Overview of immunological diseases Flashcards

1
Q

Immune system may fail to control infection

A

Pathogen factors (evasion mechanisms)

Host factors (immunodeficiency)

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2
Q

Immune system may cause disease directly

A

Failure of tolerance (e.g. allergy/ autoimmunity)

Immune system inappropriately activated for unknown reasons (e.g. IBD) or for reasons known but poorly understood (e.g. asbestosis or cigarette smoke)

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3
Q

Gell and Coombes hypersensitivity reactions type 1-4

A

Classify immunologically mediated diseases

Refers to mechanisms of disease when the immune system is inappropriately activated

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4
Q

Type 1

A

Mechanism: IgE . antibody directed against allergen triggers mast cell degranulation

e.g. seasonal rhinitis, cat allergy

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5
Q

Type 2

A

Mechanism: a pathogenic antibody directly causes diseases

e.g. autoimmune haemolysis

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6
Q

Type 3

A

Mechanism: antibody antigen complex mediated disease

e.g. serum sickness, systemic lupus, erythematosis

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7
Q

Type 4

A

Mechanism: inflammation directly mediated by T cells

e.g. contact dermatitis, tuberculin reaction

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8
Q

Type 1 hypersensitivity: IgE mediated allergy

A

B cells class switch to IgE antibody, secreted IgE is picked up by tissue mast cells and circulating basophils

Cross linking of allergen specific IgE antibodies by allergen activates the mast cell

Mast cell rapidly degranulates releasing histamine, tryptase and other pre-formed mediators

Pharmacological effects of histamine lead to symptoms in the affected organ

In health, believed to assist with parasite immunity

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9
Q

Type 2 hypersensitivity: AB blood system and transfusion medicine

A

Refers to pathology directly mediated by antibodies

Mismatch blood transfusion reactions are an example

IgM antibodies against AB antigens develop during first year of life

Antibodies are an example of isoantibodies

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10
Q

Type 2 hypersensitivity: haemolytic disease of the newborn

A

Major blood group system is ABO

D antigen (rhesus) us a secondary classification

Majority of the population are D+

Mother may be sensitised by exposure to fetal red cells during pregnancy

  • parturition
  • trauma

Antibodies may cause disease in subsequent pregnancies

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11
Q

Haemolytic disease of the newborn

A

Autoimmune haemolysis highly deleterious to fetus
- growth retardation, CV failure, hydrops fetalis, neurotoxicity from high bilirubin levels

Rhesus negative mothers with rhesus + partner are given anti-D IgG during pregnancy

Binds to fetal red cells entering circulation, fetal red cells then desstroyed, preventing sensitisation

Risk of maternal sensitisation reduced from 16% to 0.1%

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12
Q

Type 3 hypersensitivity

A

Describes disease caused by complexes of antibody and antigen

Such complexes area a normal phenomenon
- usually soluble, removed in spleen

In some situations they become insoluble and cause disease

  • large quantity of antigen
  • large quantity of antibody
  • interaction between the two is very strong
  • complexes are of the correct size
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13
Q

Local immune complex disease

A

Painful lesions in the fingertip pulp due to deposition of circulating immune complexes

May be seen in infective endocarditis

May be seen in other diseases with immune complex deposition

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14
Q

Type 3 hypersensitivity: serum sickness

A

A generalised transient immune complex mediated syndrome

Mainly results from injection of certain immunogenic drugs or anti-sera produced in animals e.g. after snake evenomation

  • rash
  • fever
  • arthritis
  • glomerulonephritis
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15
Q

Type 3 hypersensitivity: hypersensitivity pneumonitis

A

Extrinsic allergic alveolitis

Patient becomes sensitised to an environmental antigen by repeated exposure, producing large quantities of IgG antibodies

Immune complexes form in the lung upon re-exposure causing shortness of breath and cough

  • mould spores in hay
  • pigeon feathers and stool

Initially transient, lung scarring with repeated exposure

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16
Q

Type 4 hypersensitivity: delayed type hypersensitivity

A

Reactions are mediated by antigen specific effector T cells

It takes time to process and present antigen, these reactions do not develop for at least 24 hours following exposure

In the skin, known as contact dermatitis

17
Q

Contact dermatitis: sensitisation

A

Sensitising agents are typically highly reactive small molecules which can penetrate skin

These react with self proteins to create protein-hapten complexes that are pick up by Langerhans cells, which migrate to regional lymph nodes

Langerhands cells process and present the antigen together with MHCII

In some susceptible individuals the complexes are recognised as foreign, activated T cells then migrate to the dermis

18
Q

Hapten

A

Small molecule which cannot produce an immune response by itself, but can bind to a protein to alter its immunogenicity

19
Q

Contact dermatitis: elicitation

A

Contact- sensitising agent penetrates the skin and binds to self proteins, which are taken up by Langerhans cells

Langherhands cells present self peptides haptened with the contact sensitising agent to Th1 cells which secrete IFNy and other cytokines

Activated keratinocytes secrete cytokines such as IL-1 and TNFa and chemokines such as CXCL8, CXCL11 and CXCL9

The product of keratinocytes and Th1 cells activate macrophages to secrete mediators of inflammation

20
Q

Tuberculin skin test

A

Another example of a type IV hypersensitivity reaction

Used to determine previous exposure to TB

Tuberculin injected intradermally

Local inflammatory response evolves over 24-72 hours if previously exposed

Mediated by Th1 cells

21
Q

Mechanism of tuberculin skin test

A

Antigen is injected into subcutaneous tissue and processed by local antigen-presenting cells

A Th1 effector cell recognises antigen and releases cytokines which act on vascular endothelium

Recruitment of phagocytes and plasma to site of antigen injection causes visible lesion