1 - Hypersensitivity Reactions and Diseases Flashcards

1
Q

What is the main cause of immunodeficiency in the UK?

A

Malnutrition in the elderly

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2
Q

Give some examples of autoimmune conditions.

A

Disease or systemic specific

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3
Q

What is the definition of hypersensitivity?

A
  • Antigen-specific immune responses that are either inappropriate or excessive and result in harm to host by damaging tissue or changing a tissues function
  • Mechanisms are the same as the normal immune response
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4
Q

What are the two categories of triggers for hypersensitivity?

A

- Exogenous antigens:

  • Non infectious substances (pollen, dust)
  • Infectious microbes (sepsis)
  • Drugs (penicillin)

- Intrinsic anigens:

  • Infectious microbes (mimicry like rheumatic fever)
  • Self antigens (auto-immunity)
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5
Q

What are the different types of hypersensitivity reactions?

A
  • Type I / immediate (Allergy)
  • Type II / antiBody mediated
  • Type III / immune Complexes mediated
  • Type IV / cell mediated (Delayed)
  • First 3 are antibody mediated, but 4 has antibody but not primary cause
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6
Q

What are the two phases of hypersensitivity reactions?

A

Sensitisation:

  • First encounter with antigen
  • Activation of APCs and memory effector cells
  • A previously exposed individual to the antigen is said to be “sensitized”

Effector:

  • Reaction upon reexposure to the same antigen and activation of the memory cells of the adaptive immunity
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7
Q

Which antigens are involved in Type I hypersensitivity?

A

Environmental non-infectious antigens

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8
Q

How long does it take for a type II hypersensitivity reaction to be triggered, what antibodies are involved and what antigens are targeted?

A
  • 5-12 hours
  • IgG or IgM
  • Causes tissue damage or physiological change
  • Targets cell bound antigens so organ specific:
  • Exogenous: blood group antigens, rhesus D antigens
  • Endogenous: self antigens
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9
Q

What are the mechanisms in type II hypersensitivity that lead to cell/tissue damage?

A

- Complement activation: cell lysis (MC), neutrophil recruitment/activation (C3A/C5A), opsonisation (C3b)

- Antibody-dependent cell cytotoxicity: NK cells

  • Antibody binds to antigen and activates complement
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10
Q

What are some examples of diseases caused by a type II hypersensitivity reaction?

A
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11
Q

What is the mechanism behind haemolytic transfusion reactions?

A
  • Type II hypersensitivity IgM
  • Incompatability in ABO or rhesus D antigens
  • Donor RBC destroyed by recipients immune system through IgM
  • Caues shock, kidney failure, circulatory collapse and death
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12
Q

What is the mechanism behind haemolytic disease of the newborn?

A

Type II hypersensitivity reaction IgG

  • Involves Rhesus D antigen
  • Mismatch between mother(Rh-) and child (Rh+) and thus antibodies are produced against Rh+ antigen
  • After 2nd pregnancy, IgG antibodies cross placenta and cause HDN
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13
Q

How can we prevent haemolytic disease of the newborn?

A

When mother is Rh -ve she is given RhoGAM within 3 days of miscarriage or delivery of Rh +ve infant to bind all of the Rhesus antibodies

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14
Q

What mechanisms in a type II hypersensitivity reaction lead to physiological changes and give two examples of disease caused by this?

A
  • Antibody can stimulate or block a receptor
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15
Q

What therapeutic approaches can be used to combat tissue/cell damage and physiological change induced by type II hypersensitivity reactions?

A

- Immune suppression for complement activation

- Plasmapheresis for circulating antibodies and inflammatory mediators

- Splenectomy for opsonisation/Phagocytosis

  • Intravenous immunoglobulin (IVIG) for IgG degradation and hopefully bad IgG will degrade

(see image for physiological change)

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16
Q

What is plasmapheresis therapy and what diseases is it used for?

A
  • Removal of antibodies from the plasma allowing short term relief and healing of damaged tissue
  • Used in myasthenia gravis, goodpasture’s syndrome and grave’s as these all are primary antibodies that drive the disease
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17
Q

How long does it take for a type III hypersensitivity reaction to be triggered, what antibodies are involved and what are the target antigens?

A
  • 3-8 hours

- Immune complexes between IgG or IgM and antigens

  • Targets soluble antigens: foreign (infection) and endogenous (self-antigens)
  • Tissue damage by deposition of immune complexes in host tissues
18
Q

What are the 3 key factors in type III hypersensitivity pathogenesis?

A
19
Q

Where do immune complexes mainly deposit in the body with a type III hypersensitivity reaction?

A
  • MULTISYSTEMIC DISEASE unlike type II which is more organ specific
  • Joints, kidney, small vessels, skin
20
Q

What are some examples of diseases caused by type III hypersensitivity reactions?

A
  • Rheumatoid arthritis (self-antigen)
  • Glomerulonephritis (infectious)
  • SLE
21
Q

What is the pathophysiology of glomerulonephritis?

A

Type III hypersensitivity reaction following infection

  • Bacterial endocarditis
  • Hep B infection
22
Q

What are the mechanisms involved in rheumatoid arthritis and what are some poor prognosis factors?

A

- Antigen: Anti-Rheumatoid factor Fc portion of IgG

  • Articular and extraarticular features with episodes of inflammation and remission
23
Q

What is the immune mechanism involved in type III hypersensitivity?

A
  • Intermediate-sized IC’s deposited in tissue
  • Complement activated
  • Neutrophil chemotaxis, adherence then degranulation
24
Q

What type of hypersensitivity reaction is SLE?

A
  • Type III

- Antigen: Ds-DNA

  • Most prevalent immune complex disease that is more common in females
25
Q

How long does it take for type IV hypersensitivity to be triggered, which antibodies are involved and what are the different subtypes?

A
26
Q

What are the mechanisms of tissue destruction in a type IV hypersensitivity reaction?

A
  • APCs activate TH1 cells
  • Granulomas
27
Q

What is the duration of contact hypersensitivity and the reactions involved?

A
  • 48-72 hrs post exposure
  • Epidermal reaction and requires endogenous proteins but exogenous antigens

caused by things like nickel, poison ivy, organic chemicals

28
Q

What are some examples of granulomatous hypersensitivity reactions?

A
  • TB
  • Leprosy
  • Schistosomiasis
  • Sarcoidosis

Occur 21 to 48 days post exposure and forms to try and contain microbe so occurs due to persistence of antigen

29
Q

State the duration of tuberculin hypersensitivity and the reaction involved.

A
  • 48-72hr
  • Dermal reaction (induration and swelling)
  • Type IV hypersensitivity
30
Q

Whata are some diseases caused by Type IV hypersensitivity to endogenous antigens?

A
31
Q

Both Hashimoto’s and Grave’s disease are hypersensitivity reactions that affect the thyroid, however they are different categories of reactions, what are they?

A

- Hashimotos: Type IV, treat with thyroxine

- Grave’s: Type II, treat with thyroidectomy

32
Q

What are some anti-inflammatory drugs and monoclonal antibodies used in type III and IV hypersensitivity reactions?

A
33
Q

What are some of the signs and symptoms of jaundice in a newborn?

A
  • Yellow discolouration
  • Muscle and abdominal pain
  • Dark urine/pale stools
  • Loss of appetite
  • Fever

(hydrops fetalis is swelling in at least 2 compartments)

34
Q

What is the Rhesus antigen and what is the issue if a father is Rhesus positive?

A
  • If you have the Rhesus D antigen this means Rhesus +ve but if you have C,c, E,e you are negativ
  • Father could make a fetus with Rhesus +ve blood which crosses the placenta. A rhesus -ve mother will then make Anti-D IgG that can cross the placent and attack the fetus RBCs causing HDN
35
Q

What is the main complication of raised bilirubin levels in a newborn’s blood due to HDN?

A

Kernicterus = brain damage due to bilirubin accumulation in the brain

Occurs as the placenta is no longer clearing bilirubin so baby cannot conjugate all of the bilirubin itself

36
Q

How can we diagnose HDN before a baby is born and how can we predict it without testing?

A
  • Check mother and father to see what rhesus antigen they have and ask them if they have had a child before

- Indirect Coombs Test

  • Doppler scan of fetus MCA to see if anaemia and if there is take a fetal blood sample
37
Q

Why does a mismatch of ABO between mother and fetus rarely lead to HDN?

A
  • The anti-A and anti-B antibodies in the plasma are IgM so cannot cross the placenta
38
Q

What type of hypersensitivity reaction is HDN?

A

- Type II as IgG mediated against D antigen causing a loss of function

  • The antibodies opsonise the red blood cells causing them to be destroyed by the liver and spleen
39
Q

How can we treat a mismatch in rhesus antigens?

A

Give the mother RhoGAM to prevent her from making antibodies and becoming sensitised

40
Q

Which blood types are universal blood donors and universal plasma donors?

A

- Universal blood donors: O

- Universal plasma donors: AB

41
Q

What is the difference between the direct and indirect coombs test?

A