Immunopathology (Word Doc) Flashcards
(136 cards)
1
Q
What type of hypersensitivity? Occurs rapidly (minutes)
A
I
2
Q
What type of hypersensitivity?
Delayed reaction
A
IV
3
Q
What type of hypersensitivity?
Ab react against cell-surface or extracellular antigens
A
II
4
Q
What type of hypersensitivity?
Occurs in individuals previously sensitized to antigen
A
I
5
Q
What type of hypersensitivity?
mediated by immuno reaction to Ab:Ag complexes
A
III
6
Q
What type of hypersensitivity?
Affects the glomeruli
A
III
7
Q
What type of hypersensitivity?
Caused by sensitized CD4 T cells
A
IV
8
Q
What type of hypersensitivity?
May produce granulomas
A
IV
9
Q
Primary associated disease?
Anti-Scl70 (an anti-DNA topoisomerase)
A
Systemic sclerosis, diffuse
10
Q
Primary associated disease?
Anti-U1 RNP
(anti-RNP not otherwise specified)
A
Mixed connective tissue disease
11
Q
Primary associated disease?
Anti-cyclic citrullinated peptide (anti-CCP)
A
Rheumatoid arthritis
12
Q
Primary associated disease?
Anti-RNA polymerase (anti-U3 RNP)
A
Systemic sclerosis
13
Q
Primary associated disease?
Anti-centromere
A
CREST syndrome
limited systemic sclerosis
14
Q
Primary associated diseases (3)?
Anti-SSB (anti-La)
A
Sjogren syndrome
Neonatal lupus
Subcutaneous lupus
15
Q
Primary associated diseases (2)?
Anti-Jo-1
A
Polymyositis
dermatomyositis
16
Q
Primary associated disease?
Anti-nuclear (ANA)
A
Lupus
and many other rheumatic diseases
17
Q
Primary associated disease?
Anti-Smith (anti-Sm)
A
Lupus
18
Q
Primary associated diseases (3)?
Anti-SSA (anti-Ro)
A
Sjogren syndrome
Neonatal lupus
Subcutaneous lupus
19
Q
Primary associated disease?
Anti-double-stranded DNA (anti-dsDNA)
A
Lupus
20
Q
Primary associated disease?
Anti-myeloperoxidase
A
- Microscopic polyangiitis
2. Eosinophilic granulomatosis with polyangiitis (Churg Strauss)
21
Q
Primary associated disease?
Anti-proteinase-3
A
Granulomatosis with polyangiitis (Wegener’s)
22
Q
Common testing used in diagnosis of many rheumatological diseases?
A
Serology (antibody testing)
23
Q
T/f: Finding the antibody in the patient’s serum is the main diagnostic goal–determining the Ab is determining the disease.
A
F: Finding these antibodies by no means makes the diagnosis of disease. That requires what is called “clinical-pathologic correlation”. This is because many normal people have these antibodies without these diseases.
24
Q
T?F: It is common for people with one autoimmune disease to have other, overlapping diseases as well.
A
T
“many patients with autoimmune/rheumatological disease do not have clinical or pathologic manifestations limited to one single specific disease. Man have overlapping syndromes with features of more than one autoimmune disease.”
25
Patients with autoimmune diseases or transplantation are treated with:
immunosuppressive therapy
26
Common immunologic treatment that is also anti-inflammatory
corticosteroids
27
Two medications that treat immune diseases (and transplant rejection) via calcineurin inhibition:
Cyclosporine and tacrolimus
28
How does Calcineurin function in a normal lymphocyte?
1. Calcineurin dephosphorylates "intracytoplasmic nuclear regulatory proteins"
2. These regulatory proteins translocate into the nucleus, then become activated "intranuclear factors"
```
3. Once activated: promote T lymphocyte activation and secretion of:
TNF
IFN-gamma
IL-2
IL-4
```
29
Blocking calcineurin ultimately blocks:
T cell activation and secretion of signaling molecules (TNF, IFN-g. IL2, IL4)
30
Mycophenolate is used to treat what specific autoimmune disease?
systemic lupus erythematosus
31
How does Mycophenolate mofetil inhibit lymphocyte proliferation?
1. Inhibits purine biosynthesis, which:
2. Inhibits DNA replication, thus:
3. Preventing lymphocyte proliferation
32
Two drugs used to treat rheumatoid arthritis and systemic lupus erythematosus?
Azathioprine
| Hydroxychloroquine
33
Purine analog; Screws up DNA replication.
Azathioprine
34
This low-toxicity antibiotic happens to be anti-inflammatory.
Hydroxychloroquine
35
3 drugs that block TNF-alpha
infliximab
etanercept (Enbrel)
adalimumab (Humira)
(do we actually need to memorize this? Grrrr I doubt I will remember it even if I try)
36
This drug is an antibody to CD20 on B lymphocytes
Rituximab
37
This drug is an antibody to B-cell activating factor
Belimumab
38
This drug is an antibody that blocks IL-6 receptors
Tocilizumab
39
This drug is an antibody to CD52
Alemtuzumab
40
This drug decreases the incidence of transplant rejection and increases the risk of opportunistic infection; creates a permanent AIDs-like effect.
Alemtuzumab
(help me understand why anyone would take this?? no idea, I guess if you kill CD4 cells you stop transplant rejection, but then you just gave yourself AIDS. Id like to hear that commercial... Do not take Alemtuzumab on an empty stomach. All patients experience AIDS after taking this medication....)
41
What cells express CD52?
high levels:
-normal and malignant B + T lymphocytes
lower levels:
- monocytes
- macrophages
- eosinophils
42
6 gross pathological findings in Lupus (SLE)
1. synovitis
2. pleuritis
3. pericarditis
4. peritonitis
5. endocarditis (with vegitations on either side of valve)
6. moderate splenomegaly
43
Lupus is most common in what population?
Women, black, 15-45
| will be more severe in black/asian
44
5 things that cause Lupus:
| 2 specific, 3 broad
1. failure of self-tolerance
2. antinuclear antibodies
3. genetic factors
4. environmental factors (UV)
5. Immuno factors
45
What microscopic pathological feature implies active Lupus?
IgG:complement deposits in the glomerulus (this causes "wire-loop" lesions; most common in diffuse proliferative nephritis)
46
Microscopic Pathology of Lupus:
1. acute necrotizing vasculitis of small arteries and arterioles
2. nephritis (50%)
3. cerebritis (50%)
47
5 patterns of glomerulonephritis seen in Lupus:
1. minimal
2. mesangial
3. focal proliferative
4. diffuse proliferative
5. membranous
48
Major Lupus symptoms: (9 listed)
```
Most common:
joint pain
fever (sometimes of unknown origin)
fatigue
weight loss
```
```
Also:
pleuritic CP
photosensitivity
nephrotic syndrome
angina
hair loss
```
49
What common symptom of Lupus may lead to edema?
Nephrotic syndrome
50
Signs of Lupus: (8)
1. erythematous skin rash over bridge of nose and cheeks + other sites
2. edema (first in feet)
3. hematuria (usually only microscopic)
4. neuropsychiatric (psychosis, seizures)
5. oral ulcers
6. interarticular skin rash on fingers
7. peri-ungual erythema around fingernails
8. alopecia
51
Diagnosis of Lupus: (6)
1. ANA (present in 100%, also ~15% of normals)
2. anti-double-stranded DNA or anti-Sm Ab
3. hematologic abnormalities (anemia, thrombocytopenia, etc.)
4. proteinuria
5. urinary red cell casts
6. kidney biopsy
52
Treatment for Lupus: (2)
corticosteroids and immunosuppressive medications
53
Sjogren syndrome
Autoimmune chronic inflammatory disease of lacrimal glands and salivary glands, causing dry eyes and dry mouth
54
What is the term for eye problems associated with Sjogren syndrome?
kerato-conjunctivitis sicca
55
What is the term for oral problems associated with Sjogren syndrome?
xerostomia
56
Primary form of Sjogren syndrome.
limited to eyes and mouth, also called sicca syndrome
57
Secondary form of Sjogren syndrome.
Associated with other autoimmune diseases
- rheumatoid arthritis (most common)
- lupus
- polymyositis
- systemic sclerosis
- vasculitis
- thyroiditis
58
Sjogren syndrome is most common in what population?
35-45 year-old women
59
Causes of Sjogren's Syndrome (2)
1. T cell attacks self antigen in the ductal epithelial cells
2. T cells attack an antigen in glands that are virally-infected (by virus that is specific for the epithelial cells in the lacrimal/salivary glands)
60
Gross pathology of Sjogren's Syndrome:
- dry ocular and oral mucosa
| - enlarged salivary and lacrimal glands.
61
Microscopic pathology of Sjogren's Syndrome:
intense infiltration of CD4 T lymphocytes
destruction of gland architecture
+/- plasma cells, +/- germinal centers
(what does this mean?)
Renal involvement: interstitial nephritis
62
Signs of Sjogren's Syndrome:
- dry mucous membranes of eyes/mouth
- conjunctival/oral ulcers
- enlarged salivary/lacrimal glands
63
Diagnosis of Sjogren's Syndrome:
anti-SSA or anti-SSB Ab
64
Treatment of Sjogren's Syndrome:
- -Topical therapy: eyes, mouth and other dry mucosal surfaces
- -Systemic cholinergic agents to stimulate secretions
- -Hydroxychloroquine
- -Sometimes rituximab for extraglandular disease
65
What condition do people with Sjogren's Syndrome often develop?
lymphoma
66
Systemic sclerosis
Chronic disease with abnormal accumulation of fibrous tissue in skin and other organs
67
Early visceral involvement is characteristic of ____ systemic sclerosis.
diffuse
68
Late visceral involvement is characteristic of ____ systemic sclerosis.
limited
69
Involvement of the skin of fingers, forearms and face is characteristic of ____ systemic sclerosis.
Limited
70
Widespread skin involvement is characteristic of ____ systemic sclerosis.
diffuse
71
What causes the increased growth factors characteristic of Systemic sclerosis?
increased growth factors (leading to fibrosis) are caused by:
1. abnormal immune response
2. vascular damage
72
Genes (2) involved in systemic sclerosis.
HLA-II and fibrillin-1
73
T/F: Cytokines produced by CD4 T cells stimulate fibroblasts.
T (the fibroblasts then secrete collagen)
74
What is involved in the microvascular disease associated with systemic sclerosis?
1. Intimal proliferation
2. capillary dilatation
3. endothelial injury (increased vWF) + platelet activation leads to fibrosis
75
In systemic sclerosis, skin is initially _____ and ultimately ______.
edematous; fibrotic
76
In systemic sclerosis, what is the characteristic gross skin pathology?
Decreased mobility = mask-like face and clawlike hands
77
In systemic sclerosis, what is the characteristic gross GI pathology?
- -Fibrous replacement of muscular wall (often in esophagus)
- -Lower esophageal sphincter dysfunction
- -Decreased peristalsis (causing GERD and Barrett metaplasia)
78
In systemic sclerosis, what is the characteristic microscopic skin pathology?
- Dense collagen deposition in dermis with decreased appendages
- Thinning of epidermis
- Loss of rete pegs
- Perivascular infiltrates of CD4 T-cells
- Thickening of capillary/arterial basal lamina
79
In systemic sclerosis, what is the characteristic microscopic lung pathology?
Vascular changes promote:
- pulmonary hypertension
- interstitial fibrosis
80
In systemic sclerosis, what is the characteristic microscopic kidney pathology?
Vascular changes promote:
- hypertension
- renal failure
Intimal thickening of interlobular arteries leads to:
- ischemia
- infarction
81
Symptoms of systemic sclerosis:
Raynaud’s phenomenon (Numbness, tingling, cyanosis of peripheral skin)
Joint pain and / or stiffness.
Digestive problems secondary to decreased gut motility
82
Signs of systemic sclerosis:
Early: edema of the hands and feet (most prominent in the morning)
Later: thickened, hard and / or shiny skin
83
In the serology of patients with systemic sclerosis (diffuse vs limited?):
Diffuse:
Anti-DNA topoisomerase I aka Anti-Scl70
Anti-U3 RNP
Limited:
Anti-centromere
Anti-U3 RNP
84
Diagnosis of systemic sclerosis suggested by:
```
generalized cutaneous sclerosis
hypertension
renal failure
pulmonary hypertension
fibrosis
```
85
Non-pharmacologic treatment of systemic sclerosis:
Exercise, splinting, avoiding cold
86
Pharmacologic treatment and procedures of systemic sclerosis: (6)
```
Immunomodulators
antifibrotics
cyclophosphamide
methotrexate
glucocorticoids
Hematopoietic stem cell transplantation
```
87
Puffy fingers are a sign of what disease?
systemic sclerosis
88
Hyperacute rejection is characterized by ...
high titers of preformed Abs
89
Histologically, how does a transplanted kidney damaged by immunosuppressant drugs differ from a transplanted kidney damaged by host rejection?
Drug: vacuolization, calcification, and giant mitochondria
rejection: lymphocytes
90
What is polyomavirus nephropathy?
caused by BK virus and causes formation of inclusion bodies and epithelial cell injury and lysis
91
T or F: Transplant pts can have simultaneous infection and rejection
T
92
What is PLTD?
post-transplant lymphoproliferative disorder: proliferation of lymphocytes to full blown malignant lymphoma
93
The proliferative cells in PLTD have normally been infected with _____ which is "awaken" by _____
Epstein-Barr virus and is awaken by immunosuppressants
94
Bc cells from a transplanted organs leave the transplanted organ and take up residence elsewhere in the body, every transplant recipient is considered to be a ______. What type of cell most commonly leaves the transplant?
chimera; T lymphocyte --> GVHD
95
What 2 organs are especially attacked during GVHD?
skin and GI tract
96
GVHD in the skin causes _____
generalized erythematous rash which goes on to cause fibrosis
97
GVHD in the GI tract usually clinically manifests as _______
bloody diarrhea
98
All cells that are attacked in GVHD die via ...
apoptosis
99
Congenital immunodeficiency with B cells unable to make Abs and is not evident until 6 mos of age
XLA from Btk deficiency
100
What is a common feature of common variable immunodeficiency?
hypogammaglobulinemia
* diff than XLA bc it affects men and women equally and has a much later onset (20s-30s)
* not a SCID bc T cell # are fine
101
What does isolated IgA deficiency leave an individual susceptible to?
susceptible to anaphylaxis with blood transfusion
Why?????? Nichols be cray
102
Deficiency in both cellular AND humoral immunity
SCID
103
What is a congenital X linked disorder with immunodeficiency, eczema, and thrombocytopenia?
Wiskott-Aldrich syndrome
104
What is AIDS?
syndrome of opportunistic infections, neoplasms, and dementia due to deficient cellular immunity (from HIV infection)
105
What is amyloidosis?
progressive organ disfunction due to deposition of insoluble proteins in blood vessels and interstitium
106
What are the 4 categories of systemic amyloidosis?
primary
secondary
induced
hereditary
107
What is the epidemiology of amyloidosis?
- late middle aged and elderly
- primary or secondary tp another disease
- 3200 new cases a year
108
What is the common characteristic of proteins involved in the pathogenesis of amyloidosis?
they are beta pleated sheets
109
What are Bence-Jones proteins?
aggregates of light chain Ig
110
Amyloidosis with amyloid A is often secondary to ______
RA or chronic infalmmation
111
What organs does primary amyloidosis most often involve?
heart, gut, skin, nerves, and tongue
112
What is the protein that is deposited during primary amyloidosis?
AL (amyloid light chains... 1/3 kappa and 2/3 lambda)
113
Some pts with amyloidosis have multiple myeloma but only __% with multiple myeloma have amyloidosis?
10
114
Where is AL protein found?
urine and/or serum
115
What organs does secondary amyloidosis tend to involve?
kidneys, liver, spleen, lymph nodes, adrenals, and thyroid
116
With what syndromes is secondary amyloidosis assoc with?
RA, IBS, IV drug abuse, renal cell carcinoma, and Hodgkin's disease
117
What protein is deposited with secondary amyloidosis?
AA
118
What is AA thought to be derived from ?
SAA (acute phase reactant) which circulates in HDL
119
What organs does induced amyloidosis tend to involve?
nerves, joints, bone, gut, tongue
120
What protein is deposited in induced amyloidosis?
AB2M (Beta-2-microglobin) (= light chain of MHC I)
121
What is the cause of induced amyloidosis?
dialysis treatment is not able to filter out AB2M
122
What is hereditary amyloidosis?
a variety of mediterranean fever
123
What signs and symptoms are assc with hereditary amyloidosis?
fever, peritonitits, pleuritis, synovitis
124
What protein is deposited in hereditary amyloidosis? And Where?
AA --> liver, spleen, kidney and adrenal
| ATTR (amyloid transthyretin) --> affects peripheral and autonomic nerves
125
Localized cardiac amyloidosis involves the deposition of ....
ATTR in ventricles or AANF in atria
126
Localized cerebral amyloidosis involves the deposition of ....
AB (degradation product of APP in Alzheimer's and Down Syndrome
127
Localized thyroid amyloidosis involves the deposition of ....
calcitonin (medullary carcinoma)
128
Localized pancreatic amyloidosis involves the deposition of ....
amyloid in islets (type II DM)
129
What is the minor protein deposited in all of these amyloid disorders (except Alzheimer's)?
AP (amyloid P)
130
What is the gross pathology of amyloidosis of an organ?
enlarged and waxy
131
Describe the microscopic morphology of amyloidosis.
- hyaline eosinophillic materian in blood vessels, glomeruli , then interstitium
- stains red with "Congo red" and apple green bifringence under polarized light
132
What are the symptoms of amyloidosis?
nonspecific --> dyspnea --> light-headedness --> syncope (heart) --> edema (kidneys)
heart failure, renal failure, dementia, liver failure, neuropathy
133
What are the signs of amyloidosis?
macroglossia (enlarged tongue)
134
How is amyloidosis diagnosed?
biopsy showing extracellular deposit of hyaline that stains red with Congo red stain and shows apple green bifringence under polarized light
135
What is the treatment for amyloidosis?
transplant
136
What is the prognosis of amyloidosis?
poor without transplantation
