Keywords for Chapter 4, Immunopathology

Keywords: Chapter 4, Immunopathology

Acquired Immune Deficiency Syndrome (AIDS)

Acquired Immune Deficiency Syndrome (AIDS) AIDS was the acronym used early in the epidemic of human immunodeficiency virus, a retrovirus. Before the acronym of AIDS was invented, the Centers for Disease Control (CDC) called the syndrome gay-related immune deficiency or GRID. This name was changed to AIDS after it became apparent that other groups besides male homosexuals were at risk. AIDS is still in popular use by the media, but the proper terminology should be HIV infection (the cause is known, so it's not really a syndrome anymore). The exact case definitions are detailed in the references below. I have also listed some prevention guidelines, and the address of the National AIDS Clearinghouse.

References

MMWR 41 (RR-17), 1992. Revised classification system for human immunodeficiency virus infection and expanded case surveillance definition for AIDS among adults and adolescents.
MMWR 43(RR-12). Revised classification systems for human immunodeficiency virus in children less than 13 years of age.
Ibid. Adobe Acrobat format.
MMWR44 (RR-8), 1-34, 1995. Guidelines to the prevention of opportunistic infections in persons infected with human immunodeficiency virus: A summary.
Ibid. Adobe Acrobat format.
CDC National AIDS Clearinghouse Gopher

acquired immunity

Acquired immunity is that produced by the specific response of the immune system to foreign antigens. Usually, an antigen is proteinaceous, but an immune response can be mounted to other substances, such as RNA, DNA, and poly-saccharides. Acquired immunity is built up within the host after natural infection or immunization.

acute rejection

Acute rejection occurs in the first weeks or months following solid organ transplantation. It is characterized histologically by: 1) edema, 2) interstitial infiltration of lymphocytes and macrophages, and 3) focal necrosis. The most severe form may also show fibrinoid necrosis of vessel walls, perhaps with thrombosis, similar in this respect to hyperacute rejection. Acute rejection involves both humoral and cell-mediated immune reactions.

aggretope

The name aggretope is given to the macromolecular association of a peptide epitope with type I major histocompatibility antigens.

anaphylaxis

Anaphylaxis is a clinical condition that occurs when an allergen binds to specific IgE on mast cells, causing the release of histamine and other vasoactive amines. The anaphylatoxins, C3a and C5a, are also involved. This causes bronchoconstriction, which leads clinically to severe wheezing, respiratory distress, and ultimately, death. Urticaria (hives) can also occur. Anaphylaxis can only be reversed by the immediate administration of epinephrine (adrenaline), anti-histamines, bronchodilators, and systemic steroids.

Arthus reaction

The Arthus reaction is important as an experimental model of immune complex vasculitis (type III hypersensitivity reaction). The animal is injected with an antigen to which it has been previously immunized. Immune complexes form in the walls of dermal vessels. Complement is then activated and the vessel wall begins to show fibrinoid necrosis.

cell-mediated immunity

The type of immunity that requires the participation of immune cells (T-cells and monocyte/macrophages). The classic example of this type of immunity is the type IV hypersensitivity reaction. Contrast and compare to humoral immunity.

chronic rejection

A host vs. graft reaction that occurs over a period of months to years, characterized histologically in most transplanted organs by 1) arterial and arteriolar thickening (intimal layer), 2) atrophy, 3) interstitial fibrosis (page 82).

cluster designation

The cluster designation (CD) is used to denote sub-populations of leukocytes. Each CD represents an antigen that appears on the surface of a type of white cell. For example: CD-3 is present on all T-cells; CD-4 is present on T-helper cells; CD-8 is present on T-suppressor cells. Over 40 different CD antigens have been characterized.

dermatomyositis

An auto-immune disease characterized by inflammatory changes in the skin and muscle. It is linked to the HLA B-8 and HLA DR-3 loci on chromosome 6. Women are affected twice as frequently as men. It may be associated with visceral cancers (page 93).

DiGeorge syndrome

An immunodeficiency disease characterized by deficient T-cell immunity. The disease usually presents early in life, and is characterized by a defect in development of the 3rd and 4th pharyngeal pouch, which results in congenital absence of the thymus and parathyroid glands. This explains the T-cell deficiency and resultant opportunistic infections, similar in this respect to AIDS, and also the severe problems of hypocalcemia, which often bring the disease to clinical attention (page 83).

epitope

An epitope is a short, linear peptide sequence that is a portion of a larger protein antigen. Antigen-presenting cells (APC) process antigens and degrade them into short peptide sequences (epitopes), which are then expressed on the surface of the APC cell in association with Class I MHC molecules. This macromolecular complex (aggretope) is then recognized by specific helper T-cells, which can activate specific B-cells to respond to that epitope from that particular antigen. Thus, specificity of the immune response is maintained.

fibrinoid necrosis

A type of necrosis that occurs in the wall of a small artery or arteriole. It is pink in color, and resembles fibrin (thus, fibrinoid). It represents actual death or necrosis of the cell wall. It is normally seen in type III hypersensitivity reactions.

graft vs. host disease (GVH)

GVH occurs only in bone marrow transplantation, where the immune cells that are transplanted into the recipient recognize the recipient as foreign. This usually manifests as a skin rash shortly after engraftment, and may cause diarrhea and GI upset. Later, GVH may affect other organs such as the liver and kidney, leading to problems of hepatic and renal failure. Iatrogenic immunosuppression is required.

Hashimoto thyroiditis

Hashimoto disease is a form of auto-immune thyroiditis. It has a female predominance (10:1). Initially, the gland is swollen and painful. Hyperthyoidism may occur, which may be severe (Hashitoxicosis). Numerous auto-antibodies are present, including those to thyroglobulin and thyroid microsomal antigens.

hashitoxicosis

A severe form of hyperthyroidism seen in Hashimoto thyroiditis.

host vs. graft disease

The reaction of host T-cells to the foreign antigens of a tissue graft (transplant). Killer T-cells (CD-8) and natural killer (NK) cells both are capable of killing the foreign cells, unless iatrogenic immunosuppression is used.

human leukocyte antigens (HLA)

The human MHC, also known as the human leukocyte antigen (HLA) locus, is a series of genes on the short arm of chromosome 6 that code for antigens first discovered on leukocytes, but later found on all cells. These antigens determine histocompatibility, important in transplantation. They are the major antigens, but there are many minor ones. For practical purposes, they are divided into 2 types:

Class I antigens: Consist of the A, B, and C loci on chromosome 6. Alleles are co-dominantly expressed, so you have class I antigens from both parents. These antigens are recognized by cytotoxic T-cells, and are therefore important in tissue cross-matching to prevent graft rejection in the case of transplantation. They are present on all cells (except stem cells).
Class II antigens: Consist of at least 3 loci in the D region: DP, DQ, and DR. You may here them referred to as Ia antigens, because they are analogous to the mouse MHC antigens that go by that name, and are involved in the immune response. Like class I antigens, they are expressed co-dominantly.; These antigens are most important because of their role in the interaction between immune cells, particularly between antigen-presenting cells (APC) and T-cells.

human immunodeficiency virus (HIV)

A human retrovirus, HIV was co-discovered by Robert Gallo of the National Cancer Institute and Luc Montagier of the Pasteur Institute in Paris. The virus binds to CD-4 receptors, found normally on T-helper cells, but also found on cells of monocyte/macrophage linage. Thus, the virus destroys a key component of the specific immune response and makes the host susceptible to so-called opportunistic infections.

humoral immunity

The immunity represented by antibody. A humor, in ancient Greek medicine, was a fluid. Therefore, humoral immunity is that conferred by serum (plasma), which is rich in antibodies. Cells are not involved (other than they participated in the synthesis of the soluble antibody).

hyperacute rejection

In organ transplantation, hyperacute rejection of a transplanted organ occurs within seconds or minutes of exposing the organ to the recipient's circulation. The organ quickly becomes pale, and will undergo necrosis if left in the recipient's body. This hyperacute reaction is thought to occur because of preformed antibodies against the donor organ. This is most common in multiparous women, since they may have been exposed in utero to numerous non-self antigens. Recipients who have received multiple blood transfusions may also be at risk.

hypersensitivity reaction

Type I hypersensitivity: This type of immunologically mediated injury occurs when there is a local or generalized reaction after an exposure to an antigen to which the person has become sensititized. Normally, allergists call the antigen an "allergen", since the most common type of Type I reaction would be what is commonly known as hay fever. The reaction is mediated by the binding of the antigen to specific IgE present on mast cells. The anaphylatoxins, C3a and C5a, are also involved (see Figure 4-3 page 72; Figure 4-5 page 107, big Rubin).
Type II hypersensitivity: Type II hypersensitivity involves an antigen-antibody reaction that is directed against cells, or more rarely, against extracellular membrane components such as collagen or basement membrane. IgM and IgG are the isotypes generally involved. When they bind to a cellular antigen, they activate the complement system, which forms a membrane attack complex that kills the cell. Some components of the complement system also serve to attract inflammatory cells to the site, which can cause further damage, through 2 mechanisms. First, complement can act as a opsonin in the process of opsonization, which identifies a cell for phagocytosis via C3b receptors on the PMN or macrophage cell membrane. Second, antibody bound to a cell can identify it for attack by natural killer cells, via Fc receptors. (see Figures 4-4 through 4-7, pages 73-75; Figures 4-6 through 4-9, page 108-110, big Rubin).
Type III hypersensitivity: Type III hypersensitivity reactions involve tissue injury mediated by immune complex formation (antigen-antibody complexes)(see Figures 4-8 through 4-9, page 76-77; Figures 4-10 and 4-11, pages 110-111, big Rubin). The antigen-antibody complexes are deposited in tissue, where they activate complement and cause tissue damage in a manner similar to that of type II reactions. The only real difference between type II and type III reactions, then, is in the location of the antigen. Type II reactions are against antigens located on cell surfaces or extracellular matrix components, whereas type III reactions occur against soluble or circulating antigens. Systemic lupus erythematosis and most types of glomerulonephritis are due to Type III immune injury.
Type IV hypersensitivity: Type IV hypersensitivity is the only one that does not involve antibody. Therefore, it is often called cell-mediated hypersensitivity, or delayed-type hypersensitivity. It is delayed because it takes the immune cells (macrophages and T-cells) a few hours or days to get there (see Figure 4-10, page 79; Figure 4-11. page 112, big Rubin). The classic example of delayed-type hypersensitivity is the purified protein derivative (PPD) Tb skin test.

isotype switching

The term isotype refers to the heavy chain of an immunoglobulin. During B-cell maturation, induced by the influence of T-cell factors, the isotype of immunoglobulin produced by the cell switches from a less-specific form (e.g., IgM) to a highly specific form (e.g., IgG). This switching involves gene rearrangement of the immunoglobulin genes.

Kaposi sarcoma

An unusual neoplastic growth first seen in the United States among HIV infected men. It differed from the usual appearance of the neoplasm seen previously, in that Kaposi sarcoma typically occurred in old men, and principally on the lower extremities. It ran a long clinical course of many months or years, and rarely metastasized. In HIV patients, however, it appeared in many different organs, and ran a rapid clinical course to death. Histologically, it consists of a series of vascular channels lined by atypical endothelial cells. Recent evidence indicates that the neoplastic transformation may be caused by a viral infection, perhaps a Herpes virus.

Libmann-Sacks endocarditis

Small, non-bacterial vegetations occurring on the valve leaflets, often seen in conjunction with systemic lupus erythematosus.

lymphoma

A malignant neoplasm arising in lymphoid cells. It normally causes lymph node swelling, since the lymph nodes are where most lymphoid tissue resides. However, lymphoma may arise anywhere there are lymphocytes, which is to say that it may arise anywhere. During the recent HIV epidemic, we have begun to see more lymphomas arising in the gastrointestinal tract amongst the Gut-associated lymphoid tissue (GALT). Some clinicians have called these malignancies GALTomas. We have also seen an increase in lymphomas arising in the central nervous system in those patients infected with the HIV.

major histocompatibility complex (MHC)

Class I antigens: Consist of the A, B, and C loci on chromosome 6. Alleles are co-dominantly expressed, so you have class I antigens from both parents. These antigens are recognized by cytotoxic T-cells, and are therefore important in tissue cross-matching to prevent graft rejection in the case of transplantation. They are present on all cells.
Class II antigens: Consist of at least 3 loci in the D region: DP, DQ, and DR. You may here them referred to as Ia antigens, because they are analogous to the mouse MHC antigens that go by that name, and are involved in the immune response. Like class I antigens, they are expressed co-dominantly.; These antigens are most important because of their role in the interaction between immune cells, particularly between antigen-presenting cells (APC) and T-cells.

natural immunity

Natural immunity is that mediated by the non-specific action of monocyte/macrophages and polymorphonuclear leukocytes (PMNs). It does not require prior exposure, and is not enhanced by prior exposure.

natural killer (NK) cells

A sub-population of lymphocytes that have the ability to kill virus-infected and tumor cells in vivo, without the intervention of a helper T-cell (CD-4). They have no markers on their cell surface, and are sometimes referred to as null cells.

opportunistic infection

An infection which affects an immunocompromised host. In a sense, all infections are opportunistic, but we usually mean only those unusual infections that are seen only in immunocompromised hosts. The offending organism may be protozoal, viral, bacterial, fungal, spirochetal, or even algal. The key point is that if the same organism were introduced into an immunocompetent host, most likely, nothing would happen.

opsonization

Cells or bacteria can undergo opsonization by the binding of complement or antibody to their cell membranes. The opsonization process thus identifies these cells or bacteria to the phagocytic system. Neutrophils and monocyte/macrophages have receptors on their cell surface for the C3b component of complement and the Fc portion of antibodies, and attack and engulf cells or bacteria that have been identified to them by the complement or antibody system.

retrovirus

Retroviruses are a class of RNA viruses that are capable of converting their RNA into DNA, and integrating into the host genome. They do this through the action of reverse transcriptase, an enzyme found only in retroviruses. By incorporating themselves into the host genome, the viruses share the property of latency, whereby they can transcribe another copy of themselves at any time and become active within the cell cytoplasm again.

sequestered antigens

Antigens that are usually sequestered from the immune system. A good example would be the antigens (proteins) found within the anterior chamber of the eye. They are not normally exposed to immune cells since they reside in an avascular space;

severe combined immunodeficiency (SCID)

This inherited disease affects both arms of the immune system, humoral and cellular. The disease is X-linked and autosomal recessive. The essentially absence of T- and B-cells is associated with severe hypogammaglobulinemia, and infections with a wide variety of opportunistic infections. A story about this disease also launched John Travolta's movie career, The Boy in the Bubble.