A [Notes]
All cells, except sperm or eggs, contain the same complement of genetic
information. Recall that sperm or eggs contain only one-half the genetic
complement. Some of that genetic information codes for glycoprotein receptors
embedded in and projecting from the surface of the cell membrane surface.
Some of these receptors serve as identification codes for tissue or cell
type. Some serve as general identification codes to indicate that the cells
belong to the host (the concept of "self").
Whether or not certain receptors show up on the surface of the membrane
(are expressed) and when they are expressed, depends on the presence of and
interaction with various molecules such as enzymes or hormones. Thus the
cell must receive a variety of chemical messages in order for some of the
receptors to be expressed or be suppressed.
The immune system functions through a series of interactions between various
cell types and various chemicals. Sequentially, the first step in the
development of an immune response involves RECOGNITION. Various immune
system cells must recognize the presence of free or bound antigens. This
recognition involves the binding of antigen to membrane surface receptors
on the immune system cells. The second phase involves COMMUNICATION. Immune
system cells that have bound antigens send chemical messages to the other
immune system cells. These chemical messages bring about the last phase
which is ACTION. The chemical messages may cause the other cells to
(1) differentiate and divide (2) cause them to release additional chemicals
that may destroy the antigen bearing substrate, or (3) release antibodies
that bind to free antigen and make it easier to recognize and phagocytize.
I. Recognition (by membrane surface receptors)
A. Macrophages (modified monocytes that bear multiple
receptors for a variety of antigens). Macrophages
ingest (phagocytize) - digest - release and transport
digested antigens (endocytosis) to their cell membrane
receptor sites where they are displayed (presentation).
At this point the macrophages have become activated and
are sometimes called "antigen presenting cells - APC".
B. B lymphocyte cells (lymphocytes that during their
embryonic development have been exposed to and
influenced by secretions from lymphatic tissue regions
such as the Peyers Patches. These regions are sometimes
identified as GALT or MALT regions. These B-cells will give
rise to the cells that produce and release antibodies
[Ab]). B-cells contain receptors for only one type of
Ag. This commitment to producing only one type of
antigen recognizing receptor, and thus only one type
of Ab, occurs during their differentiation in the bone
marrow. This means that the genetic information to
make other types of protein receptors has been
suppressed early in their development.
C. T lymphocyte cells (lymphocytes that during their
embryonic development have been exposed to and
influenced by hormones of the thymus gland called
thymosins. These cells also contain receptors for
only one type of Ag. T-cells respond only to antigen
bound to the membrane of body cells, not free or unbound
antigens).
II. Communication (involves the binding or docking of
receptors between immune system cells and the subsequent
release of chemicals known as lymphokines or cytokines).
A. Macrophages (activated) release Interleukin-1 (IL-1).
(Interleukins are a type of lymphokine) This chemical
causes one type of T-cell called the helper T cell
(TH, T-4, CD-4) to do two things. The helper T cell
produces (expresses) receptors for a second
Interleukin (IL-2) and produces and releases IL-2.
B. B lymphocyte cells follow two possible courses. The
majority of B-cells are stimulated by IL-2 to divide
and differentiate into Ab producing cells called
Plasma cells. Some of the B-cells divide into a group
of cells called Memory cells that are available as a
reserve source of cells and converted to Plasma cells
the next time the same type of Ag enters the body.
Usually the Helper T-cells bind to the B-cells to help
the B-cells make the conversion (activate them) into
plasma cells.
C. T lymphocyte cells (TH) bind with macrophages
and B-cells. Interleukin 2 released by these cells binds
with the IL-2 receptors now expressed on their surface
and causes them to divide into a clone of active cells
and a clone of memory cells. The IL-2 also causes the
other types of T-cells to divide and differentiate
into active and memory cells. Remember that IL-2 also
caused the B-cells to divide and differentiate. Thus
you can see the significance of helper T-cells to
proper functioning of the immune system and why HIV
can lead to AIDS.
III. Action
Most of the action involves the differentiation and
division of B- and T-cells into active and memory cells.
Plasma cells produce copious quantities of a single type
of Ab. The price they pay for this action is a lifespan
of only a few days, loss of membrane receptors, and
inability to divide. Virtually all of their activity is
the production of secretory immunoglobulins (Ab).
Antibodies produced by the plasma cells bind with free
Ag and make them (the Ag) easier to recognize and phagocytize by
macrophages.
The cooperative action between T- and B-cells is called
T-dependent Ag and, because of the production of memory
cells, leads to long term immunity.
Some B-cells are not bound by TH cells but are able to
bind various types of antigens such as long chain
molecules, capsules and flagella. This type of action is
called T-independent Ag and leads to a weaker reaction
and usually no long term immunity. This may be one
reason why there is no long term immunity to Neisseria
gonorrhoeae since receptors on B-cells bind to the
capsule.
Most immature B-cells express receptors for and produce
antibodies that belong to the IgM and IgD classes of
immunoglobulins. IgM provides Ab action against first
time antigen invasion. Long term immunity requires a
switch from the IgM to the IgG class of antibodies.
Conversion to IgG, IgE, and IgA classes of Ab is the
result of a chemically induced genetic rearrangement.
Genetic information for production of the various Ig
groups is arranged on three chromosomes 2, 14, and 22.
The genetic information for the constant region of each
Ab molecule is arranged sequentially as M, D, G, E, and
A. The switch from IgM to IgG requires that the M and D
regions of chromosome 14 are looped out, excised, and
lost. This action is sometimes called Ab Class Switching.
Lecture 15B [Notes]
Miscellaneous Notes on Immunology
DEFINITION
Immunology is the study of the physiological mechanisms which allow the body
to recognize substances as foreign or abnormal and to neutralize or
eliminate those substances.
GENERAL PRINCIPLES
A. Recognition of Self vs. Non-Self
1. MHC (Major Histocompatibility Complex) - a section of
chromosome 6 containing a group of genes that code for
and produce glycoprotein molecules marking a cell as Self;
histocompatibility testing, or tissue typing involves
identifying specific markers on body tissues (on cell
membrane surface); because the typing is usually performed
on WBC's, or Leukocytes, the markers are referred to as
Human Leukocyte Antigens (HLA); each cell has a double set
of six major antigens designated as HLA-A, HLA-B, HLA-C,
HLA-DR, HLA-DP, HLA-DQ. In addition, the HLA markers are
essential for immune function. they not only determine
which antigens (foreign or self) an individual responds to,
they also determine how strongly the immune system will
respond. They also allow the immune system cells to
recognize and communicate with each other.
a. HLA antigens are found in urine and sweat and may serve
as human pheromones
b. HLA Class I ABC Group (HLA-A, HLA-B, HLA-C) are found on
all cells except red blood cells (erythrocytes)
c. HLA Class I D Group (HLA-DR, HLA-DP, HLA-DQ) are found
only on cells of the immune system
d. HLA-DR is related to autoimmune diseases such as
juvenile onset diabetes
1. Juvenile Onset Diabetes - about 90% of those having
the disease are white, blond haired and blue-eyed
2. HLA-DR3 have a 5x higher risk for JOD
3. HLA-DR4 have a 7x higher risk
4. HLA-DR3,4 have a 20x higher risk
5 Latest research suggests that the trigger may be a
virus or bovine albumin protein
B. Specificity
The ability to recognize millions of distinctive non-self
molecules and to produce substances to counteract each one
(selectivity)
C. Memory (Secondary Response)
1. Once having met a substance, it will rarely ever forget it,
and it will prevent you from getting the disease twice
2. Testing for Memory
a. Humoral - determine through Ab titer (concentration),
should be good for 60-65 years
b. CMI (Cell Mediated Immunity) - skin tests
THE SPECIFIC IMMUNE RESPONSE
A. Functions of Interleukin-1 (IL-1) -[about 15 different types
of IL]
1. Stimulates prostaglandin production in the anterior
hypothalamus - increases temperature setpoint; works best
between 101-103o (benefit of elevated temperature)
Various drugs (ASA, NSAID's [non-steroidal],
acetaminophen) are inhibitors of prostaglandin
synthesis in the anterior hypothalamus - thus, anti-pyretics
2. Increases serotonin in the brainstem (sleepy)
3. Increases serotonin release in the GI tract (causes
nausea - duodenum is organ of nausea)
4. Alters pain threshold (everything hurts)
B. The Effector Cells of the Immune System
B lymphocytes, T lymphocytes, NK (Natural Killer) Cells
1. B lymphocytes - bone marrow derived; when activated by an
antigen or IL-2 released by the T4 lymphocytes, the B
lymphocyte changes into a plasma cell that produces Ab
specific for that antigen. There are five classes or types
of Antibodies (Immunoglobulins)
a. IgG - all purpose Ab; major one in serum; crosses the
placenta; is Ab of memory; lasts 60-65 years in adult;
last 15-18 months in newborn (maternal Ab)
b. IgM - first Ab formed in response to a new Ag; causes
agglutination reactions
c. IgA (secretory) - found in secretions; saliva, breast
milk, GI, prostate; 3x as much in serum
d. IgD - not much known
e. IgE - causes release of histamine from mast cells and is
responsible for the allergic response; allergic
rhinitis; hay fever (seasonal allergies); anaphylaxis -
the systemic release of histamine in response to IgE.
Common allergens causing anaphylaxis - bee stings, food
(e.g. roach parts in chocolate), drugs, latex, husbands
semen
2. T lymphocytes - thymus-derived; two major sets are
responsible for cellular immunity; cellular immunity is the
arm of the immune system that neutralizes or destroys
viruses, fungi, parasites, protozoa, TB, cancer, and
foreign tissues
a. Helper T lymphocytes (T4 or CD4) - vital to
orchestrating the specific immune response; T4s
release IL-2 (Interleukin-2) which in turn activates B
lymphocytes, killer T cells, phagocytic cells (PMNs and
macrophages),stimulates the bone marrow and activates
suppressor T cells (T8 or CD8)
b. Clinical correlation - clinical use of IL-2 with LAK
(Lymphokine Activated Killer) cells; IL-2 and TILs
(Tumor Infiltrating Lymphocytes); Cyclosporine and
FK 506 are immunosuppressant drugs - work by inhibiting
IL-2
Normal number of T4 cells in the adult - 800-1200; HIV
infects and kills the T4 cells, count falls as disease
progresses
c. Suppressor T cells (T8 or CD8) - turn off immune system
d. NK cells - natural killer cells fight viruses and cancer
cells; represent about 4% of T cells and last 10-60
years; no prior sensitization required; cancer immune
surveillance cells
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Email: demmelut@ps.fmcc.suny.edu