Disorders of the immune system

Question 1

What is the Coombes and Gell classification of type I hypersensitivity?

Answer 1

• immediate, atopic

- IgE mediated

Question 2

What is the Coombes and Gell classification of type II hypersensitivity?

Answer 2

• Cytotoxic, antibody-dependent

- IgM or IgG bound to cell/matrix Ag

Question 3

What is the Coombes and Gell classification of type III hypersensitivity?

Answer 3

• Immune complex

- IgM or IgG bound to soluble Ag

Question 4

What is the Coombes and Gell classification of type IV hypersensitivity?

Answer 4

• Cell-mediated

- T cells (CD4 and CD8)

Question 5

What is the Coombes and Gell classification of type V hypersensitivity?

Answer 5

Likely a subclass of type II

• Receptor-mediated
• IgM or IgG bound to receptors

Question 6

What are the specific characteristics of type I hypersensitivity

Answer 6

• response to challenge occurs immediately
• tends to increase in severity with repeated challenge
• predominantly mediated by IgE bound to mast cells

Question 7

What is the process of mast cell activation?

Answer 7

1. sensitisation
2. mast cells primed with IgE
3. re-exposure to antigen
4. antigen binds to IgE associated with mast cells
5. mast cells degranulate
6. pro-inflammatory process stimulates and amplifies future responses

Question 8

What substances are released when mast cells degranulate?

Answer 8

• toxins (i.e. histamine)
• tryptase
• pro-inflammatory cytokines
• chemokines
• prostaglandins
• leukotrienes

Question 9

What is the result of histamine release?

Answer 9

• in the skin: swelling and itching

- in the respiratory tract: bronchospasm and wheeze

Question 10

What is the result of tryptase release?

Answer 10

• a type of proteinase

- degradation

Question 11

Which substances released from mast cells encourage the immune system to mount an inflammatory response?

Answer 11

• pro inflammatory cytokines
• chemokines
• prostaglandins
• leukotrienes

Question 12

What are the tissue effects of an early phase type 1 hypersensitivity reaction?

Answer 12

• occurs within minutes of exposure
• largely as a result of histamine and prostaglandin exposure

> smooth muscle constriction
increased vascular permeability

Question 13

What are the tissue effects of an late phase type 1 hypersensitivity reaction?

Answer 13

• occurs over hours to days after exposure
• principally mediated through recruitment of T cells and other immune cells to site

> sustained smooth muscle contraction/hypertrophy
tissue remodeling

Question 14

What is anaphylaxis?

Answer 14

Severe, systemic type 1 hypersensitivity reaction

Question 15

What causes anaphylaxis?

Answer 15

widespread mast cell degranulation caused by systemic exposure to antigen

Question 16

What is the principle danger in anaphylaxis?

Answer 16

vascular permeability causing:

• soft tissue swelling threatening airway
• loss of circulatory volume causing shock

Question 17

Give examples of type 1 hypersensitivity

Answer 17

• asthma (although not true type 1)
• penicillin allergy
• hay-fever

Question 18

What is the cause of type II hypersensitivity

Answer 18

caused by binding of antibodies directed against human cells

Question 19

What are the characteristics of type II hypersensitivity?

Answer 19

• delayed - generally over days, weeks or months
• uncommon cause of drug allergy
• common cause of auto-immune disease

Question 20

Name a type II hypersensitivity drug allergy

Answer 20

Drug associated haemolysis

• goes on to develop anaemia
• pretty rare

Question 21

Name a type II hypersensitivity autoimmune disease

Answer 21

bullous pemphigoid

• characterised by development of deep blisters on the skin
• antibody found between the epridermis-dermis junction

Question 22

What is the process of type II hypersensitivity reaction

Answer 22

1. sensitisation
2. opsonisation of cells
3. cytotoxicity
   - complement activation
   - inflammation
   - tissue destruction

Question 23

What is the process of type V hypersensitivity?

Answer 23

1. sensitisation
2. opsonisation of cells
3. cytotoxicity
   - complement activation
   - inflammation
   - tissue destruction
4. direct biological activation with antigen
   - Either through receptor activation (common) or receptor blocking (occasional)

Question 24

What is a common autoimmune example of type V hypersensitivity?

Answer 24

Graves’ disease

Question 25

What causes type III hypersensitivity?

Answer 25

Mediated by immune complexes bound to soluble antigen | - aggregates get stuck in small vessels, where they activate complement and cause inflammation around them

Question 26

Name examples of type III hypersensitivity reactions

Answer 26

- SLE - RA - Post-strep glomerulonephritis

Question 27

Which hypersensitivity reaction presents delayed from time of exposure?

Answer 27

- type II - type III - type IV - type V

Question 28

Name an example of type IV hypersensitivity reaction

Answer 28

contact dermatitis

Question 29

What causes type IV hypersensitivity reaction?

Answer 29

- mediated by the action of lymphocytes infiltrating the area N.B by definition, is delayed

Question 30

How may nickel cause a type IV hypersensitivity reaction?

Answer 30

Nickel is too basic in structure to trigger a response. It binds to human proteins, altering the shape. This is what is recognized by the immune system.

Question 31

What is autoimmune disease?

Answer 31

harmful inflammatory response directed against 'self' tissue by the adaptive immune response - organ specific - systemic

Question 32

What hypersensitivity reaction is seen in T1DM?

Answer 32

selective, autoimmune destruction of the pancreatic beta cells - often mix of type II and type IV

Question 33

What hypersensitivity reaction is seen in myasthenia gravis?

Answer 33

Classic example of type II(V) hypersensitivity

Question 34

What causes myasthenia gravis?

Answer 34

IgG against the acetylcholine receptor | - antibody blocks the receptor, preventing signal transduction

Question 35

What are the systemic effects of RA?

Answer 35

- pulmonary nodules and fibrosis - pericarditis and valvular inflammation - small vessel vasculitis - soft tissue nodules - skin inflammation - weight loss, anaemia

Question 36

Describe rheumatoid factor in relation to RA

Answer 36

- IgM and IgA directed against the Fc portion of IgG forming a large immune complex - high conc. in synovial fluid - also in other tissues - not specific to RA

Question 37

Describe the pathophysiology of RA

Answer 37

- Inflammation leads to the release of PAD from inflammatory cells - alters proteins to citrulline - allows immune system to recognise as foreign - anti-citrullinated protein antibodies found in RA

Question 38

Describe the immune response in RA

Answer 38

- loss of tolerance - activation of macrophages and lymphocytes - TNF alpha and IL1 produced - amplification of inflammatory cascade occurs etc.

Question 39

What are the main treatment methods for autoimmune disorders?

Answer 39

- steroids - inhibitors of metabolism - inhibitors of T cell function - biological therapies

Question 40

What is the benefit of biological therapies in treating autoimmune disorders?

Answer 40

Neutralises a specific part of the immune system without significant side effects of other drugs

Question 41

What is molecular mimicry?

Answer 41

- bacteria possesses an antigen that looks very similar to the human antigen

Question 42

Name an example of molecular mimicry

Answer 42

Rheumatic fever - caused by strep. which is similar to heart tissue - cellular infiltrate into the myocardium and you get inflammation of the heart valves, called a rheumatic valve

Question 43

What modifiable factors are linked with RA?

Answer 43

smoking - generates a lot of citrullinated proteins