Exam #3: Immunopathology III Flashcards by Jonathan Kallevang

What is Sjogren’s Syndrome?

Autoimmune destruction of the:

Exocrine glands
Primary lacrimal glands
Salivary glands

How well did you know this?

Not at all

Perfectly

Is there a sex predominance to Sjogren’s Sydrome?

Yes, females

How well did you know this?

Not at all

Perfectly

What is Sicca Syndrome?

Isolated form of Sjogren’s that causes a decrease in tears & saliva

*****Note that Sjogren’s Syndrome is a systemic autoimmune disease

How well did you know this?

Not at all

Perfectly

Describe the progression of Sjogren’s Syndrome?

CD4+ T-cell proliferation against glandular epithelial self-antigens
Systemic B-cell hyperactivity to antinuclear antigens (ANA)

*****Note that the syndrome may be induced by vial infections e.g. EBV & Hepatitis C

How well did you know this?

Not at all

Perfectly

What are hallmark ANAs in Sjogren’s Syndrome?

Anti-nuclear antigens to ribonucleoproteins called:

SS-A (Ro)
SS-B (La)

*****These are common & seen in 90% of cases; however, not that ~70% of patients are also positive for Rhematoid Factor (RF)

How well did you know this?

Not at all

Perfectly

Describe the pathogenesis of Sjogren’s Syndrome?

Activated CD4+ T-cells & B-cells infiltrate ducts & vessels in target glands
Ductal hyperplasia leads to obstruction of the glands
Acinar atrophy, fibrosis, and replacement of parenchyma w/ fat occurs

How well did you know this?

Not at all

Perfectly

Describe the symptomatic progression of Sjogren’s Syndrome.

Dry mucous membranes leads to:

Xerostomia (dry mouth)
Keratoconjunctivitis sicca (dry eyes)
Nasal septal erosion/ perforation
Dysphagia
Dypareunia

How well did you know this?

Not at all

Perfectly

What are Sjogren’s patients at risk for?

B-cell lymphoma

*****Note that lymph nodes in patients with Sjogren’s Syndrome are often massively hyperplastic

How well did you know this?

Not at all

Perfectly

What are the systemic symotoms associated with Sjogren’s Syndrome?

Systemic vasculitis & extraglandular involvement of the kidneys, lungs, skin, CNS, muscle

Leads to:

Interstitial nephritis
Pulmonary fibrosis
Peripheral neuropathy
Synovitis

How well did you know this?

Not at all

Perfectly

What antibody is associated with more systemic manifestations of Sjogren’s Syndrome?

SS-A (Ro)

**Note that SS-A (Ro) is generally associated with a worse clinical course

How well did you know this?

Not at all

Perfectly

What are the symptoms of Systemic Sclerosis?

Involvement of the skin=

Rigidity
Loss of specialized skin cells & function

Involvement of the GIT

How well did you know this?

Not at all

Perfectly

Is there a sex predominance associated with Systemic Sclerosis?

Female

How well did you know this?

Not at all

Perfectly

What is Systemic Sclerosis?

Autoimmune disorder characterized by excessive fibrosis throughout the body; furthermore there is:

1) Chronic inflammation
2) Destruction of small vessels
3) Progressive tissue fibrosis of not only the skin but multiple organs as well

How well did you know this?

Not at all

Perfectly

Describe the pathogenesis of Systemic Sclerosis.

The cause of Systemic Sclerosis is unknown.

It is proposed that there is inappropriate activation of CD4+ T-cells that release cytokines, which activate inflammatory cells & fibroblasts
There is also blood vessel injury, which causes ischemia leading to fibrosis; cause is unknown
Also, there is inappropriate humoral activation

How well did you know this?

Not at all

Perfectly

What is the predominant growth factor associated with Systemic Sclerosis?

TGF-B

**TGF-B leads to fibroblast activation & fibrosis

How well did you know this?

Not at all

Perfectly

What is CREST Syndrome?

There are two subtypes of Systemic Sclerosis, limited & diffuse

Limited is characterized by:
1) Skin involvement of the face, forearms, & figners
2) Late visceral involvement

**This limited subtype of Systemic Sclerosis is called CREST Syndrome

How well did you know this?

Not at all

Perfectly

What does CREST stand for?

Calcinosis
Raynaud's phenomenon
Esophageal dysfunction
Sclerodactyly 
Telangiectasias

How well did you know this?

Not at all

Perfectly

What is Clacinosis?

Ca++ deposits in the skin

How well did you know this?

Not at all

Perfectly

What is Raynaud’s phenomenon?

Spasm of blood vessels in response to cold or stress (white fingertips)

What is esophageal dysfunction?

GERD & decreased esophageal motility

What is Sclerodactyly?

Thickening & tightening of the skin on the fingers & hands

What is Telangiectasas?

Dilation of capillaries causing red marks on the surface of skin

What is the severe complication of Reynaud’s Phenomenon?

Marked pallor of the fingers

- Can lead to necrosis

What is the diffuse variant of Systemic Sclerosis? Symptoms?

This is the second subtype of Systemic Sclerosis that is characterized by:

Widespread skin involvement at onset
Early visceral involvement
Rapid progression

*****A worse clinical course compared to limited/ CREST

What antibody is associated with the diffuse variant of Systemic Sclerosis? What about CREST Syndrome

Antibody to DNA topoisomerase I (anti-Scl-70) is associated with diffuse variant Systemic Sclerosis *****vs. Anti-cenntromere antibody seen in CREST Syndrome

What are the early skin changes seen with diffuse Systemic Sclerosis?

- Edema | - Lymphocyte (CD4+) infiltrates

What are the late skin changes seen with diffuse Systemic Sclerosis?

- Epidermal thinning - Dermal/ appendage fibrosis - Subcutaneous calcifications Ultimately these lead to contractures i.e. claw fingers & "mask facies"

What are the vascular complications seen with Systemic Sclerosis?

Chronic vascular endothelial damage & fibrosis causes ischemia that leads to autoamputation of digits

What are the esophageal changes that are seen in Systemic Sclerosis?

Collagenization & fibrosis of the muscularis mucosa that leads to: - Esophageal dysmotility - LES dysfunction - GERD

What are the small bowel cahnges seen in Systemic Sclerosis?

- Mucosal thinning - Loss of villi & microvilli - Submucosal fibrosis ****All of these pathologic changes result in MALABSORPTION

What are the renal changes that are seen in Systemic Sclerosis? What does this cause?

- Thickening of interlobular arteries by concentric proliferation of intimal cells - Deposition of collagenous or mucinous material & hyaline *****These changes result in HTN in 30% of cases

What is the genetic predisposition for RA?

- HLA-DRB1 | - PTPN22 (Remember, gene for tyrosine phosphatase that participates in the activation & control of T-cells )

Describe the pathogenesis of RA.

1) Unknown antigenic trigger w/ underlying genetic susceptibility 2) Initiation of synovitis 3) ONGOING AUTOIMMUNE REACTION mediated by CD4+ T-cells - Produce cytokines - Activate macrophages - Activate B-cells 4) Production of Rhematoid Factor

What is RA factor?

IgM auto-antibody to Fc portion of IgG (in same individual)

What are citrullinated peptides?

Certain enzymatic reactions in the body will convert arginine-->citrulline (seen in smokers) - antibodies that develop to these peptides & contribute to RA

How does RA first present?

Typically, there is a slow & insidious progression starting with malaise, fatigue, and generalized MSK pain - Several weeks- months later joints become involved ****Joint involvement is typically symmetric with the small joint affected first, then progressing to more proximal joints

What are the hallmark deformaties associated with RA?

Ulnar deviation Swan-neck ****Note that joints are swollen, warm, painful, & stiff especially following inactivity

How does RA appear on x-ray?

- Loss of joint space - Ulnar drift of the fingers ****Patients are also diffusely osteopenic (progressing toward osteoporosis)

What is pannus formation?

Inflammatory response that includes: - Granulation tissue - Synovial & inflammatory cells - Fibrous CT

What are the systemic manifestations of RA?

Rheumatoid nodules form at the: - Skin pressure points - Viscera Small vessel vasculitis especially in cases of severe disease w/ high RF titers

Describe the clinical course of RA.

Course is variable, ranging from mild discomfort to progressive disability

What complications are associated with RA?

1) Amlyoidosis 2) Vasculitis 3) Drug complications - Bleeding - Infection

What is Juvenile Idiopatic Arthritis?

This is a diagnosis of all forms of arthritis, developing in the patient prior to 16 years-old & persisting for 6 weeks - Frequently involves large joints - ANA positive, BUT RF NEGATIVE

What is Still's Disease?

This is a variant of Juvenile Idiopathic Arthritis that is associated with: 1) Fever 2) Hepatosplenomegaly 3) Rash 4) Increased WBC count

What is mixed connective tissue disease?

Clinical syndrome with overlapping features of SLE & Systemic Sclerosis ****Note that it is DISTINCTIVE b/c of minimal renal disease & good response to steroid therapy

What antibody is associated with MCTD?

anti-U1RNP to ribonucleoprotein

Why is important to remember about MCTD clinically?

Good response to steroid therapy