1
Q
What are hypersensitivity reactions?
A
Overreactions to antigens by the immune system that result in tissue damage or even death.
2
Q
What can trigger hypersensitivity reactions?
A
A diverse range of foreign and self antigens.
e.g. drugs, pathogens, pollen, foods, chemicals, RBCs, and self proteins/DNA
3
Q
How many classes of hypersensitivity reactions are there?
A
Four
4
Q
What is Type I hypersensitivity?
A
Immediate (allergic) reaction
5
Q
What is Type II hypersensitivity?
A
Cytotoxic, antibody-dependent reaction
6
Q
What is Type III hypersensitivity?
A
Immune complex-mediated reaction.
7
Q
What is Type IV hypersensitivity?
A
Delayed-type hypersensitivity
8
Q
What are the main effectors in Type I hypersensitivity?
A
TH2 cells, IgE, and mast cells.
9
Q
What are the main effectors in Type II hypersensitivity?
A
Complement activation or IgM/IgG antibodies bound to cell surfaces.
10
Q
What are the main effectors in Type III hypersensitivity?
A
Antigen-antibody complexes (IgM or IgG) deposited in tissues.
11
Q
What are the main effectors in Type IV hypersensitivity?
A
TH1 cells, macrophages, and CD8 T cells (cell-mediated).
12
Q
What hypersensitivity reactions are antibody mediated and which are cell-mediated?
A
I, II and II are antibody mediated.
IV is cell-mediated.
13
Q
What mediates Type I hypersensitivity reactions?
A
IgE antibodies
14
Q
Which effector cells are involved in Type I hypersensitivity?
A
Mast cells and basophils.
15
Q
How quickly does a Type I hypersensitivity reaction occur?
A
Rapidly, within minutes of antigen exposure
16
Q
What can severe Type I hypersensitivity lead to?
A
Anaphylaxis, which can be fatal.
17
Q
What type of antigen triggers Type I hypersensitivity?
A
Antigen is an allergen (e.g., pollen, peanuts, dust mite proteins).
18
Q
What are common manifestations of Type I hypersensitivity?
A
Hay fever, urticaria (hives), asthma, and anaphylaxis.
19
Q
Which T helper cells are involved in Type I hypersensitivity?
A
TH₂ cells producing IL-4, IL-5, and IL-13.
20
Q
What receptor on mast cells binds IgE in Type I hypersensitivity?
A
FcεRI (high-affinity Fc receptor for IgE).
21
Q
What triggers mast cell degranulation in Type I hypersensitivity?
A
Cross-linking of IgE by multivalent antigens (allergens).
22
Q
What is the outcome of mast cell activation in Type I hypersensitivity?
A
Degranulation and release of mediators causing allergic symptoms.
23
Q
What is required for Type I hypersensitivity to occur?
A
Sensitisation through first exposure to the allergen.
24
Q
What happens during the first exposure to an allergen?
A
Allergen taken up by antigen-presenting cells
Activation of Th2 cells
B cells undergo class switching to IgE
IgE binds FcεRI on mast cells/basophils (cells become “armed”)
25
What does it mean when an individual is “sensitised”?
Mast cells and basophils are coated with allergen-specific IgE, ready to react upon re-exposure
26
What happens upon re-exposure?
Cross-linking of IgE on mast cells/basophils
Mast cell degranulation
Release of preformed granules (histamine, proteases, heparin)
Synthesis of leukotrienes, prostaglandins, cytokines
27
What preformed mediators are found in mast cell and basophil granules?
Histamine, serotonin, heparin, IL-8, and other chemokines.
28
What are the effects of histamine and serotonin released from mast cells?
Smooth muscle contraction, increased vascular permeability, and acid release in the stomach.
29
What is the function of heparin in mast cell granules?
Anticoagulation.
30
What is the role of IL-8 and other chemokines released from mast cells?
Recruitment of neutrophils and eosinophils.
31
How can allergies be detected?
Allergies can be detected using a skin prick test or by measuring IgE levels.
32
What are the main routes of allergen exposure?
Skin contact, injection, ingestion, and inhalation
33
Give examples of allergens from skin contact.
Poison plants, animal dander, pollen, and latex.
34
What allergic conditions can result from skin contact with allergens?
Urticaria and eczema.
35
Give examples of allergens introduced by injection.
Bee sting and medications.
36
What allergic condition is commonly associated with injection allergens?
Urticaria.
37
Give examples of allergens introduced by ingestion.
Medications, nuts, and shellfish.
38
What symptoms can the ingestion of allergens cause?
Diarrhoea, vomiting, and urticaria.
39
Give examples of allergens introduced by inhalation.
Pollen, dust, mould & mildew, animal dander.
40
What conditions are associated with inhalation allergens?
Rhinitis and wheeze
41
Can all types of allergens trigger anaphylaxis?
Yes, any allergen can potentially trigger anaphylaxis.
42
What are key symptoms of anaphylaxis?
Difficulty and/or noisy breathing
Swelling of the tongue
Swelling or tightness in the throat
Difficulty talking or a hoarse voice
Wheeze or persistent cough
43
What severe signs indicate anaphylaxis in young children?
Pale and floppy appearance.
44
What are the most critical outcomes of untreated anaphylaxis?
Loss of consciousness and death within 5–20 minutes.
45
What is the first step in managing allergies?
Avoid the allergen where possible.
46
How do antihistamines help treat allergies?
They block histamine receptors to reduce symptoms.
47
What is the role of corticosteroids in allergy treatment?
Suppress inflammation.
48
How do leukotriene antagonists work?
Prevent bronchoconstriction.
49
What is the main treatment for anaphylaxis?
Epinephrine (adrenaline).
50
What does immunotherapy involve?
Allergen desensitisation and anti-IgE antibody therapy.
51
Why do humans have IgE and TH2 responses?
They are the correct type of immune response against parasites.
52
Where does the allergic response go wrong?
Sensitisation skews the immune response against harmless antigens toward a TH2/IgE pathway.
53
How common are allergic diseases in Australia?
Around 30% overall, and 40–50% of children experience allergic disease in the first four years of life.
54
What trend has been observed in allergic diseases globally?
The frequency of allergic diseases has been rising for decades.
55
Where are allergies increasing at a higher rate?
In developed countries.
56
How do genetics influence allergy risk?
Children with allergic parents have about 2× higher risk of developing allergies.
57
What environmental factor is linked to increased allergies?
The hygiene hypothesis
58
How do lifestyle changes contribute to allergy prevalence?
Changes in diets and food preparation methods may affect immune tolerance.
59
How does parasite control relate to allergy development?
With fewer parasitic infections, the immune system has less to fight, potentially leading to increased TH2/IgE responses to harmless antigens.
60
What does the hygiene hypothesis propose?
Reduced exposure to microbes during childhood leads to an underdeveloped immune system, skewing responses toward TH2 and IgE-mediated allergies.
61
How does reduced microbial exposure affect immune balance?
It deprives the immune system of stimuli needed to boost TH1 responses, resulting in inappropriate TH2/IgE responses to harmless antigens
62
What evidence supports the hygiene hypothesis?
Higher allergy prevalence in developed countries compared to developing countries.
63
What does the helminth hypothesis suggest?
IgE and eosinophil responses evolved to fight parasitic worms; in their absence, these pathways are misdirected against allergens.
64
What epidemiological observation supports the helminth hypothesis?
Low allergy rates in populations with ongoing helminth infections.
65
How are helminths being studied for allergy treatment?
Some studies investigate using helminths or helminth proteins to modulate immune responses and treat allergies.
66
What is another name for Type II hypersensitivity?
Antibody-mediated cytotoxic hypersensitivity.
67
Which antibodies are involved in Type II hypersensitivity?
IgG or IgM antibodies directed against cell-surface or tissue antigens.
68
What does Type II hypersensitivity lead to?
Cell destruction, inflammation, and impaired cell function.
69
How quickly does Type II hypersensitivity develop?
Within hours to days after exposure.
70
What triggers Type II hypersensitivity?
Binding of IgG or IgM antibodies to the surface of cells.
71
What are the four mechanisms of Type II hypersensitivity?
Complement-mediated lysis – Antibody binding activates complement, causing cell lysis.
Opsonisation & phagocytosis – IgG-coated cells are recognised by Fc receptors on macrophages/neutrophils.
ADCC (Antibody-Dependent Cell-Mediated Cytotoxicity) – NK cells kill antibody-coated cells.
Anti-receptor binding – Antibodies block or alter receptor signalling.
72
What does ADCC stand for in Type II hypersensitivity?
Antibody-Dependent, Cell-Mediated Cytotoxicity.
73
Which cells act as killers in ADCC?
NK cells, neutrophils, eosinophils, and macrophages.
74
How does ADCC work?
Antibodies bind to target cells, allowing killer cells to attach via Fc receptors and kill the target.
75
What molecules are released by killer cells during ADCC?
Enzymes, perforins, and TNF
76
What causes transfusion reactions in Type II hypersensitivity?
IgM (mainly) or IgG antibodies bind to incompatible RBC surface antigens (A or B proteins).
77
What happens when antibodies bind to incompatible RBCs?
Complement activation → intravascular haemolysis
Opsonisation → phagocytosis of RBCs
Rapid destruction of red blood cells
78
What are common symptoms of haemolytic transfusion reactions?
Bloody urine, chills, dizziness or fainting, fever, flank/back pain, rash.
79
What is the ultimate result of a severe transfusion reaction?
Rapid and extensive haemolysis of red blood cells.
80
What is the Rh factor?
An antigen (protein) present on the surface of red blood cells.
81
When does Rhesus incompatibility occur?
In an Rh⁻ mother carrying an Rh⁺ fetus.
82
Why is the first pregnancy usually safe in Rh incompatibility?
The mother develops anti-Rh IgG antibodies only after fetal RBCs enter her circulation, so problems occur in subsequent pregnancies.
83
How do anti-Rh antibodies harm the fetus?
IgG antibodies cross the placenta and attack fetal RBCs, causing hemolysis
84
What is Hemolytic Disease of the Newborn (Erythroblastosis fetalis)?
A condition caused by Rh incompatibility leading to anemia, hypotonia, developmental delay, polyhydramnios, jaundice, and other complications.
85
How can Rh incompatibility be prevented?
Treating the mother with anti-Rh immunoglobulins during the last trimester.
86
How do some drugs trigger Type II hypersensitivity?
They act as haptens and bind to cell surface proteins (often on RBCs or platelets), forming a hapten–protein complex recognised as foreign.
87
What immune response occurs against drug-modified cells?
IgG or IgM antibodies are produced against the drug-modified cells.
88
What mechanisms lead to cell destruction in drug-induced Type II hypersensitivity?
Complement activation, phagocytosis, and ADCC
89
What conditions can result from drug-induced Type II hypersensitivity?
Hemolytic anemia, platelet destruction (thrombocytopenia), and occasionally neutrophil destruction.
90
91
Do all Type II hypersensitivity reactions destroy cells?
No, some involve antibodies binding to receptors, altering their function.
92
What happens when antibodies block receptors in Type II hypersensitivity?
Loss of function, e.g., Myasthenia gravis.
93
What happens when antibodies stimulate receptors in Type II hypersensitivity?
Inappropriate activation, e.g., Graves' disease.
94
What causes Myasthenia gravis?
IgG antibodies against acetylcholine receptors (AChR) on skeletal muscle.
95
How does Myasthenia gravis affect muscle function?
Prevents acetylcholine from triggering muscle contraction, leading to muscle weakness and rapid fatigue of voluntary muscles.
96
What is another name for Type III hypersensitivity?
Immune complex–mediated hypersensitivity.
97
What causes Type III hypersensitivity?
Antigen–antibody (IgG or IgM) complexes that are not adequately cleared and deposit in tissues.
98
What happens when immune complexes deposit in tissues?
Complement activation, neutrophil recruitment, inflammation, and tissue damage.
99
What symptoms occur in Type III hypersensitivity and when?
Fever, urticaria, arthralgias, lymphadenopathy, and proteinuria (~5–10 days after antigen exposure).
100
Where do immune complexes typically lodge?
Blood vessel walls, joints, and kidneys.
101
What is the mechanism of tissue damage in Type III hypersensitivity?
Complement activation
Neutrophils release enzymes and reactive oxygen species (ROS)
102
Where can immune complexes deposit in Type III hypersensitivity?
Kidneys, joints, blood vessels, skin, eyes, gut, and lungs.
103
What often causes immune complex deposition?
Prolonged exposure to bacterial and viral antigens (e.g., Streptococcal infections).
104
What infection precedes post-streptococcal glomerulonephritis?
Group A Streptococcus (GAS) infection.
105
How do immune complexes form in post-streptococcal glomerulonephritis?
Streptococcal antigens released during infection bind antibodies, forming circulating immune complexes.
106
Where do these immune complexes deposit?
In the glomerular basement membrane of the kidney.
107
What happens after immune complex deposition?
Complement activation leads to neutrophil recruitment. Neutrophil enzymes and ROS cause glomerular inflammation and damage.
108
What mediates Type IV hypersensitivity reactions?
T cells (not antibodies).
109
Which T cell subtype causes inflammation and activates macrophages in Type IV hypersensitivity?
CD4⁺ Th1 cells.
110
What is the role of CD8⁺ cytotoxic T cells in Type IV hypersensitivity?
They kill target cells directly.
111
How long after antigen exposure does a Type IV hypersensitivity reaction develop?
24–72 hours (sometimes weeks) — delayed onset.
112
What are the two stages of Type IV hypersensitivity?
Sensitisation phase and Effector phase (re-exposure).
113
What happens during the Sensitisation phase?
Initial exposure to antigen
Antigen presented by APCs
Activation of T cells
Memory T cells generated
114
What triggers the Effector phase?
Re-exposure to the antigen.
115
What occurs during the Effector phase?
Memory T cells recognise antigen
Release cytokines (IFN-γ, TNF)
Recruit and activate macrophages and cytotoxic T cells
Result: inflammation and tissue damage
116
What do activated Th1 cells respond to in macrophages?
Captured antigens.
117
Give examples of antigens that trigger Th1 responses in skin and tissues.
Skin (contact dermatitis): Chemical/protein conjugates (haptens), e.g., poison ivy
Tissues (granulomas): Metal/protein chelates, e.g., nickel; Intracellular pathogens/foreign proteins, e.g., tuberculosis
118
What do activated Th1 cells produce that causes tissue damage?
Cytokines and chemokines.
119
Name key cytokines involved in Type IV hypersensitivity and their roles.
Chemokines: Recruit macrophages to the site
IFN-γ: Activates macrophages, increases inflammatory mediators
TNF-α & TNF-β: Cause tissue destruction, increase adhesion molecules on blood vessels
IL-3/GM-CSF: Stimulate monocyte production in bone marrow
120
What is the overall result of Th1 activation in Type IV hypersensitivity?
Tissue destruction and macrophage infiltration.
121
What is contact dermatitis, and give examples?
Skin reaction caused by hapten-carrier complexes triggering T-cell response
Examples: poison ivy, nickel, cosmetics
122
What is the tuberculin skin test, and how does it work?
Injection of purified protein derivative (PPD) from Mycobacterium tuberculosis
Localised skin induration after 48–72 hrs if previously sensitised
123
What causes granulomatous inflammation in Type IV hypersensitivity?
Persistent antigen
Th1 cells activate macrophages and form granulomas
BMS211
flashcards
Decks in class (21)
# Cards
-
Cells and organs of the adaptive immune system5
-
Preformed / Innate Defences25
-
Phase II responses & Local Inflammation32
-
Phase III Responses & Systemic Inflammation20
-
Antigen Presentation and MHC33
-
T cell biology and Thymus32
-
Effector T cells I32
-
Effector T cells II44
-
Antibodies/B cells I103
-
Antibodies/B cells II89
-
T and B cell memory51
-
Extracellular defence101
-
Intracellular defence84
-
Intracellular defence II103
-
Immunisation115
-
Tumour Immunology74
-
Cancer Immunotherapy44
-
Hypersensitivity123
-
Autoimmunity/Tolernance59
-
Transplants/HLA0
-
Immunodeficiency0
