Diseases of the Immune System:, Part 2

This condition is associated with a number of inherited and inflammatory disorders in which extracellular deposits of fibrillar proteins are responsible for tissue damage and function compromise.

Amyloidosis

Amyloid is produced by the aggregation of :

misfolded proteins

The congo red stains the amyloid red but turns refrigerant:

green, upon examination with polarized light, it is used to detect amyloid

Systemic (generalized) amyloidosis is caused by:

immunoglobulin light chain misfolded proteins

Hereditary amyloidosis is an autosomal recessive condition, also known as:

Mediterranean fever

Hereitary amyloidosis is associated with:

amyloid associated protein (AA)

Familial amyloidotic neuropathies are associated with:

transrethrin

This type of amyloidosis is seen in patients on long term hemodialysis, depost Beta 2 microglobulin.

Hemodialysis associated amyloidosis

The beta 2 microglobulin is deposited in:

joints, muscles, tendons, ligaments and is a rare cause of carpal tunnel syndrome

this type of amyoidllosis is limited to a single organ, such as the lungs, larynx, skin, bladder, tongue, and around the eye. lymphocytes are often seen around the deposits. Consists of AL proteins and may represent a form of plasma cell amyloid.

Localized amyloidosis

this amyloid is deposited in multiple organs with age (heart dysfunction). Previously called senile cardiac amyloidosis. The amyloid present is a form of TTR.

Amyloid of aging

Cardiac amyloidosis results in progressive:

congestive heart failure

the major protein in primary amyloidosis is:

alpha light chain AL, gamma type

Immunoglobulin light chain amyloidosis (primary) is associated with:

Multiple myeloma

other monocondral plasma cell proliferations

Reactive systemic amyloidosis (secondary) results from:

chronic inflammatory conditions

The major protein in secondary amyloidosis is:

amyloid associated protein AA

Hemodialysis associated amyloidosis is seen in:

chronic renal failure

The major protein in hemodialysis associated amyloidosis is:

A beta-2m

Diagnosis of amyloidosis can be made using what stain and what kind of biopsy?

Congo red stain

fat pad biopsy

AL amyloidosis has an average survival of:

2 years following diagnosis

A bone marrow biopsy may discover (regarding amyloidosis):

monoclonal plasmacytosis

For more sensitive testing (for amyloidosis), the tests that should be used are:

serum and urine electrophoresis and immunoelectrophoresis

Deposition in the stomach and intestine may result in:

malabsoprtion

Vascular amyloidosis results in:

vessel fragility and bleeding

By electron microscopy, all types of amyloid’s consist of:

continuous non-branching fibrils with a diameter of approximately 7.5-10 nm

this characteristic is responsible for the distinctive Congo red staining and birefringence of amyloid, demonstrated by X-ray crystallography and infrared spectroscopy.

cross beta-pleated sheet conformation

this is the final phase of HIV infection, characterized by breakdown of host defenses, dramatic increase in viral load and severe, life-threatening clinical disease.

AIDS

this is the most common fungal infection in patients with AIDS and frequently heralds the transition to AIDs

Candidiasis

Patients with AIDS present with:

fever

weight loss

diarrhea

generalized lymphadenopathy

neurologic disease

multiple opportunistic infections as secondary neoplasms

These infections account for the majority of deaths in uncreated patients with aids.

opportunistic infections

Cryptococcus targets the ____ and occurs in AIDS patients:

CNS

This sarcoma is caused by infection by human herpes virus (HHV8) consists of a proliferation of spindled cells that express markers of both endothelial cells (vascular or lymphatic) and smooth muscle cells

Kaposi’s scarcoma

AIDS associated KS affects the:

skin

mucous membranes

GI tract

lymph nodes

lungs

There is incidece of certain tumors in AIDS patients, such as:

Kaposi’s sarcoma

B-cell lymphomas

cervical cancer

anal cancer in men

When a combination of at least 3 effective drugs is used in a compliant patient, HIV viral load is:

reduced to below the level of detection and can remain there indefinitely

This syndrome is caused by mutations in transcription factors that are required for class II MHC gene expression, prevents the development of CD4 positive T cells that are involved in cellular immunity and provide help to B cells. This leads to combined immunodeficiency.

Bare lymphocyte syndrome

Patients who are affected with this syndrome have IgM antibodies but are deficient in IgA, IgG, and IgE antibodies. Affected individuals present with pyogenic infections because of the level of opsonizing IgG antibodies is low and because of affinity maturation.

Hyper IgM syndrome

This is a frequent condition, encompassing a heterogenous group of disorders in which the common feature is:

hypergammaglobulinemia

Most affected individuals of isolated IgA deficiency are asymptomatic but because IgA is a major antibody in mucosal secretions, they are:

prone to sinopulmonary infections and diarrhea

IgA deficiency is common in what population?

1 in 600 individuals of European descent

this disease is characterized by an inability to eliminate EBV, eventually leading to fulminant infectious mononucleosis and the development of B-cell tumors.

X-linked lymphoproliferative disease

X-linked lymphoproliferative disease is caused by:

gene encoding for adapter molecule called SLAM-associated protein

SAP is required for the development of:

T follicular helper cells

Defects in SAP attenuate NK and T cell activation, resulting in:

increased susceptibility to viral infections

This syndrome is an X-linked disease characterized by thrombocytopenia, eczema, and a marked vulnerability to recurrent infection, resulting in early death.

Wiskott-Aldrich syndrome

Wiskott-Aldrich syndrome is caused by mutations in the gene:

located at Xp11.23 that encodes WASP, believed to link membrane receptors such as antigen receptors DISIDA skeletal elements

Individuals who are affected by Wiskott-Aldrich syndrome suffer progressive:

Loss of T lymphocytes in the peripheral blood and T zones of lymph nodes, variable effect and cellular immunity. Patients do not make antibodies to polysaccharide antigens

This an autosomal recessive disorder characterized by abnormal gait (ataxia), vascular malformations (telangiectases), neurological deficits, increase of tumors and immunodeficiency.

Ataxia telangiectasia

The gene responsible for ataxia telangiectasia is located on:

chromosome 11, encode for protein kinase called ATM

In response to DNA damage, ATM activates:

p53 by phosphoylases, which in turn activate cell cycle checkpoints and apoptosis in cells with damaged DNA

Affected individuals of ataxia telangiectasia have a marked increased incidence of:

lymphoma

Abnormalities in DNA resulting from ATM deficiency may impair the generation of:

antibody receptors and lead to DNA recombination events, involved in IgA isotype switching

this disease occurs when immunologically competent cells or their precursor are transplanted into immunologically compromised recipients and the transferred cells recognize alloantigens in the host and attack the host tissues.

Graft-versus-host disease (GVHD)

GVHD can occur following transplantation of:

solid organs that are rich in lymphoid cells, like the liver, or with transfusion of non-irradiated blood

To minimize GVHD, human stem cell transplants are done between donor and recipients that are:

HLA matched, using precise DNA sequencing based methods for molecular typing HLA alleles

Chronic GVHD may follow acute GVHD or can occur slowly, manifestations include:

extensive cutaneous injury with destructions of skin appendages

fibrosis of the dermis resembling systemic sclerosis

It seems that T-cells not only mediate GVHD but are also required for:

engraftment of the transplanted human stem cells

suppression of EBV infected B cells

control leukemia cells

Because GVHD is mediated by T lymphocytes, depletion of donor T cells before transplantation virtually:

eliminates the disease

Keratoconjunctivitis sicca

dry eyes

xerostomia

dry mouth

this disease is a chronic disease characterized by dry eyes and dry mouth due to immunologically mediated destruction of lacrimal and salivary glands.

Systemic sclerosis (Sjogren syndrome)