Immunodeficiency

Question 1

What are the 3 types of autoimmune diseases? What is each one dependent upon?

Answer 1

Systemic: Ab-dependent damage

Organ Specific: Ab-dependent damage & T-cell dependent damage.

Question 2

How does Systemic Ab-dependent damage occur?

Answer 2

Immune complex mediated damage: Immune complexes activate complement + bind to Fc receptors on phagocytes causing inflammation + tissue damage.

Question 3

Describe the systemic Ab-dependent disease systemic lupus erythematosus (SLE).

Answer 3

Ab-Ag complexes lodge into capillaries bursting the blood vessels creating a “butterfly” like rash mostly in the face.

Question 4

Describe the systemic Ab-dependent disease Rheumatoid arthritis (RA).

Answer 4

Self Antibodies are made against IgG rheumatoid factor or collagen, creating a reaction against self.

Question 5

What is a common complication of systemic lupus erythematosus (SLE)?

Answer 5

Glomerular Nephritis: immune complexes (DNA+anti-DNA) get trapped on the kidney endothelium where activated macrophages bind, causing damage to the endothelium and basement membrane causing kidney dysfunction (proteinuria).

Question 6

In systemic lupus erythematosus (SLE), what do macrophages recognize in order to bind to the immune complex

Answer 6

Either Fc-Fab complex or complement on Fc.

Question 7

How does organ specific Ab-dependent damage occur?

Answer 7

Ab’s react against organ specific antigens.

Question 8

Describe Graves disease.

Answer 8

Increase thyroid function - Ab’s stimulate the release of thyroid hormones when they bind to the receptor for thyroid stimulating hormone.

Question 9

What is Graves disease also known as?

Answer 9

Hyperthyroidism or Thyrotoxcosis

Question 10

Describe Hashimoto’s thryoiditis.

Answer 10

Decreased thyroid function-Ab’s cause the progressive destruction of the thyroid when they are in contact with Thryoglobulin.

Question 11

What is Hashimoto’s thryoiditis also know as?

Answer 11

Hypothyroidism

Question 12

Describe Myasthemia Gravis.

Answer 12

Muscle weakness due to Ab’s binding and thus blocking the acetylcholine receptor which impairs nerve impulses + fixes complement, recruiting phagocytes and causing damage

Question 13

In Myasthemia Gravis, what does the breakdown of acetylcholine receptors inhibit and what does this lead to macrophysically?

Answer 13

Inhibits Na+ influx –> no muscle contraction –> ocular movement dysfunction

Question 14

How does Organ specific T cell-dependent damage occur?

Answer 14

T-cell damaged by cytokines, cytotoxicity, inflammation, etc.

Question 15

Describe Insulin-dependent diabetes mellitus (type I or juvenile-onset diabetes).

Answer 15

T-cells cause the destruction of the insulin producing beta cells in the islets of Langerhans in the pancreas.

Question 16

Describe Multiple Sclerosis.

Answer 16

T-cells are implicated in the disease featuring damage to the CNS.

Question 17

What is diabetes linked to?

Answer 17

Specific HLA alleles; 96% of diabetics have either or both HLA DR4 or DR3.

Question 18

List some ways that immunodeficiency diseases can be acquired.

Answer 18

1. Malnutrition
2. Immunosuppressant drugs/radiation
3. AIDS

Question 19

List some ways that immunodeficiency diseases can be inherited.

Answer 19

SCID, IgA deficiency

Question 20

In genetic basis oh inherited immunodeficiency, most disease traits are recessive or dominant? Many or X-linked or Y-linked?

Answer 20

Recessive; X-linked

Question 21

Deficiencies of Ab, complement or phagocyte function cause an increased risk of infection with what type of bacteria?

Answer 21

Pyogenic (pus forming) bacteria

Question 22

What is the pathway for bacterial toxins?

Answer 22

Ab’s neutralize toxins –> ingested by macrophage

Question 23

What is the pathway for bacteria in the extracellular space?

Answer 23

Opsonization of bacteria by Ab’s –> ingested by macrophage

Question 24

What is the pathway for bacteria in plasma?

Answer 24

Complement activation –> lysis and ingestion

Question 25

Is deficiency of T-cells or B-cells worse in immunodeficiency?

Answer 25

T-cells deficiency is worse.

Question 26

What does SCID stand for and what does describe?

Answer 26

“Severe Combined Immunodeficiency Disease” – Lack B and T cells

Question 27

How are deficiencies of T-cell function presented in individuals?

Answer 27

Increased susceptibility to infection - recurrent/chronic/opportunist

Autoimmune complications – SLE or RA

Gastrointestinal Disease – Chronic diarrhea/malnutrition

Hematologic Disease – Anemia, leucopenia, thrombocytopenia

Question 28

What types of laboratory diagnosis are there for the evaluation of B and T cell function?

Answer 28

Ig levels/titers, DTH skin tests, FACS analysis with mABs specific for T/B cells, Mitogen responses

Question 29

What types of laboratory diagnosis are there for the evaluation of phagocyte function?

Answer 29

White blood count/differential. NBT test (oxidative burst). Chemotaxis/phagocytosis/intracellular killing.

Question 30

What types of laboratory diagnosis are there for the evaluation of the complement system?

Answer 30

Assays for hemolytic complement

Question 31

How do you treat B cell defects?

Answer 31

Replacement immunoglobulin therapy. Antibiotics.

Question 32

How do you treat T cell defects?

Answer 32

Bone marrow transplant. Replacement immunoglobulin therapy. Antibiotics.

Question 33

How do you treat phagocyte defects?

Answer 33

Antibiotics. Anti-fungal drugs.

Question 34

How do you treat complement defects?

Answer 34

Antibiotics.

Question 35

How do you treat SCID?

Answer 35

Replacement immunoglobulin therapy. Antibiotics. Bone marrow transplant.

Question 36

Is deficiency in IgA fatal? How many people are affected by this?

Answer 36

No, has potential association with recurrent respiratory infections, but IgM can reach secretions (substitute for IgA); 1/700 people

Question 37

What disease is related to IgA deficiency?

Answer 37

Common Variable Hypogammaglobulienemia – increase susceptibility to pyogenic bacteria (symptomatic 15-35 years old).

Question 38

A defect in what leads to Bruton’s X-linked Agammaglobulinemia (XLA).

Answer 38

Defect in B cell development where very few B cells mature.

Question 39

The above disease has a defect in what gene?

Answer 39

BTK gene (a tyrosine kinase), which causes a signaling defect and impairs B cell development.

Question 40

Describe Huper IgM Syndrome.

Answer 40

Defect in a form of costimulation where the absence of CD40 ligand disables T cell help for B cells (IgG, A, E decrease) & T cells are impaired, cannot make germinal centers.

Question 41

What happens in DiGeorge syndrome? Bare Lymphocyte Syndrome?

Answer 41

No thymus; MHC class II not made (CD4 T cells can’t develop).

Question 42

Impaired T cell function causes failure in?

Answer 42

Failure to fight viral/fungal infections and failure to help B cells (which can’t make antibody responses and susceptible to bacteria).

Question 43

Describe X-linked SCID.

Answer 43

Defect in gene encoding a common component of several cytokine receptors (impairs gamma chain, IL-2,4,7,15, B cell function, T cell development).

Question 44

Name 2 enzyme disorders that cause SCID?

Answer 44

Adenoside deaminase deficiency & nucleoside phosphorylase deficiency.

Question 45

What do adenoside deaminase deficiency & nucleoside phosphorylase deficiency disorders cause?

Answer 45

An accumulation of dATP which reduces ribonucleotide reductase activity inhibiting DNA synthesis and ↓ #’s of B/T cells.

Question 46

Describe Chronic Granulomatous Disease (CGD).

Answer 46

Phagocyte defect where inability to generate a respiratory burst due to the defect in genes for NADPH oxidase (normally generate superoxide ions). This causes failure to kill ingested microbes.

Question 47

Individuals with the Chronic Granulomatous Disease are susceptible to what bacteria?

Answer 47

Staphylococci. Pseudonomas. Aspergillus.

Question 48

What is the most severe complement deficiency?

Answer 48

C3 deficiency – susceptible to pyogenic bacteria

Question 49

What is the most common complement deficiency?

Answer 49

C2 deficiency

Question 50

Which complement deficiency inhibits Membrane Attack Complex (MAC) formation?

Answer 50

C5,6,7,8,9 deficiencies (increased neisserial infections).