Hypersensitivity and Autoimmunity

Question 1

What is autoimmune disease?

Answer 1

An autoimmune disease is a disease which involves a failure/breakdown in the part of the immune system which maintains tolerance to self-tissues.

Question 2

Who can develop autoimmune disease?

Answer 2

Anyone.

Question 3

What characterises autoimmune disease in terms of mortality and morbidity?

Answer 3

Low mortality but very high morbidity.

Question 4

Is there a cure for autoimmune disease?

Answer 4

No- therapies are managed on a symptomatic basis rather than a cure basis.

Question 5

What is the loss of tolerance in autoimmune disease usually caused by?

Answer 5

Abnormal selection or lack of control of self-reactive lymphocytes.

Question 6

What are hypersensitivity responses?

Answer 6

Hypersensitivity responses are hyper (too much) responses from the immune system- they may produce tissue injury and cause serious disease.

Question 7

What are the 4 categories of hypersensitivity response?

Answer 7

I, II , III , IV

Question 8

What types of hypersensitivity response are antibody-mediated?

Answer 8

I , II , III

Question 9

What types of hypersensitivity response are T-cell mediated?

Answer 9

IV

Question 10

What types of hypersensitivity responses do autoimmune diseases usually tend to fall into?

Answer 10

II , III , IV

Question 11

What do Type I hypersensitivity reactions involve?

Answer 11

Allergy

Question 12

What happens during Type I hypersensitivity reactions?

Answer 12

Initiated by allergen, stimulating TH2 reactions and IgE production. IgE binds to a FceR1 protein and sensitises mast cells to produce an immune response.

Question 13

What do Type I reactions stimulate?

Answer 13

TH2 reactions and IgE binding to FceR1 proteins to sensitise mast cells.

Question 14

What protein does IgE bind to in order to sensitise mast cells?

Answer 14

FceR1.

Question 15

What are the effects of mast cell stimulation?

Answer 15

Vasodilation, bronchioconstriction, oedema, vascular congestion.

Question 16

What is seen in the immediate hypersensitivity reaction to allergy?

Answer 16

IgE mediation of mast cells to produce vasodilation/oedema/vascular congestion.

Question 17

What is seen in the late-phase hypersensitivity reaction to allergy?

Answer 17

Inflammatory infiltrate rich in eosinophils, neutrophils, and T-cells.

Question 18

When does an immediate hypersensitivity reaction occur?

Answer 18

Within minutes of allergen exposure.

Question 19

When does a late-phase hypersensitivity reaction occur?

Answer 19

Within 2-24 hours of allergen exposure.

Question 20

What is atopy?

Answer 20

Predisposition to allergy- patients more susceptible to autoimmune conditions such as asthma/eczema/thyroiditis.

Question 21

What is higher in atopic patients?

Answer 21

IgE levels.

Question 22

What do Type II hypersensitivity reactions involve?

Answer 22

Cytotoxic cells.

Question 23

What happens in Type II hypersensitivity reactions?

Answer 23

Mediated by IgG/IgM antibodies binding to cell-surface antigens or matrix-associated antigens on basement membrane. This results in complement leading to the inflammatory response or involvement with cytotoxic T-cells.

Question 24

What are Type II hypersensitivity reactions mediated by?

Answer 24

IgG/IgM antibodies binding to cell/matrix antigens.

Question 25

What does mediation result in within Type II hypersensitivity reactions?

Answer 25

Complement- inflammatory response | Cytotoxic cell involvement.

Question 26

Can Type II reactions include autoimmune disease?

Answer 26

Yes- if the antigen involved is a self-antigen.

Question 27

What do Type III hypersensitivity reactions involve?

Answer 27

Formation of immune complexes.

Question 28

What happens in Type III hypersensitivity reactions?

Answer 28

Soluble antigens bind with IgG in a ration that results in the accumulation of immune complexes (aggregates of antibody/antigen). These form on vascular epithelial cells and are not phagocytose so lead to a cascade of inflammatory events. (Mast cells, Complement, Permeability).

Question 29

What are immune complexes?

Answer 29

Aggregates of antibody/antigen.

Question 30

Where do immune complexes form?

Answer 30

Vascular epithelium of blood vessels.

Question 31

Can immune complexes be phagocytosed?

Answer 31

No.

Question 32

What happens during the cascade of inflammatory events caused by immune complexes?

Answer 32

IgG stimulates mast cells Complement activation- pro inflammatory C3a/C5a Increased vascular permeability due to chemotactic recruitment of neutrophils and macrophages.

Question 33

What is recruited in the complement activation in this inflammatory cascade?

Answer 33

C3a / C5a

Question 34

Why is there an increased vascular permeability within the inflammatory cascade?

Answer 34

Chemotactic recruitment of neutrophils and macrophages.

Question 35

How are immune complexes removed?

Answer 35

Lysosomal degradation- results in damage to local cells resulting in coagulation pathway activation.

Question 36

Why is the coagulation pathway activated during Type III reactions?

Answer 36

Localised cell damage due to the lysosomal degradation of immune complexes.

Question 37

What do Type IV hypersensitivity reactions involve?

Answer 37

T-cells.

Question 38

Are Type IV reactions antigen-mediated?

Answer 38

No- regulated by T-cells and involve effector cells.

Question 39

What happens during Type IV hypersensitivity reactions?

Answer 39

Involve tissue damage mediated by activated macrophages and cytotoxic T-cells.

Question 40

What are the 3 types of Type IV reaction?

Answer 40

CD4 Th1- delayed CD4 Th2- inhalation CD8 cytotoxic T lymphocyte- transplant rejection

Question 41

What happens during CD4 Th1 reactions?

Answer 41

Delayed reaction.

Question 42

What happens during TD4 Th2 reactions?

Answer 42

Soluble antigen is inhaled- eosinophil recruitment and activation occurs with cytokine and inflammatory mediator release. Cause of asthma / rhinitis.

Question 43

What happens during CD8 cytotoxic T-lymphocyte reactions?

Answer 43

Cell killing and tissue injury- seen within tissue transplant rejection.

Question 44

What is immunological tolerance?

Answer 44

Immunological tolerance is a state of tolerance in the immune system when it would usually be expected to excite an immunological response.

Question 45

What is the difference between systemic autoimmune disease and tissue-specific autoimmune disease?

Answer 45

Systemic autoimmune disease involves the holistic system whereas tissue-specific autoimmune disease is localised.