Immuno: Inherited Immune Deficiency of Innate Immunity

Question 1

Patients with asplenia are significantly more susceptible to ________ infections, especially with encapsulated bacteria.

Answer 1

Septic

Question 2

________ (leukocytes) in the spleen are important for recognizing and phagocytosing complement labeled or Ab opsonized bacteria from the bloodstream.

Answer 2

macrophages

Question 3

If a pt doesn’t have a spleen, they should be counseled to receive vaccines for _________ bacteria.

Answer 3

encapsulated

Question 4

_________ involves either the complete absence of NK cells (and NKT cells) or total lack of NK cell function.

Answer 4

Absolute NK cell deficiency (ANKD)

Question 5

Individuals with ________ lack NK cells and NK cell function. This condition is distinguished from ANKD by the presence of NKT cells.

Answer 5

Classical NK cell deficiency (CNKD)

Question 6

Pts with ________ usually do not have NKT cells, although this is not a criterion for Dx. Normal/near normal NK cell numbers, but absent or severely decreased NK cell function.

Answer 6

Functional NK cell deficiency (FNKD)

Question 7

NK cell deficiencies make pts especially susceptible to these viral infections:

Answer 7

varicella zoster virus (chickenpox/shingles), herpesvirus, cytomegaloviruses, Epstein-Barr virus

Question 8

NK cell deficiencies make pts especially susceptible to these bacterial infections:

Answer 8

Mycobacterium avium/intracellulare (MAI; opportunistic pathogens)

Question 9

NK cell deficiencies make pts especially susceptible to this fungal infection:

Answer 9

Trichonphyton (one of the leading causes of hair, skin, and nail infections in humans)

Question 10

______ is a genetic defect in a protein that is required for NfkB activity.

Answer 10

NEMO

Question 11

Let’s play “Do you Remember from Block 1?”

NfkB is important for __________ of genes (following PRR engagement; TLRs) that are invilved in innate immune responses.

Answer 11

transcription

Question 12

What clinical presentation do pts with NEMO present?

Answer 12

Increased susceptibility to recurrent bacterial and viral pathogens. Pts also suffer from developmental defects.

Question 13

Describe the cellular abnormality present in a leukocyte adhesion deficiency.

Answer 13

Defective CD18 (an integrin cell adhesion molecule)

Question 14

Describe the immune defect present in a leukocyte adhesion deficiency.

Answer 14

Defective migration of phagocytes into infected tissues

Question 15

Describe type of organism that leads to widespread infections in a leukocyte adhesion deficiency.

Answer 15

Encapsulated bacteria

Question 16

Describe the cellular abnormality present in chronic granulomatous disease (CGD).

Answer 16

Defective NADPH oxidase. Phagocytes cannot produce O2- (superoxide)

Question 17

Describe the immune defect present in chronic granulomatous disease (CGD).

Answer 17

Impaired killing of phagocytosed bacteria

Question 18

Describe the associated infections and other diseases found in chronic granulomatous disease (CGD).

Answer 18

Chronic bacterial and fungal infections. Granulomas.

Question 19

Describe the cellular abnormality present in Glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Answer 19

Deficiency of glucose-6-phosphate dehydrogenase. Defective respiratory burst

Question 20

Describe the immune defect present in Glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Answer 20

Impaired killing of phagocytosed bacteria

Question 21

Describe the associated infections and other diseases present in Glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Answer 21

Increased susceptibility to extracellular pathogens due to inability to produce and release O2- and H2O2. Chronic bacterial and fungal infections. Anemia is induced by certain agents that interfere with erythrocyte metabolism.

Question 22

Describe the cellular abnormality present in Myeloperoxidase deficiency.

Answer 22

Deficiency of myeloperoxidase in neutrophil granules and macrophage lysosomes and impaired production of toxic oxygen species.

Question 23

Describe the immune defect present in Myeloperoxidase deficiency.

Answer 23

Impaired killing of phagocytosed bacteria

Question 24

Describe the associated infections and other diseases present in Myeloperoxidase deficiency.

Answer 24

Chronic bacterial and fungal infections

Question 25

Describe the cellular abnormality present in Chediak-Higashi syndrome.

Answer 25

Defect in vesicle fusion

Question 26

Describe the immune defect present in Chediak-Higashi syndrome.

Answer 26

Impaired phagocytosis due to inability of endosomes to fuse with lysosomes.

Question 27

Describe the associated infections and other diseases present in Chediak-Higashi syndrome.

Answer 27

Recurrent and persistent bacterial infections. Granulomas. Effects on many organs. Albinism because of improper trafficking of melanosomes.

Question 28

Describe a childbirth abnormality present in pts with leukocyte adhesion deficiency.

Answer 28

Delayed detachment and sloughing off of the umbilical cord.

Question 29

What is the most common infection that infants with chronic granulomatous disease contract?

Answer 29

Serratia marcescens

Question 30

The nitroblue tetrazolium dye test is used to confirm the presence of this condition:

Answer 30

chronic granulomatous disease

Question 31

A positive nitroblue tetrazolium dye test (old standard) shows what under microscopic examination? Why?

Answer 31

Blue color around neutrophils because normal phagocytes that produce NADPH oxidase that give rise to ROS that oxidize the NTB, produce a blue color. Blue color means negative for CGD but indicates a positive test.

Question 32

The new standard of testing for chronic granulomatous disease is what?

Answer 32

The dihydrorhodamine test

Question 33

A positive dihydrorhodamine test produces:

Answer 33

Green fluorescence when neutrophils produce oxidative burst that can reduce dihydrorhodamine to rhodamine. Measured by flow cytometry.

Question 34

Chediak-Higashi syndrome is caused by a genetic defect of the gene that encodes a protein that is involved in __________ ________ formation, known as the _____ protein.

Answer 34

intracellular vesicle formation; LYST protein

Question 35

List the three main symptoms that pts with Chediak-Higashi syndrome suffer from.

Answer 35

1) partial albinism
2) recurrent pyogenic infections
3) neurological disorders

Question 36

How do you treat pts with Chediak-Higashi syndrome?

Answer 36

bone marrow transplant

Question 37

List the two inherited disorders that result in neutropenia (low neutrophil blood count).

Answer 37

1- Severe congenital neutropenia (Kostmann syndrome)

2- Cyclic neutropenia

Question 38

Describe the mode of inheritance and what cellular component is missing in severe congenital neutropenia

Answer 38

autosomal recessive. Associated with a gene abnormality of granulocyte colony stimulating factor (G-CSF) or its receptor (G-CSFR); G-CSF stimulates granulocyte growth

Question 39

Describe the mode of inheritance, what gene defect is implicated, and what happens in cyclic neutropenia.

Answer 39

autosomal dominant. gene defect termed ELA-2. neutropenia occurs every 2-4 weeks and lasts about a week.

Question 40

Is benign chronic neutropenia a life-threatening condition?

Answer 40

No. It is often asymptomatic

Question 41

X-linked hyper IgM syndrome, X-linked aggamaglobulinemia, WHIM syndrome, and Griselli syndrome are immunodeficiencies that are complicated by neutropenia. Describe why.

Answer 41

Some of these patients produce autoantibodies that are specific for neutrophil determinants that result in decreased neutrophil numbers.

Question 42

Let’s play: “Do You Remember from Block 1?”
Pts with complement deficiencies that reduce deposition of C3b are significantly more susceptible to _________ infections.

Answer 42

Bacterial

Question 43

Let’s play: “Do You Remember from Block 1?”

Deficiencies of components C5-C9 result in susceptibility only to one bacterial genus:

Answer 43

Neisseria

Question 44

Let’s play: “Do You Remember from Block 1?”

Deficiencies of complement regulatory proteins can also cause problems. List two.

Answer 44

susceptibility to encapsulated bacteria due to depletion of C3
Autoimmune-like disease: complement activity destroys RBCs (paroxysmal nocturnal hemoglobinuria) bc no CD59 or CD59 anchor protein&raquo_space; excessive MAC formation on RBCs.

Question 45

Deficiencies of C1, C2, or C4 all result in ______________ disease. Why?

Answer 45

immune complex disease. Small immune complexes created by antibody binding to its antigen are usually further opsonized by activation of the classical complement cascade, promoting uptake and destruction of these small immune complexes.

Question 46

C3 deficiency results in:

This leaves the pt susceptible to bacterial infections, especially ________ bacteria.

Answer 46

No ability to activate any of the complement cascades.

Encapsulated bacteria

Question 47

This factor is a critical component of the alternative pathway. Susceptibility to encapsulated bacteria and Neisseria results from this deficiency.

Answer 47

Factor D

Question 48

Deficiency of this factor is similar in phenotype to a C3 deficiency because the final result is depletion of C3b. In this condition, there is reduced cleavage of C3b or C4b, allowing for abnormally high amounts of C3 convertase to form, resulting in an accelerating reaction that uses up all of the C3.

Answer 48

Factor I

Question 49

Treatment of paroxysmal nocturnal hemoglobinuria is:

Answer 49

Allogenic bone marrow transplantation. Complement C5-specific monoclonal antibody is effective at reducing the need for blood transfusions, improving quality of life and reducing risk of thrombosis.