Test 3 Flashcards
Lupus staining pattern
- Rim-staining**: Antibody to dsDNA
- Speckled**: Antibody to ENAs – Smith Antigen
- Diffuse: Non-specific
Sjogren Syndrome ANA’s
- Antibody to SS-A and SS-B
- Antibody to soluble nuclear non-histone proteins
- Rheumatoid factor – IgM antibody to IgG
Scleroderma ANA’s
Antibodies to Scl-70 (non-histone nuclear protein)
Anti-centromere antibodies
Rheumatoid factor
the second most common C.T. disorder
after SLE
Sjogren Syndrome
ANA Associated with the CREST variant of Scleroderma
Anti-centromere antibodies
Most common ANA in Scleroderma
Antibodies to Scl-70 (non-histone nuclear protein)
50% of ANA, Associated with more severe glandular and extra glandular manifestations in Sjogren Syndrome
Antibody to SS-A and SS-B
Rim staining patterns stains for ANAs in… And indicates…
Double stranded DNA, Systemic Lupus (SLE)
Speckled staining patterns stains for ANAs in… And indicates…
Extractable nuclear antigens (ENA’s)
Mixed CT disorder
Nucleolar staining patterns stains for ANAs in… And indicates…
Nucleolar RNA
Progressive systemic sclerosis (PSS)
Centromere staining patterns stains for ANAs in… And indicates…
Centromeric protein
CREST syndrome
Other name for scleroderma
AKA progressive systemic sclerosis
progressive systemic sclerosis (scleroderma) is Characterized by…
Excessive collagen deposition in the skin and internal organs by activated fibroblasts
Most common organs affected by progressive systemic sclerosis (scleroderma)…
GI tract, heart, kidneys, muscles and lungs
What is SCLERODACTALY ?
Scleroderma effect. Changes in microvasculature damages small blood vessels (the smallest of blood vessels that go around the fingers are the digital arteries). This along with the fibrosis of the tendons results in a claw hand.
Scleroderma effect on kidneys
⅔ patients; most common involve renal vessel
○ Deposition of collagenous material
○ Intimal thickening leading to cortical infarcts
○ 20% affected: sudden malignant HTN and renal failure (progressive insufficiency → chronic failure)
What are the 5 components of CREST syndrome? (A milder form of scleroderma)
- Calcinosis (calcium deposits form in the skin)
- Raynauds phenomenon
- Esophageal dysfunction (esophagus stiffens – hypomotility and dysphagia)
- Sclerodactyly (claw hand)
- Telangiectasia (spider veins – small dilated blood vessels near the surface of the skin)
What is Polymyositis/dermatomyositis?
● Chronic inflammatory myopathies
● Rare group of autoimmune disease of muscle
● Affects children and adults
○ 2x as common in women
● Many patients (especially adult men): association between myositis and cancer
The difference between Polymyositis dermatomyositis?
Polymyositis - no evidence of angiopathy
Dermatomyositis - humorally mediated microangiopathy
■ Early deposition of immune complexes and complement causes muscle atrophy and fibrosis secondary to ischemia
■ Involves eyelids (heliotropic rash) - specific for dermatomyositis
How is Polymyositis/dermatomyositis diagnosed?
- Histologic appearance of involved muscles (inflammation of the myocytes by T-lymphocytes, macrophages and microangiopathy
- Location of involved muscles
- electromyography alterations
- Elevated muscle enzymes in the blood (especially MM isoenzymes of CPK)
What is a heliotropic rash?
Erythematous rash involving eyelids. Considered specific for dermatomyositis
What are the cancers someone can get with dermatomyositis (both males and females)?
- Association with malignancy is particularly evident in men >50 years (3/4 of them will already have cancer when diagnosed or will get it within 1 year of diagnosis)
- Men: Lungs, colon, and stomach
- Women: breast, ovaries and uterus
Which autoimmune diseases would have ANAs to Centromeres
CREST syndrome
Which autoimmune diseases would have ANAs to a Speckled pattern
Mixed CT disorder
What are the risk factors for systemic lupus?
Female sex hormones – specifically estrogen
Genetic
• Family members have an increases risk
• Higher rate among monozygotic twins (identical)
Drugs induced
• Procainamide (arrhythmias)
• Hydralazine (hypertension)
• Isoniazid (for TB)
Age: Most patients are >50 years
Lupus causes glomerularnephritis – which is the mildest form of glomerularnephritis in lupus?
mesangial lupus
What does lupus causes in Skin
- Erythematous rash in sun exposed sites (butterfly malar rush)
- Microscopically: perivascular lymphoid infiltrate (vasculitis)
- Liquefactive degeneration of the basal cells at the dermal-epidermal junction (Immunofluorescence studies show deposition of IgG and/or complement at the DEJ)
What does lupus causes in Joints
- Most common manifestation of SLE
* >90% of patients have polyarthralgia’s (pain in 2 or more joints)
What does lupus causes in the Kidneys
- Glomerulonephritis
* ¾ of patients have evidence of renal disease
What does lupus causes in Serous membrane
More than 1/3 of patients have pleuritis with a pleural effusion
What does lupus causes in the Lungs
- Pleural disease pneumonia
- Caused by deposition of immune complexes in the alveolar septae with patychy acute inflammation
- Progressive interstitial fibrosis develops in some patients
What does lupus causes in the Heart
- All layers of heart involved
- Pericarditis is the most common finding
- Myocarditis and endocarditis are also seen. Characterized by Libman-Sacks endocarditis – small nonbacterial vegetations on the valve leaflets
What does lupus causes in the Brain
- Involvement of the CNS is livethreatening
* Vasculitis leads to hemorrhage and infarction
What does lupus causes in the spleen
• Vasculitis cause thickening and concentric fibrosis of smaller arteries – onion-skin pattern
Lupus is the 3rd major reason to need a kidney transplant (after diabetes and hypertension) Describe the differing clinical manifestations.
- Mild: hematuria and proteinuria
* Severe: crescent formation leads to fulminant renal failure
What are the characteristic features of someone who has a congenital agamma-globunemia of Bruton?
● Very common primary immunodeficiency - virtually no serum immunoglobulins
○ Aka. B cell problem
● X-linked recessive; males only
clinical features of DiGeorge’s
● Aka. Thymic hypoplasia
● Deficient cell-mediated (T-cell) immunity from defective embryological
development of 3rd and 4th pharyngeal pouches (develop into thymus + parathyroid)
● ~ 90% = sporadic deletion of chromosome 22 (occurs 1/3000 - 1/4000 births)
● ~ 10% = inherited deletion
● Usually in infants with congenital heart defects (VSDs) and defects of great vessels
(interrupted aortic arch)
Genetic deficits of severe combined immunodeficiency
o Defect is in the receptor for various cytokines that are required for proliferation of lymphoid stem cells
o Deficiency of the enzyme adenosine deaminase (ADA)
o ADA leads to accumulation of deoxyadenosine and its derivatives (toxic to immature developing lymphocytes)
How is SCIDs passed on genetically?
- Occurs both in an X-linked and autosomal recessive forms
- Autosomal recessive deficiency (~40%)
- Most common form is X-linked form (> 60%) – affects young boys
- Affects both T-cells and B-cell lymphocytes (and no complement)
- Defect in all lymphoid stem cells (the most immature cell of the hematopoietic system is affected)
SCID AKA Swiss-type agammaglobulinemia
How does SCID present itself?
- Typically appears before 6-months of age
- Characterized by recurrent viral, bacterial, fungal and protozoan infections
- Thymus is hypoplastic (instead of T-cell tissue, there is fatty CT)
- Lymph nodes and appendix lack germinal centers
How is SCID treated?
Bone marrow transplantation
the only bacteria that AIDs patient succumbs to
Mycobacterium avium complex (MAC) – cousin of TB
T cell deficiency you get…
Parasitic(cryptosporidium of intestine, toxoplasma of brain)
Fungi (Cryptococcus, candidiasis, Histoplasma - brain)
Viruses (Herpes, cytomegalovirus)
B cell Deficiency you get…
Bacteria
1What are the 2 lollipops on the surface of the HIV virus that make up the 2 glycoproteins – seen on the outside of the enveloped viruses. That is also used in the diagnoses using the western blot analysis
Glycoproteins: Gp120 (lollipop part), gp41 (stem)
P17 matrix (outer), p17 capsid (inside)
All 4 are used in the presumptive test (ELISA) and the confirmatory test (Western Blot)
What organism is the most common cause of meningitis in aids patients
Cryptococcus
HIV attacks…
CD4+ T-cells (you get progressive immunosuppression over time)
Most common mode of transmission for HIV?
o (>50% of reported cases)
o Heterosexual contact (33%)
o Vaginal secretions and sperm contain HIV
o Male to male or male to female is 20x more common than female to male (in the US)
Cells that serve are reservoir for HIV…
Helper T-lymphocytes (CD4+ T cells) Monocytes Macrophages (tissue-derived monocytes) Dendritic cells Microglial cells
3 neoplasms involved with HIV…
Kaposi’s Sarcoma
Carcinoma of the Cervix
B-cell Non-Hodgkin’s Lymphoma
Name the disease…
• Malignant disease
• Affects endothelial cells
• High prevalence among male homosexuals (reasons unknown)
• Multifocal, may involve internal organs as well
• Gross-examination: bluish-red nodules
• Histologically: nodules are made of anastomosing vascular spaces filled with blood (blood vessels merging)
• Grow slower than lymphomas, but can cause excessive bleeding
• Mass lesions may compress vital organs and cause death
Kaposi’s Sarcoma
Name the disease…
- Increased incidence in patients with AIDS
- HPV is associated with high incidence of squamous cell carcinoma
- HIV-infected women 10x more likely to have HPV associated cervical dysplasia compared to unaffected women
Carcinoma of the Cervix
Name the disease…
• Originates in the brain
• Worst type of lymphoma
• Only occurs in AIDS patients
Describe B-cell Non-Hodgkin’s Lymphoma
Whats this test?
• Antigen (HIV bug part) is added to the bottom of the well
• Add patient’s serum (blood sample) - If there are antibodies to HIV the IgG will attach to the antigen
• You add an antibody for human IgG which has an enzyme on top
• Add substrate for the enzyme. The enzyme will act on the substrate and change the color
Enzyme-linked immunosorbent Assay (ELISA)
Whats this test?
- Viral proteins from HIV are separated by acrylamide gel electrophoresis
- Then transfer from gel to paper
- Add patient serum – if there are HIV antibodies, they bind to the proteins
- Enzyme-labeled antibodies to human IgG are added
- An enzyme substrate is added. The enzyme acts on the substrate to change the color of the band
Western Blot
Confirmatory test, final word
Positive Result for Enzyme-linked immunosorbent Assay (ELISA)?
Substrate changes color
Positive result for Western Blot?
Color bands appear
Which phase of HIV and CD4+ count?
- 3-6 weeks after exposure (incubation period)
- B-Cells are stimulated to produce antibodies
- Non-specific symptoms (fever, night-sweats, nausea, myalgia, head ache, sore throat, skin rash)
- Towards the end of acute phase - mild lymph node enlargement: virus goes into lymph nodes etc.
- Self-limiting acute illness
Acute phase
1000 - 500/mm3
Which phase of HIV and CD4+ count?
- Variable in length – lasts from a few months to years
- Relative containment of the virus (virus is not in blood)
- Low level of HIV replication
- Virus is predominantly in lymphoid organs (lymph nodes enlarge)
Chronic phase (Latency) Early – exceed 500/mm3, then decline
Which phase of HIV and CD4+ count?
- Breakdown of host defenses
- Recrudescence (comeback of virus in blood) of viral replication and clinical diseases
- Long-lasting fever, fatigue, weight loss, diarrhea
- CD4 count is very reduced
- Opportunistic infections increase
Crisis phase (CDC considers this as AIDS) < 200/ mm3
most common cause of meningitis in AIDS
Cryptococcus (fungi
most important viruses that affect the
brain in AIDS
Herpesvirus and Cytomegalovirus (CMV)
Cause periventricular calcifications that also affect the brain in AIDS
Toxoplasmosis (histoplama and protozoa)
typically have microglial nodules with multinucleated giant cells in subcortical gray matter of cerebrum
AIDS encephalopathy
Brain = only organ that shows HIV specific changes what are the changes?
○ Evokes microglial response
i. Intermittent Ischemia of fingers – marked by pallor and pain
ii. In scleroderma it can be accompanied with edema of the fingers, hands and thickening of the skin
Raynauds phenomenon…
i. Inflammation of the serous tissues of the body
ii. Tissues lining the lungs, heart and inner lining of the abdomen
Serositis
i. Caused by dematomyositis
ii. Rash near the eyelids
Heliotropic rash
“Claw hands”
Scelerodactaly
What is the conformational make up of amyloid?
• Amyloid is made up of fibers
o 95% fibrillar proteins and 5% glycoproteins
o Proteins are arranged in β-pleated sheets
The shape of amyloid
Amorphous (no clearly defined shape)
amyloid appearance when died
Eosinophilic (basic, like the acidic dye eosin) hyaline-appearing (appears glassy and pink when dyed with eosin and haemotoxylin dye)
In what way does amyloid effect tissue?
It does not infiltrate into cells, but pushes all functional cells aside and causes them to die (pressure atrophy to adjacent cells)
When amyloid is focal, what organ is mostly seen seen (involved with focal rather than systemic manifestation)
• Kidneys are the most commonly affected organ
• The most deaths from amyloidosis are due to progressive renal failure
• Deposition of either AL or AA amyloid in the glomeruli, interstitium, vessels and tubules
o Deposits in the glomeruli leads to proteinuria – protein in the urine
o Also deposits in the interstitium (contains tubules and glomeruli), arteries and renal tubules
Pathology of amyloid infiltrating the kidneys
• Pathology: deposition of amyloid in the masangium (within the glomerular capillary tufts) and then capillary walls of the glomerulus
o Results in large eosinophilic pale spheres
o Can cause total obliteration of all glomeruli (each kidney has 1.2 million nephrons, if you have amyloid in all of them you get kidney failure)
What is the stain for amyloid
- Congo Red stain – specific for the detection of amyloid
- Gives amyloid a red color under the light microscope
- When examined under polarized light, congo red stains the amyloid in a “apple-green” color (birefringence) – this is how we make a definitive diagnosis
- NOTE: under normal light, amyloid looks very pink
two types of amyloid…
AL Amyloid
AA Amyloid
Which Amyloid is?
• Derived from the light chains of immunoglobulins
• Formed by neoplastic B-cells (abnormal growing)
o These abnormal B-cells are seen in multiple myelomas or lymphomas
AL Amyloid
Which Amyloid is?
• Derived from liver into the serum in response to:
o Infections – tuberculosis
o Inflammations – Alzheimer’s, rheumatoid arthritis, and inflammatory bowel diseases
o Neoplasms – renal cell carcinomas
o IV drug abuse
AA Amyloid
Amyloid is NOT a…
cancer
These depositions impairs neural cell function and contributes to dementia
• Deposits of amyloid in blood vessels and senile plaques – typical feature of Alzheimer disease
Produce autoantibodies - particularly ANAs against soluble nuclear nonhistone proteins
Sjögren’s syndrome
