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Flashcards in Hypersensitivity Deck (42)
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1
Q

Define: Hypersensitivity

A
  • Unnecessary, non-beneficial immunopathology driven by an external antigen
  • Set of undesirable reactions ranging from irritating (allergy) to life-threatening (anaphylaxis)
2
Q

Define: Autoimmunity

A
  • System of immune responses of an organism against its own healthy cells and tissues
  • Any disease that results from this response = an autoimmune disease
3
Q

What is Immunopathology?

A

Branch of medicine focusing on immune responses associated with disease

4
Q

What causes hypersensitivity and autoimmunity?

A

When damage is caused by adaptive immune mechanisms and no hazard can be identified

5
Q

What is the difference between hypersensitivity and autoimmunity in terms of source of antigen?

A
  • Hypersensitivity = external source of antigen
  • Autoimmunity = internal source of antigen
6
Q

What is the difference between hypersensitivity and autoimmunity in terms of effector mechanism?

A

A

7
Q

How are hypersensitivities classified?

A

By the effector mechanism by which damage occurs:

  • Different types of antibody
  • Binding and blocking
  • Histamine
  • Phagocytosis

or

  • T-cells
  • CD8 Killers (direct killing of infected cells)
  • CD4 helpers (cytokine release and inflammation or control B cell antibody responses)
8
Q

What do all hypersensitivity reactions have in common?

A

Sensitisation to external antigen

9
Q

Explain the cellular basis of hypersensitivity

A
  • Not born with allergy, at some point develop hypersensitivity reaction to particular antigen
  • Expansion of B lymphocytes = lots of them = sensitisation
  • Can be identified in blood samples - B cells sticking strongly to the particular antigen
10
Q

Define: Atopic

A

A form of allergy in which a hypersensitivity reaction may occur (e.g. eczema, asthma) in a part of the body not in contact with the allergen

11
Q

What are the 4 classes of hypersensitivities?

A
  1. Type I
  2. Type II
  3. Type III
  4. Type IV
12
Q

What is the effector mechanism of Type I hypersensitivity reaction?

A

IgE antibody-mediated degranulation of mast cells

13
Q

What is the effector mechanism of Type II hypersensitivity reactions?

A

IgM and IgG antibody-mediated cell killing

14
Q

What is the effector mechanism of Type III hypersensitivity reactions?

A

IgG antibody immune complexes

15
Q

What is the effector mechanism of Type II hypersensitivity reactions?

A

T-cells

16
Q

Give 3 examples of a Type I hypersensitivity reaction

A
  1. Hayfever
  2. Asthma
  3. Anaphylaxis
17
Q

Give 3 examples of a Type II hypersensitivity reaction

A
  1. Mismatched blood transfusion
  2. Penicillin
  3. Haemolytic anaemia of a newborn
18
Q

What is haemolytic aneamia?

A

Abnormal breakdown of red blood cells in the body

19
Q

Give 2 examples of a Type III hypersensitivity reaction

A
  1. Serum sickness
  2. Long-term use of monoclonal antibodies
20
Q

Give 1 example of a Type IV hypersensitivity reaction

A

Contact dermatitis

21
Q

What is the most common type of hypersensitivity reaction?

A

Type I

22
Q

Explain the Type I hypersensitivity reaction

A
  1. Allergen binds to IgE antibodies on surface of mast cells
  2. Triggers degranulation of mast cells and histamine release
  3. Causes swelling, sneezing, itching, swelling, vasodilation, sudden death
23
Q

Describe hayfever as a Type I reaction

A

Allergen/antigen (pollen) in upper respiratory tract and eyes

  • Itching
  • Sneezing
24
Q

Describe asthma as a Type I reaction

A

Allergen/antigen (pollen, dust mites etc.) in lower respiratory tract

  • Air vessel constriction
  • Shortness of breath
  • Wheezing
25
Q

Descibe anaphylaxis as a Type I reaction

A

If enough mast cells in the body are triggered at the same time, systemic vasodilation leads to catastrophic blood pressure loss and death

Also:

  • Swelling
  • Hives (urticaria)
26
Q

How can an antigen be identified?

A
  1. Removal of antigen
  2. Skin prick test
27
Q

What is the normal role of IgG and IgM?

(Type II)

A

Killing pathogens

28
Q

What is the role of complement?

(Type II)

A
  • Part of the immune system
  • Works with antibodies to enhance their ability to kill microbes
  • Antigen becomes coated with antibodies (IgG and IgM) which activates complement → punches holes in the microbe’s cell wall = lysis
29
Q

Explain the Type II hypersensitivity reaction

A

In the case of allergic reactions to e.g. antibiotics, penicilin:

  1. Drug molecule may stick to RBCs
  2. IgG and IgM antibodies bind to drug
  3. Because of complement, immune system thinks RBCs are pathogens
  4. RBCs are lysed

= Drug-induced haemolytic anaemia

Direct cell-killing by an antibody-mediated response

30
Q

What is the normal role of IgG?

(Type III)

A
  • Neutralising toxins and virus
  • IgG molecules bind to toxin = immune complex = inactivated toxin
31
Q

Explain the Type III hypersensitivity reaction

A
  1. Caused by high levels of antibody bound to soluble foreign proteins (immune system sees them as antigens)
  2. = Accumulation of immune complexes of varying sizes
  3. Larger complexes can be cleared by macrophages but they cannot clear smaller complexes
  4. These smaller complexes can insert themselves in blood vessels, joints and glomeruli
  5. Gives rise to inflammatory response and attraction of leukocytes (WBCs)
  6. = Immune complex disease
32
Q

What could the foreign proteins which cause a Type III hypersensitivity reacition be?

A

The foreign proteins could be:

  • A protein drug e.g. monoclonal antibodies
  • Anti-venom
33
Q

What is serum sickness?

(Type III)

A

A reaction to the proteins in anti-serum derived from an animal source

Starts Type III hypersensitivity reaction:

  1. Body’s immune system sees these foreign proteins as antigens
  2. IgG antibody produced to bind with proteins
  3. = Immune complexes
  4. Starts inflammatory response
34
Q

How are therapeutic monoclonal antibodies made?

A

A single re-arranged antibody is selected that binds to a desired antigen - can be made to bind to any antigen

35
Q

How does anti-venom differ to therapeutic monoclonal antibodies?

A
  • Mixture of all antibodies vs Only 1 antibody
  • Horse protein vs Human protein
  • Made in animals vs Made in bioreactor
  • Made by animal immune response vs Engineered by molecule biologists
36
Q

What is the normal role of T-helper cells?

(Type IV)

A

Triggering inflammation in response to microbial peptides (via epitope and MHC)

37
Q

Explain the Type IV hypersensitivity reaction

A
  • CD4+ T-helper cells recognise the antigen’s epitope/peptide in a complex with MHC on antigen-presenting cells (e.g. dendritic cells)
  • Takes a while for allergic reaction to develop (2-3 days)

→ Shows it is T-cell mediated hypersensitivity not histamine (would be instantaneous)

= Type IV also known as Delayed Type Hypersensitivity

e.g. Contact dermatitis - irritant will interfere with MHC complex with T receptor, will take a couple of days for swelling to show

38
Q

List 2 anti-inflammatory treatments

A
  1. Antihistamines
  2. Sodium cromoglicate
39
Q

How do antihistamines work?

A
  • Antagonists of H1 receptor - inhibit the release/action of histamine
  • e.g. Loratidine, Cetirizine
  • Side effects - drowsiness
  • Also available as cream - Anthisan (bites etc)
40
Q

How does Sodium cromoglicate work?

A
  • Prevents release of histamine from mast cells, mechanism not fully undertsood
  • Available as nasal spray (Rynacrom), inhaler (Intal) and eye drops (Opticrom)
41
Q

What effect do Glucocoticoids/Corticosteroids have on the immune system?

A
  • Anti-inflammatory steroid molecules
  • Suppress release or action of pro-inflammatory molecules (e.g. histamine)
  • Synthetic mimics developed - used in a huge range of conditions = most potent anti-inflammatory
  • Major side effects if taken systemically
42
Q

What is the solution to adverse hypersensitivity effects from glucocorticoids/corticosteroids?

A
  • Topical use
  • Delivery to site of inflammation
  • Skin response (e.g. insect bite) = hydrocortisone cream
  • Inhaled antigen (hayfever) = nasal spray - beclometasone dipropionate