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