T1 L10 Overview & classification of immunological diseases

Question 1

What are the 2 ways an immunological disease can occur?

Answer 1

Immune system may fail to control infection

Immune system may cause disease directly

Question 2

What are the 2 ways the immune system can fail to control the infection?

Answer 2

Pathogen factors

Host factors

Question 3

What are the 2 ways the immune system can directly cause disease?

Answer 3

Failure of tolerance e.g. allergy / autoimmunity

Inappropriate activation of immune system

Question 4

What is Gell and Coombes classification’?

Answer 4

System to classify immunologically mediated diseases in 1963

Question 5

What does the Gell and Coombes classification refer to?

Answer 5

Mechanisms of disease when the immune system is inappropriately activated

Question 6

What are the benefits of the Gell and Coombes classification?

Answer 6

Only successful attempt to classify disease by mechanism

Useful framework to describe and understand various diseases

Question 7

What are the cons of the Gell and Coombes classification?

Answer 7

Not useful in clinical practice
Oversimplifies immunology
Many diseases are much more complex, particularly chronic inflammatory diseases which involve multiple immunological effector mechanisms

Question 8

What is type I hypersensitivity?

Answer 8

IgE antibody directed against allergen triggers mast cell degranulation

Question 9

What are some examples of type I hypersensitivity?

Answer 9

Seasonal rhinitis

Cat allergy

Question 10

What is the mechanism of type II hypersensitivity?

Answer 10

Pathogenic antibody directly causes disease

Question 11

Give examples of type II hypersensitivity conditions

Answer 11

Autoimmune haemolysis

Question 12

What is the mechanism of type III hypersensitivity?

Answer 12

Antibody-antigen-complex mediated disease

Question 13

Give examples of type III hypersensitivity

Answer 13

Serum sickness

Systemic lupus erythematosus

Question 14

What is the mechanism of type IV hypersensitivity?

Answer 14

Inflammation directly mediated by T cells
Delayed-type hypersensitivity
Reactions don’t develop for at least 24h after exposure as it takes time to process and present antigen.

Question 15

Give examples of type IV hypersensitivity

Answer 15

Contact dermatitis

Tuberculin reaction

Question 16

What is the mechanism of type I hypersensitivity?

Answer 16

1) B cells class switch to IgE antibody
2) Secreted IgE picked up by tissue mast cells and circulating basophils
3) Cross-linking of allergen-specific IgE antibodies by allergen which activates mast cel
4) Mast cell degranulates releases histamine, tryptase and other pre-formed mediator
5) Pharmcaological effects of histamine cause symptoms in affected organ

Question 17

What is haemolytic disease of the newborn?

Answer 17

Type 2 hypersensitivity
Mother is sensitised by exposure to foetal red cells during pregnancy
Antibodies can then cause disease in subsequent pregnancies

Question 18

What are the consequences of autoimmune haemolysis to the foetus?

Answer 18

Growth retardation
Cardiovascular failure
Hydrops fetalis
Neurotoxicity

Question 19

How is haemolytic disease of the newborn prevented?

Answer 19

Rhesus negative mothers with rhesus positive partners are given anti-D IgG during pregnancy
Binds to foetal red cells entering the circulation causing them to be destroyed to prevent sensitisation

Question 20

When can antibody-antigen complexes cause disease?

Answer 20

If they become insoluble

• large quantity of antigen
• large quantity of antibody
• strong interaction between the 2
• complexes are of correct size

Question 21

Describe local immune complex disease

Answer 21

Painful lesions in fingertip pulp caused by deposition of circulating immune complexes
Seen in infective endocarditis (Osler’s nodes)
Seen in other diseases with immune complex deposition (SLE)

Question 22

Describe serum sickness

Answer 22

Generalised transient immune complex-mediated syndrome
Results from injection of certain immunogenic drugs or anti-sera produced in animals
- fever
- rash
- arthritis
- glomerulonephritis

Question 23

Describe hypersensitivity pneumonitis

Answer 23

Extrinsic allergic alevolitis (EAA)
Patient becomes sensitised to environmental antigen by repeated exposure to produce large quantities of IgG antibodies
Upon re-exposure, immune complexes form in the lung leading to shortness of breath and cough

Question 24

Describe sensitisation in contact dermatitis

Answer 24

Sensitising agents react with self-proteins to create protein-hapten complexes are picked up by Langerhans cells which migrate to regional lymph nodes
Langerhans cells process and present antigen with MHC II

Question 25

Describe elicitation in contact dermatitis

Answer 25

Langerhans' cells present self-peptides haptenated with contact-sensitising agent to Th1 cells which secrete IFN-y and other cytokines Activated keratinocytes secrete cytokines such as IL-1, TNF-a as well as chemokines such as CXCL8, CDCL11, CXCL9 Products of keratinocytes and Th1 cells activate macrophages which secrete mediators of inflammation

Question 26

What is the tuberculin skin test (TST)?

Answer 26

Use to determine previous exposure to TB Tuberculin injected intradermally Locally inflammatory response evolves over 24 to 72 hours Mediated by Th1 cells

Question 27

What is the mechanism of the TST?

Answer 27

Antigen injected into subcutaneous tissue which is presented by local antigen-presenting cells Th1 effector cell recognises antigens to release cytokines to act on vascular endothelium Recruitment of phagocytes and plasma to site of antigen injection leading to visible lesion

Question 28

Describe the response of IGRA for previous TB exposure

Answer 28

Memory Th1 cells recognise antigen | Secondary immune response so cytokines are released within short timeframe

Question 29

Describe the response of IGRA for no previous TB exposure

Answer 29

No primed memory T-cells specific for MTB | No interferon gamma produced in such a short timeframe