Type IV Hypersensitivity and Autoimmunity Flashcards

1
Q

Autoimmune hemolytic anemia

Ab against cell-surface/matrix antigen (type II)

A

Autoantigen: Rh blood group antigens, I antigen
Consequence: Destruction of RBCs by complement and phagocytes, anemia

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2
Q

Autoimmune thrombocytopenia purpura

Ab against cell-surface/matrix antigen (type II)

A

Autoantigen: Platelet integrin gpIIb:IIIa
Consequence: Abnormal bleeding

Increased bleeding time

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3
Q

Goodpasture’s syndrome

Ab against cell-surface/matrix antigen (type II)

A

Autoantigen: Non-collagenous domain of basement membrane collagen type IV (IgG against alpha3 chain of the collage)
Consequence: Glomerulonephritis, pulmonary hemorrhage, hemoptysis, dyspnea, anemia

Treatment: plasma exchange, immunosuppressive drugs

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4
Q

Pemphigus vulgaris

Ab against cell-surface/matrix antigen (type II)

A

Autoantigen: Epidermal cadherin
Consequence: Blistering of skin

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5
Q

Pemphigus foliaceus

Ab against cell-surface/matrix antigen (type II)

A

Autoantigen: Desmoglein
Consequence: Mild blistering of skin

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6
Q

Acute rheumatic fever

Ab against cell-surface/matrix antigen (type II)

A

Autoantigen: Streptococcal cell wall antigens; antibodies cross-react with cardiac muscle
Consequence: Arthritis, myocarditis, late scarring of heart valves

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7
Q

Graves’ disease

Ab against cell-surface/matrix antigen (type II)

A

Autoantigen: Thyroid-stimulating hormone receptor (mimic TSH)
Consequence: Hyperthyroidism (anti-TSH receptor autoantibodies)

MHC class II on thyroid cells; HLA-DR3

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8
Q

Myasthenia gravis

Ab against cell-surface/matrix antigen (type II)

A

Autoantigen: Acetylcholine receptor
Consequence: Progressive weakness

Treatment: Pyridostigmine (acetylcholinesterase inhibitor); Azathioprine (immunosuppressive); Thymectomy

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9
Q

Type 2 diabetes (insulin-resistant diabetes)

Ab against cell-surface/matrix antigen (type II)

A

Autoantigen: Insulin receptor (antagonist)
Consequence: Hyperglycemia, ketoacidosis

Insulin is bound by antibodies and is not effective

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10
Q

Hypoglycemia

Ab against cell-surface/matrix antigen (type II)

A

Autoantigen: Insulin receptor (agonist)
Consequence: Hypoglycemia

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11
Q

Subacute bacterial endocarditis

Immune-complex disease (type III)

A

Autoantigen: Bacterial antigen
Consequence: Glomerulonephritis

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12
Q

Mixed essential cryoglobulinemia

Immune-complex disease (type III)

A

Autoantigen: Rheumatoid factor IgG complexes (with or without hepatitis C antigens)
Consequence: Systemic vasculitis

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13
Q

Systemic lupus erythematosus

Immune-complex disease (type II and III)

A

Autoantigen: DNA, histones, ribosomes, snRNP, scRNP
Consequence: Glomerulonephritis, vasculitis, arthritis (deposition of immune complexes)

HLA-DR2, HLA-DR3

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14
Q

Type 1 diabetes (insulin-dependent diabetes mellitus)

T-cell-mediated disease (type II and IV)

A

Autoantigen: Pancreatic beta-cell antigen
Consequence: Beta-cell destruction by antibodies and T-cells

HLA-DR3, HLA-DR4

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15
Q

Rheumatoid arthritis

T-cell-mediated disease (type II and IV)

A

Autoantigen: Rheumatoid factor: Synovial joint antigen - Fc region of IgG (create IgM/G/A to it)
Consequence: Joint inflammation and destruction by CD4, CD8, B-cells, neutrophils, macrophages

HLA-DR4

Treatment: Anti-inflammatory / immunosuppressive drugs (anti-TNF-alpha)

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16
Q

Multiple sclerosis

T-cell-mediated disease (type II and IV)

A

Autoantigen: Myelin basic protein, proteolipid protein
Consequence: Brain degeneration, paralysis (inflammatory demyelination)

Activated T-cells are implicated: IL-17 producing Th17 cells
- also IFN-gamma

Treatment: IFN-beta injection (suppress Th17); immunosuppressive drugs; Natalizumab (anti-VLA4/integrin)

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17
Q

APECED (Autoimmune PolyEndocrinology Candidiasis Ectodermal Dystrophy)

A

Mutations in AIRE gene
- defective thymic deletion of autoreactive T cells (b/c can’t express peripheral antigens in thymus)

The defective negative selection leads to autoimmunity

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18
Q

IPEX (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked syndrome)

A

Mutations in T-cell transcription regulator FOXP3
- FOXP3 necessary for generation of Tregs

–> no immune cell regulation

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19
Q

HLA allotype for ankylosing spondylitis?

A

B27

20
Q

HLA allotype for celiac disease?

A

DQ2 and DQ8

wheat flour gluten peptide-specific CD4+ T-cells
–> auto-antibodies to gut anti-transglutaminase (villi destruction)

21
Q

HLA allotype for multiple sclerosis?

A

DQ6

22
Q

Infections and autoimmunity:

Group A Streptococcus (pyogenes)

A

HLA: unknown

Consequence: Rheumatic fever (carditis, polyarthritis)

23
Q

Infections and autoimmunity:

Chlamydia trachomatis

A

HLA: HLA-B27

Consequence: Reiter’s syndrome (can’t pee, can’t see, can’t climb a tree)

24
Q

Infections and autoimmunity:

Campylobacter jejuni

A

HLA: HLA-B27

Consequence: Reactive arthritis (…and Guillain-Barre?)

25
Q

Infections and autoimmunity:

Borrelia burgdorferi

A

HLA: HLA-DR2, DR4

Consequence: Chronic arthritis in Lyme disease

26
Q

Infections and autoimmunity:

Coxsackie A, B

A

HLA: HLA-DQ2, HLA-DQ8, DR4

Consequence: Type 1 diabetes

27
Q

Infection/inflammation induces ____, which increases _____ expression on tissue cells, inducing T cells and autoimmunity

A

IFN-gamma; MHC class II

autoimmune thyroid disease

28
Q

Autoimmune hemolytic anemia is a type II hypersensitivity rxn where anti-erythrocyte autoantibodies bind and induce…

A
  • Phagocytosis in spleen by FCR+ cells
  • Opsonization and phagocytosis (CR1+ cells) in spleen
  • Complement activation and intravascular hemolysis
29
Q

What is chronic thyroiditis? (Hashimoto’s Disease)

A

Type II and IV

Antithyroglobulin and antithyroid peroxidase (decrease thyroid hormone; destroy thyroid - complement-mediated)

30
Q

What is Crohn’s Disease?

A

Abnormality of mucosal T-cell regulation –> granulomatous reaction; bacteria in gut induce immune response

31
Q

What is ulcerative colitis?

A

Continuous mucosal ulceration; possibly Type II

32
Q

What is pernicious anemia?

A

Impaired absorption of B-12 (required for thymine synthesis) due to lack of intrinsic factor (in gastric secretions)

Anti-parietal cell antibodies and anti-intrinsic factor antibodies

33
Q

What is autoimmune chronic acute hepatitis?

A

HLA-B8/DR3

Liver cells express MHC II; anti-liver antibodies are present

34
Q

What is polyomyositis / dermatomyositis?

Type IV

A

Skeletal muscle disease; serum muscle enzymes elevated

HLA-DR3, HLA-DR

35
Q

How does smoking lead to autoimmunity?

A

Increase PAD enzyme –> Injury –> convert arginine to citrulline –> citrulline residue generation (presented by MHC II) –> activation of CD4

36
Q

What is acute disseminated encephalomyelitis?

A

Follows infection / vaccination

Type IV directed at Myelin basic protein, other myelin antigens

37
Q

What is acute inflammatory polyneuropathy (Guillain-Barre)?

A

Type II / IV

Peripheral nerve antigens

Plasmapharesis / Ig therapy

38
Q

Type II, III, and IV mediate transplant rejection. Which kinds, respectively?

A

II: hyperacute
III: chronic
IV: acute

39
Q

List some antigens that cause delayed-type hypersensitivity (DTH) and consequences.

A

Proteins (injected): insect venom, Mycobacterial proteins (tuberculin, lepromin)

  • erythema, induration, cellular infiltrate, dermatitis (local skin swelling, in general - deeper)
40
Q

List some antigens that cause contact hypersensitivity and consequences.

A

Haptens: Pentadecacatechol (poison ivy), DNFB
Small metal ions: Nickel, chromate

  • (local epidermal reaction; more shallow) erythema, cellular infiltrate, vesicles, intraepidermal abscesses
41
Q

List some antigens that cause gluten-sensitive enteropathy (celiac disease) and consequences.

A

Gliadin

  • villous atrophy in small bowel, malabsorption
42
Q

Langerhans cells are in the ______

Dendritic cells are in the ______

A

Epidermis; dermis

Also in dermis: blood vessel, lymph vessels, T cells, NK cells, mast cells, macrophages, etc.

43
Q

Lymphocytes in the skin have…

A
  • CLA (cutaneous lymphocyte antigen), a specialized adhesion molecule
  • P-/E- selectin ligands
  • Chemokine receptors (CCR4, CCR8, CCR10)
44
Q

Secretions by Th1 cells in skin DTH reaction:

A
  • Chemokines: IL-8, IP-9, MIG
  • Cytokines: IFN-gamma, IL-3, GM-CSF
  • Cytotoxins: TNF-alpha, LT, IL-1
45
Q

Treatment of contact hypersensitivity…

A

Corticosteroids (suppress inflammation and activate immune cells)

46
Q

Pharmacological control of MS:

A

(in bold) Rapamycin and Fingolimod

Natalizumab, Daclizumab, Azathioprine, Methotrexate