Clinical Micro - Immunodeficiency

Front 1

3 yo male presents with upper respiratory infections. Mother states he was perfectly fine his first year but has been suffering recurrent infections since his first birthday. Bone marrow biopsy shows mostly cells with a cytoplasmic Mu. Dx?

Back 1

X linked agammaglobulinemia.

this is where there is a defective bruton's tyrosine kinase,

Front 2

A person was in an MVA, admitted into hospital and needed a blood transfusion, which was properly cross matched. Regardless, the patient has a transfusion reaction. Why

Back 2

IgA subclass deficiency

1:800 people

Front 3

IgD is formed from _

Meanwhile, IgG, IgA, and IgE are formed via _

Back 3

alternate splicing

Class switching

Front 4

In case of Hyper IgM syndrome, where is the problem?

Back 4

T cells are not expressing CD40 L

Since CD40 L is required for B cells to undergo class switching, there is a lot of IgM and no or hardly any IgG, IgA, or IgE.

Front 5

4 yo boy presents with recurrent sinusitis. Hx noteable for pneumocystis pneumonia when he was 2. Lab shows neutropenia, elevated monocytes, low igG, low IgA, high IgM and normal IgD. Dx?

What would a lymph node biopsy look like in this patient?

Back 5

Hyper IgM syndrome

Germinal centers will be absent,
(germinal centers are where activated B cells go, in these patients, there are no activated B cells (because T cells don't have CD40L to activate them)

Front 6

6 mo male comes in with oral thrush. Mother informs you that for the last 4 months he has been suffering from recurring ear infections, pneumonia, and runny noses. He is far below the normal growth for his age. Labs show No anti-CD3 ab, and 99% of cells binding antiCD20 ab.
What interaction in lymphocytes is deficient in this patient?

Back 6

(X linked SCID)

defect in common gamma chain of IL-2 receptor
(also affects IL7 and IL4)

(labs show No T cells, almost all B cells.

Front 7

What is the definitive treatment for SCID?

Back 7

Bone Marrow transplant

Until then, give gamma globulin infusions and antibiotics.

Front 8

If ADA deficiency affects adenosine metabolism, why aren't all cells in the body affected?

Back 8

Only Lymphocytes are affected because they have a relative deficiency of 5' nucleotidase (compensatory enzyme).

This enzyme will save all other cells from being affected.

Front 9

To test a donor/recipient MHC I compatibility, what are we measuring?

Back 9

Chrome 51 (CTL response)

When cells are killed (by CTL), chrome 51 will be released

Front 10

_ is responsible for B and T cell recombination.

Back 10

Rag

Front 11

What enzymes are required for antibody class switching?

Back 11

AID and UNG

Front 12

6 mo male comes in with oral thrush. Mother informs you that for the last 4 months he has been suffering from recurring ear infections, pneumonia, and runny noses. He is far below the normal growth for his age. Labs show No anti-CD3 ab, and 99% of cells binding antiCD20 ab.
What interaction in lymphocytes is deficient in this patient?

Back 12

(X linked SCID)

defect in common gamma chain of IL-2 receptor
(also affects IL7 and IL4)

(labs show No T cells, almost all B cells.

Front 13

What is the definitive treatment for SCID?

Back 13

Bone Marrow transplant

Until then, give gamma globulin infusions and antibiotics.

Front 14

If ADA deficiency affects adenosine metabolism, why aren't all cells in the body affected?

Back 14

Only Lymphocytes are affected because they have a relative deficiency of 5' nucleotidase (compensatory enzyme).

This enzyme will save all other cells from being affected.

Front 15

To test a donor/recipient MHC I compatibility, what are we measuring?

Back 15

Chrome 51 (CTL response)

When cells are killed (by CTL), chrome 51 will be released

Front 16

_ is responsible for B and T cell recombination.

Back 16

Rag

Front 17

What complement defiency is mc?

Back 17

C2

Front 18

6 mo old girl suffering from recurrent respiratory infections. Blood differential shows no abnormality, NBT test is Positive. Dx?

Back 18

Leukocyte Adhesion Deficiency

NBT = nitroblue tetrazolium,

If NBT were negative, it would be Chronic granulomatous Disease (CGD)

Front 19

4 yo boy is evaluated because of a lifelong hx of bacterial and fungal infections. He is noted to be small for his age, and has hepatosplenomegaly on p/e. Peripheral blood smear demonstrates normal appearing neutrophils and macrophages. The NBT test is negative. An inherited deficiency of what whould likely cause this child’s sx?

Back 19

NADPH oxidase system

NBT tests to see if NADPH is working, a neg result means it's not working --> CGD

Front 20

G6P Deficiency patients present with _

Back 20

Chronic bacterial and fungal infections WITH anemia

(essentally, CGD with anemia)

Front 21

G6P Deficiency patients present with _

Back 21

Chronic bacterial and fungal infections WITH anemia
(essentally, CGD with anemia)

Front 22

4 yo boy is evaluated because of a lifelong hx of bacterial and fungal infections. He is noted to be small for his age, and has hepatosplenomegaly on p/e. Peripheral blood smear demonstrates normal appearing neutrophils and macrophages. The NBT test is negative. An inherited deficiency of what whould likely cause this child’s sx?

Back 22

NADPH oxidase system
NBT tests to see if NADPH is working, a neg result means it's not working --> CGD

Front 23

6 mo old girl suffering from recurrent respiratory infections. Blood differential shows no abnormality, NBT test is Positive. Dx?

If NBT were negative, it would be _

Back 23

Leukocyte Adhesion Deficiency

Chronic granulomatous Disease (CGD)

Front 24

What complement defiency is mc?

Back 24

C2

Front 25

C5-C9 deficient Patient will suffer from recurrent _ infections

Back 25

Neisseria

Front 26

G6P Deficiency patients present with _

Back 26

Chronic bacterial and fungal infections WITH anemia
(essentally, CGD with anemia)

Front 27

4 yo boy is evaluated because of a lifelong hx of bacterial and fungal infections. He is noted to be small for his age, and has hepatosplenomegaly on p/e. Peripheral blood smear demonstrates normal appearing neutrophils and macrophages. The NBT test is negative. An inherited deficiency of what whould likely cause this child’s sx?

Back 27

NADPH oxidase system
NBT tests to see if NADPH is working, a neg result means it's not working --> CGD

Front 28

6 mo old girl suffering from recurrent respiratory infections. Blood differential shows no abnormality, NBT test is Positive. Dx?

If NBT were negative, it would be _

Back 28

Leukocyte Adhesion Deficiency

Chronic granulomatous Disease (CGD)

Front 29

What complement defiency is mc?

Back 29

C2

Front 30

C5-C9 deficient Patient will suffer from recurrent _ infections

Back 30

Neisseria

Front 31

In X linked agammaglobulinemia, the _ is defective.

Back 31

Bruton's tyrosine kinase (Btk) --> Therefore, B cells are unable to mature.

These patients suffer from infection with normal flora (H influenza, step pyogenes, giardia, etc) and recurrent sinopulmonary infections

Front 32

Hyper IgM syndrome is a problem with _ cells.

If you were to biopsy a lymph node from one of these patients, what would you see?

Back 32

T Cells (they are not expressing CD40 L which is critical for class switching. Therefore There will be IgM but no IgG, IgA, or IgE.

In lymph nodes, GERMINAL CENTERS will be ABSENT, --because this is where activated B cells hang out. There are not activated B cells here

Front 33

A patient presents with lots of sores and blisters in the mouth. They have a history of recurrent infections, noting a Staph infection 6 months ago and Pneumocystis about a year ago. Lab shows low CM-CSF. Dx?

Back 33

Hyper IgM Syndrome

(T cells don't express CD 40 L), CD40 on macrophages will be low, resulting in low CM-CSF

Front 34

An immunodeficiency that is acquired later in life?

Back 34

Common variable immunodeficiency (teens)
---B cells are not defective, but T cells don’t give proper help. The difference between XLA and CVID is that in the latter normal B cells are present in the peripheral blood

Also, Hereditary Ataxia Telangiectasia (school age)
-chromosomal breaks in 7 and 14. First occurs in eyes, face, neck, hands, knees. Infants develop wobbly gait around 18 mo

Front 35

A patient who has a defect in the gene that encodes for gamma chain of IL-2 receptors on T cells is said to have what condition?

What is the treatement?

Back 35

X linked SCID (results in defective T and B cells) - these patients are susceptible to infection by normal flora, thus suffer recurrent sinopulmonary infections

These patients need a BONE MARROW TRANSPLANT by their 2nd birthday, or they will die

Front 36

A 3 mo old presents with pneumonia. Mom says he has recurrent diarrhea. CXray shows a clear cardiac shadow. Lab reveals a WBC count of 11,000 and a lymphocyte count of 850.

If you were to take a biopsy of the child's thymus, what would you see?

Back 36

(X linked SCID)

histo of thymus shows loss of corticomedullary differentiation, lack of hassal's corpuscles.

Front 37

A 3 mo old presents with pneumonia. Mom says he has recurrent diarrhea. CXray shows fetal appearing thymus. Lab reveals a WBC count of 11,000 and a lymphocyte count of 850.

What is the pathogenesis of this disorder?

Back 37

(X linked SCID)

Defect in gene that encodes gamma chain of IL2 receptors of T cells. This chain also plays a role in IL4, 7, 9, 11, resulting in lack of T cell maturation (IL7)

Front 38

RAG enzymes are essential for _.

Back 38

VDJ recombination in B and T cell maturity.

Without RAG, both T and B cells will be affected

Front 39

What is the most common cause of an MHC Class I deficiency?

This results in...

Back 39

DEFICIENT TAP GENE (transport of cysolic proteins, so peptide won't be transferred to ER, won't have MHC I expressed on surface

RECURRENT VIRAL AND INTRACELLULAR INFECTIONS

Front 40

MHC Class II deficiency is usually due to _.


tHIS results in _

Back 40

CIITA, a transcriptional factor (RFX) in X box

Results in failure to develop CD4 T cells, and these patients suffer from RECURRENT FUNGI AND EXTRACELLULAR INFECTIONS

Front 41

Patient presents with involuntary contractions of hands and fingers. PE shows wide eyes, low set ears, shortened philtrum of upper lip.

What other abnormalities of this patient should you be concerned with?

Back 41

DiGeorge Syndrome (thymic hypoplasia)

CARDIAC AND GREAT VESSEL ABNORMALITIES
-- these patients have defective 3rd and 4th pouch development, so anything made from these will be affected: thymus, parathyroid glands (tetany), great vessels

Front 42

Patient presents with involuntary contractions of hands and fingers. PE shows wide eyes, low set ears, shortened philtrum of upper lip.

What do you suspect lab work of this patient would show you?
What would a biopsy of this patients lymph node show?

Back 42

DiGeorge Syndrome (thymic hypoplasia)
T CELL DEFICIENCY, CA DEFICIENCY, LOW PTH

Spleen: hypocellular paracortical region in lymph node and (PALS in spleen)

Front 43

Patient presents with involuntary contractions of hands and fingers. PE shows wide eyes, low set ears, shortened philtrum of upper lip.

What is the pathogenesis of this disorder?

Back 43

DiGeorge Syndrome (thymic hypoplasia)

Defective 3rd and 4th pouch developmentso anything made from these will be affected: thymus, parathyroid glands (tetany), great vessels

Front 44

18 mo old presents with wobbly gait. She has a history of severe sinus and lung infections.

Lab work shows an IgA deficiency, dx?

pathogenesis?

Back 44

Hereditary Ataxia Telangiectasia

chromosomal breaks in 7 and 14

Front 45

18 mo old presents with wobbly gait. She has a history of severe sinus and lung infections. The attendee tells you this patient has Hereditary Ataxia Telangiectasia.

What immunoglobulin is deficient in this patient?

Back 45

IG A

d/t a chromosomal break in 7 and 14, 7 has gene for heavy chain of B cell receptor and beta chain of T cell
14 has light chain and alpha chain.

Front 46

2 yo is brought in by mother because she noticed blood in his urine. He has a hx of recurrent infections. P/E reveals eczema and small purple bumps.

You recognize this patient has a deficiency in _, which regulates the arrangement of the cytoskeleton of the T cells

Back 46

WASP

(Wiskcott aldrich syndrome)

Front 47

2 yo is brought in by mother because she noticed blood in his urine. He has a hx of recurrent infections. P/E reveals eczema and small purple bumps.

What abnormalities (if any) would you expect to see in the thrombocytes of this patient?

Back 47

Low number and small size of thrombocytes

This patient has Wiskott-Aldrich syndrome - (where there is a deficiency in WASP --> defective cytoskeleton)

Front 48

2 yo is brought in by mother because she noticed blood in his urine. He has a hx of recurrent infections. P/E reveals eczema and small purple bumps.

What lab work would you expect, assuming this patient has a deficiency in the WASP protein?

Back 48

Low number and small thrombocytes.
Low IgM, normal IgG, increased IgA and IgE

Thrombocytopenia - low number
and small size


(Wiskott-aldrich syndrome: TIE)

Front 49

X linked lymphoproliferative syndrome is associated with _

Back 49

EBV virus

This results in unregulated proliferation of CTL cells (SH2D1A --> SLAM on lymphocytes), ultimately results in aplastic anemia, fatal infectious mono or agammaglobulinemia

Front 50

What is the most common complement deficiency?

What is the mc complement regulatory deficiency?

Back 50

C2

C1 inhibitor (Hereditary Angioedema) --> results in lots of C2 being made which is vasoactive --> edema

Front 51

C3 deficient patients suffer from recurring _ infections

C5-C9 deficient patients suffer from recurring _ infections

Back 51

encapsulated pathogens

Neisseria infections

Front 52

IFN gamma and IL12 receptor deficient patients get _ infections

Back 52

MAC

Front 53

Paraoxysmal nocturnal hemoglobinuria? What should you be thinking of?

Back 53

deficient DAF - Decay Accelerating Factor (CD59)

lack of these leads to uninhibited effect of complement system

Front 54

Which of the following enzyme(s) is/are required for antibody class switching?

Back 54

AID (along with UNG)

Front 55

Rag is responsible for _

Back 55

B and T cell recombination.

Front 56

A patient who suffers from a deficieny in a gene encoding for CD 18 is likely to have what manifestations?

Back 56

Leukocyte Adhesion Deficiency
(CD 18 is a beta su of LFA1)

-->Can not form PUS, hx of omphalitis. These patients suffer from recurrent pyogenic infections

--> this is where neutrophils cannot migrate out to the periphery bc of a deficient LFA1

Front 57

A patient suffers from pyogenic infections, can not form pus. Hx of omphalitis, Dx?

Pathogenesis?

Back 57

LEUKOCYTE ADHESION DEFICIENCY

DEFICIENT CD 18 - Neutrophils cannot migrate out into periphery. (remember cells must attaché to endothelium via ICAM and LFA1 before they undergo rolling, and squeeze through to then migrate to the infection. If they can’t bind, they can’t get to the infection)

Front 58

Chronic Granulomatous Disease patients suffer from _ infections

Back 58

catalase producing bacterial

When NADPH oxidase is deficient, MPO can still rescue us, because bacteria produces some H2o2. But in bacteria who produce catalase, the catalase splits H2o2, and we can’t defend against those organisms.

Front 59

Patient has developed a granuloma, probably from recurrent Staph or actinobacter infections. What is this patient likely deficient in?

What is the diagnostic test you would want to run?

Back 59

NADPH Oxidase (this patient has chronic granulomatous disease and suffers from catalase producing organisms)

NITROBLUE TETRAZOLIUM W/ A NEGATIVE RESULT (YELLOW)

Front 60

Patient has recurrent Staph or actinobacter infections. Lab work shows decreased hemogloblin. What is the diagnosis?

Back 60

G6PDH

Same manifestations as CGD but with anemia because it produces non - reduced glutathione, which acts as a free radical and will burst the RBC.

Front 61

What disease has a defect in S2D1A:

Back 61

X linked lymphoproliferative syndrome

Front 62

Pt complains that in the mornings they pee and it’s blood tinged:

Back 62

DAF deficiency, “paraoxysmal nocturnal hemaglobinuria”

Front 63

A normal WBC count is _
Values _are suggestive of an acute infection, _ suggest a viral or overwhelming bacterial infection

Back 63

4500-10500 cells/microL.

>11000

<4000

Front 64

Normal values of CRP are _ an increase indicates _

Back 64

<0.8,

inflammation.

Front 65

What is the one condition that an elevated ESR could be diagnostic for?

Normal values of ESR?

Back 65

Malignant Otitis Externa


o Normal male: 0-15, female: 0-20, children: 0-10

Front 66

CD3:
CD16:
CD19:
CD21:

Back 66

CD4 and CD8 cells (T)
NK cells
B cells
B cells

Front 67

The DHR measure what

Back 67

Neutrophil Oxidative Burst (phagocytic activity)


(In neutrophils, ROIs are generated following phagocytosis. Label with DHR, and the more fluorescence you see, the more activated they are. )

Front 68

What would be DHR result of a patient who suffers from recurrent infections by catalse producing bacteria?

Back 68

(Chronic Granulomatous Dz)


Negative, DHR measures the neutrophil oxidative burst, and as these patients will not generate ROIs, you will not see any fluroesnces

Front 69

What is the main purpose of a Coombs test?

Back 69

•Main purpose is to id antibodies that are interacting with erythrocytes.
Hemagglutination tells you there are ab present


RH (-) antibodies

Front 70

What key cells express the IL2 receptor?

Back 70

Treg Cells.

Front 71

20 mo old girl who has been hospitalized with fever, dehydration, etc. CT scan shows intracranial edema, CSC shows raised neutrophils with a left shift. When would protection of maternal antibodies be subsided?

Back 71

6 months

Front 72

If both CH50 and AH 50 show abnormal results, what does that suggest?

Back 72

defect in MAC.