Y2B3 Micro- Immunodeficiency Diseases Iii

Front 1

What is mutated in the MHC I molecule deficiency? how would that manifest clinically?

Back 1

TAP gene---> Viral infections and increased susceptibility to incracellular bacteria.

Fxn of TAP is to transport processed peptides from the cytosol to the ER. There they will join MHC 1 class and ascend to the surface. W/o TAP= no CTL response d/t no MHC class I

Front 2

what is the defect in MHC class II molecule deficiency? what is its function? How does this clinically manifest?

Back 2

transcriptional regulators

esp: Class II transactivator and RFX's which is the transcriptional complex which binds to a conserved sequence of the promotor region of HLA class II gene Called XBOX

Manifests as a failure to develop CD4 cells resulting in recurrent fungal and extracellular pathogens

Front 3

what transcriptional protein involved in MHC class II molecular deficiency induces Expression of all MHC molecules? what does it encode?

Back 3

Class II transactivator which induces IFN-y to induce expression

encodes: Tapasin-TAPBP, TAP-TAO, proteasome

Front 4

How many chains does MHC class II have? what are the chains? how did they come to be?

Back 4

3 chains
alpha, beta and invariant

The invariant chain is bound to the MHC while it is in the ER so no peptides can bind to it. Once it enters the vesicle, the chain is cut leaving just CLIP in the peptide groove. Peptide loading is facilitated by HLA-DM which releases CLIP and the MHC molecule ascends to the surface.

Front 5

A 5 month old is brought to your office because the mother is concerned about these random nose bleedings that her son has been having. On examination, you notice that the baby has some dry, patchy areas on his skin that are erythematous. You do a CBC and notice that his thrombocytes are hovering near 50,000. What is the main defect?

Back 5

Baby has WIscott aldrich syndrome

Defect is in the X chromosome that encodes the WAS protein causing the T cells to have an inacbility to reorganize their actin cytoskeleton.

therefore: lytic granules containing cytotoxic proteins will not occur sufficiently in these patients.

Front 6

After doing a flowcytometry, if you discovered it was a T cell defect, where would you find it? B cell defect?

Back 6

T cell- PALS in spleen or paracortical area in LN would be hypocellular

B cells- LN follicle (germinal center)- hypocellular

Front 7

A 5 month old is brought to your office because the mother is concerned about these random nose bleedings that her son has been having. On examination, you notice that the baby has some dry, patchy areas on his skin that are erythematous. You do a CBC and notice that his thrombocytes are hovering near 50,000. What would you expect in this pt if an immunoglobulin panel was done?

Back 7

IgM would be low
IgG would be normal
IgA and IgE would be high

Front 8

A 4 month old is presented to your office with a recurrent case of Tinea capitis. You notice that the child's eyes have a larger gap between them than normal and that his ears are set a little lower than normal. You do some genetic testing and find out that this child has a 22q11 deletion. What other symptoms might you expect for this child to have? Where does the defect lie?

Back 8

defect: 3rd and 4th pharyngeal pouches which will cause a defect in the Parathyroid (leading to tetany) and the great vessels

I would also expect (besides tetany and great vessel defects) a completely absent thymus, a shortened philtrum of the upper lip and viral infections.

Front 9

A 5 year old is brought to your office for yet another sinus infection. Upon physical examination you notice that she has erythematous elevations of blood vessels on her sclera and on her cheeks. Where in the defect in this pt's condition?

Back 9

condition: Hereditary ataxia-Telangiectasia (AR)

Defect is d/t chromosomal break at 7 (heavy chain/beta chain) and 14(alpha/ light chain) at the site of the TCR gene.

Front 10

How does herediatry ataxia-telangiectasia cause a T cell defect?

Back 10

D?t the deficiency of IFN-y leading to decreased macrophage activation and defciency in IL-12 leading to ILF-y deficiency

IL-12--> NK cells --> IFn-y--> more IL-12 --> differentiation of Tho to Th1.

Il-12 is the bridge between innate and memory

Front 11

which immunodeficiency disease is triggered by a viral infection? what virus? where is the defect?

Back 11

X-linked Lymphoproliferative syndrome (XLP)
virus: EBV--> leading to a failure to control normal proliferation of CTLs

defect: in the SH2D1A gene which encodes for SLAM assoc protein (SAP- which regulates proliferation of cytotoxic T cells) which allows SLAM to be expressed on surface of T cells and B cells.

Front 12

what is the MC complement deficiency? What diseases have a higher instance of this complement deficiency?

Back 12

C2 deficiency

higher incidence in SLE-like Autoimmune diseases

Front 13

what deposits and where when you have a lack of C1, 2 and 4?

Back 13

aggregation of deposition of immune complexes on basement membranes of small blood vessels (esp kidney)

Front 14

what is the minimum requirement for immune complexes to be engulfed by phagocytes?

Back 14

2 IgGs and 1 IgM

Front 15

what is the most abundant complement in serum? What does this complement divide into? what happens if this is deficient?

Back 15

C3
C3a- chemotactic factor
C3b- will be deposited on the pathogen surface and signaled for opsonization.

deficiency will result in no opsonization

Front 16

What is the only pathogen is C5-9 susceptible to?

Back 16

Neisseria

Front 17

what is the function of factor 1? what will happen if their is a deficiency of factor 1? absence?

Back 17

fxn: Plasma serine protease. It inactivates C4b component of C3 convertase following the binding of C4b by C4 binding protein

deficiency: lack of C3 since C3 will be degraded

absence: conversion of C3-C3b will be left unchecked and cause a complete absence of C3

Front 18

which complement regulatory protein enhances the alternate pathway, but when deficient, becomes increasingly susceptible to neisseria?

Back 18

Properdin (Factor P)- plasma protein.

deficiency of FP --> dec deposition of C3 --> dec MAX formation --> NEISSERIA!!!

Front 19

What complement regulatory protein will cause paroxysmal nocturnal hemoglobulinurea?

Back 19

Decay-accelerating Factor (DAF) which regulates the action of the alternative pathway. A deficiency of DAF causes an uninhibited effect on complement system. The complement mediated lyses of erythrocytes causes the pt to pass red urine in the morning.

Front 20

what is the MC complement regulatory deficiency? What does it cause?

Back 20

C1inhibitor

Hereditary angioneurotic edema

Front 21

20 year old pt presents to your ER with periorbital edema, swollen lips, and some dysphagia. You give her an epi pen, and it doesn't work. Do you send her home? Dx

Back 21

hereditary angioneurotic edema

NOOOO- don't send her home... suffocation d/t epiglottal swelling is the biggest worry

absence of C1 inh leads to uncontrolled actcivation of the classical pathway which leads to accumulation of fluid in the tissues.

Front 22

A pt presents to your office with her 7 month old child complaining of recurrent infections of the umbilical cord. You take a look and notice that there is no pus in the infection site. What other sx would you expect? what is the mutation?

Back 22

Leukocyte adhesion deficiency

Sxs: recurrent pyogenic infections, delayed separation of the umbilical cord and delayed would healing

defect: d/t mutation in gene encoding CD18 (common B-subunit of leukocyte integrins CR2, CR4 and LFA-1)

Front 23

Pt presents to your office a swollen erythematous mass just underneath her nipple. She says that she is currently breast feeding, but that she's had this same issue multiple times while breast feeding. You take a sample and see gram positive clusters under the microscope. You then noticed some white spots along the inner mucosa of her mouth. Dx and confirm

Back 23

Chronic Granulomatous Dz

confirmation: negative nitroblue tetrazlium reduction. This means that the MPO is defective and yellow.

This pt will be more susceptible to catalase producing organisms like all staph, P. aeurginosa, candina, aspergillus and enterobacter d/t a mutation in any of the 4 proteins of the NADPH oxydase system.

Front 24

CGD vs G6PD deficiency?

Back 24

G6PD --> same sxs except it will present w/ anemia

Front 25

Aggressive dz w/ opportunistic pathogens and a failure to clear infections.... what type of Cell deficiency is this? (T or B)

Back 25

T

Bacterial sepsis, CMV, EBV, severe varicella, chronic infections w respiratory intestinal viruses, candida and PCP

Front 26

Recurrent sinopulmomnary infections, sepsis and chronic meningitis..... what type of cell deficiency is this? (T or B)

Back 26

B

Strept, staph, haem, enteroviral encephalitis, severe giardiasis