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Patients with AIDS suffer from a variety of infectious diseases, including Pneumocystis
carinii pneumonia, Toxoplasma gondiiencephalitis, and enteritis caused by a variety of
organisms, including Candida, Cryptosporidium, Giardia and Amoeba. These infections
ultimately lead to the death of the patient.
Why does a person with AIDS (acquired immune deficiency syndrome) develop these
infections, with organisms which ordinarily do not cause problems in most individuals?
The body has several mechanisms which allow it to resist foreign invaders,
both nonspecific and specific. The acquired immune deficiency syndrome causes a failure
in the specific mechanisms by which the body resists infection in other words, there is a
failure in the immune response.
The immune response is characterized by its specificity the ability to direct reactivity
toward the inducing agent through recognition of specific surface molecular markers
(termed antigens) but also by its ability to remember the inducing agent, and respond in
an enhanced way when the agent is again encountered. In this way, it differs from the acute
inflammatory response, which we discussed in the previous unit. Inflammation is
nonspecific the inflammatory response is similar regardless of the initiating injury.
In truth, this Unit should be called the Acquired Immune Response. When the terms
Immune Response and Immunity are discussed, we are referring to the Acquired
Immune response. You might recall from Unit 03 that we discussed something called the
Innate Immune Response, wherein phagocytes could recognize surface molecules on
pathogens (PAMPs). Innate immunity provides a much-needed overlap in function between
inflammation and acquired immunity, and as such was discussed under Acute Inflammation.
antigens
antibodies
immunization
serology
hypersensitivity reactions
transplantation
auto-immune disorders
immunodeficiency
AIDS
describe what an antigen is, and give examples of extrinsic and intrinsic antigens
describe what happens when both B and T cells comes into contact with their
specific antigen
outline the mechanisms of the four types of hypersensitivity reactions, and give
clinical examples of each
outline how the human immunodeficiency virus causes AIDS, and why
opportunistic infections are problems in AIDS patients
Before we move into a discussion on the immune response, I would like to spend a little bit
of time discussing nonspecific protective mechanisms. These can be considered the first
line of defense.
Nonspecific defense mechanisms
The skin and mucous membranes have an important function as a physical barrier to
foreign agents. Cells are routinely sloughed from the surfaces of both, helping to remove
organisms which might have gained a foothold. The skin surface normally has a
slightly acidic pHwhich helps prevent the growth of some organisms. The mucus secreted
by membranes of the digestive, urogenital and respiratory tracts acts as a protective
coating. Cilia help move foreign particles out of the respiratory tract by their directional
movement, sweeping out a film of mucus and any entrapped particles. The cough
mechanism helps to expel such material more forcefully.
A variety of substances produced by these membranes also have protective
functions. Lysozyme in tears, acid in the stomach, digestive enzymes... all help prevent
foreign agents from gaining a foothold.
Inflammation, the subject of the last unit, is a further example of a nonspecific defense
mechanism. The cells of the inflammatory response, the neutrophils and macrophages,
have important roles as phagocytes this nonspecific phagocytosis has an important early
role in defense. (This phagocytic role can be enhanced by opsonization well return to
this later. The macrophages also have important roles in the immune response.)
Antigens
Antigens are molecules which evoke an immune response when introduced into a
host. (The term is also used more narrowly, to describe molecules which induce
an antibody response, with the term immunogen being used to indicate molecules which
elicit an immune response.)
They are large molecules, typically protein or polysaccharide in nature. Smaller molecules
(termed haptens) can also become antigenic if they complex with larger carrier molecules.
Foreign (extrinsic) antigens include infectious agents (such as bacteria, viruses, protozoa,
and fungi we will discuss these in unit VI), transplanted foreign cells (eg. blood
transfusions, tissue transplantations), and a variety of other particles that may gain entry
into the body.
Components of the body can also become antigenic under certain circumstances. For
example, when cells undergo neoplastic transformation (become cancerous) they may be
recognized as being foreign by the body this is beneficial as the body can then combat
the tumour. Normal molecules in the body may be altered by the binding of a hapten, so the
body begins reacting against them. Certain antigens (eg. lens protein in the eye) are
normally separated from the immune system since early embryonic life, so tolerance to
them doesnt develop if these are released in later life (eg. due to lens injury), an immune
response to them may develop.
How does the body know what is foreign?
How does the body know what to react against why doesnt it destroy its own tissues? To
be able to react against something, it must first be able to recognize what is foreign, or
non-self. Many molecules in the body will induce an immune response if introduced into
another individual, whereas in the body of origin they are tolerated. Self (or natural)
tolerance refers to this lack of response to our own antigens.
How does self tolerance develop?
The mechanisms of self tolerance are not completely understood, but several theories have
been developed to explain how it occurs. One of the more accepted of these theories is that
of clonal deletion (central tolerance), which suggests that during embryonic development
our lymphocytes go through a selection procedure in the thymus -- those that are potentially
reacting against self antigens are deleted. There are also several back-up mechanisms in
the peripheral tissues which can help prevent potentially self reactive T cells (which have
escaped central deletion) from having an effect.
The immune response is quite complex, with numerous interactions occurring between
different cell types. I thought it might help if I first gave a brief overview, so you can have
some idea of where were headed!
From the bone marrow (and thymus, in the case of T cells) T and B cells travel
to peripheral lymphoid tissues, such as the lymph nodes, spleen, tonsils, and gut
associated lymphoid tissue (GALT). Lymphocytes travel in the blood, so can be seen on
routine blood smears. These are a pool of cells which traffic between the
peripheral lymphoid tissues.
Where and what are the thymus and the bursa of Fabricius?
The thymus is a gland--like tissue situated in the connective tissues within the chest cavity
(the anterior or cranial mediastinum) in both man and animals. It is the largest in the young,
and involutes with age in the adult it is often little more than a fibrous remnant.
The bursa of Fabricius is an outgrowth of the cloaca in birds. Similar to the thymus, it is
largest in young birds, involuting with age. When active, both the thymus and the bursa
contain lymphoid follicles, sites of lymphocyte development.
B and T cells look the same, so cannot be differentiated by their appearance on blood
smears. They can be differentiated by the presence of antigens which act as immunologic
markers specific monoclonal antibodies can be used to identify these antigens. Genetic
techniques can also be used to detect T cell receptor genes.
This development of the T and B cells is summarized in Fig. 11-13 (p. 430) of your textbook.
Read the section titled Cells & Tissues of the immune system on pages 100-105 of
your textbook, and complete the following discussion.
that can react to the antigen in question and invoke a rapid immune response. It is
these cells that are responsible for the Memory characteristic of immunity, and
why most individuals who contract chicken pox will only do so once!
o Th2-Cell Response
2. CD8 is expressed on about 30% of T-cells. CD8+ T-cells have an important role
as cytotoxic T-cells, which directly kill virus-infected cells and/or tumor cells, but
have a lesser role in secretion of cytokines.
View Figure 4-6 on p108 of your text, which schematically illustrates the two arms of the
immune system, humoral and cellular immunity.
Reviewing page 104 on your text, write down five features of NK cells
Antigen-Presenting Cells
What are three functions of macrophages in the development of the immune response?
Because of these functions, macrophages play a key role in the early immune response.
The cytokine IL-1 activates resting T cells, and antigen presentation is crucial to the
stimulation and differentiation of both T and B cells.
The antigen-processing role of macrophages involves phagocytosis and internalization of
the Ag by the macrophage. The Ag is then expressed at the macrophage surface together
with MHC molecules (these will be described later, when we discuss transplantation), which
leads to T cell activation and lymphokine release. B cell activation usually involves
interaction with both macrophages and T cells, though some multivalent antigens can be
recognized by B cells directly.
Dendritic Cells
Refer to the discussion on page 104 of your text and complete the following:
Reviewing page 104 in your textbook, what are the two major types of dendritic cells, and
what are their features?
The antigen-processing role of macrophages and the amplification aspect of both the T and
B cell response can be summarized in the following diagram:
You can see that the end result of the activation of T cells by antigen is the production of
effector T cells, but, what then?
FUNCTION
Antigen-Presenting Cells
(APCs)
Macrophages
1) Filtration/Phagocytosis
2) Antigen Presentation to
T-cells
3) Cytokine secretion
Interdigitating Dendritic
Cells
1) Antigen capture in
tissues
2) Migration to lymphoid
tissues
3) Antigen presentation to
lymphoid tissue T-cells
4) Cytokine secretion
Follicular Dendritic Cells
1) Antigen/antibody and
antigen/ complement
capture in lymphoid tissues
2) Antigen presentation to
lymphoid tissue B-cells
B-cell Lineage
B-cells/Memory Cells
1) Recognition of
circulating antigen
(via BCR)
2) Proliferation into
Plasma Cells and
Memory Cells
Plasma Cells
T-cell Lineage
CD8+ T-cells (Tc-cells,
Cytotoxic T-cells)
1) Recognition of antigen
fragments on cell surface
MHC molecules
2) Cytolysis/cytotoxicity
(kills affected cells)
1) Recognition of antigen
fragments on cell surface
MHC molecules
2) Secretion of cytokines
that activate
B-cells, Tc-cells
Nonspecific cytolysis of
cells with atypical
surface antigens, loss of
normal MHCI
antigens
Read the section titled Humoral Immunity: Activation of B Lymphocytes & Elimination of
Extracellular Microbes on pp. 108-109 of your textbook, then complete the following: The
antibodies comprise a family of serum proteins called immunoglobulins, part of the globulin
fraction of serum. Three main classes of immunoglobulins are recognized.
What are the three main classes of immunoglobulins, and what are their key features?
Ive included a schematic diagram of an immunoglobulin molecule below, to show the
heavy (longer) and light chains. Each chain has both constant and variable parts. The
constant part is the same in all members of the same Ig class, and is shown as white. The
variable part (shown as black) shows great variability in its amino acid sequences it is this
region which gives the antibody its specificity. Thus, the antigen-binding sites are in these
variable regions. The constant region has receptors for complement, which we will discuss
shortly. (Note also the Fc portion, the function of which will be described later.)
Ig Molecule
Open Learning and Educational Support/D. Schaefer
Antibody production
When the body is exposed to an antigen, what steps must take place before antibodies
appear in the serum?
Colostrum is the thick, yellow milky fluid secreted by the mammary gland of all mammals
(including man) for a few days before and after parturition. It contains a high percentage of
protein, predominantly consisting of immunoglobulins derived from the maternal blood. The
gut of the neonate is especially able to absorb these proteins.
How does the antigen come into contact with macrophages and
lymphocytes?
Up to this point the discussion has been rather abstract how does the antigen come into
contact with macrophages and lymphocytes?
Antigens can enter the body in a variety of ways through the skin if it has been injured, or
through the mucosal membranes of the respiratory tract, alimentary tract or urogenital tract.
Local nonspecific defenses, which I described at the beginning of this unit, may not be
adequate to stop the organism from gaining entry. Once within the body, the nonspecific
inflammatory response with its associated phagocyte activity may be able to stop the
antigen from going further (Unit 03!). However, some antigens may be carried via lymphatic
flow to local lymph nodes, where they will first be exposed to large numbers of
macrophages and lymphocytes.
Within the lymph node, the antigen is processed by macrophages and presented to T and
B cells, leading to T cell transformation, T immunoblast formation and the production of
activated T cells; B cells are transformed into plasma cells, which begin actively secreting
antibody. The end result of this is that antibody is secreted into the lymphatic vessels
leaving the node (the efferent vessels), and ultimately enters the blood plasma via the
thoracic duct.
The stimulation of lymphocyte activity within the lymph node also causes the lymph node to
become enlarged (and possibly tender). This is why, for example, the lymph nodes under
your jaw (which many people refer to as glands) may be enlarged in the case of a sore
throat. Such nodes, enlarged because of response to an antigenic stimulus, are referred to
as reactive or hyperplastic. The T and B cells are arranged in units called follicles
enlarged, prominent follicles are characterictic of a reactive node.
Weve spent some time discussing what antibodies are and how they are produced. The
most important thing about antibodies, however, is that they react with antigen.
If the antigen is a toxin, then agglutination may serve to neutralize the toxin.
Opsonization refers to the process of coating the antigen with antibody, allowing
increased phagocytosis by leukocytes having receptors for the antibody
(particularly the Fc portion again, refer to the Ig molecule diagram on p.156).
For example, a cell with an attached Ag/Ab complex initiates the complement cascade,
resulting in formation of the cytotoxic complex and lysis of the cell.
Complement activation also has other effects. It is closely associated with the inflammatory
response. Both C3a and C5a contribute to vasodilation and increased vascular permeability,
as well as being chemotactic for neutrophils. C3b can act as an opsonin, inducing immune
phagocytosis by neutrophils and macrophages. Complement was introduced earlier, in Unit
03.
Note that agglutination and opsonization occur when the antigenic stimulus is cellular,
(bacteria, for example). If the antigen is a macromolecule, Ag -Ab complexing leads to
formation of a large macromolecular complex, which is also more easily phagocytosed. The
activation and functions of the complement system are illustrated in Fig. 2-18, on p. 50 of
your text.
To summarize, the formation of immune complexes in vivo (in the living body) ultimately
leads to:
Im sure that you are aware that the purpose of vaccinations, the shots which we all
undergo as children (and as adults), is to give immunity to particular diseases. How does
this work? We can use some of the principles weve learned so far to discuss immunity.
Early in this unit, I said that the immune response was characterized by
its specificity, its memory, and the characteristic of amplification the enhanced response
occurring on the second exposure to an antigen.
Depending on whether or not the immune system has previously been exposed to an
antigen, two types of immune response are recognized:
Immunization
These principles are used to advantage in the practice of immunization. Immunity can
be either active or passive.
Passive immunity refers to transfer or administration of pre-formed antibody from another
person or animal (who is immune to the particular agent) is given to either prevent or help in
treatment of a specific disease. This is useful for emergency treatment, but has
disadvantage of being only temporary, as the administered antibody will be metabolized and
removed and the patient will retain no immunologic memory. Good examples of passive
immunity include:
vaccine, by complexing with the antigen before it can induce an immune response. There is
considerable individual variability as to the optimum time to vaccinate, depending on the
level of maternally acquired antibody and the state of development of the immune response.
To cover this window of time, vaccines are given in a series, beginning at about 8 weeks of
age.
Serology
The term serology refers to the study of antigen-antibody reactions in a laboratory
setting. Tests for antibodies in a patients serum are called serologic tests, and the level of
antibody present can be measured by determining its titer: titer indicates the dilution at
which reactivity between Ag and Ab is still noted. Thus, the higher the level of Ab in the
serum, the greater the dilution of that serum with reactivity still being apparent. A high titer is
therefore indicative of high antibody levels.
Serologic tests are often used to aid in the diagnosis of certain infectious diseases, such as
systemic fungal infections, bacterial infections (brucellosis, leptospirosis), and many viral
diseases. Serum antibody levels can also be measured to determine the adequacy of
response to a vaccine, or whether a neonatal animal has suckled sufficient colostrum.
It is important to note that the presence of serum antibodies only indicates previous
exposure to the organism, and does not necessarily indicate the presence of active disease.
Were going to turn now to a discussion of diseases caused by the immune response. Much
as thrombosis can be thought of as clotting (a beneficial response) gone wrong causing
undesirable effects the hypersensitivity reactions can be thought of as the normal
protective immune responses gone wrong the immune system leads to tissue damage
and disordered function.
The terminology used to describe this type of reaction is often confusing. You should read
the discussion in your textbook Hypersensitivity Diseases: Mechanisms of ImmuneMediated Injury, on pp.109-111.
It is worth emphasizing that:
Type I
Anaphylactic
Type II
Antibody-Dependent
Type III
Complex-mediated
Type IV
Cell-mediated
Types I, II, and III are mediated by antibody reactions, while Type IV is caused by cell
mediated responses.
Well spend some time discussing each of these in turn.
Read pp. 111-114 of your textbook, then complete the following: Type I hypersensitivity may
occur as (two points).
cells are activated by the cross-linking of IgE bound to their surfaces by Fc receptors
(recall that the Fc is the nonvariable base of the antibody molecule).
Other triggers of mast cell degranulation include C5a and C3a, macrophage derived
cytokines, bee venom, physical stimuli (heat, cold), and a variety of drugs. The
mediators released from mast cells can be grouped as:
o Primary (preformed) mediators
destroys cells which the body needs - the red blood cell or platelet is destroyed because the
antigen was attached to its surface.
These mechanisms can be summarized in the following diagram. Note that only one
exposure to the antigen is needed.
View figure 4-11 (p. 116, text), a schematic illustration of the three phases in the
induction of systemic type III (immune complex-mediated) hypersensitivity.
Note that complement activation by the Ab/Ag complexes is central in the
pathogenesis of tissue injury.
Type IV hypersensitivity is mediated by sensitized T cells, which are either directly cytotoxic
(T cell mediated cytotoxicity) or secrete cytokines, which recruit other cells, which then act
as effector cells and cause injury (delayed-type hypersensitivity).
Read the section titled T-Cell-Mediated (Type IV) Hypersensitivity on pp. 117-120 of your
textbook. Complete the following:
1. Delayed type hypersensitivity is characterized by the presence of (list the cell
types)
2. Poison ivy dermatitis (a contact dermatitis) is a good example of delayed
hypersensitivity. Describe what would happen when a sensitive person undergoes
both first exposure (sensitizing exposure), then second exposure (and
subsequent exposures) to this plant (four points)
3. What cytokines are primarily responsible for the development of the DTH
response? List four, and briefly describe their roles.
Type IV hypersensitivity is used diagnostically in the tuberculin test. Tuberculin, an
inactivated antigen extracted from the mycobacteria which cause tuberculosis, is injected
intradermally (within the skin). A delayed (24-72 hours) reaction (a firm nodule consisting of
T cells and macrophages, and fibrin deposition) occurs at the site in people which have
been sensitized to the antigen, providing evidence of previous exposure.
MHC II by interferon-alpha. The genetics of this can get a bit complicated I just wanted to
introduce these terms so you can recognize them but, basically, the similarity between
donor and recipient with regard to these antigens is a major determinant of the
success of the graft. Notable is the polymorphism at major HLA loci, with each individual
expressing a unique MHC antigenic profile.
Read the section Rejection of Transplants on pp. 135-139 of your text.
A. T Cell-Mediated Rejection
Describe how Type IV hypersensitivity (both DTH and CTL mechanisms) leads
to classic acute rejection(two points).
B. Antibody-Mediated Rejection
Anti-HLA antibodies are also developed, along with the T cell-mediated rejection.
Antibody-mediated injury targets vascular endothelium, with platelet aggregation and
coagulation leading to further ischemic injury to tissue.
Complete the following: Hyperacute rejection occurs when:
You can probably appreciate that finding compatible donors can be very difficult,
so immunosuppressant therapywith drugs is a major part of managing transplants
post-surgically. What are the possible side effects of using drugs such as this?
(Refer to p. 138 of your textbook, Methods of Improving Graft Survival).
(Text, pp. 120-124)
At several points in the discussion of hypersensitivity reactions I have referred to autoimmune disorders, such as systemic lupus erythematosus and myaesthenia gravis. An
immune-mediated process can be called auto-immune if the response is truly directed
against self as your text points out, a fundamental issue is to decide whether the patient
is reacting against unmodified cell or tissue components.
Why does auto-immunity develop?
Earlier, the issue of self-tolerance was discussed (p. 146). A major theory to explain the
occurrence of auto-immunity (failure of self-tolerance) is that this clonal deletion phase in
embryonic development is somehow faulty, so an individual is born with clones of
lymphocytes capable of reacting against normal tissue components. Another theory holds
that all individuals probably have numbers of lymphocytes with receptors for self antigens,
but these are normally suppressed by T suppressor cells dysfunction of this process
would lead to auto-immunity. Alternatively, perhaps auto-immunity is really against slightly
altered (slightly nonself) tissue components.
Well finish our discussion of hypersensitivity reactions at his point. You should realize that
the classification scheme developed for these reactions is only a manmade device to help
us in our effort to understand how immunologic reactions can lead to disease. Not all
diseases fit neatly into these classifications. Many diseases show more than one type of
hypersensitivity process.
The preceding discussion of hypersensitivity reactions focused on diseases resulting from
increased reactivity against an antigen. Equally serious disease can result from
an insufficient immune response. The acquired immune deficiency syndrome (AIDS) is an
example of such a immunodeficiency disease.
Text, pp. 139-143)
Immunodeficiency diseases may be either inherited (primary immunodeficiency) or acquired
(secondary immunodeficiency), resulting from secondary effects of other diseases or states.
In both cases, clinical presentation relates to an increased susceptibility to infections as well
as to the development of certain types of cancer.
Primary Immunodeficiencies
Read the discussion on primary immunodeficiencies, found on pp. 139-143 of your
textbook. Primary immunodeficiency states are rare; they generally are genetically
determined, affecting either specific humoral or cellular immunity, or nonspecific host
mechanisms (e.g., complement, phagocytes, NK cells).
A particularly serious type of primary immunodeficiency is severe combined
immunodeficiency (SCID); these are a group of genetically distinct syndromes which show
defects in both humoral and cell-mediated immunity.
Secondary Immunodeficiencies
Malnutrition, cancers, chemotherapy, radiation therapy, and infection are some of the
conditions leading to secondary immunodeficiency. As a group, these secondary
immunodeficiencies occur more frequently than the primary immunodeficiencies. The most
important of the secondary immunodeficiencies is AIDS.
Complete the following: What are the three major routes of transmission of HIV?
HIV is a retrovirus, and is spherical in shape. The outer lipid envelope (derived from the
host cell membrane) is studded by two viral glycoproteins (gp120 and gp41) that have a
critical role for HIV infection of cells. Of the inner core proteins, p24 (a capsid protein) is
important as the most readily detected viral antigen; antibodies used to detect HIV infection
in blood are against this p24 antigen. The viral genome codes for various viral proteins , as
well as having genes that regulate the assembly of infectious viral particles. There is
considerable variability in the viral genome; variability in viral envelope antigen structure
means that development of a vaccine will be very difficult.
Pathogenesis of HIV disease (Text, pp. 144-150)
AIDS is characterized by profound immunosuppression, which primarily affects cellmediated immunity. The virus shows a tropism for CD4+ cells, which includes CD4+ T cells,
macrophages, and dendritic cells.
View Fig. 4-27, on p. 146 of your text, which illustrates how HIV enters host cells. Note that
the viral gp120 protein must bind to bothCD4 and other coreceptors to be able to enter the
cell. Once inserted into the cell, the HIV genome undergoes reverse transcription, with
formation of cDNA.
In resting T cells, this cDNA may remain in the cell cytoplasm. However, in activated,
dividing T cells, the cDNA enters the host cell nucleus.
Complete the following: What are the possible outcomes of integration of viral cDNA into
the target cell genome? (two points)
Note that proviral DNA transcription (which leads to productive infection, and hence cell
death) is initiated when the infected cell is activated by exposure to antigens or
cytokines. Thus, anything which promotes T cell activation and growth (such as concurrent
infection) will promote the death of HIV-infected cells. This loss of CD4+ T cells is the
defining characteristic of AIDS.
Ultimately, the death of CD4+ lymphocytes leads to increased susceptibility to viruses,
fungi, protozoa, and some bacteria (such as the mycobacteria), all microorganisms for
which cellmediated immunity plays an important defensive role. There is also an increased
susceptibility to certain cancers, such as Kaposis sarcoma and lyphoma.
The loss of CD4+ T cells occurs due to increased destruction of infected cells, as noted
above, but also due to reduced production of CD4+ T cells. Additionally, there is evidence
that T cell function may also be defective.
Are other cell types affected?
The infection of monocytes and macrophages is also very important in the pathogenesis of
HIV infection. Macrophages and monocytes act as important viral reservoirs and
producers. HIV can infect and multiply in non-dividing macrophages, and macrophages are
relatively resistant to cytopathic effects of the virus. Macrophages can transport HIV to
other body sites, notably the nervous system. Finally, the impaired function of infected
monocytes has negative effects on host immune function.
Dendritic cells at muscosal surfaces have important roles in viral capture and transport to
regional lymph nodes, where CD4+ T cells are then infected. Dendritic cells in lymph nodes
likely act as important viral reservoirs.
Thus, CD4+ T cells, macrophages, and dendritic cells in lymph nodes are the major
sites of HIV infection and persistence.Because of the central role of CD4+ T cells in
regulation of the immune response, virtually all other cell types of the immune
system are affected in AIDS.
Table 4-11 (on page 147, textbook) summarizes the resulting major abnormalities of
immune function seen in AIDS.
The course of HIV infection can be described in phases. The early acute phase is usually a
self limited illness, culminating in a virus specific immune response, with the detection of
virus-specific antibodies (by 3-17 weeks post exposure). In the middle, chronic phase,the
HIV test is positive, but there are few signs of disease this can last for up to 8-10 years,
though the median is 4 1/2 years. However, during this phase, viral replication continues in
the lymphoid tissues. Disease may then progress from chronic lymphadenopathy (enlarged
lymph nodes) to one of severe opportunistic infections and a very low CD4+ cell count.
There is a marked increase in viremia. This is the final, crisis phase. Once this stage is
reached, most patients die within 2 years.
Weve reached the end of this unit! In the next unit, we will put together this unit and the
last by discussing chronic inflammation, as well as healing and repair.
Kaposi sarcoma is described on pp. 151-152 and 360-361 of your textbook. It is
characterized by blotchy purple patches, plaques or nodules in the skin which may
ulcerate. It can also affect the viscera (intestine, lung, liver), where it appears as
hemorrhagic masses.
You may have heard the term AIDS - related complex (ARC) used. This refers to patients
which are HIV+ and symptomatic, but have none of the indicator diseases used to define
AIDS (such as many of the opportunistic infections listed in Table 4-12 (p. 151) of your
textbook, as well as Kaposis sarcoma and lymphoma of the brain).