CLS 251 EXAM 2 CONCEPT MAP

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what is a complement?

a series of more than 30 different soluble and cell-bound proteins that circulate in the blood as inactive precursors that when activated interact to enhance host defense mechanisms against foreign cells

most plasma complement proteins are synthesized in the liver

what do complements act as?

acts as opsonins which are activated by IgG and IgM

what else do complements do?

• increase vascular permeability (vasoactive substances)

• recruit monocytes and neutrophils to the area of antigen concentration (chemotactic substances)

what is the end product in the complement pathways?

lysis of the invading cell (through MAC)

what activates the classical pathway?

activated by IgM, IgG1, IgG2, and IgG3

IgM: most efficient due to multiple binding sites

what is the end product of the classical pathway?

MAC

what are the subunits for C1 (the recognition unit) for the classical pathway?

• one Clq

• two Clr

• two Cls

• C1qrs

what is formed in the classical pathway that is considered the activation unit?

C4b2a3b → bridges two adjacent IgG FC regions or single IgM bound to antigen

what is the process that happens when MAC is activated in the classical pathway?

C5b attaches to the cell membrane to initiate formation of the MAC (C5b6789) → MAC perforates the cell membrane by creating a hole in the membrane leading to lysis of the cell

what does the lectin pathway serve as?

a defense mechanism in infancy in between loss of maternal antibody and development of full antibody response & involves three classes of recognition molecules (lectins, ficolins, CL-L1)

what is the definition of hypersensitivity?

exaggerated immune response to a typically harmless antigen

what type of hypersensitivity is delayed reactions?

type IV

what is type 1 hypersensitivity known as?

anaphylactic hypersensitivity

what are the key components of type 1 hypersensitivity?

• IgE

• mast cells

• basophils

• eosinophils

what is the sensitization phase also called?

allergen sensitization phase

what is the activation phase process in hypersensitivity?

allergen cross-links adjacent cell-bound IgEs → mast cells and basophils degranulate → chemical mediators are released and bind to target organs → allergy symptoms are produced

what is a common allergen for type 1 hypersensitivity?

pollen “hay fever”/rhinitis

how is the in vivo skin test done to test for type 1 hypersensitivity?

apply a panel of allergens to separate sites on the skin and wait 15 to 20 minutes… a positive test would be a wheal and flare at the site of application

percutaneous or intradermal

what is allergen-specific IgE immunoassay testing?

the most appropriate way to detect IgE to a specific allergen in patient serum

what is type 2 hypersensitivity?

type involved in transfusion reactions and hemolytic disease of the newborn, HDN

what does ADCC stand for in type 2 hypersensivitiy?

antibody-dependent cell-mediated cytotoxicity

what do cytotoxic T lymphs do in type 4 hypersensitivity?

cytotoxic T lymphocytes are recruited and destroy target cells

what does the direct antiglobulin test (DAT or direct coombs test) detect?

detects RBC coated with complement components or IgG (in vivo sensitization of RBCs) antibody by incubation with a poly-specific anti-human Ig directed against IgG and C’

RBC sensitization occurs in vivo

what does the indirect antiglobulin test (IAT or indirect coombs test) test for?

tests patient serum for allo-antibodies to RBC antigens, sensitization occurs in vitro

what is the process for the indirect antiglobulin test?

incubate reagent RBCs with known antigenic makeup with patient serum at 37C; wash to remove excess serum and serum proteins and add anti-human globulin → positive test = RBC agglutination

what are autoimmune disease due to?

due to loss of self-tolerance → ability of the immune system to accept self antigens and not initiate an immune response against them

essentially an immune response against self-antigens results in autoimmune diseases

what is systemic lupus erythematosus (SLE)?

a chronic systemic inflammatory disease that affects multiple organ systems in which patients develop numerous autoantibodies

ex. to dsDNA and other nuclear components, lymphocytes, RBCs, and platelets

what is the process in how SLE develops?

immune complexes form, and are deposited on tissue of kidneys and the joints, and auto-antibodies to ds-DNA triggering C’ activation, chemotaxis of neutrophils, and inflammation

95% of patients have ds-DNA antibodies

what are the screening tests to detect autoimmune disease?

• CRP

• ESR

• CBC

• antinuclear antibodies (ANA)

• DS DNA screen with Crithidia luciliae (up to 95% of SLE patients have ds-DNA antibodies)

what is immunofluorescence using Crithidia lucillae (flagellated parasite of houseflies) used for?

used to detect antibodies to dsDNA

is IIF using C. luciliae as the substrate which contains a kinetoplast that is rich in dsDNA)

what can phospholipid antibodies cause?

can cause false-positive results in nontreponemal tests for syphilis

ex = lupus anticoagulant (produces prolonged APTT and PT

what are anti-neutrophil cytoplasmic antibodies (ANCA)?

produced against proteins in neutrophil granules and are strongly associated with syndrome including vascular inflammation

ex. granulomatosis with polyangiitis (wegener granulomatosis)

what is hashimoto’s thyroiditis?

immune destruction of the thyroid gland produces hypothyroidism

what is graves disease?

an AITDS characterized by hyperthyroidism

how does insulin deficiency start in type 1 diabetes mellitus?

type 1 destruction of beta cells in pancreas

what are the laboratory results in type 1 diabetes mellitus?

• increased glucose blood level

• elevated HbA1c

• autoantibodies to GAD and IA-2, ICA

what is celiac disease?

an immune reaction to eating gluten, a protein found in wheat, barley, and rye → autoantibodies form in genetically pre-disposed people triggered by gluten

what two tests are performed together to ensure accurate screening for celiac disease?

tissue transglutaminase IgA antibody (tTG-IgA), plus an IgA antibody

done in order to ensure that the patient generates enough of this antibody to render the celiac disease test accurate

what are the laboratory findings in multiple sclerosis (MS)?

• CNS lesions seen on magnetic resonance imaging

• increased immunoglobulins in spinal fluid and increased IgG index

• oligoclonal bands on protein electrophoresis of CSF

what happens in myasthenia gravis?

affects neuromuscular junction, resulting in weak skeletal muscles

what do patients produce in goodpasture’s syndrome?

produces autoantibodies (anti-glomerular basement membrane antibodies) to basement membranes lining the renal glomeruli and lung alveoli (specifically directed against alpha-3 chain of type IV collagen) → auto-antibodies immune complexes bind to basement membranes, attract C’, and cause damage by type 2 hypersensitivity

what can goodpasture's syndrome progress to?

can progress to renal failure and respiratory problems (cough, shortness of breath, hemoptysis)

what methods are used to detect circulating anti-GBM antibodies?

• IIF (indirect immunofluorescence) on frozen kidney sections

• ELISA for antibodies against the alpha-3 subunit of type IV collagen

tissue-bound anti-GBM detected by direct immunofluorescence on kidney biopsy sections; produces a smooth, linear, ribbon-like fluorescence along the GBM

how are secondary immunodeficiencies acquired?

acquired as a result of other conditions, such as infection (e.g. HIV), autoimmune disease, malignancy, or immunosuppressive therapy

what happens to the neutrophils in chronic granulomatous disease (CGD)?

neutrophils are unable to generate oxidative burst → genetic defect in a component of the NADPH oxidase system which decreases killing of catalase (+) organisms

how is chronic granulomatous disease (CGD) detected in the lab?

• negative nitroblue tetrazolium (NBT) test

• dihydrorhodamine (DHR) assay

how are those for suspected immunodeficiency screened?

• CBC and WBC differential

• quantitative serum levels of IgG, IgM, IgA, and IgG subclasses

• isohemagglutinins (natural ABO antibodies)

  • decreased levels in reverse grouping of elderly and newborns

• CH50 assay for complement function