immunology final

SCID-like condition in which a patient fails to transcribe the genes that encode class II MHC molecules

w/o these molecules, a patient's lymphocytes cannot participate in cellular interactions w/ Th cells

severity of this x-linked disorder increases w/ age

initially, T and B lymphocytes are present in normal numbers

first manifests itself by defective responses to bacterial polysaccharides and lower-than-average IgM levels

syndrome includes thrombocytopenia (lowered platelet count) which may lead to fatal bleeding
also eczema in varying degrees

defect has been mapped to the short arm of the X chromosome and involves a cytoskeletal glycoprotein present in lymphoid cells called SIALOPHORIN (CD43)
this protein is required for assembly of actin filaments required for the formation of microvesicles

this deficiency was found in patients suffering from infection w/ atypical mycobacteria (intracellular organisms related to bacteria that cause TB and leprosy)

most of those carrying this autosomal recessive trait are from families w/ a history of inbreeding

characterized by extremely low IgG levels and by the absence of other immunoglobulin classes

no peripheral B cells and suffer from recurrent bacterial infections

defect in B-cell signal transduction due to a defect in a transduction molecule called Bruton's tyrosine kinase (Btk)

B cells in these patients remain in the pre-B stage w/ H chains rearranged but L chains in their germ-line configuration

first thought to result from a B-cell defect, recently shown to result from defect in a T-cell surface molecule

characterized by a deficiency of IgG, IgA, and IgE... w/ elevated levels of IgM

normal numbers of B cells expressing membrane-bound IgM and IgD, but lack B cells expressing membrane-bound IgG/A/E

generally inherited as an X-linked recessive disorder

affected individuals have high counts of IgM-secreting plasma cells in their blood and lymphoid tissue
also often have high levels of auto-antibodies to neutrophils, platelets, and RBCs.

defect is in the gene encoding CD40L (CD154) ---> lack of CD40/CD40L interaction = inhibition of B cell activation

fail to produce germinal centers during a humoral response

characterized by a profound decrease in numbers of Ab-producing plasma cells, low levels of most Ig types, and recurrent infections

usually manifested later in life than other deficiencies, however, has a genetic component and is considered a primary immunodeficiency

B cells fail to mature into plasma cells, underlying defect is not known, however

primary immunodeficiency characterized by skin abscesses, recurrent pneumonia, eczema, and elevated levels of IgE accompanies facial abnormalities and bone fragility

multisystem disorder, autosomal dominant with variable expressivity

gene maps to chromosome 4

immunogenic signs include recurrent infection and eosinophilia in addition to elevated IgE levels

immunodeficiency states characterized by significantly lowered amounts of specific Ig isotypes

of these, IgA is by far the most common

characterized by recurrent respiratory or gentiourinary tract infections resulting from lack of secreted IgA on mucosal surfaces

in addition, problems such as intestinal malabsorption, allergic disease, and autoimmune disorders may be associated w/ low IgA levels

reason for some, but not all, may be the ability to substitute IgM for IgA as a mucosal Ab

not classified primarily as an immunodeficiency

syndrome that includes deficiency of IgA and sometimes of IgE

characterized by difficulty in maintaining balance and by the appearance of broken capillaries in the eyes

primary defect appears to be in a kinase involved in regulation of the cell cycle

in its most severe form is the complete absence of a thymus

developmental defect, associated w/ the deletion in the embryo of a region of chromosome 22

causes immunodeficiency along w/ characteristic facial abnormalities, hypoparathyroidism, and congenital heart disease

includes a profound depression of T-cell numbers and absence of T-cell responses

B cells are present in normal numbers, but affected individuals do not produce Ab in response to immunization w/ specific Ags

an almost complete absence of neutrophils

reduction in the concentration of peripheral blood neutrophils below 1500/mm^3

a genetic disease that has at least 2 distinct forms:
- an X-linked form that occurs in about 70% of patients
- autosomal recessive form found in the rest

rooted in a defect in the oxidative PW by which phagocytes generate hydrogen peroxide and the resulting reactive products that kill phagocytosed bacteria

sufferers undergo excessive inflammatory reactions that result in gingivitis, swollen lymph nodes, and nonmalignant granulomas
-also susceptible to bacterial and fungal infection

autosomal recessive disease characterized by recurrent bacterial infections, partial oculo-cutaneous albinism, and aggressive but nonmalignant infiltration of organs by lymphoid cells

phagocytes from patients contain giant granules but do not have the ability to kill bacteria

molecular basis of defect is a mutation in a protein (LYST) involved in the regulation of intracellular trafficking
---> this mutation impairs the targeting of proteins to secretory lysosomes, which makes them unable to lyse bacteria

immunodeficiency related to dysfunction of the adhesion molecules, rooted in a defect localized to the common beta chain and affects expression of all three of the molecules that use this chain (LFA-1, Mac-1, gp150/95)

causes susceptibility to infection w/ both gram-positive and gram-negative bacteria as well as various fungi

impairment of adhesion of leukocytes to vascular endothelium limits recruitment of cells to sites of inflammation

varies in severity

results from biosynthesis of a defective beta chain in LFA-1, CR3, and CR4, which all contain the same beta chain

caused by a single autosomal locus and displays a recessive inheritance pattern

characterized by multiple autoimmune endocrinopathies, chronic mucocutaneous candidiasis, and ectodermal dystrophies

gene encodes for a novel protein known as AIRE which regulates the presentation of peripheral tissue self-antigens on thymic medullary epithelial cells, thus linking it to the development of central tolerance

fatal disorder known to share several features in common w/ a naturally occurring mutation in mice known as scurfy

both conditions mapped to mutations in the Foxp3 gene - a transcription factor known to be required for the formation of CD4/CD25 Treg cells

mutations in the Foxp3 gene lead to early and multifocal autoimmune disease

organ-specific autoimmune disease most often seen in middle-aged women

individual produces auto-Abs and sensitized Th1 cells specific for thyroid antigens

attending DTH response is characterized by an intense infiltration of the thyroid gland by lymphocytes, macrophages, and plasma cells, which form lymphocytic follicles and germinal centers

ensuing inflammatory response causes goiter, a physiological response to hypothyroidism

caused by auto-antibodies to intrinsic factor, a membrane-bound intestinal protein on gastric parietal cells

IF facilitates uptake of vit B12

w/o sufficient B12, which is necessary for proper hematopoiesis, the number of functional mature RBCs decreases below normal

individual makes auto-Ab to RBC antigens, triggering complement-mediated lysis or Ab-mediated opsonization and phagocytosis of the RBCs

certain drugs such as penicillin or the anti-hypertensive agent methyldopa interact w/ RBCs, the cells become antigenic

auto-antibodies specific for certain basement membrane Ags bind to the basement membranes of the kidney glomeruli and the alveoli of the lungs

subsequent complementation activation leads to direct cellular damage and an ensuing inflammatory response mediated by a buildup of complement split products

damage leads to progressive kidney damage and pulmonary hemorrhage

biopsies from patients stained w/ fluorescent-labeled anti-IgG and anti-C3b reveal linear deposits along the basement membranes

caused by an autoimmune attack on the pancreas

attack is directed against beta cells that are located in the islets of Langerhans

results in reduced production of insulin and consequently increased levels of blood glucose

local cytokine production caused by CTL migration and attack includes IFN-gamma, TNF-alpha, and IL-1

first CTL infiltration and activation of macrophages is referred to as insulitis, followed by cytokine release and presence of auto-Abs, which leads to a cell-mediated DTH response

patient produces auto-Abs that bind the receptor to thyroid-stimulating hormone (TSH) and mimic the normal action of TSH, activating adenylate cyclase and resulting in the production of thyroid hormones

these auto-Abs are not regulated---unlike TSH---and they consequently overstimulate the thyroid
---> for this reason the auto-Abs are called long-acting thyroid-stimulating (LATS) antibodies

patient produces auto-antibodies that bind the acetylcholine receptors on the motor end plates of muscles, blocking the normal binding of acetylcholine and also inducing complement-mediated lysis of the cells

result is a progressive weakening of skeletal muscles

early signs of this disease are drooping eyelids and inability to retract the corners of the mouth, which gives appearance of snarling

w/o treatment, can leads to severe impairment of eating as well as problems w/ movement

typically appears in women b/t the ages of 20-40, ratio of female to male patients is 10:1

characterized by fever, weakness, arthritis, skin rashes, pleurisy, and kidney dysfunction

may produce auto-Abs to a wide array of tissue antigens, such as DNA, histones, RBCs, platelets, leukocytes, and clotting factors

these autoantibodies may result in complement-mediated lysis and hemolytic anemia, or complexes of auto-antibodies w/ various nuclear antigens can be deposited along the walls of small blood vessels, a type III hypersensitivity reaction occurs
--these complexes activate the complement system that damages the walls of blood vessels resulting in vasculitis and glomerulonephritis

excessive complement activation in patients w/ severe SLE produces elevated serum levels of complement split products C3a and C5a (3-4 times higher than normal)

most common cause of neurologic disability associated w/ disease in Western countries

symptoms may be mild, such as numbness of limbs, or severe, such as paralysis or loss of vision

most people are diagnosed b/t 20-40

individuals produce autoreactive T cells that participate in the formation of inflammatory lesions along the myelin sheath of nerve fibers

CSF of patients contains activated T lymphocytes, which infiltrate brain tissue and cause characteristic inflammatory lesions, destroying the myelin

women 2-3 times more freq than men

some indications that infection by certain viruses may predispose a person

most often affects women b/t 40-60

major symptom is chronic inflammation of joints, although the hematologic, cardiovascular, and respiratory systems are also highly affected

may individuals produce a group of auto-Abs called rheumatoid factors that are reactive w/ determinants in the Fc region of IgG

the classic rheumatoid factor is an IgM Ab w/ that reactivity
--such auto-Abs bind w/ normal circulating IgG, forming IgM-IgG complexes that are deposited in the joints

these immune complexes can activate the complement cascade, resulting in a type III hypersensitive reaction, which leads to chronic inflammation of the joints

new zealand black (NZB) mice and F1 hybrids of NZB and new zealand white (NZW) mice spontaneous develop autoimmune diseases that closely resemble ....

nonobese diabetic mouse (NOD) spontaneously develops a form of diabetes that resembles human...

gram negative bacteria, cytomegalovirus, and Epstein-Barr virus (EBV) are all known to be..

these agents block signal transduction mediated by the the T-cell receptor

thus, they inhibit only antigen-activated T cells while sparing nonactivated ones

presence of HLA B27 is strongly associated w/ the development of this disease

autoimmune disease affecting the vertebrae

mitotic inhibitor used to block proliferation of graft-specific T cells

block activation of resting T cells by interfering w/ a signal transduction PW that leads to assembly of the transcription factor NFAT

inhibits the activation of Th cells by arresting the cell cycle

tumor antigens that are unique to tumor cells and do not occur on normal cells in the body

may result from mutations in tumor cells that generate altered cellular proteins

antigens not unique to tumor cells, may be proteins that are expressed on normal cells during fetal development when the immune system is immature and unable to respond

reactivation of the embryonic genes that encode these proteins in tumor cells results in their expression on the fully differentiated tumor cells

may also be proteins that are normally expressed at extremely low levels on normal cells but are expressed at much higher levels on tumor cells

genetic defects causing marked impairment of NK cells and an associated increase in certain types of cancer

results from inactivation of both alleles of Rb, a tumor suppressor gene

translocation of c-myc gene is found in many patients w/

enhance the expression of class I MHC molecules on tumor cells -- > increasing the CTL response to tumors

increases the activity of CTLs, macrophages, and NK cells, each of which plays a role in the immune response to tumors

have direct antitumor activity, inducing hemorrhagic necrosis and tumor regression

activates LAK and TIL cells, both of which have antitumor activity