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1

What is the main cause of immunodeficiency in the UK?

Malnutrition in the elderly 

2

Give some examples of autoimmune conditions. 

Disease or systemic specific

3

What is the definition of hypersensitivity?

- 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

4

What are the two categories of triggers for hypersensitivity?

- Exogenous antigens:

- Non infectious substances (pollen, dust)

- Infectious microbes (sepsis)

- Drugs (penicillin)

 

- Intrinsic anigens:

- Infectious microbes (mimicry like rheumatic fever)

- Self antigens (auto-immunity)

5

What are the different types of hypersensitivity reactions?

- 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

6

What are the two phases of hypersensitivity reactions?

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

7

Which antigens are involved in Type I hypersensitivity?

Environmental non-infectious antigens 

8

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

- 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

 

9

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

- 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

10

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

11

What is the mechanism behind haemolytic transfusion reactions?

- 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

12

What is the mechanism behind haemolytic disease of the newborn?

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

13

How can we prevent haemolytic disease of the newborn?

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

14

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

- Antibody can stimulate or block a receptor 

15

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

- 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)

16

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

- 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

17

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

- 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

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

19

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

- MULTISYSTEMIC DISEASE unlike type II which is more organ specific

 

- Joints, kidney, small vessels, skin

20

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

- Rheumatoid arthritis (self-antigen) 

- Glomerulonephritis (infectious)

- SLE

21

What is the pathophysiology of glomerulonephritis?

Type III hypersensitivity reaction following infection

 

- Bacterial endocarditis 

 

- Hep B infection

22

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

- Antigen:  Anti-Rheumatoid factor Fc portion of IgG 

 

- Articular and extraarticular features with episodes of inflammation and remission

23

What is the immune mechanism involved in type III hypersensitivity?

- Intermediate-sized IC's deposited in tissue

- Complement activated

- Neutrophil chemotaxis, adherence then degranulation

24

What type of hypersensitivity reaction is SLE?

- Type III 

 

- Antigen: Ds-DNA

 

- Most prevalent immune complex disease that is more common in females

25

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

26

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

- APCs activate TH1 cells 

 

- Granulomas

27

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

- 48-72 hrs post exposure 

- Epidermal reaction and requires endogenous proteins but exogenous antigens

 

caused by things like nickel, poison ivy, organic chemicals

28

What are some examples of granulomatous hypersensitivity reactions?

- 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

State the duration of tuberculin hypersensitivity and the reaction involved.

 - 48-72hr

- Dermal reaction (induration and swelling)

- Type IV hypersensitivity 

30

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