hypersensitivity and autoimmune study guide

Type 1 HS:

·                                          Hypersensitivity;                            minutes

·      What major/life threatening reaction does this cause?

·      What Ab is this meditated by?

·      What is Atopic Syndrome?

immediate; 2-30 min

• anaphylaxsis

• IgE

• localized (i.e. urticaria, asthma, rhinitis)
  o Often “genetic predisposition” + sensitization

·       What is the role of Mast Cells in Type I Hypersensitivity? (understand the process and ultimately what is released)

Regulation by Th2 cells
IgE binds to mast cell
receptors
Antigen binds
Crosslinking causes
degranulation
Histamine released

·      What other WBC has histamine rich granules and high affinity receptors for IgE?

Basophils

·      List the common types, symptoms, and examples of Type I Hypersensitivity:

o   Types/Examples:

 

o   Symptoms:

• Venom from bees, wasps, hornets
   Penicillin
   Shellfish, peanuts, dairy products
   Latex

• Bronchospasm, laryngeal edema, vascular congestion, hives (urticaria), D intractable shock

·      What is the difference between RIST and RAST testing? What does each measure?

Rist- total IgE

Rast- allergen/antigen specific

Type II HS

·                                      Dependent                                 ;                       hours

·      Explain what cytotoxic hypersensitivity is/does.

 

o   What Abs mediate this reaction?

o   Is complement involved?

• antibody dependent; cytotoxcicity; 5-8hrs

• Ab attaches to cell bearing corresponding Ag → Cell Death

• Mediated by IgG and IgM antibodies binding to specific cells or tissues

• no complement

·      What are 5 types/examples for Type 2 HS

Transfusion Rxn
 Autoimmune Hemolytic Anemia (AIHA)
 Hemolytic Disease of the Fetus and Newborn (HDFN)
 Hashimoto Thyroiditis
 Goodpasture Disease

What 4 tests are typically done to help identify Type 2 HS hypersensitivity?

• coombs DAT

• indirect coombs

• direct Fluorescence (ANA)

• Thyroid testing

Type III

·      This type is known for                            complexes;                     hours

·      What 3 things mediate this hypersensitivity?

immune; 2-8hrs

• IgG, IgM, Complement

·      How does the soluble Ag eventually lead to damage in Type 3 HS? ·      What are the common human tissues damaged in this hypersensitivity?

• complexes are formed and deposited in tisues, they bind to complement and cause damage

• glomerular basement membrane, vascular endothelium, joint lnings, pulmonary alveolar membrane

What are the 3 most common types/examples of Type 3 HS?

• serum sickness

• rheumatoid arthritis

• SLE

·      What is the Arthus reaction? What was its significance?

• a localized type III sensitivity

• clumps of antibody develop and get lodged in the kidneys and cause severe inflammation

Type IV

·      Also known as the                               hypersensitivity;                        hours

·       This is a                          mediated reaction

·      What 2 things are NOT involved in this hypersensitivity?

delayed; 24-72hrs

• Tcell mediated

• 1. Ab

• 2. Complement

What are the 4 most common types/examples of Type 4 HS

1. poision ivy

2. nickle

3. rubber

4. detergents

o   How does the damage from contact dermatitis happen?

small substances enter the skin and attatche to proteins forming immunogens that cause damage

o   What type of graft vs host disease is most common for this type of hypersensitivity (type 4 HS)

Bone marrow or stem cell transplants

o   What is another name for the TB test?

mantoux test

·      What types of testing are done to help identify type 1 hypersensitivity?

• skin tests

• patch test

Define Autoimmunity

the immune system mistakenly recognizes self tissues as foreign, and mounts an immune response

·      Self-tolerance is established by what 3 facts:

• the ability to identify and not react against self-produced antigens

• active regulation by T cells

• Maintained by a balance of T helper cell type 1 and type 2

o   Which T helper cells are primary mediators of autoimmunity?

Th1

o   Inheritance of gene coding for a specific MHC molecule may make a person:

more susceptible to and autoimmune disease

o   MHC I complex will be on:

all nucleated cells

o   MHC II complex will be on:

APC

o   MHC III genes code for:

complement

·      Define molecular mimicry:

 o   What is an example of molecular mimicry?

viral or bacterial agents containing ags that resemble self-ags

• strep infections

·      Antinuclear Antibodies (ANA)

o   What 2 types of cells are used for this testing?

mouse kidney or human epithelial (HEp-2 cells)

o   What is an anti-nuclear antibody?

Ab formed to nuclear ags that have been released into the blood

Where do the immune complexes commonly get trapped in the body?

• kidney

• synovium

• blood cells, vessels, skin, lungs, liver, nervous system, heart

o   What are the most common symptoms you would see with SLE?

• butterfly rash on the face

• arthraligia

• fever

• polyarthritis

• fatigue

• skin rash

• anemia

• kidney involvement

o   When screening with the ANA test what 2 patterns would you find for SLE?

 

What are they specifically staining in the cell?

homogenous and peripheral rim

• ds-DNA/ FANA

o   What happens to complement levels in SLE? Why?

decreased because it is getting used up

o   What is the substrate of the confirmation test you would use, that has ds-DNA in the kinetoplast?

Crithidia luciliae

o   What type of antibody is seen in Drug induced SLE? What pattern?

antihistone antibody- homogenous pattern

o   What is a common but separate antibody seen with SLE?

 

§  What are the most common antibodies tested for this syndrome?

 

 

§  What does this syndrome cause in the patient?

 

§  What are some common abnormal labs seen?

• antiphospholipid antibody

• anti-cardiolipin, lupus anticoagulant, Beta 2 glycoprotein 1

• multiple miscarriages and clotting issues

• prolonged PTT and low plts

·      Rheumatoid Arthritis (RA)

o   Ig__ or Ig__ antibodies are formed against the ____ portion of ______.

o   What type of hypersensitivity is this?

o   What are the 3 most common characteristic symptoms (a pt would have):

• IgG or IgM, Fc portion of IgG

• type III hypersensitivity

• 1. synovium inflammed

• 2. deformity

• 3. decrease life expectancy

§  What is the screening test for RA called?

·      It detects what type of Ab?

Rheumatoid factor

detects serum igM

§  What is the confirmatory test called in RA?

anti-cyclic citrullinated peptide assay

o   _________ titers of complement will happen with RA

low

What are the 4 main organ diseases specifically affected by AI diseases?

• hashimotos

• graves

• type 1 diabetes

• addisons

o   Hashimoto’s Thyroiditis:

§  AutoAbs are produced against _______________ and ____________ cell components

§  ____ TSH (________thyroidism)

§  What type of hypersensitivity?

§  Main symptoms for these pts are:

thyroglobulin and thyroid cell components

• high TSH (hypothyroid)

• type IV

• weight gain, lethargy, intolerance to cold, goiter, enlarged thyroid

Hashimotos:

§  __________ ____________ Antibody is seen in 90-95% of pts

§  __________ Antibody is seen in 80% of pts but may also be seen in __________ cancer pts.

Thyroid peroxidase antibody

thyroglobulin Ab

thyroid

o   Graves’ Disease

§  ____ TSH (_________thyroidism)

§  What type of hypersensitivity?

§  Main symptoms for these pts are:

low, hyper thyroidism

type II hypersensitivity

• thyrotoxicosis, goiter, exophthalmos, heat intolerance

Graves Disease:

§  __________ ____________ Antibody is seen in ~75% of pts

§  __________ ____________ ________________ are a better Ab to help diagnose.

·      These antibodies will lead to continual production of _____ & ______

Thyroid stimulating immunoglobulin

thyroid stimulating hormone receptor ab

T3 and T4 increase

o   Type 1 Diabetes Mellitus

§  Type 1 results from destruction of _______  ______ in the ____________.

beta islet cells

pancreas

§  What are the 4 most common AutoAbs of βcell autoimmunity?

·       

·       

·       

·       

• GAD

• ICA

• IAA

• IA-2A

§  Hyperglycemia and the ADA classification of DM

Review or type out here the glucose/A1C values that indicate DM.

§  Why would AutoAb testing be done for patients with T1DM?

serological tests to screen for beta cell destruction if a family member has T1DM

o   Addison’s Disease

§  Results from destruction or dysfunction of the _________ __________.

§  List below which classes of adrenal steroids that will be deficient:

·       

·       

·       

·       

• adrenal glands

• mineralxorticoids

• glucocorticoids

• adrenal androgens

• adrenalin

§  Main symptoms for Addison are:

 

§  ____ glucose, cortisol, aldosterone, Na, Cl

§  ____ K and renin levels

§  These pts can also have Abs against ______________________

• bronze pigmented skin, Gi issues, weight loss, hypoglycemia

• decrease

• increase

• 21-hydroxylase

o   Myasthenia Gravis

§  Results from Abs against ______________ ______________ at _______________  _____________.

§  What are clinical signs that would be seen with this disorder?

acetylcholine receptors at neuromuscular junctions

• drooping eyelids, inability to retract the corners of the mouth, inability to support the trunk

o   Multiple Sclerosis (MS)

§  This is an inflammatory AI disorder of the __________.

§  What important component is destroyed by AutoAbs?

CNS

myelin sheath

MS:

§  Another important characteristic is: _____________ formation in the white matter of the ___________

§  Main symptoms for these pts are:

plaque, brain

• tinnitus, urinary retention, blurred vision, paralysis, ataxia, vertigo

§  What key characteristic is seen with CSF electrophoresis?

 

§  How is MS confirmed? What are they looking for?

oligoconal band

• MRI to look for lessions

o   Celiac Disease

§  Results from an intolerance to dietary ___________ causing poor ______________ of nutrients

What are some key clinical signs of these pts?

gluten; absorption

• anemia, diarrhea, bloating fatigue, weight loss

§  What are the 3 most common AutoAbs found in celiacs:

·        

·        

·        

• anti-tissue transglutaminase

• antigliadin

• anti-endomysial

o   Goodpasture’s Syndrome

§  This is due to an AutoAb towards the ______________ ______________ ______________

§  Damage to the glomerulus rapidly progresses to _________ __________

§  The damage is done by ______________ antibody making it a type ___ hypersensitivity

• glomerular basement membrane

• renal failure

• cytotoxic antibody; II

§  What are some key clinical signs of these pts with good pastures syndrome?

________________ can help remove circulating antibodies

proteinuria, dec creatinine clearance, blood in urine, pulmonary hemmorhage, dyspnea, weakness, fatigue, cough

plasmapheresis

o   Scleroderma

§  A disorder that results in normal tissue/skin being replaced with:

§  Will eventually lead to death when organs are changed (heart, lung, kidneys)

• thick tissue due to extra collagen

§  What does CREST stand for?

·      C –

·      R –

·      E –

·      S –

·      T –

calcinosis

raynauds

esophogeal dysmotility

sclerodactyl

telangiectasis

§  ANA (scleroderma):

·      Will show ____________ or _____________ pattern

·      ___________ antibody is specific but only seen in 15-20%

___________ antibody is a marker for ____________.

speckled or nucleolar

• Scl-70

• centromere, crest

o   Sjögren’s Syndrome

§  An AI that affects the __________ glands, causing mostly dry ________ and _________.

exocrine, mouth and eyes

§  ANA(Sjögren’s Syndrome):

·      ____________ pattern

·      What are the 2 AutoAbs called?

o    

o    

speckled

• SSA/RO

• SS-B/LA

summary chart

Specificity	Disease	Auto Antibody Against:	Problem	Testing
Organ-Specific                                                Systemic	Hashimoto’s thyroiditis Type 2 hypersensitivity	Thyroglobulin (+ thyroid cell components)	Hypothyroidism	TPO-AB and TgAb ↑TSH ↓T4,T3
	Graves’ disease	Receptors for TSH	Hyperthyroidism	TSI and TPO-Ab (less likely) ↓TSH ↑/N T4,T3
	Pernicious anemia	Gastric parietal cells	Vit B-12 def.	Vit B12, CBC, P.cells Abs
	Addison’s disease	Adrenal glands	1° Adrenal Insuf. All adrenal steroids deficient	↓ Na, Cl, Cort, Ald, Ur Steroids. ↑K ACTH Stim: no Cort response (still low)
	Type I diabetes mellitus	β-cells in Pancreas	Hyperglycemic	Glucose Tolerance Test Family Anti: GAD, ICA, IAA, IA-2A
	Myasthenia Gravis	Acetylcholine Receptors at Neuromuscular Junctions	Neuro-muscular disorder Weakness/fatigability of skeletal muscle	Anti-ACh receptor Less tested Anti muscle specific kinase
	Multiple Sclerosis	Myelin Sheath of Nerves or Myelin Basic Protein	Weakness, visual disturbances	Oligoclonal IgG Band testing in CSF/serum MRI for white matter plaques
	Goodpasture’s Syndrome Type 2 hypersensitivity	Basement membrane (kidney, lungs)	Hematuria, glomerulonephritis, hemoptysis	Anti-glomerular basement membrane
	Celiac Disease	IgA Abs against Tissue Transglutaminase Gliadin, and Endomysial (intest. lining)	Malabsorption, diarrhea, steatorrhea, nutritional def.	Anti-TTG, Anti-Gliadin, Anti-Endomysial Bowl biopsy (blunting of villi)
	Sjogren’s Syndrome	Salivary and Tear Ducts	Dry Eyes and mouth	Speckled Pattern: SS-A/Ro and SS-B/La
	Rheumatoid Arthritis Type 3 hypersensitivity	IgG/IgM against Fc	Synovium attacked, deformity of joints	Rheumatoid Factor: IgM Confirm w/: Anti-CCP; low complement
	Systemic Lupus Erythematosus Type 3 hypersensitivity	Anti-nuclear Antibodies ds-DNA,	Systemic issues Skin, joints, kidney, brain, heart, lungs	ANA testing, Crithidia luciliae, Anti: ds-DNA, Sm