I2 Diseases

Question 1

• 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

Answer 1

X-Linked Agammaglobulinemia

Question 2

Inhibits antigen presentation Inhibits proteasomal activity

Removal of MHC I molecules from ER. Degrades NKG2D on NK cells.

Answer 2

CMV (cytomegalovirus)

Question 3

CATCH-22. Developmental failure of the 3rd & 4th pharyngeal pouches. T-/B+/NK+

Answer 3

DiGeorge Syndrome

Question 4

IgG autohemolysin binds RBCs @ low temps

Causes intravascular hemolysis after warming

Answer 4

Autoimmune hemolytic anemia

Question 5

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

Answer 5

Ataxia-Telangiectasia (ATM)

Question 6

Defective resistance or abnormal responses to intestinal microbes. Defective NOD signaling pathway.

Answer 6

Chron’s disease

Question 7

Chronic mast cell activation with increased mucous secretion and bronchoconstriction. Eosinophil recruitment which can initiate damage to mucosal epithelium

Answer 7

Allergic Asthma

Question 8

Found in Central and Southeastern US. Dimorphic fungi that is a granulomatous disease.

Answer 8

Blastomyces dermatitidus

Question 9

Howell-Jolly bodies and loss of IgM and T-independent response. Susceptibility to encapsulated bacteria

Answer 9

Asplenia

Question 10

CD18 deficiency leading to poor neutrophil adhesion and poor opsonophagocytosis.

Answer 10

LAD-1

Question 11

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

Answer 11

Scleroderma

Question 12

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

Answer 12

Tuberculosis

Question 13

• 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

Answer 13

Stevens-Johnson Syndrome

Question 14

Ab’s against streptococci cross-react w/ myocardial antigen

Answer 14

Rheumatic fever

Question 15

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

Answer 15

CVID

Question 16

Defective phagolysosomal formation results in:
Impaired granule release from NK & CTLs
Frequent & severe bacterial infections

Answer 16

Chediak-Higashi Syndrome

Give away: partial albinism due to defective MT trafficking of melanin from melanocytes to keratinocytes

Question 17

Systemic granulomatous disease of unknown cause that may involve many d/f tissues & organs

Answer 17

Sarcoidosis

Question 18

CD4 is less than 400 and patient has an opportunistic infection

Answer 18

AIDS

Question 19

• W prophylactic GvHD medications (tacrolimus, cyclosporine) we have shut down CTLs that would normally kill EBV
  Virus runs rampid

Answer 19

PTLD EBV-related

Post-transplanted Lymphoproliferative Disorder

Question 20

Impaired NADPH oxidase activity. Granulomas form in lungs, liver & spleen when microbes that can’t be killed are walled off

Answer 20

Chronic Granulomatous Disease

Question 21

Type IV Autoimmune

Immune atack of myelin sheath that covers nerve fibers

Answer 21

Multiple Sclerosis

Question 22

Mutation in TAP1/TAP2/Tapasin expression. Low CD8+ T cells counts No MHC I expression. Viral infections.

Answer 22

Bare lymphocyte Syndrome Type I

Question 23

Characterized by a triad:

1. Thrombocytopenia 
2. Eczema 
    3. Recurrent pyogenic infections

Answer 23

Wiskott-Aldrich Syndrome

Question 24

ii. Silver stain- BAL GMS DIAGNOSTIC
· Thick-walled, rounded w/ inctracystic bodies
Encysted organisms have cup or “goblet shape”

Answer 24

Pneumocystis jirovecii

Question 25

``` ○ Any type III hypersensitivity reaction against some kind of therapy Local reaction = arthus reaction ○ Clinical findings: • Vasculitis • Hemorrhage arthralgia • Skin rashed Nephritis ```

Answer 25

Serum sickness

Question 26

Due to mutations in Sialyl Lewis X receptor for selectins • Defective leukocyte adhesion Defects in selectin or selectin ligand binding

Answer 26

LAD-2

Question 27

"soap bubble appearance" on histolgical staining. India ink staining. Presents with meningitis.

Answer 27

Cryptococcus

Question 28

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.

Answer 28

Acute Pneumonia

Question 29

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.

Answer 29

Bare Lymphocyte Syndrome Type II

Question 30

Infective arthroconidia | Blocks phagolysosomal fusion. Found in desert southwest. Sphericles with endospores. Cauliflower White Staining.

Answer 30

Coccidiodes immitus

Question 31

Problems with formation of the MAC complex leads to infections by what?

Answer 31

Nesseria

Question 32

1. Necrotizing inflammation of blood vessel walls 2. Causes vessels to have increased permeability & fibrin moves in 3. Thrombosis in vessel walls - Clinical presentation is widespread from this: Pain in the vessel being obstructed Type III

Answer 32

Polyarteritis Nodosa

Question 33

1. Reaction to foreign material 2. Sarcoidosis 3. Beryllium exposure 4. Chrohns disease Cat scratch disease These all have what in common

Answer 33

Noncaseating granulomas

Question 34

• 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

Answer 34

Paroxysmal Nocturnal Hemaglobinura (PNH)

Question 35

. 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)

Answer 35

Mycobacterium TB

Question 36

Defective elimination of self reactive lymphocytes. FAS:FASL disorder.

Answer 36

Human ALPS

Question 37

``` Intracellular pathogen residing in phagocytes • Induces cell-mdeiated imunity • CD4+ • IFNy Heat-shock proteins ○ Elicits granulomas Some caseate (mimics TB) ```

Answer 37

Histoplasmosis

Question 38

Ab inhibits acetylcholine binding--> down modulates the receptor

Answer 38

Myasthenia gravis

Question 39

• Ab-mediated stimulation of TSH receptors | Agonistic thyroid-stimulating Ab's

Answer 39

Graves Disease

Question 40

• IgG Ab against NC1 domains of the alpha-3/alpha-5 chain of type IV collagen (basement membrane) of the kidney Predominantly IgG1 & IgG3

Answer 40

Goodpasture Syndrome

Question 41

``` 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 ```

Answer 41

SLE

Question 42

C1 inhibitor absence lead to ongoing cleavage of C4 and C2. Presents with random swelling.

Answer 42

Hereditary angiodema