13 HIV Amyloidosis (starts at amyloid) Flashcards
On standard light microscopy amyloid forms what on H&E?
amorphous pink deposits
The amyloid proteins form 7.5 to 10 nm fibrils arranged in alpha helix or beta sheets?
beta sheets
Does amyloid take up congo red? What happens when polarizing filters are applied?
Yes—conge red stain reveals apple-tree birefringence
What are the 3 types of insoluble fibrils in the chart on amyloid formation?
AL protein
AA protein
ATTR protein
What is the soluble precursor misfiled protein for AL protein?
Immunoglobulin light chains
What is the soluble precursor misfiled protein for AA protein?
SAA protein
What is the soluble precursor misfiled protein for ATTR protein?
Transthyretin
Which precursor of amyloid is due to production of normal amounts of mutant protein?
transthyretin
Which precursor of amyloid is formed by production of abnormal amounts of protein with chronic inflammation?
SAA protein
Which precursor of amyloid is formed by production of abnormal amounts of protein with an unknown or possibly carcinogenic stimulus?
Immunoglobulin light chains
Review the list of secondary causes of amyloidosis-
- Tuberculosis/Leprosy
- Chronic suppuratio
- Rheumatic Diseases
- Ulcerative colitis
- Lymphogranulomatous
- Sarcoidosis
- Regional ileitis
- Malignant tumors/especially kidneys
T-F–almost any organ can be effected with amyloid deposits?
True–remember pictures of heart, shin, flank, tongue, extremely dark black eye.
T-F– amyloidosis is a consideration in only 2 diagnostic differentials?
False--multiple diagnostic differentials [Review the List] -Neuropathy, sensory -nephrotic syndrome -heart failure and arrhythmias -malabsorption -organomegaly -carpal tunnel syndrome -intracerebral hemorrhage -bleeding disorders
What are the 6 classic primary immunodeficiency diseases we need to know?
- severe combined immunodeficiency SCID
- Immunodeficiency with Hyper IgM
- Common Variable Immunodeficiency CVID
- X linked agammaglobulinemia (Bruton’s)
- Selective IgA deficiency
- DiGeorge Syndrome
Infections that are unexpected, too frequent, too severe, or abnormally persistent suggest what?
immunodeficiency
Opportunistic infections in patients without known risk factors?
immunodeficiency
T-F –typical autoimmunity is a reason to suspect immunodeficiency?
False–atypical
What does unexplained lymphadenopathy or splenomegaly suggest?
immunodeficiency
Atypical presentations of hematopoietic malignancies suggest?
immunodeficiency
What type of inflammation and fever might suggest immunodeficiency?
recurrent unexplained
Does a family history of any factors of immunodeficiency suggest immunodeficiency in that person?
Yes [any factors suggesting immunodeficiency in combination with developmental abnormalities also makes it stronger]
Humoral immune deficiency has what 3 strong clinical characteristics?
- recurrent infections with extracellular encapsulated bacterial pathogens
- Recurrent sinopulmonary disease
- Few fungal or viral infections, giardiasis
T-F–humoral immune deficiency may or may not lack B cells?
True
T-F humoral immune deficiency usually has striking growth retardation?
False
What are 3 strong clinical characteristics of cellular immune deficiency?
- Recurrent infections with low grade opportunistic agents like fungi, virus or pneumocystis
- Near fatal reactions to live virus vaccines or BCG
- Susceptibility to graft-versus host disease
T-F– cellular immune deficiency is commonly accompanied by growth retardation, wasting, diarrhea?
True
T-F– cellular immune deficiency has an increased incidence of malignancy?
True
Are there tons of new immune deficiencies identified every year?
Yes…15 in the last 2 years
According to the 2009 IUIS update, how many categories of primary immune deficiencies are there?
8 [Just to review]
- combined
- defined syndromes
- predominantly antibody
- immune dysregulation
- congenital defects of phagocytes
- defects in innate immunity
- autoinflammatory
- complement
What is the most common SCID severe combined immune deficiencies?
x linked recessive-50%
[autosomal recessive SCID is also a popular one]
In x linked recessive SCID, what is the defect?
common gamma chain shared by a bunch of IL receptors
[IL-2,4,7,9,15]
The absence of which IL receptor may be most critical in SCID> why?
IL-7- essential for the proliferation of lymphocyte precursors
A deficiency in what protein which transducer signals from the common cytokine receptor gamma chain can also produce autosomal recessive SCID?
Janus Kinase 3 JAK3
What is the most common cause of autosomal recessive SCID?
deficiency in adenosine deaminase
In the less severe combined deficiencies, either due to the CD40L (XLR) and CD40 (AR) what is seen among the B-cells?
They are present. IgM is increased. IgG, IgA, and IgE are absent because there is not class switching.
What type of infections are seen in Hyper IgM combined deficiencies?
Opportunistic infections, autoimmune cytopenias, gastrointestinal disease
What are the 2 defined syndromes with immunodeficiency?
DiGeorge
Wiskott-Aldrich
What syndrome with immunodeficiency is caused by defective thymic development? Which type of T cells are most depressed?
DiGeorges
CD8 cells are usually most depressed
Severe for of Di georges clinical spectrum is embraced by what acronym? Where is the micro deletion?
Catch 22 (22q11.1-22q11.2) cardiac abnormal faces thymic hypoplasia cleft palate hypocalcemia
What syndrome with deficiency is described as T cells progressively declining, IgM down and IgA and IgE are up?
Wiskott-Aldrich Syndrome
What are the causes of death for wiskott-aldrich syndrome?
infection, hemorrhage and lymphoid neoplasms
What type of response to polysaccharide antigens is found in wiskott-aldrich syndrome?
defective response
What chromosome contains the wiskott-aldrich syndrome? what other syndrome is mutated on the same gene?
x chromosome
x-linked thrombocytopenia
What are the cellular effects of the gene from wiskott-aldrich syndrome? Does the mutation in it exhibited phenotypic variation?
actin polymerization and signal transduction
yes, significant phenotypic variation
A severe decrease in Ig and B cell numbers suggests which disease?
x linked recessive agammaglobulinemia (Brutons)
[tyrosine kinase mutation]
A severe decrease in Ig and variable B cell numbers suggests what disease?
common variable immunodeficiency
Selective immunoglobulin deficiency and normal B cells?
Selective IgA deficiency
What are the 4 characteristics of Bruton’s agammaglobulinemia?
- B cells and Ig decreased
- Infections usually by 8-9 months, heterogenous
- Organisms: pyogenic bacteria, enterovirus, Giardia lamblia
- defect encodes cytoplasmic tyrosine kinase (btk)
What type of bacterial infections happen in common variable immunodeficiency?
recurrent pyogenic [also, enterovirus, herpes, G lamblia]
What type of deficiency do relatives of people with common variable immunodeficiency have? If you want to review…what are the mutations?
IgA deficiency
[mutations=TACL, BAFF-R, CD19, ICOS]
What is the most common immunodeficiency in people of european origin? Most individuals are asymptomatic or symptomatic?
IgA
asymptomatic, some have bacterial infections
What can occur in IgA deficiency people when exposed to IgA?
anaphylaxis
T-F–there are familial associations between IgA deficiency and CVID?
True…mutations of both diseases are sometimes found in the TACI gene.
What disease is defined by defect in Tcell apoptosis and deletion?
Autoimmune lymphoproliferative syndrome [can be autosomal dominant or recessive]
What cellular effect is caused by autosomal recessive autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy APECED?
Defect in T cell deletion in the thymus
What is the defect of IPEX immune dysregulation polyendocrinopathy enteropathy x linked?
defect of immunoregulatory T cells
What disease is a defective respiratory burst with infections with organisms such as catalase positive staph
chronic granulomatous disease CGD
What disorder has delayed cord separation, infection and leukocytosis?
LAD leukocyte adhesion deficiency
What infections are commonly seen with gamma interferon disorders?
mycobacteria and salmonella
Defects of innate immunity [that lead to bacterial, mycobacterial, viral, papillomavirus, and herpes simplex] are caused by defects/mutations in what 3 main areas?
-modulation of NFkB
-mutation of TLRs
-Mutation of chemokine receptors
[and the signaling pathways with these proteins]
The disordered production of IL1B and its closely related antagonist IL1RN are associated with what kind of disorder ?[what are some of the symptoms for review]?
Autoinflammatory disorders
[recurrent fevers, serositis, cold urticaria, uneitis, hearing loss, arthritis, aseptic meningitis, osteomyelitis, inflammatory skin rashes and bowel disease, AMYLOIDOSIS]
Early component complement deficiency (C1q and C1r and C4) lead to what diseases?
SLE-like syndrome
rheumatoid-like disease
LAter component complement deficiency (C5, 6, 7, 8a, 8b, and 9) lead to what diseases
neisserial infections and SLE-like disorders
C1 esterase inhibiotr deficiency leads to what disease?
angioedema
CD55 and CD59 deficiency leads to what disease?
acquired paroxysmal nocturnal hemoglobinuria
Ebstein barr virus is a common diagnosis reflex for what PID?
XLR lymphoproliferative disorder
Papilloma and HSV is a common PID diagnostic reflex for what disorder?
gamma IFN
opportunistic infections in infants is a sign of what PID diagnosis? older children?
SCID
CD40/CD40L
Common bacterial repeated infections is a PID diagnostic reflex for what?
XLA and CVID
REVIEW THE GENERAL PID DIAGNOSTIC REFLEXES
autoimmunity allergies/anaphylaxis lymphadenopathy/splenomegaly development abnormalities graft vs. host radiation sensitivity *fever without infection *inflammation without infection
