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Immunopathology Flashcards

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1
Q

Define hypersensitivity

A

Pathologic or excessive, inadequately controlled or inappropriately targeted immunological reaction

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2
Q

Type I Hypersensitivity

A

Immediate type, rapid immunological reaction within minutes after the combination of an antigen with antibody bound to mast cells in individuals previously sensitized to the antigen. Anyphylaxis is systemic T1H (shock, edema, respiratory compromise)

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3
Q

Type II Hypersensitivity

A

Anti-body mediated immunological reaction caused by antibodies against cell surface or extracellular matrix antigens

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4
Q

Type III Hypersensitivity

A

Antibody mediated; damaging inflammatory reaction to antigen-antibody complexes, especially in blood vessels or glomeruli

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5
Q

Type IV Hypersensitivity

A

Cell mediated delayed immunological reaction caused by sensitized CD4 T-lymphocytes, sometimes producing aggregates of activated macrophages working together (granulomas)

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6
Q

Define serology

A

Serum testing for antibodies

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7
Q

Define Lupus

A

Prototype multi-system autoimmune disease with immune complex deposition in kidneys and blood vessels causing glomerulonephritis and vasculitis

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8
Q

Define Sjorgen syndrome

A

Autoimmune chronic inflammatory disease characterized by abnormal accumulation of fibrous tissue in skin and other organs

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9
Q

Define transplant rejection

A

When an organ transplanted from one person to another elicits an immunological rejection of the foreign tissue

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10
Q

Define AIDS

A

Syndrome of opportunistic infections due to deficient cell immunity due to an HIV infection

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11
Q

Define Amyloidosis

A

Group of chronic diseases characterized by progressive organ dysfunction due to the relentless deposition of abnormal insoluble proteins

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12
Q

Anti-cyclic citrullinated peptide (anti-CPP)

A

Rheumatoid arthritis

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13
Q

Anti-centromere

A

CREST syndrome, limited syndrome sclerosis

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14
Q

Anti-Jo-1 (an anti-synthetase)

A

Polymyositis/dermatomyosis

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15
Q

Anti-Scl70 (anti-DNA topoisomerase)

A

Systemic sclerosis, diffuse

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16
Q

Anti-RNA polymerase (anti-U3 RNP)

A

Systemic sclerosis

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17
Q

Anti-U1 RNP

A

mixed connective tissue disease

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18
Q

Anti Smith (Sm)

A

Lupus

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19
Q

Anti-dsDNA

A

Lupus

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20
Q

Anti-Nuclear (ANA)

A

Lupus and many other rheumatic diseases

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21
Q

Anti-SSA (anti-Ro) and Anti-SSB (anti-La)

A

Sjorgen Syndrome, neonatal lupus, subcutaneous lupus

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22
Q

Anti-myelopoeroxidase (perinuclear anti-neutrophil cytoplasmic, P-ANCA)

A

Microscopic polyangitis, eosinophilic granulomatosis with polyangiitis (Churg Strauss)

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23
Q

Anti-proteinase-3 (diffuse cytoplasmic anti-neutrophil cytplasmic, C-ANCA)

A

Granuomatosis with polyangiitis (Wegener’s)

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24
Q

Epidemiology of Lupus?

A

Fairly common, 13x more in women, more in blacks, more in child bearing ages, more severe in blacks and asians

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25
Pathogenesis of Lupus?
Failure of self-tolerance, antinuclear antibodies, genetic factors, environmental factors, immunologic factors
26
Gross Pathology of Lupus?
Non erosive synovitis, pleuritis, pericarditis, Libman-sacks andocarditis, moderate splenomegaly
27
Microscopic pathology of Lupus?
Acute necrotizing vasculitis of small arteries and arterioles, nephritis, cerebritis
28
Symptoms of lupus?
Commonly relapsing and remitting joint pain, fever, fatigue, weight loss, pleuritic chest pain, photosensitivity, nephrotic syndrome (edema), angina, alopecia, myalgias
29
Signs of Lupus?
Erythmatous skin rash over bridge of nose and cheeks and on other sites, edema (feet first), hematuria, neuropsychiatric, oral ulcers, others....
30
How to diagnose lupus?
ANA (present in 100%, but 15% in normal), anti-dsDNA or Anti-SM (more specific), hematologic abnormalities, proteinuria, urinary red cell casts, kidney biopsy
31
Treatment of Lupus?
Corticosteroids and immunosuppressive medications
32
Prognosis of Lupus?
90% 5 yr survival, 80% 10 yr
33
What is keratoconjuctivitis sicca?
Eye involvement of Sjorgen syndrome
34
What is xerostomina?
Oral involvement of Sjorgen syndrome
35
What is the epidemiology of Sjorgen syndrome?
Uncommon, most in 35-45 yr old women, primary less common than secondary
36
Pathogenesis of SS?
T-lymphocyte mediated immunological attack on some self-antigen in ductal epithelial cells of the glands or an antigen in cells in these glands infected by a virus that has a tropism for epithelial cells.
37
Gross pathology of SS?
Dry ocular and oral mucosa, enlarged salivary and lacrimal glands
38
Microscopic pathology of SS?
Intense infiltration of CD4 lymphocytes, destruction of gland architecture, +/- plasma cells, +/- germinal centers. Renal involvement = interstitial nephritis rather than glomerulonephritis
39
Symptoms of SS?
Dry eyes and mouth
40
Signs of SS?
Dry mucous membranes of eyes and mouth, conjunctival ulcers, oral ulcers, enlarged salivary and lacrimal glands
41
Diagnosis of SS?
With Anti-SSA (ro) and/or Anti-SSB (la) antibodies
42
Treatment of SS?
Topical therapy of dry eyes and mouth, systemic cholinergic agents to stimulate secretions, hydroxychloroquine, sometimes rituximab for extraglandular disease
43
Prognosis of SS?
Not too bad, lymphoma develops
44
Epidemiology of systemic sclerosis?
10-20 cases/million/yr, +3x chance in women, highest in 50-60 year olds, most severe in african americans, specifically women
45
Pathogenesis of systemic sclerosis?
Abnormal tissue response and vascular damage lead to increased growth leading to fibrosis. CD4 T cells respond to unidentified antigen stimulating cytokines which make collagen. HLA II and fibrillin I genes involved.
46
Gross pathology of systemic sclerosis?
Skin involved in all cases, edematous areas become fibrotic. Begins in face and fingers, progress proximal. Masklike face and clawlike hands. Fibrous replacement of things (esophagus)
47
Microscopic pathology of systemic sclerosis?
In skin = dense collagen, Perivascular infiltrates of CD4 t cells, thickened capillary/arterial basal lamina.
48
Symptoms of systemic sclerosis?
Raynauds Phenomenon, numbness/tingling/cyanosis of peripheral skin, joint pain and stiffness, digestive problems
49
Signs of systemic sclerosis?
Early signs are edema of hands and feet, later is thickened or hard/shiny skin over long bones. Eventually mask like face and claw like hands
50
Diagnosis of systemic sclerosis?
Suggested by generalized cutaneous sclerosis, hypertension, renal failure, pulmonary hypertension, and fibrosis. Supported by anti-DNA topoisomerase I (anti-Scl70)
51
Treatment of systemic sclerosis?
Non-pharmacologic; exercise, splinting, no cold. Pharmacologic; immunomodulators, antifibrotics, cyclophosphamides, methotrexate, glucocorticoids. Hematopoeietic stem cell transplant (risky)
52
Why is it difficult to diagnose and treat organ transplant?
Varies organ to organ, responses are different in each case, very complex
53
What attacks host organs in GVHD?
Lymphocytes from the donor of a transplant
54
Does GVHD happen earlier or later?
More common early, can happen later
55
What does GVHD lead to in skin?
Generalized erythematous rash which causes fibrosis similar to systemic sclerosis
56
What does GVHD lead to in liver?
Biliary and hepatocytic injury = jaundice and elevated liver transaminases
57
What does GVHD lead to in GI?
Epithelial injury = bloody diarrhea
58
What is the essential feature of x-linked agammaglobulinemia of Bruton?
Congenital immunodeficiency with failure of B cells to produce antibodies (not evident until 6 months old)
59
What is the essential feature of common variable immunodeficiency?
Heterogeneous grop of congenital IMD conditions, featuring hypoammaglobulinemia
60
What is the essential feature of Isolated IgA deficiency?
Lack of serum and secretory IgA, susceptibility to anaphylaxis with blood transfusion
61
What is the essential feature of severe combined IMD?
Group congenital diseases causing both cellular and humeral immunity deficiencies, commonly X-linked
62
What is the essential feature of Wiskott-Aldrich syndrome
Congenital X-linked with IMD, eczema, and thrombocytopenia
63
What is the essential feature of AIDS?
Opportunistic infections, neoplasms, and dementia due to deficient cell immunity from HIV
64
What are the 4 types of amyloidosis? What is different about each?
Primary, secondary, induced, hereditary; The type of protein deposited
65
What is the epidemiology of amyloidosis?
Uncommon, primarily in middle aged and elderly, it can be fatal
66
What is the pathogenesis of amyloidosis?
Abnormal folding of proteins all folded into beta-pleated sheets, immunoglobulin light chains, amyloid A, and transthyretin
67
What does primary amyloidosis usually involve?
Heart, gut, skin, nerves, and tongue
68
What is the protein involved in primary amyloidosis?
AL, most have free light chains in urine (Bence-jones proteins)
69
What does secondary amyloidosis usually involve? And what is it associated with?
Kidney, liver, spleen, lymph nodes, adrenals, and thyroid; Rheumatoid arthritis, inflammatory bowel disease, chronic injection drug abuse, renal cell carcinoma, Hodkin's lymphoma
70
What protein is involved in secondary amyloidosis?
Protein AA, thought to be derived from serum amyloid A
71
What is usually involved with induced amyloidosis?
Nerves, joints, bone, gut, and tongue
72
What protein is involved with induced amyloidosis?
Protein AB2M, light chain of the GLA class 1 histocompatibility surface receptor
73
True of False. hereditary amyloidosis is a single disease.
False
74
What are two examples of hereditary amyloidosis?
Familial mediterranean fever (aa deposition in spleen, kidneys, and adrenals), autosomal recessive in Arabs, Sephardic, Jews, and Armenians Amyloid poly-neuropathy; peripheral autonomic neuropathy due to ATTR deposition; abnormal version of pre albumin carrier for thyroid hormone and retinol. Autosomal dominant in indians, portuguese, japanese, swedish, and jewish
75
What protein is deposited in localized (senile) cardiac amyloidosis?
ATTR in ventricles or AANF in atria
76
What protein is deposited in localized thyroid amyloidosis?
Calcitonin
77
What protein is deposited in cerebral amyloidosis?
Deposition of AB (beta), a degradation product of APP (alzheimers and downs), Deposition of APrP protein in Creutzfelt Jacob disease
78
What protein is deposited in pancreatic amyloidosis (feature of diabetes type II)?
Amyloid in islets of Langerhans
79
What protein is deposited in localized cutaneous amyloidosis?
AL or AA
80
What is the gross pathology of amyloidosis?
Enlarged, firm, waxy organs
81
What is the microscopic pathology of amyloidosis?
Amorphous hyaline eosinohiic material, first in blood vessels/glomeruli then interstitium
82
What are the symptoms of amyloidosis?
Initially nonspecific (weakness/weightloss) then dyspnea, light headnedness, syncope, edema (kidneys)
83
What are some presentations of amyloidosis?
Heart failure (depositions in heart), renal failure (depositions in glomeruli), dementia (in brain)
84
What are the signs of amyloidosis?
Microglossa
85
How do you diagnose amyloidosis?
Biopsy, immunostains
86
How do you treat amyloidosis?
Transplant
87
Whats the prognosis for amyloidosis?
Poor if no transplant
88
True or false. Many people with no apparent rheumatological disease have antibodies associated with rheumatological disease.
True; and they should not be falsely diagnosed on serology alone
89
True or false. Patients with rheumatological disease have syndromes of only one disease at a time.
False, multiple diseases
90
True or false. There is usually a trade off between efficacy and toxicity of medications used to treat autoimmune diseases.
True
91
Is lupus common and protean?
Yes, making it important and difficult
92
What is often the first manifestation of systemic sclerosis?
Puffy fingers (edema)
93
True or False. Transplant patients can only reject or infect, not both.
False, they can have rejection, infection, or both. Some infections are only treatable by reducing immunosuppresson which makes post-transplant management more difficult.

Pathology (6 decks)

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