Unit 4 MMSC 360

B cell deficiencies

- Bruton's Agammaglobulinemia (Tyrosine kinase deficiency) - Defect in protein Kinase - B cells don't mature - Decrease in IgG and absence of other antibodies

tumor immune surveillance

theory of Paul Ehrlich (1909) Tumor cells have weak immunogens and decreased expression of MHC antigens Anti-tumor antibodies

allograft (homograft)

transplantation of healthy tissue from one person to another person

autograft

transplantation of healthy tissue from one site to another site in the same individual

Alphafetoprotein (AFP)

High in embryonic and fetal developement reduced after birth, cancer makes this molecule concentration elevated

Anti-Sm

(Smith) Most specific test for SLE

Adenosine deaminase (ADA) deficiency

- An immunodeficiency disorder and one type of SCIDS that is caused by an inborn error in the metabolism of adenine. The accumulation of adenine destroys both B and T lymphocytes. - Leads to accumulation of toxic metabolic by products - similar to PNP deficiency

Cryoglobulins

- Antibodies that precipitate at temperatures below body temperature - Seen in certain infectious diseases (hepatitis C virus), RA, plasma cell dyscrasia (e.g., multiple myeloma), etc.

Ataxia Telangiectasis (Louis-Bar syndrome)

- Ataxia-telangiectasia mutated (ATM) is a serine/threonine kinase - Decreased IgA - Increased α-fetal protein and carcinoembryonic antigen

Hyper acute rejection

- Caused by pre-existing antibodies specific for graft antigens (repeated transplants, blood transfusions, pregnancies) Starts in about 10 days T cell Direct killing

Type IV delayed type hypersensitivity

- Cell Mediated Hypersensitvity - Lymphokines amplify the response by t Cells while recruiting seccondary cells and macrophages, neutrophils and other T cells -Tdth cells appear to be TH1 cells - Release IFNγ, lymphotoxin-α, IL-2, IL-3, etc. - Mononuclear Infiltration Stimulated by endothelial cells - PMNs followed by monocytes -lesions at 24-48 hr post antigen exposure peaks at 72 hr

multiple sclerosis diagnosis

- Clinical signs and symptoms - CNS MRI Increased - oligoclonal IgG in CSF - Anti-MBP antibody, serum and CSF

complement

- Decrease in C1qrs, C4, C2, C3 - Increase in immune complexes

T cell deficiencies

- Increased susceptibility to viral, fungal, intracellular bacteria, and protozoan infections - Defect in CD40L on activated T cells Ex. - DiGeorge Syndrome,

Diabetes mellitus type 1

- Insulin dependent diabetes (IDDM) Epidemiology: - Affects 0.5% of population - High in developed countries - patients with IDDM have more infections Diagnosis: - Generally, by the time disease is diagnosed, about 70% of the beta cells are lost - Fasting blood glucose, oral glucose tolerance test - Antibodies to islet cells and insulin Pathogenesis: - Genetics - Polygenic—genotype of MHC II genes (DR3 & 4) strongest determinants, susceptibility genes - Concordance rate in monozygotic twins 50%

causes of autoimmune diseases

- May result when an individual begins to make antibodies or cytotoxic T cells against normal body cells - Imparied Treg cell enhanced Th, viral infections, release of sequestered antigens, heredity, sex hormones, mimicry/cell damage - Multifactorial could be polygenic and caused by environmental factors - Organ specific or systemic

Selective IgA deficiency

- Most common primary immunodeficiency - Seen in many URT infections

myasthenia gravis symptoms

- Muscle weakness - Ocular disturbances Blepharoptosis Diplopia - Oropharyngeal muscle weakness

Tumor CMI response

- NK cells, macrophage, CD8+ T cells - Some T cells suppressed by tumor cells - T reg cell activity increased by some tumor cells

Contact sensitivity

- Poison ivy, poison oak, nickel, turpentine, etc. - Most are haptens - Langerhans cells present Ags to Tdth cells Type IV

Scleroderma (Crest syndrome)

- Progressive systemic sclerosis, Vascular damage, activation of auto immune system

Mastocytosis

- Proliferation of mast cells

Wiskott-Aldrich Syndrome (WAS)

- X-linked disorder - Was protein is defective hindering reaction between T and B cells - Severity increases with age - small abnormal platelets also appear - Thrombocytopenia also apparent

Duncan disease

- X-linked lymphoproliferation syndrome - patients w/Duncan disease who get Epstein Barr Virus (EBV) will have severe illness w/chronic infectious mononucleosis, agammaglobulinemia, B-cell lymphoma, death (1/3)

systemic lupus erythematosus (SLE)

- chronic autoimmune inflammatory disease of collagen in skin, joints, and internal organs - Sunlight can exacerbate symptoms: - Highly variable chronic inflammatory disease, alternating flares and remissions - Fever, fatigue, butterfly rash, arthritis, hepatic inflammation, glomerulonephritis, hemolytic anemia, lymphadenopathy Facts: - Worldwide—estimated 500 million people affected - In US, approximately 500,000 people affected (prevalence) - Ratio female to male, 8:1

systemic lupus erythematosus (SLE) genetic factors

- complex, different genetic contributions produce the same phenotype - Includes alleles of MHC, complement, α & β chains of TCR, etc.

multiple myeloma

- malignant tumor of bone marrow cells - Plasma cell neoplasm proliferation of a single clone, monoclonal gammopathy Pathogenesis—unknown - Plasma cells not endstage cells, they continue to divide and produce antibodies (myeloma [M] protein), most common is IgG - Immune suppression - Poor prognosis

Granulomatous hypersensitivity

- most serious and usually occurs when macrophages have engulfed pathogens but have failed to kill them - Antigen (allergen) persists - Cells in granulomatous lesion—lymphocytes, macrophages, epitheloid cells, and multinucleated giant cells

Autoimmunity

- reaction of immune response to one's own tissues - loss of self tolerance

evaluation of T cells (CMI response)

- screen for HIV - absolute lymphocyte count - T cell number and function

Graves disease diagnosis

-Decreased (TSH) Thyroid stimulating hormone -Increased free T4 and T3 -Radionuclide scan (use in equivocal cases)

Type III Hypersensitivity (Immune Complex)

-Deposition of circulating immune complexes in tissues1. Mechanism -Antigens—infecting microorganisms, drugs, or self-antigens -Immune complexes usually cleared by monocyte-macrophage system -IgG or IgM mediated Complement activation -Lysis of bystander cells by MAC -Anaphylatoxins causing local degranulation and platelet aggregation -PMNs attempt to phagocytyze immune complexes -Local antigen-antibody complexes destructive inflammation of small blood vessels, i.e., vasculitis

Type II Cytotoxic Hypersensitivity

-Mechanisms of cellular damage -IgG or IgM against cell surface molecules or tissue components -Antibody binds target cells, blocks normal function -Complement-mediated lysis of target cells -Antibody-dependent cell-mediated cytotoxicity (ADCC)o Cytotoxic T cell -By-stander cells also damaged by lysosomal enzymes

DiGorge Anomaly

-Thymus fails to develope -chromosome deletion resulting in monosomy 22q11

Graves disease

-an autoimmune disorder that is caused by hyperthyroidism and is characterized by goiter and/or exophthalmos - Thyrotoxicosis Symptoms: Goiter, heat intolerance, nervousness, irritability, depression, warm moist skin, weight loss

immunodeficiency diseases

A group of inherited or acquired disorders in which some part or parts of host defense are either absent or defective.

Histocompatibility

A state of mutual tolerance between tissues that allows them to be grafted effectively

Autoimmune Addison's disease

Adrenal Antibodies attack and destroy the adrenal cortex cells that make Cortisol and aldosterone

immunotherapy

Allergy shots (desensitization)—repeated injections of the allergen Patient becomes tolerant to allergen

Type 1 hypersensitivity

Anaphylactic hypersensitivity IgE Response

Acute humoral rejection

Antibodies damage graft VASCULATURE. Occurs over days to weeks

SLE serology

Antinuclear antibody (ANA)—nonspecific, ~95% patients with SLE will be positive, but positive predictive value (PPV) 5-10%

Immunoflourescence

Assay used to detect the presence of specific proteins on the surface of a cell

Waldenstrom's macroglobulinemia

B-cell lymphoma that produces monoclonal IgM(it's a BIG Ig), patients present with generalized lymphadenopathy. Igm should be 120mg/dL in this it is ~ 3g/dL 1/10 as frequent as mutiple myeloma

T cells

Cells created in the thymus that produce substances that attack infected cells in the body.

phagocytic cells

Chronic granulomatous disease

Diagnosing immunodeficiency diseases

Clinical manifestations - lungs and sinus infections - MAC infections - Recurrent deep seated cutaneous infections

primary immunodeficiency

Condition resulting from a genetic or developmental defect

Goodpasture syndrome

Damage to alveolar and renal glomerular basement membranes by cytotoxic antibody.

Tuberculin-type hypersensitivity

Dermal phenomenon in which a person with TB Abs is exposed to tuberculin in PPD test -Forms red nodule and can causes tissue necrosis *Type IV hypersensitivity rxn

ANA methods

Elisa, and Immunofluoresence

servere combined immunodeficiency disease (SCID)

Family of disorders resulting from a defect in lymph development that affects either T cells or T and B cells

Autoimmune thyroiditis (Hashimoto disease)

Gradual inflammatory destruction of thyroid tissue by lymphocytes and autoantibodies Symptoms - Lump in Neck, and tiredness - Inflammation triggers goiter (swelling of thyroid gland) - Binding of Ab interferes with iodine uptake and the production of thyroid hormones— hypothyroidism

Isograft (syngraft)

Graft from different but identical individual

C1 inhibitor (C1-INH)

Hereditary angioedema

Arthus reaction

localized areas of erythema and hard swelling caused by Type III Hypersenstivity

B cell deficiency

IgA deficiency: recurrent sinus and lung infections

Reaginic Antibody

IgE

Decreases MAC, C5

Increase in septicemias

lymphomas

Initial malignant cells present in the lymphoid tissue

leukemias

Initial malignant cells present in the peripheral blood stream or bone marrow

Proto-oncogenes and oncogenes

Oncogenes are permanently switched on protooncogenes that cause uncontrolled cell division • A single base change can produce an altered gene product • Mutations can increase the number of copies of a normal gene

rheumatoid arthritis (RA) symptoms

Joint pain and swelling, progressive destruction of cartilage

Acquired immumodeficiency

Loss of function after exposure to some agent

Radioimmunosorbent test (RIST)

Measures total serum IgE

Anti-RNP

Mixed connective tissue disease ribonucleoprotein

Cold agglutinins

Mycoplasma pneumoniae, infectious mononucleosis

Xolair

Omalizumab (anti-IgE)

Anti-Jo-1

Polymyositis, dermatomyositis

Farmer's lung

RLD; lung reaction against thermophilic bacteria in moldy hay

Scl-70

Scleroderma

Anti-SSA, anti-SSB (anti-Ro, anti-La)

Sjögren syndrome ANA and Anti-ribonuclear proteins Risk of neonatal lupus and congenital heart block

rheumatic fever

Streptococcus pyogenes and antibodies to M proteins

glomerulonephritis

Streptococcus pyogenes, nephritogenic strains can produce two proteins with affinity for glomeruli

Bone Marrow Differential

Use bone marrow from patients to count white blood cells looking to see if plasma cells are present to indicate multiple myeloma

Flow cytometry

Uses differences in electrical conductivity between species or fluorescence

Drug-induced hemolytic anemia

penicillin can cause RBCs to become antigenic

myasthenia gravis

a chronic autoimmune disease that affects the neuromuscular junction and produces serious weakness of voluntary muscles Pathogenesis: Neuromuscular junction releases acetylcholine (ACh) which binds to acetylcholine receptor (AChR)

rheumatoid arthritis

a chronic autoimmune disorder in which the joints and some organs of other body systems are attacked Epidemology: - 1-3% of US population - 70% patients with RA exhibit HLA-DR4 haplotype - Several different patterns of disease - Juvenile and adult onsets Pathogenesis: - Stimulation of B cells that make IgM, IgG, & IgA to the Fc region of IgG - Autoantibodies are called rheumatoid factor (RF) - Form immune complexes - Cytokines

serum sickness

a classic example of type III hypersensitivity that involves a drug allergy to antitoxin serum from horses If Ag in excess, small complexes not easily cleared

ankylosing spondylitis

a form of rheumatoid arthritis that primarily causes inflammation of the joints between the vertebrae

Atopic Eczema

a genetically determined inflammatory allergic skin disorder characterized by itching; also called atopic dermatitis

xenograft

a graft from another species

Bence Jones protein

a special protein found in the blood and urine, indicative of multiple myeloma

allergen

a substance that causes an allergic reaction

Hypogammaglobulinemia

an abnormally low concentration of gamma globulin in the blood and increased risk of infection

Angioedema

an allergic reaction in the skin. It causes Localized areas of swelling beneath the skin, often around the eyes and lips, but it can also involve other body areas as well.

evaluation of B cells (HMI response)

an antibody concentration of IgG, IgA, and IgM

Hypersensitivity

an exaggerated response by the immune system to a particular substance 4 types 1-3 are immediate 4 is delayed cell mediated

Anti-dsDNA

are specific for SLE Anti-smith is also specific for SLE

Sjorgen syndrome

autoimmune disease that attacks the glands that produce saliva and tears

prostate-specific antigen (PSA)

blood test that measures the level of prostate-specific antigen in the blood found only in males. Increases as males get older

SCIDS (severe combined immunodeficiency syndrome)

caused by diverse genetic mutations that lead to complete absence of all immune function

systemic anaphylaxis

characterized by sudden respiratory and circulatory disruption that can be fatal within minutes due to airway blockage can be caused by drugs, food , or insect venom

indicators of immunodeficiencies

chronic and recurrent infections, increased incidence of tumors

Graft vs. Host Disease (GVHD)

complications during bone marrow transplants, or transfusions where graft attacks the host. 3 criteria - Histocompatibility - Graft cells immunocompetent - Host cells immunodeficient

CRAB

criteria of hypercalcemia, renal insufficiency, anemia, bone lesions

decrease in C3

decrease in opsonization

Late Phase Hypersensitivity

eosinophils, PMNs, macrophage arrive and degranulate—second release of mediators

diabetes mellitus type 1 symptoms

fatigue, joints ache, poor-circulation, kidney disease, impaired visual acuity, peripheral neuropathy

Sensitization

first exposure to an immunogen (allergen)

mast cells

found around blood vessels in connective tissue, lungs, uterus, liver, kidney, spleen, heart, etc.

human chorionic gonadotropin (hCG)

found in Urine in women during pregnancy. Produced by germ cells in males and ovaries in female

granules contain

histamine, neutrophilic chemotactic factor, eosinophilic chemotactic factor

Autoimmune Hemolytic Anemia (AIHA)

idiopathic disease in which the body destroys its own good RBCs Symptoms: Cas peripheral necrosis in cold weather, Anemia and intravascular hemolysis

rhinitis

inflammation of the nose

Early Phase of Hypersensitivity

mast cells degranulation occurs within seconds—activates platelets, increases capillary permeability, vasodilatation, etc.

Insect bites

may initially be type I, then an arthus reaction

Multiple sclerosis

myelin sheath destruction. disruptions in nerve impulse conduction Epidemiology: - Most common autoimmune disease affecting the nervous system, 250,000 people in US - Greatest incidence in temperate zones Symptoms: - Disturbance in visual acuity, motor disturbances affects walking & use of hands, incontinence, etc. Pathogenesis: - Genetic factors HLA DR2 - Molecular Mimicry

Chronic rejection

occurs months or years after transplant

Cancer Antigen 125 (CA-125)

ovarian cancer

molecular mimicry

structural similarities between a microorganism and self Ags

Allergens

substances that produce allergic reactions ex: airborne—pollen, fungal (mold) spores, cigarette smoke, animal dander, cockroaches & dust mites; other—insect venom, drugs, food, etc.

Xenotransplant

the process of grafting or transplanting organs or tissues between members of different species

Radioallergosorbent test (RAST)

used to measure IgE in pts serum specific for a given allergen