Hypersensitivity, Autoimmunity and Skin, Muscle and Joints

Question 1

What are the four types of hypersensitivity reactions?

Answer 1

Type I/Immediate hypersensitivity (allergies)
Type II/Antibody-mediated diseases
Type III/Immune complex-mediated diseases
Type IV/T cell-mediated diseases

Question 2

What is a type I hypersensitivity reaction?

Answer 2

Common allergies

Question 3

Atopy

Answer 3

Propensity to develop immediate hypersensitivity

Question 4

What causes Type I hypersensitivity?

Answer 4

Triggered by environmental antigens that elicit strong Th2 response and IgE production

Question 5

What signalers are attributed to immediate hypersensitivity?

Answer 5

Vasoactive amines and lipid mediators

Question 6

What signalers are attributed to late phase reaction in allergies?

Answer 6

Cytokines

Question 7

What does IgE bind to in Type I reactions?

Answer 7

FcERI on mast cells

Question 8

What does release of vasoactive amines (histamine) cause?

Answer 8

Vascular dilation

Smooth muscle contraction

Question 9

Secretion of what two cytokine causes inflammation?

Answer 9

TNF
IL-4
(occurs in late-phase/re-exposure)

Question 10

What does anaphylaxis cause?

Answer 10

Fall in BP caused by vasodilation leading to shock and airway obstruction due to laryngeal edema

Question 11

What causes hives?

Answer 11

Localized mast cell degranulation and dermal microvascular hyperpermeability

Question 12

What is Type II hypersensitivity most commonly caused by?

Answer 12

Antibodies specific for normal cell or tissue antigens

Question 13

What causes phagocytosis in type II?

Answer 13

IgG binding to tissue and phagocytes binding to FcyRI receptors
C3b binding to C3b receptor on phagocytes

Question 14

What antibodies are found in type II?

Answer 14

IgM and IgG for complement fixation

Question 15

What complements are chemoattractants causing inflammation?

Answer 15

C3a and C5a

Question 16

When does pemphigus vulgaris present in life?

Answer 16

40-60 years

Question 17

What causes pemphigus vulgaris?

Answer 17

IgG autoantibodies specific for desmogleins in desmosomes

Question 18

What are the three phases in immune complex-mediated hypersensitivity type III?

Answer 18

1. ) Immune complex formation
2. ) Immune complex deposition
3. ) Inflammation and tissue injury

Question 19

What are the therapeutic approaches to Type II and Type III hypersensitivity?

Answer 19

1.) Corticosteroids (anti-inflammatory)
2,) Plasmapheresis
3.) Administration of IV IgG: may turn off B cells and inflammatory binding cells
4.) Biologics: monoclonal antibodies, soluble receptors

Question 20

How do Th1 cells facilitate Type IV?

Answer 20

Helper T cells release IFN-y activating macrophages which release TNF, IL-1, chemokines

Question 21

How do CD8+ T cells facilitate Type IV?

Answer 21

Kill antigen-expressing cells via specific recognition of class I MHC-peptide complex

Question 22

What facilitates hypersensitivity in rheumatoid arthritis?

Answer 22

CD4+ helper T cells

Question 23

What CD4 helper T cells produce inflammatory cytokines in RA?

Answer 23

Th1 -> IFN-y -> Mac activation
Th17-> IL-17 -> neutrophil and monocytes
Macrophages -> TNF and IL-1 -> inflammation; proteases that degrade hyaline

Question 24

Antibodies produced in RA are specific for what?

Answer 24

Citrullinated peptides

Question 25

How are Citrullinated proteins made?

Answer 25

Self proteins in RA have arginine converted into citrulline

Question 26

What happens to Citrullinated proteins?

Answer 26

Antibodies against Citrullinated proteins form immune complexes which deposit in joints (Type III)

Question 27

What promotes Citrullinated proteins?

Answer 27

Inflammation such as infection or smoking

Question 28

What are rheumatoid factors?

Answer 28

IgM and IgA antibodies specific for their own IgG

Question 29

What are the three therapies for Type IV?

Answer 29

Corticosteroids Methotrexate: inhibits DNA synthesis by blocking metabolism of folic acid Biologics