Primary immunodeficiencies + Pathology Flashcards
Mutation in BTK gene gives rise to___
X linked Agammaglobulinemia (aka Bruton’s agammaglobulinemia)
The most common bacterial infections you’ll see with antibody deficiency are Strept. pneumo, __- and ___
S. pneumo, H. flu, S. aureus, N. meninigitidis
(note that you can be infected with pretty much any bug)
The most common viral and protozoan infections ass’d w/ Ab deficiency are ___ and ___
Enterovirus (e.g. poliovirus)
Giardia lamblia
The most common immunodeficiency in adults is ___ which is mainly due to sporadic mutations in genes involved in B cell activation and maturation. The disorder typically presents with sinopulmonary infections, some resulting in bronchiectasis
Common Variable Immunodeficiency
What’s one disease that can be misdiagnosed as Common Variable Immunodeficiency and is the reason why you can’t Dx a kid as having CVID until 4 yoa?
Transient hypogammaglobulinemia of infancy
Basically these kids get a similar presentation of recurrent infections at about 6 months of age, but they actually have good IgA and IgM amounts (normal or low-normal) and they have decent vaccine titers. So really their IgG is low because its just taking a while to kick in and their IgG levels are normal by the time they are 4 yo
So basically don’t Dx CVID until at least 4 yo for this reason
The most common primary immunodeficiency (period) is ___
IgA deficiency (super low or absent IgA)
**note that you also don’t Dx this disease until 4yoa**
The most common type of SCID is ___ and this results from ___
X-linked SCID
Mutation in the common gamma chain (recall that this is the receptor for IL2, 4, 7, 9, 15, 21)
The autosomal recessive form of SCID is due to ____
Adenosine Deaminase Deficiency
Other forms of SCID include:
___, which has a similar phenotype as ADA deficiency, but milder and doesn’t involve B cells
___, which involves signaling by the gc cytokine receptor chain and has imilar clinical phenotype as X-linked SCID
___, which is failure to express class II major histocompatibility complex (MHC) >> no CD4 helper T cells (CD8 normal)
The most common of type of Hyper IgM syndrome is ___, resulting from a deficiency of CD40L on T cells
X linked Hyper IgM syndrome
Autosomal recessive HyperIgM syndrome results from ___
Deficiency of CD40 on B cells
___ is an X-linked recessive disorder resulting from a mutation in the WASP gene that is important for regulating the actin cytoskeleton of lymphocytes
Wiskott-Aldrich Syndrome (WAS)
____ is an autosomal recessive disorder that results from a mutation in the ATM gene and is characterized by a triad of telangiectasias, neurological issues, and variable immune isses
Ataxia telangiectasia
___ is a very rare autosomal dominant (most common) disorder resulting from a mutation in the STAT3 gene that leads to Th17 cell differentiation. The defect leads to impaired mucosal and epithelial immunity to Staph aureus or Candia sp
Hyper IgE syndrome
___ is a disorder resulting from NADPH oxidase deficiency. Hallmarks of this disease are the frequent occurence of abscesses all over the body and infection with catalase positive organisms (namely Stap, Burkholderia, Serratia, Aspergillus and Nocardia)
Chronic Granulomatous Disease
The uncontrolled stimulation of thyroid epithelial cells in Graves Disease leads to 3 changes, namely
- Hypercellularity.
- Papillae formation (because more interface between the cells and the colloid.
- Scalloped margins of the colloid, leaving empty spaces in the areas of the rapidly resorbed thyroglobulin.
Who disease this is?
Graves disease
Notice those #scalloped margins
Which disease is indicated by the pathology? (mononuclear cell infiltrate with well defined germinal centers)
Hashimoto’s thyroiditis
The cells indicated with the red arrows are called ___ and are indicative of glandular atrophy in Hashimoto’s thyroiditis
Hurthle cells
A ___ is mass of fibroblastic, vascular and inflammatory cells driven by the action of IL1 and TNFa which drive the secretion of prostaglandins, proteolytic enyzmes
Pannus (“inflammed joints”)
The image below is characteristic of which disease?
Rheumatoid arthritis
___ are extra-auricular lesions that are also characteristic of Rheumatoid Arthritis
Rheumatoid nodules
**Rheumatoid nodules are extra-articular (as in not in the joints) but they’re essentially the same as the pannus. These nodules form in areas like the elbow that are easily susceptible to stress**
The pathology indicated is characteristic of which disease?
In the rheumatoid nodule, there’s a central zone of fibrinoid necrosis surrounded by inflammatory cells
**RA**
2 hallmarks of rheumatoid arthritis are the presence of __ and __
Pannus (within a joint)
Rheumatoid nodule (in soft tissues outside joints)
3 characteristic features of SLE are ___
Malar rash
Small vessel vasculitis
Lupus nephritis
Where in the body do the immune complexes formed in lupus deposit?
In lupus, recall that there are antibodies against various antigens (mostly nuclear antigens) that form complexes with these antigens and deposit in blood vessels, kidneys, skin (hence the rash) and so on. Basically, wherever is hemodynamically favorable
Immune flourescence for Lupus is characterized what type of flourescence?
Full house flourescence
Below is an example of which disease? Describe the pathology indicated by the arrow
Lupus (nephritis)
Wire loops
Severe glomerulonephritis would show what kind of histopathology?
These loops become leaky and allow proteins to leak into the Bowman’s space, which forms #crescents
(indicated by the white stars)
The “wire loops” formed in Lupus are caused by___
The staining here is ___ because the deposits are everywhere in the basement membrane
Granular
Deposition of immune complexes in the subendothelium
What are the two types of proliferative glomerulonephritis in lupus?
Intracapillary and extracapillary
What is the difference between intra-capillary and extra-capillary proliferative glomerulonephritis?
Intracapillary proliferation: the glomerulus of the lupus patient has tons of lymphocytes/inflammatory cells; Extra-capillary proliferation is happening outside, in the Bowman’s space
Both will usually occur together. The intra version is always there, whereas extra version shows up when you have more severe nephritis
The hallmarks of Lupus are ___
Malar rash
Wire loops in the glomerulus due to subendothelial deposition of immune complexes
Intra and extra capillary proliferation of inflammatory cells and lymphocytes
Irregular and GRANULAR immune fluorescence
The image below is characteristic of which disease?
Goodpasture (pulmonary hemorrhage)
____ is also characteristic of Goodpasture disease. The presence of ___ indicates severity
Severe necrotizing glomerulonephritis
Crescents
What type of immunefluorescence would you get in Goodpasture disease? (hint: opposite of lupus)
In Goodpasture disease, the auto antibodies are deposited in a specific place (i.e. the basement membrane of the glomerulus and the lungs), whereas in lupus, the antibodies are just depositing everywhere and not settling in one place. Hence linear and smooth immunofluorescence with GP disease, vs granular and irregular fluorescence with Lupus
**Linear fluorescence that is NOT full house**
The hallmarks of Goodpasture disease are___
Linear immunofluorescence
Pulmonary hemorrhage
Glomerulonephritis (w/ crescents if severe)
What are the types of allograft rejection?
Hyperacute
Acute
Chronic
What are the subtypes of allograft rejection?
Which one of these is accompanied by specific changes in the chronic rejection?
Antibody mediated rejection
T cell mediated rejection
Mix of both
There are chronic changes that apply only to antibody mediated rejection
In terms of rejection, there are 4 main targets:
Small vessels (glomeruli and peritubular capillaries)
Large vessels (usually arteries)
Renal tubules
And the interstitium
The hallmarks for antibody mediated rejection are
Microvascular injury (Glomerulitis or peritubular capillaritis) and/or thrombosis
*Glomerulitis – filling of glomerulus with neutrophils (again, antibody mediated rejection)*
*Peritubular capillaritis- you have neutrophils surrounding the peritubular capillaries*
___ is the activated part of C4 (from #complement) that stays bound in the tissues where it is activated so you can use it in immune staining to determine Ab mediated rejection
C4d
The 3 diagnostic criteria for ACUTE antibody mediated rejection that all have to be met include:
Microvascular injury
C4d linear deposition in peritubular capillaries
Presence of circulating donor specific antigen
Contrary to antibody mediated rejection, T cell mediated rejection is characterized by
Tubulitis (again, this is for ACUTE T cell mediated rejection)
Which type of rejection is indicated in the diagram below?
T cell mediated rejection (you can see lymphocytes infiltrating into the tubules)
T/F: Endarteritis is also Dx of T cell mediated rejection
Nah. More severe phenotype but not really Dx
**endarteritis - infiltration of the intima by T Cells**
Chronic antibody mediated rejection is characterized by ___
Peritubular capillary basement membrane multilayering: the glomerulus becomes multiplied so instead of having one layer you have several
The antibodies mainly attack endothelial cells which when attacked, will make a new layer so basically you got #stacks (of membranes tho, not money dollars unfortunately)
**remember double contours** for CHRONIC ANTIBODY MEDIATED REJECTION
What is IFTA and what state of rejection does it indicate?
Interstitial fibrosis/tubular atrophy
Chronic rejection (irreversible, NON specific change)
Describe the pathology below
IFTA
Instead of having renal tubules back to back, you have the tubules spaced out and there’s a lot of fibrosis in between
