I2 Diseases Flashcards
• Mutation in Bruton Tyrosine Kinase (BTK)
○ Required for B cell to become plasma cell
○ Autoimmunity:
• BTK required in signaling in central tolerance.. When you don’t get negative signals you produce self-recognition
X-Linked Agammaglobulinemia
Inhibits antigen presentation Inhibits proteasomal activity
Removal of MHC I molecules from ER. Degrades NKG2D on NK cells.
CMV (cytomegalovirus)
CATCH-22. Developmental failure of the 3rd & 4th pharyngeal pouches. T-/B+/NK+
DiGeorge Syndrome
IgG autohemolysin binds RBCs @ low temps
Causes intravascular hemolysis after warming
Autoimmune hemolytic anemia
Defective VDJ recombination results in low lymphocyte numbers (b/c can’t get out of primary lymphoid organs) Mutations in a DNA repair enzyme. Gait abnormalities. IgA deficiency and cerebellar problems leading to ataxia and, in this case, multiple falls
Ataxia-Telangiectasia (ATM)
Defective resistance or abnormal responses to intestinal microbes. Defective NOD signaling pathway.
Chron’s disease
Chronic mast cell activation with increased mucous secretion and bronchoconstriction. Eosinophil recruitment which can initiate damage to mucosal epithelium
Allergic Asthma
Found in Central and Southeastern US. Dimorphic fungi that is a granulomatous disease.
Blastomyces dermatitidus
Howell-Jolly bodies and loss of IgM and T-independent response. Susceptibility to encapsulated bacteria
Asplenia
CD18 deficiency leading to poor neutrophil adhesion and poor opsonophagocytosis.
LAD-1
Disease results from: 1. CD4+ T cells & ANAs 2. Vascular damage Fibrosis A. 2 ANAs: 1. DNA topoisomerase 1 Ab = AKA Scl-70 Anticentromere Ab
Scleroderma
Pathogenesis MOA:
- Main players: Th1 & macrophages
- Infection proceeds from initial infection of macrophages to a Th1 response that both contains the bacteria & causes tissue damage
- Process:
1. Bacteria uptake by macrophages
2. Blockage of phagolysosomal fusion
3. TB PAMPs recognized by innate receptors, initiating a Th1 response
4. Th1 cells produce IFN-y
IFN-y = the critical mediator that enables macrophages to contain the TB infection
Tuberculosis
• Disease causes release of cytotoxic enzymes leading to widespread keratinocyte cell deal w/ blistering & sloughing of the skin
• Majorly involved molecules:
1. CD8+ T cells
2. Fas
3. Perforin
4. Granzyme B
• Proposed mechanism:
1. Meds binds MHC I & TCR
2. Leads to CTL clonal expansion
3. CTLs kill keratinocytes via cell-mediated cytotoxic rxn via death domains
a. Dysregulation of Fas-FasL death ligand receptor on keratinocytes
4. NK cell recruited & they secrete soluble death mediators
Massive apoptosis
Stevens-Johnson Syndrome
Ab’s against streptococci cross-react w/ myocardial antigen
Rheumatic fever
Low Ig due to B cell or CD4+ T cell defects
Pathogenesis results from reduced serum IgG, IgA, IgM levels
Poor Ab response to infections
Recurrent infections, autoimmunity & lymphomas
They have normal B cell #’s but Ab’s either aren’t produced or don’t work
CVID
Defective phagolysosomal formation results in:
Impaired granule release from NK & CTLs
Frequent & severe bacterial infections
Chediak-Higashi Syndrome
Give away: partial albinism due to defective MT trafficking of melanin from melanocytes to keratinocytes
Systemic granulomatous disease of unknown cause that may involve many d/f tissues & organs
Sarcoidosis
CD4 is less than 400 and patient has an opportunistic infection
AIDS
- W prophylactic GvHD medications (tacrolimus, cyclosporine) we have shut down CTLs that would normally kill EBV
Virus runs rampid
PTLD EBV-related
Post-transplanted Lymphoproliferative Disorder
Impaired NADPH oxidase activity. Granulomas form in lungs, liver & spleen when microbes that can’t be killed are walled off
Chronic Granulomatous Disease
Type IV Autoimmune
Immune atack of myelin sheath that covers nerve fibers
Multiple Sclerosis
Mutation in TAP1/TAP2/Tapasin expression. Low CD8+ T cells counts No MHC I expression. Viral infections.
Bare lymphocyte Syndrome Type I
Characterized by a triad:
1. Thrombocytopenia
2. Eczema
3. Recurrent pyogenic infections
Wiskott-Aldrich Syndrome
ii. Silver stain- BAL GMS DIAGNOSTIC
· Thick-walled, rounded w/ inctracystic bodies
Encysted organisms have cup or “goblet shape”
Pneumocystis jirovecii
○ Any type III hypersensitivity reaction against some kind of therapy Local reaction = arthus reaction ○ Clinical findings: • Vasculitis • Hemorrhage arthralgia • Skin rashed Nephritis
Serum sickness
Due to mutations in Sialyl Lewis X receptor for selectins • Defective leukocyte adhesion
Defects in selectin or selectin ligand binding
LAD-2
“soap bubble appearance” on histolgical staining. India ink staining. Presents with meningitis.
Cryptococcus
Congestion of RBCs in capillary, strings of fibrin in the air space, and neutrophil infiltrate. Need to put patients on antibiotics to prevent scarring of lung tissue.
Acute Pneumonia
Mutations in 1 of 4 genes encoding TFs regulating MHC II expression. No MHC II expression. Responsible for internalizing extracellular antigens. Lack CD4+ T cells.
Bare Lymphocyte Syndrome Type II
Infective arthroconidia
Blocks phagolysosomal fusion. Found in desert southwest. Sphericles with endospores. Cauliflower White Staining.
Coccidiodes immitus
Problems with formation of the MAC complex leads to infections by what?
Nesseria
- Necrotizing inflammation of blood vessel walls
- Causes vessels to have increased permeability & fibrin moves in
- Thrombosis in vessel walls
- Clinical presentation is widespread from this:
Pain in the vessel being obstructed
Type III
- Clinical presentation is widespread from this:
Polyarteritis Nodosa
- Reaction to foreign material
- Sarcoidosis
- Beryllium exposure
- Chrohns disease
Cat scratch disease
These all have what in common
Noncaseating granulomas
• Results from a deficiency in enzyme that creates an anchor that tethers DAF & MCP to the membrane
• Makes a stable membrane-bound C3 convertase
Pathogenesis: Sporadic hemolysis due to spontaneous C4 activation on RBC membranes
Paroxysmal Nocturnal Hemaglobinura (PNH)
. Process of pathogenesis:
1. Infected macrophage drains to LN
2. Here, activates CD4+ * CD8+ T cells
3. Macrophages & T cell activation leads to granuloma formation
Granulomas develop central necrosis (Caseous necrosis)
Mycobacterium TB
Defective elimination of self reactive lymphocytes. FAS:FASL disorder.
Human ALPS
Intracellular pathogen residing in phagocytes • Induces cell-mdeiated imunity • CD4+ • IFNy Heat-shock proteins ○ Elicits granulomas Some caseate (mimics TB)
Histoplasmosis
Ab inhibits acetylcholine binding–> down modulates the receptor
Myasthenia gravis
• Ab-mediated stimulation of TSH receptors
Agonistic thyroid-stimulating Ab’s
Graves Disease
• IgG Ab against NC1 domains of the alpha-3/alpha-5 chain of type IV collagen (basement membrane) of the kidney
Predominantly IgG1 & IgG3
Goodpasture Syndrome
Type 3 Hypersensitivity Anti-dsDNA Ab • Ab's against nuclear antigens 1. dsDNA 2. snRNP • Criteria for SLE classification: 1. Malar rash 2. Discoid rash 3. Photosensitivity 4. Oral ulcers 5. Arthiritis 6. Serositis - Pleuritis - Pericarditis 7. Renal disorder 8. Neurologic disorder 9. Hematologic disorder: - Hemolytic anemia (w/ reticulocytosis) - Leukopenia - Lymphopenia - Thrombocytopenia 10. Immunologic disorder ANA
SLE
C1 inhibitor absence lead to ongoing cleavage of C4 and C2. Presents with random swelling.
Hereditary angiodema
