immunology test 4

neutrophilia

an increase in neutrophils; above 8,500 per cubic mm

neutropenia

a decrease in neutrophils; mild - less than 1500, moderate - less than 1000, severe - less than 500

severe congenital neutropenia

neutrophils stop maturing in the bone marrow; symptoms include omphalitis (inflammation of the umbilical stump), respiratory infections, skin and liver abscesses; treatment with subcutaneous granulocyte colony stimulating factor helps

Chediak-Higashi syndrome

lysosomes in neutrophils cannot break down bacteria that have been engulfed; symptoms include albinism, frequent infections, fevers, enlarged spleen and lymph nodes, high blood lipids; treatment with steroids and etoposide and methotrexate

Griscelli syndrome

mutation in a myosin gene from moving organelles within cells; symptoms include silver hair, light skin, retardation, frequent infections, macrophages can overly phagocytize RBC and CD8 T cells can overpopulate the organs

chronic granulomatous disease

usually an inherited X linked trait that prevents neutrophils from making toxic oxygen molecules to destroy microbes; symptoms include recurring infections, abscesses, pneumonias

myeloperoxidase deficiency

recessive defect in which neutrophils cannot convert peroxide into an acid to kill Candida so patients have widespread Candidiasis

leukocyte adhesion deficiencies

defects in the ability of a neutrophil to stick tot he endothelium and squeeze out of blood vessels tissues; symptoms include skin and mucus membrane infections, delayed wound healing, neutrophilia; treatment includes neutrophil transfusion, antibiotics, bone marrow transplant

cytokine signaling defects

absent or defective receptors for cytokines; mycobacteria, salmonella, viruses

hyper IgE syndrome

dominant defect causing high levels of IgE which diminishes monocyte activity; patients have frequent infections and connective tissue abnormalities which affect the skeleton, teeth, facial features, they also usually develop eczema shortly after birth; treatment is usually prophylactic antibiotics

complement defects

recurrent infections, autoimmune disorders, vasculitis, angioedema, glomerulonephritis, anemia, thrombosis

NEMO

mutations for nuclear factor kappa beta cause anhidrotic ectodermal dysplasia with immune deficiency causing symptoms of cone shaped teeth, fewer teeth, sparse hair, decreased ability to sweat, increased infections, skin redness, blister or irregular pigment

chronic mucocutaneous candidiasis

deficiency of a pattern recognition receptor on monocytes and dendritic cells for glucans in Candida’s cell wall so the patient has continual infections of the skin and mucus membranes

SCID

sever combined immune deficiency; total or nearly total lack of T and B cells; infants fail to thrive, have diarrhea, and recurring infections; treatment includes bone marrow transplant and antimicrobial medicines but still has risk of fatality; most have mutation in an interleukin or recessive gene that results in no signals for immune cells to grow or be produced; some are du to defects in DNA’s ability to rearrange and make the wide variety of T and B cells needed to fight diseases and cancers

bare lymphocyte syndrome

genetic defects that causes cells to be unable to put either MHC I or MHC II on their surface; patients tend to have recurring respiratory or skin infections

PNP deficiency

purine nucleoside phosphorylase; recessive defect in an enzyme that metabolizes purines so they build up and are toxic to lymphocytes; patients suffer from anemia, ataxia and paresis; bone marrow transplant is the only treatment

X linked agammaglobulinemia

genetic defect in an enzyme required for B cells to develop; symptoms include respiratory infection, diarrhea, cellulitis, meningitis, sepsis; treatment is injections with immunoglobulins

common variable immune deficiencies

caused by mutations in the genes for various cytokines causing low IgG and IgA with variable amounts of B cells; patients have sinus, ear, and respiratory infections and 20% develop autoimmune diseases

hyper IgM syndrome

defects in either CD molecules or enzymes for nucleotides; results in low IgG and IgA and normal or elevated IgM and B cells that cannot switch from making IgM to making other types of antibodies especially G and A; patients usually suffer with pneumocystis and cryptosporidium infections; drinking filtered water can prevent cryptosporidium infections while IV IgG can help with pneumocystis; mortality can be 40%

lymphoproliferative syndromes

triggered by EB infection; the virus affects genes involved in signaling pathways inside T and natural killer cells; symptoms include acute mononucleosis followed by hepatitis, anemia, thrombocytopenia and lymphoma

Wiskott-Aldrich syndrome

X linked recessive defect in a protein that regulates the formation of actin filaments; symptoms include eczema, thrombocytopenia, bloody diarrhea, decreased antibody production leading to frequent infection, lymphoma or leukemia

Ataxia-Telangiectasia

genetic defect on chromosome 11 for DNA repair; symptoms include jerky movements, dilated veins, chronic sinus and respiratory infections, cancers, premature aging

bloom syndrome

recessive defect in helicase which is required for DNA to unwind, replicate, or repair; symptoms include short stature, bird like face, facial rash with sun exposure, high pitched voice, learning disabilities, diabetes, cancer especially leukemia and lymphoma

DiGeorge syndrome

defective development of the thymus resulting in facial defects, heart defects, learning disabilities, hypocalcemia, and T cell deficiency

signs used to indicate primary immune deficiency in children and adults

four or more new ear infections within 1 year

two or more serious sinus infections within 1 year

two or more months on antibiotics with little effect

two or more pneumonias within 1 year

failure of a infant to gain weight or grow normally

recurrent deep skin or organ abscesses

persistent thrush in mouth or fungal infection on skin

need for IV antibiotics to clear infections

two or more deep-seated infections including septicemia

type I hypersensitivity

type II hypersensitivity

type III hypersensitivity

type IV hypersensitivity

Clemens von Pirquet

describe IgE mediated allergy

early: occurs in minutes and is caused by molecules such as histamine, leukotrienes, prostaglandins

late: occurs hours later and involves inflammatory cells migrating to the area

3 main routes of entry for allergens

IgE

mastocytosis

role of eosinophils in allergies

attracted to inflammatory or allergic sites by several molecules but the most prevalent is IL-5 from T cells; contain granules of toxic molecules that help kill worms and viruses; molecules can cause local tissue damage in allergic response

eosinophilia

3 phases of allergic response

effects of histamine

causes vasodilation allowing fluid to leak into the tissue; can also cause the secretion of mucus and stimulate nerve endings to produce the sensation of itching

effects of leukotrienes

attract neutrophils and eosinophils, constrict bronchioles, and increase vascular permeability

effects of prostaglandins

constrict bronchioles, increase vascular permeability, inhibit platelets, stimulate the nerve endings for pain, affect the hypothalamus to produce fever, inhibit stomach acid secretion, increase mucus production

role of IL-4

required for the synthesis of IgE

role of IL-5

required for eosinophils to mature and activate

role of TNF-alpha

required for cells to move from the blood into tissues

factors contributing to the development of an allergy

anaphylaxis

contact with allergen causes massive immediate degranulation of mast cells and basophils; triggers the release of platelet activating factor which causes vasodilation; symptoms include itching, hypersecretion of mucus, bronchoconstriction and wheezing, flushing, hives,, edema of lips and tongue, couch, hoarseness, dyspnea, hypotension, syncope, arrhythmia, nausea, vomiting, diarrhea, sense of doom

immunoassays

allergen is attached to a surface such as a slide or petri plate, patient’s serum is added, washed, then anti IgE antibodies with enzyme attached are added, then washed, then substrate is added and analyzed for color change or fluorescence

diagnostic tests for allergies

allergy immunotherapy

involves subcutaneous injections of a substance in increasing dosage over time to build up a tolerance; proposed that this stimulates the production of IgG and IgA which bind to the allergen before it can come in contact with a mast cell and bind to its IgE

omalizumab

tolerance

central tolerance of T cells

in the thymus T cells with strong attraction to MHC or self antigens are eliminated by apoptosis

role of Treg cells in autoimmunity

able to suppress the activity of other T cells; are important in reducing inflammation once the invader is defeated ad for inhibiting any self reactive T cells that escape the thymus; can suppress by direct contact or by releasing transforming growth factor beta (TGF-beta)

tolerance inside MALT tissues

contain CD8+ T cells with gamma delta TCRs instead of the usual alpha beta TCRs and they secrete I-10 and TGF-b to suppress immune reactions against food, commensal bacteria, and self

B cell tolerance

B cells start maturing in the bone marrow then leave and travel to the spleen where they complete their maturation so most apoptosis of self reactive B cells occurs in the spleen

multiple sclerosis

Grave’s disease

immune system attacks the thyroid resulting in weight loss, nervousness, diarrhea, bulging eyes, heart palpitations

Hashimoto’s disease

immune system attacks the thyroid a different way resulting in weight gain, constipation, dry skin, swelling, confusion

pernicious anemia

immune system attacks intrinsic factor in the stomach; patient has a B12 deficiency with symptoms of anemia, numbness, tingling, difficulty walking and thinking, weakness, pale skin

Crohn’s disease and ulcerative colitis

diabetes mellitus I

immune system attacks islet cells or insulin causing excessive thirst and urination, weight loss, and high blood sugar

immune thrombocytopenia

immune system attacks glycoproteins on the surface of platelets causing easy bruising and bleeding

myasthenia gravis

immune system attack acetylcholine receptors so muscles can’t be stimulated and are weak or easily fatigued

Sjogren’s syndrome

immune system attacks nuclear antigens in salivary and lacrimal glands causing dry eye and mouth and lung and kidney diseases

rheumatoid arthritis

lupus

immune system attacks DNA and histones usually causing arthritis, skin rashes, kidney and nerve damage

3 main factors involved in developing an autoimmune disease

describe treatments for autoimmune diseases

immunologic surveillance theory

mutations regularly produce cancer cells whose antigens are different from normal cells so the immune system recognizes them and kills then before they can produce more

immunoediting

tumor antigens

can be unique to tumor; can be overexpressed normal antigens and they can be viral antigens from an oncogenic virus that infected the person; sometimes can be taken up by antigen presenting cells and used to stimulate T cells

KAR

normal cell receptor that activates killing

KIR

normal cell receptor that inhibits killing

IDO

converts tryptophan into kynurenine; increase in this enzyme suppresses a tumor suppressor gene so tumor cells are free to grow; kynurenine inhibits T cells

cetuximab

antibody against epidermal growth factor receptors so cells can’t grow

trastuzumab

antibody against growth factor receptors in breast cells

rituximab

antibody against CD20 on the surface of B cells so they are killed by cytotoxic T cells to help with lymphoma

beracizumab

antibody against vascular endothelial growth factor so that tumors cannot form blood vessels

benign monoclonal gammopathy

immunoelectrophoresis

smoldering multiple myeloma

no symptoms but have a higher concentration of antibodies in their blood and bone marrow is 10+ percent plasma cells; have a 10%-20% chance that increases every year of developing multiple myeloma

multiple myeloma

lymphomas

autograft

transplant of one’s own tissue; no rejection

isograft

transplant between identical twins; no rejection; sometimes called syngeneic

allograft

transplant between two nonidentical individuals of the same species; HLA is typed and matched as closely as possible so sometimes there is no rejection and sometimes there is

xenograft

transplant from another animal species; massive rejection unless the tissue has little or no blood supply such as cartilage or cornea

2 phases of rejection

main cytokines involved in rejection

time line of rejection

ABO antigens and rejection

HLA and rejection

mHA

minor histocompatibility antigens are various proteins on the surface of various cells in each person; can stimulate a rejection response but it is usually slower and weaker

hyperacute rejection

occurs if patient already has antibodies for one of the donor’s antigens such as blood type; within minutes antibodies join to the transplant cells and complement destroys the cells

acute rejection

most common; occurs days or weeks after transplant and damage is caused by both antibodies and cells

chronic rejection

stem cell transplants

transfer stem cells through aspirating bone marrow with a large needle from the pelvic bones from a donor and infused by IV into the patient

GVHD

immunosuppressive drugs commonly used with transplantation

CDC assay

complement dependent lymphocytotoxicity; donor lymphocytes are incubated with recipient serum then complement is added to see if cells are attacked