Important words and
concepts from Chapter 18, Black, 1999 (3/28/2003):
by Stephen T. Abedon (abedon.1@osu.edu)
for Micro 509
at the Ohio State University
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Course-external links are
in brackets Click [index] to access site index Click here to access
text’s website Vocabulary
words
are found below |
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(1) Chapter title: Immunological Disorders and Tests
(a)
[immunological disorders and
tests (Google Search)]
[index]
HYPERSENSITIVITY
(a)
Hypersensitivities
are inappropriate immune responses to foreign material that is either within or
in contact with the body
(b)
Essentially,
the body mounts a sometimes dramatic immune response against an otherwise
harmless, or at least less-harmful substance, thereby doing more harm to the
body in the course of the immune response than might have the original allergen
(c)
Hypersensitivities
may be divided into four types:
(i)
Type I: Immediate hypersensitivity
(ii)
Type II: Cytotoxic hypersensitivity
(iii)
Type III: Immune complex
hypersensitivity
(iv)
Type IV: Cell-mediated Hypersensitivity
(Delayed Hypersensitivity)
(d)
[hypersensitivity reactions
(Google Search)]
(3) Anaphylaxis (anaphylactic shock)
(a)
Anaphylaxis
is a general term used to describe the detrimental effect(s) associated with hypersensitivities
(b)
Anaphylaxis
may be localized (annoying but not life threatening) or generalized (systemic
and life threatening)
(c)
Anaphylactic
shock is a generalized anaphylaxis characterized by a significant,
life-threatening drop in blood pressure
(d)
[hypersensitivity reactions
(Google Search)]
[index]
(a)
Prophylaxis
refers to the protective effects associated with an immune response
(b)
[prophylaxis (Google Search)] [index]
(5) Immediate
hypersensitivity (type I hypersensitivity; allergy)
(a)
Immediate
hypersensitivity occurs following the production of IgE antibodies against
typically otherwise-harmless foreign antigens (which are known as allergens)
(b)
Type
I sensitivities are allergies
(c)
[immediate hypersensitivity,
allergy, reagin and (anaphylaxis OR
hypersensitivity) (Google Search)] [index]
(a)
An
allergen is an antigen, the exposure to which results in a hypersensitivity
reaction
(b)
Note
that allergens are non-self (i.e., foreign) antigens
(c)
Since
hypersensitivity (e.g., immediate hypersensitivity)
is the result of a kind of specific immunity, an individual must be exposed to
the allergen at least once (to sensitize the individual by inducing B cells
that produce specific IgE antibodies) before exposures (subsequently) result in
an allergic
response
(d)
[allergen (Google Search)] [index]
(a)
The
signs and symptoms of immediate hypersensitivity
are a consequence of the release of histamine and other chemical mediators from
body cells
(b)
In
the case of histamine, release occurs when IgE antibodies bound to basophils or
mast cells bind to allergens
(c)
Histamine
is found intracellularly within vesicles (the
granules within these cells) and degranulation is the term used to
describe the release of histamine via the fusion of these vesicles with the
basophil or mast-cell plasma membranes
(d)
(in
addition to histamine, prostoglandins and leukotrienes are reaction mediators
that play important roles in mediating airway constriction)
(e)
See Figure 18.1, The
mechanism of immediate (Type I) hypersensitivity, or anaphylactic
hypersensitivity
(f)
[histamine, degranulation, degranulation and histamine
(Google Search)]
[index]
(8) Cytotoxic hypersensitivity (type II hypersensitivity)
(a)
The
term cytotoxic in cytotoxic
hypersensitivity refers to host-cell damage caused by an over-zealous immune
response
(b)
Recall
that a normal aspect of both specific and non-specific immune responses is extracellular killing, particularly the killing
of host cells that are thought to be pathogen-infected
(c)
Cytotoxic
hypersensitivities are mediated by the binding of antibody's to body tissues
which leads to the lysis of cells (either via ADCC or via the activation of
complement)
(d)
The
negative consequences of not correctly matching blood types for transfusions
are examples of the damaging effects of cytotoxic hypersensitivities
(erythroblastosis fetalis is a related, additional example of a cytotoxic
hypersensitivity)
(e)
[cytotoxic hypersensitivity,
type II hypersensitivity
(Google Search)]
[index]
(9) Immune complex
hypersensitivity (type III hypersensitivity)
(a)
One
role of phagocytic cells (macrophages) is the removal of debris from body
tissues (e.g., blood) and one kind of debris that results from specific immune
reactions (specifically humoral immunity) are large complexes of antibody and
antigen
(b)
These
complexes form as a consequence of the multivalent nature of both antibodies
and antigens (i.e., an individual antibody molecule can bind to more than one
epitope and thus, potentially, more than one antigen, while a large antigen or
organism can display large numbers of individual epitopes)
(c)
The phrase immune complex as in immune complex
hypersensitivity refers to these antigen-antibody complexes, and type III
hypersensitivity refers to an immune response that produces an excess of these
immune complexes, particularly faster than macrophages (and the liver) can
remove them
(d)
The
accumulation of these immune complexes can result in their depositing in
otherwise healthy tissues followed by a damaging hypersensitivity immune
response in those tissues to the not-engulfed immune complexes
(e)
Certain
autoimmune diseases (rheumatoid arthritis and lupus) are consequences of type
III hypersensitivities as well as the serum sickness that results from a second
exposure to an antitoxin
(f)
[immune complex
hypersensitivity (Google Search)] [index]
(10) 
Cell-mediated
hypersensitivity (type IV hypersensitivity, delayed hypersensitivity)
(a)
Cell-mediated
hypersensitivity is mediated by T lymphocytes (rather than by antibodies)
(b)
Cell-mediated
hypersensitivity is also known as delayed hypersensitivity because the time
between exposure to the eliciting antigen and the occurrence of symptoms can
take many hours
(c)
A
common example of type IV hypersensitivity is poison ivy sensitivity (where, of
course, the rash appears only after many hours—e.g., next day—following
exposure to the poison ivy urushiol, the triggering oil)
(d)
[cell-mediated hypersensitivity,
delayed hypersensitivity
(Google Search)]
[index]
IMMUNODEFICIENCY
(a)
Immunodeficiency
is characterized by an inadequate immune response, either in general or against
specific antigens or pathogens
(b)
This
inadequacy contrasts with the temporary inadequacy of specific immunity as
immune responses normally develop following first-time exposure to antigens
(c)
Instead,
immunodeficiency is characterized by an abnormally under response to antigens
over the long (as well as the short) term and is indicated by a weakness in the
ability of the body to fight legitimate pathogens
(d)
We
may speak of immunodeficiencies as being either inborn (primary) or acquired
(secondary)
(e)
Things
that can lead to acquired immunodeficiencies include:
(i)
Drugs
(e.g., anti-cancer chemotherapies)
(ii)
Pathogens
(e.g., HIV/AIDS)
(iii)
Inadequate
nutrition and injury
(iv)
Some
cancers
(f)
[immunodeficiency -AIDS
(Google Search)]
[index]
(g)
Extreme
exposure to sunlight that comes from maintaining a deep tan can also lead to
pathogen-fighting inadequacies [impacts of UV radiation on the
globe today (UV Rays and Global Changes)]
[the ultraviolet light in
sunlight can also stimulate herpes infections and might stimulate HIV infection
(AIDS Treatment News)…
and other infections
(UV Rays and Global Ghanges) [safe sun? (MicroDude)] [index]
(a)
Cyclosporin
is a transplant anti-rejection drug that intentionally serves to induce a
highly specific immunodeficiency
(b)
That
is, cyclosporin interferes with cell-mediated immunity, which is one of the mechanisms by which
organ-transplant rejection occurs
(c)
Unfortunately,
cell-mediated immunity is important in fighting viral infections, serving as
the means by which virus-infected cells are destroyed by the immune system;
consequently, individuals on a cyclosporin regimen are more susceptible to viral
infections
(d)
This
immunosupression is not complete, however (i.e., the rest of
the immune system still functions), thus allowing the benefits of the drug
(significant boost in transplantation efficacy since it greatly reduces the
need to type-match tissues) to outweigh the costs (increased susceptibility to
viral infections)
(e)
In
addition to viruses, cyclosporin increases tumor risks, an observation that is
consistent with the tumor-fighting role of cell-mediated immunity, but,
apparently, may also be a consequence of cyclosporin actually promoting the
growth of certain tumors [Nature review on cyclosporin and TGF
Beta (Biocognizance.com)]
(f)
To
prevent the rejection of transplanted organs, organ-transplant recipients must
remain on a cyclosporin regimen for life
(g)
[cyclosporin (Google Search)] [index]
(13) Acquired Immune Deficiency
Syndrome (AIDS)
(a)
The
most-popularly understood cause of immunodeficiencies
is, of course, AIDS, which is an immunodeficiency brought on by the infection
with the Human Immunodeficiency Virus (HIV)
(b)
(note
that AIDS typically stands for acquired immunodeficiency
syndrome as well as the immune deficiency
phrase used in your text; a Google search for
"acquired immunodeficiency
syndrome" gives 79,800 hits on 3/14/02 while a Google search on the same day for "acquired immune deficiency
syndrome" gives 54,600 hits)
(c)
Immunodeficiency
caused by HIV occurs because this virus preferentially infects host immune
system cells, specifically those that carry the antigen that designates T
lymphocytes as helper T lymphocytes (but the same antigen also is carried by
macrophages and other cell types)
(d)
HIV
ultimately kills the cells it infects (e.g., via cell-mediated immunity by the
body against HIV-infected cells); this creates a constant drain on the number
of helper T cells present in the body, which in turn interferes with the
functioning of both the cell-mediated and the humoral arms of specific immunity
(e)
The
virus is always replicating and the body is always fighting off the virus, with
the virus mutating to evade specific immunity (more scientifically stated, with
mutationally generated evavion-capable HIV variants are selected by specific
immunity), and the specific immunity of the body must periodically produce new
primary immune responses against the new variants of the virus
(f)
Thus,
HIV infection is characterized by
(i)
an
initial (~6 week) period of flu-like disease before specific immunity brings
the infection under control
(ii)
a
steady-state period during which viral replication is kept more-or-less under
control, with some break outs of viral replication as immune-system evading
virus variants arise (this steady state can occur over many years, usually
<10)
(iii)
a
gradual decline in immune system resilience and functioning until the growth of
newly arising virus variants is no longer successfully brought back under
immune-system control (AIDS)
(g)
See Figure 18.22, CDC
classification of HIV disease and AIDS
(h)
The
immunodeficiency characterized by AIDS is actually only the end-product of a
long decline in immune system functioning and represents only the end stage of
a typically decade-long disease process; that is, not all individuals who are
HIV infected have AIDS (though all people with AIDS are HIV infected), but most
people who are HIV infected (95%+), who are not successfully treated using
modern antiviral chemotherapeutics, will eventually succumb to AIDS
(i)
As
a further complication, note that most HIV-infected people do not die with AIDS
as a direct cause, but instead from secondary infections
that are brought on the increases in susceptibility to infection that results
from immunodeficiency
(j)
Various
external links: [index]
(i)
[AIDS (Google Search)]
(ii)
[The AIDS Knowledge Project]
(iii)
[AIDS
lectures: (1) definitions, origins, and
prevalence, (2) the virus, (3) HIV disease and therapy,
(4) the human immune response,
(5) the biology the stages of HIV
disease, (6) how is HIV transmitted?
(7) preventing HIV transmission,
(8) HIV testing, (9) AIDS and social issues
(University of Michigan Bio 118)]
(iv)
[does HIV prevention work?
(JAMA HIV/AIDS Information
Center)]
(v)
[early impact on HIV infection,
effects of treatment (JAMA HIV/AIDS Information Center)]
(vi)
[the origin of AIDS
(HIV InSite)]
(14) Human Immunodeficiency Virus (HIV)
(a)
HIV
is a plus-stranded, diploid, single-stranded RNA
virus
(b)
HIV
is an enveloped virus that derives its envelope
from the host-cell plasma membrane
(c)
Also
as part of the maturation of an HIV virion the virus
envelope proteins are formed via the proteolytic cleavage of a precursor
(larger) protein (without this cleavage the resulting virus particle is not
functional and it is this cleavage that is blocked by anti-HIV protease
inhibitors)
(d)
HIV
is a retrovirus that employs the enzyme reverse transcriptase to process its
single-stranded RNA genome into a double-stranded DNA genome
(e)
This
double-stranded DNA genome is then inserted into a host chromosome
(f)
See Figure 10.13,
Replication of RNA viruses
(g)
Not
all inserted genomes are immediately active, thus allowing some virus-infected
cells to evade immune system recognition (as well as drug treatment) over long
periods (years, perhaps decades) thus making it nearly impossible to cure an
HIV infection
(h)
There
are two major groups of HIV viruses in circulation among humans, HIV-1 which is
probably derived from a chimpanzee virus (the revenge of the chimpanzees, who
probably passed on the virus to humans as “bush meat”) and HIV-2 which is
probably derived from a monkey virus (one kind of SIV or simian
immunodeficiency virus) (ditto re: the revenge of…) [Nature on HIV origin
(Biocognizance.com)] [the AIDS pandemic is new, but
is HIV new? (Systematic Biology)]
(i)
HIV-1
is by far the more prevalent (in the U.S.) and the more virulent of the two
(j)
[HIV (Google Search)] [anti-HIV strategies (and additional HIV
information) (Biocognizance.com)]
[index]
(a)
HIV/AIDS
is a pandemic disease with estimates of world-wide
cumulative prevalence (i.e., including those that have died—so far a minority)
as high as 50 million people or more
(b)
HIV
is transmitted via body fluids such as semen and blood
(c)
Contact
with the body fluids of others can occur particularly
(i)
During
unprotected vaginal intercourse (the prominent route of transmission in
sub-Sahara Africa) or during anal intercourse (in both cases the recipient is
the more susceptible to infection)
(ii)
From
needle sharing during intravenous drug use
(iii)
From
the transfusion of blood or blood products (rare since the implementation of immunological testing of the blood supply)
(iv)
From
mother to child either in utero, during passage down the birth canal, or from
breast milk
(d)
“It
is not possible to acquire the HIV virus by donating blood because new, sterile
needles are used.”
(e)
Health-care
workers should observe universal precautions to avoid exposure to blood-borne
pathogens including HIV
(f) &n