Weeks 3 & 4 (Diseases of the immune system/ hypersensitivities)

what is the definition of a hypersensitivity?

an abnormal physiologic condition in which there is an undesirable and adverse immune response to an antigen occurs

A type 1 hypersensitivity is an _______ mediated hypersensitivity. It causes a condition known as _____ due to the degranulation of mast cells which releases _____ causing a host of symptoms.

IgE, allergies, histamine

How quickly do type 1 hypersensitivity reactions occur?

almost immediately

what 4 main processes does histamine release cause?

vasoconstriction, bronchial constriction, inflammation, mucus secretions

what is the theory behind why an allergic reaction might have been evolutionarily advantageous?

IgE antibodies may have evolved to protect us from potentially toxic amounts of venom from bees or snakes

what is an antigenic trend?

specific proteins produced by classes or organisms tend to cause allergies in predisposed patients in predictable ways

What is the hygiene hypothesis for allergies?

lack of exposure to microbial organisms in childhood may cause the development of allergies

what is the minimum welt measurement that is considered concerning in an allergy skin test?

greater than 3 mm

The two pros of skin allergy testing are ____ and _____. The con with skin allergy testing is ___.

less expensive, can screen for several types of allergens at once, risk of systemic reaction

What are the two cons for allergy testing in vitro (tube test)? What is the pro for allergy testing in vitro?

can only test for one allergen at a time, less sensitive than skin testing, less traumatic

What type of assay is used for in vitro allergy testing?

Sandwich immunoassay

Does presence of an IgG imply an allergy?

no

what are the two types of autoimmunity?

organ specific, systemic

what are the six organ specific autoimmune disorders we covered in class?

Grave’s disease, Hashimoto’s thyroiditis, Diabetes mellitus type 1, Addison’s disease, Celiac disease, Chron’s disease

what are the three Hematologic autoimmune disorders we talked about in class?

TTP, ITP, AHA

what are the two neuromuscular autoimmune diseases we talked about in class?

MS, Guillan Barre syndrome

what are the seven systemic autoimmune disorders we talked about in class?

Lupus, rheumatoid arthritis, Sjogren’s syndrome, scleroderma, polymyositis, psoriasis, mixed connective tissue disorders

What is Grave’s disease? What are thy symptoms?

TSH receptor antibodies or Thyroid stimulating antibodies mimic TSH and cause too much thyroid activity, goiter, weight loss, rapid irregular heart rate, heat intolerance, restlessness, exophthalmos

What is Hashimoto’s disease?

Antibody to TPO prevents it from adding iodine to thyrosine preventing the production of T3 and T4 and causing hypothyroidism

How is Diabetes mellitus type 1 an autoimmune disorder?

autoantibodies to insulin or isle of Langerhan’s cells or beta glutamic acid decarboxylase

what is MS? Where are the antibodies detected? what are the symptoms? What are the possible causes?

autoantibodies against the myelin sheath of neurons, autoantibodies detected in the CSF only, vision problems, muscle weakness, numbness, pins and needles, balance issues, cognitive decline

What is addison’s disease?

antibodies destroy the cortex of the adrenal glands, low cortisol, low aldosterone

what is TTP?

autoantibody to ADAMS-13 prevents vWF from being broken into pieces, leads to DIC and MAHA

what is pernicious anemia?

antibodies to intrinsic factor make RBC’s unable to absorb B12

Certain HLA/MHC variants (determined genetically) can cause a higher risk of developing an ______

autoimmune disease

Besides HLA/MHC variants, what factors contribute to the likelihood of developing an autoimmune condition?

20-40 yrs old, sex, radiation, viruses, bacteria, drugs, EBV infections, presence of another autoimmune disease

what are the 5 theories of autoimmunity?

Hidden antigens, Altered antigens, Mutation of immunocompetent cells, Loss of T-cell immunoregulation, common epitopes

In type 2 hypersensitivity _____ or _____ antibodies bind to our own cells and mark them for destruction via _______, _______, or _______. These hypersensitivities are referred to as ______

IgM, IgG, T-cells, Complement activation, direct alteration of cell’s ability to function, Autoimmune hypersensitivities

What will the lab tests for Grave’s disease show?

low TSH, High T3 and T4, Autoantibodies against TSH receptor

What is Mysathenia Gravis? What are the symptoms?

Neuromuscular disorder, Antibodies against acetocholine receptors, muscle weakness in voluntary or cardiac or respiratory muscles

What will a SPEP show for a patient with MS?

4+ oligoclonal bands

What autoimmune disease is this SPEP showing?

MS

A type 3 hypersensitivity is _____ mediated. Antigens bind to antibodies and create an _______ that circulates freely through the _____. The _____ deposits in tissues where they cause damage particularly in the ____ and _____. When the _____ is in excess the _____ cannot circulate and is gobbled up by phagocytic cells. When the ______ is in excess the _____ leaves circulation to attack organs/tissues.

immune complex, immune complex, blood, immune complex, Joints, Kidneys, antibody, immune complex, Antigen, immune complex

What are ANA’s?

Anti-Nuclear Antibodies, Antibodies against the nucleus of cells

What is the theory behind the development of ANA’s?

Nuclear antigens that are usually hidden become exposed during apoptosis causing out body to see these antigens as invaders and create ANA’s against them

What are the 6 disorders that involve ANA’s?

Lupus, Rheumatoid arthritis, Sjogren’s syndrome, Polymyositis, Mixed Connective Tissue Disease

What is IFA testing? What kind of cells are used?

Indirect fluorescence antibody basically glowing antibodies, Hep 2 from Hela cells

What is an endpoint control in IFA testing?

minimum staining of cells that is considered a positive

___ % of people have ANA’s naturally and ____ % of elderly people have ANA’s

2, 75

a low titer is considered ____ for an IFA test

negative

Up to ___ % of Lupus patients test negative on IFA

5

The IFA screening test begins with a ___:____ serum dilution

1:80

What is this IFA pattern called? What is it associated with?

centromere, Scleroderma

What is this IFA pattern called? what is it associated with?

diffuse/homogenous, antibody to DNA and Histones

what is this IFA staining pattern called? What is it associated with?

Nucleolar, Lupus or Scleroderma

what is this IFA pattern called? What is it associated with?

peripheral/rim, Lupus

What is this IFA pattern called? what is it associated with?

Speckled, ENA’s and several autoimmune diseases

What are the Lab findings consistant with Lupus?

positive ANA with titer >160, diffuse or speckled or rim pattern IFA, decreased WBC, decreased PLTs, Proteinuria, anti-phospholipid antibody

What are the lab findings consistent with rhumatoid arthritis?

RF factor antibodies, anti-CCP antibodies, ANA’s

what are the lab findings consistent with Sjogren’s syndrome?

ANA’s with diffusely speckled pattern, elevated ESR, elevated CRP, anemia, leukopenia, eosinophilia, hypergammaglobulinemia, increased IgA in saliva, reduced creatinine clearance

What does Scleroderma look like in terms of lab tests?

positive ANA with diffusely speckled pattern, SLC-20 antibody

What does CREST look like in terms of lab tests?

calcinosis, Raynauds’s, Esophageal dysmobility, Sclerodactylia, Telangiectasis, positive ANA with discretely speckled pattern, centromere antibody

What is Polymyostitis? What does it look like in terms of lab tests?

persistent or chronic inflammation in skeletal muscle, positive ANA with diffusely speckled pattern

What is Mixed Connective Tissue Disease? what does it look like in terms of lab tests?

a combination of autoimmune disorders, positive ANA with a diffusely speckled pattern, Anti-RNP

A type 4 hypersensitivity is _______ mediated. APC’s present an antigen to ____ cells which release cytokines and chemokines to cause tissue damage. This reaction is considered a _____ reaction and is the ______ of all hypersensitivity reactions

cell mediated, T cells, delayed, slowest

Celiac disease is considered what type of hypersensitivity?

Type 4 cell mediated hypersensitivity

what are the symptoms of celiac disease?

chronic diarrhea, abdominal distention, malabsorption, loss of apatiteC, failure to grow normally

Celiac sufferers have a variant _____ called ____ which binds tightly to a part of gluten called ____. The stronger binding confuses the body causing it to attack it’s own ______ in the _______. The inflammatory process is mediated by ____ cells.

MHC, DQ2.5, Gliadin, villi, small intestine, T cells

What are the three things we look for when testing for celiac disease?

Anti-Gliadin IgA, Anti-TTG IgA, Anti-endomysial IgA

Why would we test for IgG’s in a Celiac diagnosis when it’s typically associated with IgA’s?

Because some people don’t make IgA’s

What is Multiple Myeloma? What does it look like in terms of lab testing?

one plasma cell clone is going nuts pumping out tons of antibodies, M-spike on SPEP, hypercalemia, renal failure, Anemia, Bone pain

What condition is indicated by this IFE?

Multiple myeloma

Urine Bence-Jones proteins are associated with what disorder? What is another name for them?

multiple myeloma, free light chains

what disorder does this IFE indicate?

Waldenstrom’s macroglobulinemia

What is Waldenstrom’s macroglobulinemia? What are the symptoms? What will we see on IFE?

over production of lymphocytes and plasma cells, hyperviscosity of blood, congestive heart failure, tons of IgM antibodies