Chapt 6 pt 3 Flashcards
SLE
Immunofluorescence microscopy of the skin in patient with SLE will show?
Are these finding diagnostic?
ig/complexes that are going to deposit in the dermo-epidermal junction, EVEN AT THE UNAFFECTED AREAS
These are not diagnostic, bc also seen in scleroderma and dermomytotis
SLE
Histo of the skin in patient with SLE will show?
degeneration of the basal cell later of the skin. (vacuolated spaces will appear between degenerating cells)
What kind of effusions may be present with SLE?
Pleural and pericardial effusions (sometimes with LE cells)
What cardiovascular system effects are present with SLE?
- Symptomatic or asymptomatic pericardial involvement (50% of pt’s)
- Myocarditis
- Valvular abnormalities (mitral and aortic)
- Valvular (Libman-Sack) endocarditis (see photo)
- CAD (angina, MI) owing to coronary atherosclerosis
What other organs are involved in SLE?
CNS
Spleen (onion-skin lesions from smooth muscle cell hyperplasia)
Lungs (effusions), interstitial fibrosis and secondary pulmonary HTN
What are signs of renal involvement in SLE?
-
Hematuria, proteinuria, red cell casts, nephrotic syndrome
What are the main clinical features of a patient presenting with SLE?
- Butterfly rash over the face
- Fever
- Pain but no deformity in one or more peripheral joints (feet, ankles, knees, hips, fingers, wrists, elbows, shoulders)
- Pleuritic chest pain
- Photosensitivity
What are the most common causes of death in patients with SLE?
- Renal failure
- Infections
- CAD
-
What is chronic discoid lupus erthymetasus?
Skin manifestations of Lupus, without systemic effects
- Discoid rash: deep rash usually on skin and scalp (areas exposed to sun)
- +ANA (but anti-dsDNA is NOT present)
- immunoflorueces
What will immunofluroscence show in person with chronic discoid lupus erthymetasus?
Immune complex deposition only in the SUN EXPOSED EARS OF SKIN
NO anti-dsDNA
What is drug-induced lupus erythematous
what drugs
LE- like syndrome that arises due to someone taking [hydralazine, D-penicillimin, procainamide , isoniazid] => formation of ANAs, but asymptomatic.
Goes away once drug is removed
What criteria do ppl with drug-induced LE have?
- Arthralagia (joint pain) and fever
- Dicscoid rash
- Hematologic disease
- ANA (anti-histone Ab)
- immunofuleuosces
What systems are NOTTTT affected in person with drug-induced LE?
- Kidney
2. CNS
• Individuals with certain alleles are at higher risk for drug induced lupus than others.
what are they?
HLA-DR4 => hydralazine
HLA-DR6=> procainamide
Sjorgen Syndrome can occurs as a primary form (sicca syndrome) or most commonly as a secondary form, which disease is it most commonly associated with?
- Rheumatoid arthritis
Even if the patient does not have RA, they will still have rheumatoid factor
What is Sjogren syndrome?
D/t infiltration of what?
Chronic disease characterized by dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia) due to T/B cell infiltration => inflammation => fibrosis and destruction of the lacrimal and salivary glands.
What type of hypersensitivity rxn is sjogren?
Type 4 w fibrosis
Who is more likely to get sjogren syndrome?
What clinical sx will a pt present with?
Women 50-60
Kerajunctivitis => dry eyes, itchy, burny eyes, blurred vision “sand” in eye
Xerostomia: diff swallowing, decrease in taste, cracks and fissures in mouth. Root caries and smooth tongue
enlarged parotid gland
Which autoantibody found in patients with Sjorgen syndrome is associated with early disease onset, longer disease duration, and extraglandular manifestations, such as diffuse pulmonary fibrosis, cutaneous vasculitis and nephritis?
SS-A
What is the earliest histological in patients with Sjorgen Syndrome?
Later, we will see?
Infiltration of polyclonal T/B cells in the major and minor salivary glands
Later, we will see B-cell infiltration => marginal B-cell zone lymphoma => enlargement of parotid gland, later in disease
Patients with Sjorgen Syndrome are at a high risk for developing?
marginal zone B cell lymphomama, thst enlarges parotid gland
-
What is essential for the diagnosis of Sjorgen Syndrome?
Biopsy of the lip to examine minor salivary glands
PAtients with Sjrogen syndrome have:
- ANA
- anti-SSA (Rho) and SSb(La)
what else do moost patienets have
Rheumatoid factor (IgM autoAb that binds to self-IgG)
What is systemic sclerosis (scleroderma)
chronic, progessive fibrosis of the skin** and visceral organs d/t to collagen deposition and widespread damage to BV
Ssystemic sclerosis (scleroderma) is most common in what population
W 50-60
Death from sclerosis is often d/t what
pulmonary insuffiency
What causes the fibrosis we see in systemic sclerosis?
- Trigger of T-cells (and thus cause of SS) is not known fact
- alternativively + MO
- cause inflammation (increase adhesion molecules), vasoconstriction (increased endothelin and decrease MO), secretion of GF (cause fibroblasts => collagen)
- Collagen deposits on BV and they bcome hyalinized
Some patients with the limited form of Systemic Sclerosis (Scleroderma) also develop?
What areas of the body does the limited form affect?
Fingers, forearm and face; with late visceral involvement .
CREST syndrome;
Calcinosis: Ca2+ deposits in skin
Rayneud phenomenon: after stress, vasoconstriction causes finger turn white => blue
Esophageal dysmotility => hard time swallwing
Scerodactyl => tightening of skin on fingers and hand
Teleangiectasia=> dilation of capillaries, producing a pattern on skin
How are diffuse scleroderma and limited (CREST scleroderma) different on immunofluroreces?
Diffuse systemic sclerosis: Anti-Scl70 will produces a speckled pattern
Limited: Anti-centromere Ab will produce a Centromeric pattern
How can systemic sclerosis manifest in kidneys?
Proteinuria
MALIGNANT HTN can CAUSE FATAL RENAL FAILURE
Mixed Connective Tissue disease is characterized serologically by high titers if antibodies to?
high titers of antibodies to ribonucleotide particle-containing U1 ribonucleotide protein (anti-RNP; ribonucleoprotein)
Mixed CT disease presents with clinical features that are a mixture of what?
Overtime, what can happen?
- SLE
- Systemic sclerosis
- Polymyotitis
Overtime, it can become systemic sclerosis or SLE
What is the most common feature seen in mixed CT disease?
Can it be treated?
Rayneuds phenomenon
In the short term, it has a good response to corticosteroids.
What is IgG4 related disease characterized by?
IgG4 producing Ab and T cells that infiltrate tissue and cause:
- Storiform fibrosis.
- Obliterative Phlebitis
- Increased serum IgG4
IgG4 related diseases in the… is called
Pancreas Thyroid Glands Eyes, lungs and kidneys: Heart:
autoimmune pancreatis Riedels thyroiditis Mikulicz syndrome Inflammatory pseudotumors Inflammatory aortitis
also; idiopathic retroperitoneal fibrosis
What disease often affects middle-aged and older men and is 1st characterized in autoimmune pancreatitis?
IgG4 related diseases
What is Mikulicz syndrome?
Seen in what conditions?
fibrosis and enlargment of the salivary and lacrimal glands; often seen in sjrogen syndrome
Rejection: T cells and antibodies made against the grafts antigens attack and destroy it.
Major antigenic differences between a donor and recipient that cause rejection are differences in what?
HLA alleles, because they’re highly polymorphic
what are the differences between allografts and xenografts?
Allografts: grafts from the SAME species
Xenografts: grafts from DIFFERENT species.
After transplantation, the recipient’s T cells recognize donor antigens from the graft in 2 ways:
- Direct allorecognition: donors DC’s present the antigen directly to receipients MHC I and II complexes of T cells => immediate anti-graft response
- Indirect allorecogntion: RECIEPEINTS DC’s capture the antigen and present them to their own cells
In direct allo-recognition, what is the most important for initiating an anti-graft response?
Donor’s APC
What is the direct pathway for recognition of alloantigens in organ grafts?
Why are the DCs in the donor organs most important for initiating the antigraft response?
- Donor APC presents antigen on MHC Class 1/2 and presents to hosts CD4+/CD8+ molecules.
- CD4+ release IFN-y and + MO => tissue damage and inflammation
- CD8+ => CTLs and kill GRAFT CELLS IN BV
APCs are the most important because they express alot of MHC complexes and co-stim molecules
What is involved in the indirect pathway of allorecognition in organ grafts?
Which immune cells are involved here?
Hosts APC presents to its own T-cells
- The host/recipients DC capture grafts antigens, display them onto MHC 2 molecules and presents to the CD4 cell => => activate macrophages (by releasing IFN-y) or B cells, which then make AB-secreting plasma cells =>attack BV
CD8+ CTLs may be made BUT CANNOT KILL graft cells because these CTLs recognize graft antigens presented by the host’s APCs and cannot recognize the graft cells directly.
Which is a type 4 delayed hypersensitivity reaction?
Direct or indirect pathway of allorecognition?
INDIRECT PATHWAY
What kind of damage occurs from CD8+ CTLs that may be generated from the indirect pathway for recognition of alloantigens in organ grafts?
In indirect allo-recognition, what is the most important for initiating an anti-graft response?
CTLS cannot KILLL!!!!
Cytokines released from T-cells and inflammation
What characterizes acute cellular rejection; cell type responsible?
Graft injury is caused by?
Commonly seen when?
- CD4+ T cells secrete cytokines => cause inflammation ( increased vascular permeability and local accumulation of mononuclear cells (lymphocytes and macrophages))
- Graft injury is caused by activated macrophages
- Occurs within initial months following transplantation or if patient stops taking immune regiman
Acute cellular (T cell-mediated) rejection may be seen as 2 patterns histologically, what are they?
- Tubulointestinal pattern: Tubulitis; interstitial inflammation and infiltration of tubules with CD4/8 cells
- Vascular pattern: endothelitis (inflammation of vessels) and sometimes necrosis of vascular walls.
What is chronic rejection?
NK and plasma cells react to alloantigens in the walls of the vessels => release cytokines => inflammation => [vascular endothelial and smooth muscle cells proliferate]
What morphology can be seen in chronic rejection
- Progressive renal failure (increase in serum creatinine over 4-6 months)
- Thickening of intima in BV inflammation=> narrowing of the lumen
- Interstitial and glomerular fibrosis
What causes hyperacute rejection of an donor organ?
Most commonly seen in what circumstances?
How fast is the rejection?
- Occurs when preformed antidonor antibodies are present in circulation of reciepient
- Can be caused by: previous transplant, prior blood transfusions, and multiparous women
- Occurs within minutes to hours
Hyperacute rejection typically will cause what?
- Fibrinoid necrosis and thrombosis
What is acute antibody-mediated rejection?
how fast does it occur?
Anti-donor AB made AFTER transplantation attack the gradfts vasculature
within days or appear suddenly after immunosupression is tapered/terminated
how can we diagnose acute anti-body mediated rejection?
+C4d stain (there will be deposits of C4d in compliment system)
How is chronic antibody-mediated rejection different from acute?
Primarily affects what part of grat?
- Occurs slower (more insidiously); without preceding acute rejection
- Antibodies are in circulation, but NOT in the graft
- Primarily affects graft vasculature
Chronically rejecting kidneys usually have interstitial mononuclear cell infiltrates, including what cells?
NK and plasma cells
HLA matching: standard of care of transplantation. Value of HLA matching differs dep on organ.
What alleles do we match for in kidneys, which has SUBSTANTIAL benefit?
What organs is HLA matching NOT done for?
HLA-A, HLA-B and HLA-DR
Liver, <3 and lungs
to increase graft survivial you can also give immunosupressants (needed for all EXCEPT ____)
What 3 drugs are given for immunosuppressive therapy?
Basic function of each?
twins
- Steroids (reduce inflammation)
- Mycophenolate mofetil (inhibits lymphocyte proliferation)
- Tacrolimus (FK506) (inhibits T cell functions)
What can be given as an immunosuppressant that is a suppressor of inflammation by unknown mechanisms?
What is used in cases of severe antibody-mediated rejection?
Pooled intravenous IgG
Plasmapheresis => take plasma out, skin it and reomve ab and put back
_____ one of the more common viral infection that can be caused by immunosuppression
polyoma virus
Immunosuppressed individuals such as those receiving organ transplants are at increased risk for developing what from the reactivation of latent viruses?
- EBV-induced lymphomas
- HPV-induced squamous cell carcinomas
- Kaposi sarcoma (HHV8)
• What is the morphology of rejection mediated by preformed antibodies?
hyperacute rejection => thrombosis, ischemic daamage
and rapid graft failure
• How does acute cellular rejection damage tissue?
• T cells destroy graft parenchyma (and vessels) by cytotoxicity and inflammatory reactions
What do the antibodies in acute humoral rejection target?
graft vasculature
• What sign is a hallmark of chronic rejection?
- arteriosclerosis
* intimal thickening and luminal narrowing
