Immuno Diseases Flashcards

1
Q

Cyclic Neutropenia: description, inheritance pattern, cause

A

Monthly neutropenia (cycles through highs and lows). Clinically serious during episodes of neutropenia

Mutation in Neutrophil elastase (ELANE)

Autosomal dominant

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2
Q

Chediak-Higashi Syndrome: description, inheritance pattern, cause, treatment

A

Abnormal WBC inclusions (Dohle bodies), lymphoma

Caused by LYST gene (lysosomal trafficking regulator)

Autosomal recessive

Treatment: bone marrow transplant

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3
Q

Myeloperoxidase inheritance pattern?

A

Autosomal recessive

Clinically mild (late enzyme)

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4
Q

Chronic Granulomatous Disease description, cause and inheritance pattern

A

“Broken” NADPH enzyme prohibits the creation of superoxide and inhibits phagocytes from digesting what they’ve taken up. We then end up with granulomas.

Inheritance pattern can be x-linked or autosomal recessive (multiple parts of NADPH enzyme can be defunct)

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5
Q

Leukocyte Adhesion Deficiency description and inheritance pattern

A

Defective leukocyte attachment to endothelium, defective entry of WBCs into sites of infection, and defective innate immune response leading to bacterial infection

Autosomal recessive

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6
Q

What are the two subtypes of Leukocyte Adhesions Deficiency and where is their defect?

A

LAD-1: CD18 deficiency (part of LFA-1 and MAC-1); decreased adhesion

LAD-2: Sialyl-Lewis^x deficiency; decreased rolling

***LAD-1 is more severe. Adhesion is more important than rolling

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7
Q

What is the clinical phenotype seen in a patient with Leukocyte Adhesion Deficiency?

A

Widespread bacterial infections in infancy, impaired pus formation, impaired wound healing, persistent leukocytosis, and delayed umbilical cord separation (LAD-1! About 3 weeks)

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8
Q

Bruton’s X-linked agammaglobulinemia (XLA) description, cause, inheritance pattern, treatment

A

Defective B-cell development. B-cells are arrested in the large Pre-B cell stage due to defective Bruton tyrosine kinase (BTK) enzyme.

Present in infancy/early childhood (have mom’s IgG at first!)

Problem with some viruses too like enterovirus, coxsackie, and echovirus

Also present with arthritis

X-linked recessive & rarely autosomal recessive

Treatment: IV immunoglobulins (IVIG)

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9
Q

Do men with XLA have follicles and germinal centers in their lymph nodes?

A

No, because they don’t have B cells to develop

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10
Q

People with this disease lack tonsils and adenoids

A

XLA

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11
Q

Hyper-IgM description and causes

A

Defective class switching (so we end up with a ton of IgM)

Defects in:
1. CD40L-CD40 signaling. CD40L on CD4 cell, CD40 on B cell, or signaling via NEMO to NFkB is broken

  1. B cell defects in AID (Activation-Induced cytidine deaminase) or UNG (Uracil-DNA-glycosylase - DNA repair enzyme)
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12
Q

What is the most common defect that causes Hyper-IgM syndrome and what is its inheritance pattern?

A

Broken CD40L on CD4 T Cell

X-linked recessive

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13
Q

Will there be issues with macrophage actions in hyper-IgM syndrome?

A

If there is a defect in CD40L-CD40 signaling (primarily issues with CD40L or the downstream TFs, aka NEMO) then yes

CD40 defects will affect B cells and the other class-switching defects are B cell specific

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14
Q

In a patient with hyper-IgM syndrome, were their B cells stimulated by thymus dependent or thymus independent antigen?

A

independent

we have defects in signaling between CD4 t cells and B cells! No message is getting between them

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15
Q

What type of leukocyte is needed to control Pneumocystis?

A

Macrophage!

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16
Q

What is the most common inherited immune deficiency?

A

IgA deficiency

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17
Q

What are the consequences of IgA deficiency?

A

Most people are asymptomatic; symptomatic if IgG deficiency also present

Sinopulmonary and GI tract infections present

**Sepsis does not occur because IgM and IgG are normal

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18
Q

What is transient hypogammaglobulinemia of infancy?

A

Delayed production of IgG by the infant. Eventually maternal IgG wanes and there is a transient period with low levels. Self-limited; eventually IgG production increases

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19
Q

What is common variable immunodeficiency (CVID)?

A

A late-onset form of panhypogammaglobulinemia. Onset in childhood or adulthood

Causes: defective terminal differentiation of B cell to plasma cell, defective T cell help to B cell or autoimmunity

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20
Q

What are the gene mutations known so far in CVID?

A

TACI, CD19, ICOS

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21
Q

IL-2R gamma chain deficiency description, cause, and inheritance pattern

A

Common gamma chain shared with multiple receptors is defective. Two of those receptors are necessary for T cell and NK cell development

X-linked recessive inheritance pattern

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22
Q

What would the levels of T cells, NK cells, and B cells be in a person with IL-2R gamma chain deficiency?

A

T Cell and NK cells would be deficient and B cells would be normal

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23
Q

Adenosine deaminase deficiency (ADA) description, cause, and inheritance pattern

A

ADA is needed for purine salvage pathway, without this the metabolites of ADA are toxic to common lymphoid precursor

Less CLP means less T, B, and NK cells

Autosomal recessive

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24
Q

What is Wiskott-Aldrich syndrome? Inheritance pattern?

A

T cell immunodeficiency

WASP protein defect involved in lymphocyte and platelet development (involved w/ cytoskeleton)

X-linked recessive

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25
Q

Clinical phenotype in Wiskott-Aldrich Syndrome:

A

Lack of antibody production to polysaccharide antigens, thrombocytopenia (& small platelets), eczema

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26
Q

What is ataxia telangectasia?

A

T cell immunodeficiency

Defect in ATM gene (seronine/threonine kinase) involved in VDJ recombinations

autosomal recessive

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27
Q

Clinical phenotype in ataxia telangectasia?

A

Loss of coordination (ataxia)/gait disturbance, dilated capillaries of skin and conjunctiva, T cell immune deficiency, predisposition to leukemias and lymphomas

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28
Q

DiGeorge Syndrome description, cause, and inheritance pattern

A

Malformation of the 3rd & 4th pharyngeal pouches (endoderm!) leading to congenital heart disease: aortic arch, hypoparathyroidism (low calcium), thymic aplasia or hypoplasia, unusual facial appearance

Autosomal dominant on chromosome 22

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29
Q

Sjorgren Syndrome (Sicca syndrome): tissue/organ involvement, clinical presentation, and autoantibodies

A

Destruction of lacrimal and salivary glands

Presents with dry eyes (conjunctivitis, corneal ulceration, corneal perforation) and dry mouth (caries, oral cancer)

AutoAb: SS-A/Ro, SS-B/La

Note: can be primary (unassociated with other autoimmune diseases) or secondary (associated with other autoimmune diseases)

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30
Q

Scleroderma (aka systemic sclerosis): tissue/organ involvement, clinical presentation, and autoantibodies

A

Involves skin & esophagus

Presents with fibrosis of hands, reflux in esophagus, and loss of facial expression

AutoAb: Scl-70

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31
Q

Dermatomyositis: tissue/organ involvement, clinical presentation, and autoantibodies

A

Skeletal muscle & skin involvement

Presents with skin rash & skeletal muscle tenderness and weakness

AutoAb: anti-Jo-I

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32
Q

Goodpasteur sydrome: tissue/organ involvement, clinical presentation, and autoantibodies

A

Involves kidney and lungs

Key clinical presentation: glomerulonephritis and pulmonary hemorrhage

AutoAb against glomerular basement membrane (seen as linear deposits; type II hypersensitivity)

33
Q

What are the five classic signs of glomerulonephritis?

A

Hypertension, Edema, Hematuria, Proteinuria, and RBC casts

34
Q

Reactive arthritis (formerly Reiter syndrome): tissue/organ involvement, clinical presentation, and autoantibodies

A

Involves urethra/cervix, joints, and eye

Presents with urethritis or cervicitis, arthritis, and conjunctivitis

Genetic predisposition: young males with HLA-B27

35
Q

Rheumatic fever: tissue/organ involvement, clinical presentation, and autoantibodies

A

Involves heart, joints, CNS, and skin

Presents with carditis/valvulitis, arthritis, Syndenham chorea (St. Vitus dancing), Erythema marginatum & subcutaneous nodules

Caused by cross reaction of M protein after group A beta-hemolytic streptococcus infection

36
Q

Rheumatoid arthritis: tissue/organ involvement, clinical presentation, and autoantibodies

A

Involves joints (+/- fever and extra-articular disease)

Presents with destructive, erosive arthritis, systemic inflammation, rheumatoid nodules & vasculitis, pleural-pulmonary manifestations. Ulnar deviation of hands common

AutoAb: Rheumatoid factor & Anti-CCP (better marker for RA)

37
Q

What tissues/organs are involved in SLE?

A

Skin, joints, kidney, serosal surfaces, CNS, heart, RBCs, WBCs, platelets

38
Q

What is Mixed Connective Tissue disease (MTCD)?

A

Autoimmune disease that presents with SLE, polymyositis, rheumatoid arthritis, systemic sclerosis/scleroderma

39
Q

Who is most likely to be affected by SLE?

A

African American women in their reproductive years

40
Q

Clinical presentation of SLE?

A

KNOW THESE: Glomerulonephritis, splenomegaly, pleuritis (pain on inspiration), pleural effusion, heart issues

Plus: malar rash, discoid rash, arthritis, occlusion of small blood vessels leading to seizures and psychosis, hemolytic anemia

41
Q

How many SLE criteria do you need for diagnosis?

A

More than 4

42
Q

What levels of C4 and C3 do you expect in a patient with SLE?

A

Decreased levels (complement is consumed with immune complexes)

43
Q

In an asymptomatic patient with SLE, a decline in what will predict an episode of glomerulonephritis?

A

Complement

44
Q

What type of gammaglobulinemia is observed in chronic inflammatory, autoimmune or infectious conditions?

A

Polyclonal hypergammaglobulinemia (the gamma “hump” is higher than normal on the SE chart)

45
Q

Three steps of immune complex diseases?

A
  1. Formation of ICDs in circulation
  2. Deposition of ICDs in blood vessel walls/joints/serosa
  3. Inflammatory reaction at site of deposition
46
Q

What self-antigens are frequently targeted in collagen-vascular diseases?

A

Ubiquitous ones (non-organ specific) like DNA, histones, RNPs, nucleolar antigens

47
Q

What autoantibody test is commonly ordered as an initial screen for autoimmunity?

A

Antinuclear antibodies (ANA)

Rim pattern on ANA = SLE

Homogenous pattern on ANA = SLE, RA, or drug-induced ANA, etc

48
Q

What two systems are generally not involved in drug-induced LE?

A

Renal and CNS

49
Q

Most common causes of death in SLE?

A

Renal failure and intercurrent infections

50
Q

Maternal antibodies crossing the placenta can lead to the clinical manifestation of what?

A

Neonatal lupus

51
Q

Is SLE a humoral or CMI disease?

A

Humoral (type II and type III hypersensitivities)

52
Q

In what autoimmune disease would you expect to see Syndenham Chorea?

A

Rheumatic fever

53
Q

What is Lymphocytic Hypophysitis?

A

Lymphocytic hypophysitis is a condition in which the pituitary gland becomes infiltrated by lymphocytes , resulting in pituitary enlargement and impaired function.

Believed to be an autoimmune disease. Only way to diagnose is via biopsy

54
Q

What does IHC staining of lymphocytic hypophysitis often show?

A

Mixed infiltrate of CD3-positive T cells and CD20-positive B cells

55
Q

Streptococcus infection M protein has a cross-reactive self-antigen, cardiac myosin, that when attacked by antibodies causes what autoimmune disease?

A

Rheumatic Fever

56
Q

Klebsiella infection nitrogenase has a cross-reactive self-antigen, HLA-B27, that when attacked by antibodies causes what autoimmune diseases?

A

Reactive Arthritis (Reiter syndrome) and Ankylosing spondylitis

57
Q

Mycobacterial antigen, proteoglycan wall component, has a cross-reactive self-antigen, cartilage protein, that when attacked by antibodies causes what autoimmune disease?

A

Rheumatoid Arthritis

58
Q

What are three examples of sequestered antigens that can cause autoimmunity when exposed?

A

Retinal antigens following trauma, spermatozoa (in infertility), and myelin basic protein (MBP) in MS

59
Q

What autoantigens are present in T1DM?

A

Glutamic acid decarboxylase

60
Q

What autoantigens are present in Hashimoto thyroiditis?

A

Thyroperoxidase, thyroglobulin

61
Q

What autoantigens are present in Pernicious anemia?

A

H+/K+ ATPase pump

62
Q

What autoantigens are present in Celiac disease?

A

Transglutaminase

63
Q

What autoantigens are present in Graves Disease?

A

TSH receptor (agonistic autoantibody)

64
Q

What autoantigens are present in myasthenia gravis?

A

Acetyl choline receptor

65
Q

What autoantigens are present in MS?

A

Myelin basic protein

66
Q

What autoantigens are present in SLE?

A

dsDNA and anti-Sm (smith)

67
Q

Higher iodine intake is associated with what autoimmune disease?

A

Hashimoto’s thyroiditis

increased iodination of thyroglobulin increases its immunogenicity

68
Q

T1DM is associated with what congential syndrome?

A

Rubella

69
Q

What is Autoimmune Polyglandular Syndrome Type 1 (APS 1)? Inheritance mechanism?

A

Mutations in AIRE (autoimmune regulator gene that is a TF). Autosomal recessive

Must have 2/3:

  1. Addison disease (or adrenal autoantibodies)
  2. Mucocutaneous candidiasis
  3. Hypoparathyroidism

Also called APECED. Presents as early as infancy

70
Q

What is Autoimmune Polyglandular Syndrome Type 2 (APS 2)? Inheritance mechanism?

A

Polygenic inheritance affecting women more than men. Onset in childhood or early adulthood

Diagnosed when Addison’s Disease occurs together with autoimmune thyroid disease (Hashimoto>Graves) and/or T1DM

71
Q

What is IPEX syndrome?

A

Immunodysregulation Polyendocrinopathy Entereopathy X-linked

X-linked recessive inheritance

Mutations in FoxP3 (normally expressed in Tregs). Without FoxP3 you can’t immunmodulate

All kinds of autoimmune presentations. He showed Bullous Pemphigoid!!

72
Q

What is autoimmune proliferative disorder? Inheritance pattern?

A

Failure to control lymphocyte proliferation via Fas-FasL interactions

autosomal dominant

73
Q

How is Autoimmune Thyroid Disease inherited?

A

Autosomal dominant

74
Q

Which HLA alleles are associated with T1DM?

A

HLA-DR3 and HLA-DR4

75
Q

What HLA allele is protective for T1DM?

A

HLA-DR2

76
Q

HLA-DR2 is protective for T1DM but increases risk for what two diseases?

A

MS and SLE

77
Q

HLA-B27 is associated with what two diseases?

A

Ankylosing spondylitis and Reactive arthritis

78
Q

Among autoimmune diseases, which three “common” ones occur as often in men as in women?

A
  1. T1DM
  2. Ankylosing spondylitis (Side note: associated with Klebsiella infection and HLA-B27 too!)
  3. Polyarteritis nodosa (type of vasculitis)