Hypersensitivity

Question 1

What is hypersensitivity ?

Answer 1

Hypersensitivityis an abnormal physiological condition in which there is an undesirable and adverse immune response to an antigen

Question 2

What is a Type 1 hypersensitivity ?

Answer 2

IgE-mediated allergic reaction
-Involves mast cell and basophil degranulation
-Causes immediate responses (15–30 min) after allergen exposure.

Most common type - can start after only a minute also

Question 3

How does Type I hypersensitivity occur?

Answer 3

After sensitization, allergen-specific IgE binds to mast cells/basophils. Upon re-exposure, allergen crosslinks IgE, triggering degranulation and mediator release.

Question 4

What are the (inflammatory) mediators and outcomes of Type I hypersensitivity?

Answer 4

Release of histamine, tryptase, leukotrienes, cytokines and prostaglandins → causes allergies, asthma, anaphylaxis, etc.

These are inflammatory mediators

Question 5

What determines immune outcome ?

Answer 5

The immune environment

Question 6

How can the immune system cause disease ?

Answer 6

-Mistakenly attacks the body’s own tissues (autoimmune disorders)
-Causes excessive reactions (hypersensitivity).

immunopathology isthe study of how the immune system’s response causes disease

Question 7

What is histamine and what does it do ?

Answer 7

Is an inflammatory mediator
-H1 causes H1 smooth muscle contraction, vasodilation, increased vascular permeability
-H2 increase gastric acid secretion
-H4 causes chemotaxis of mast cells and eosinophils.

Question 8

What is tryptase and what does it do ?

Answer 8

Protease that cleaves extracellular proteins and activates enzymes
-Causes inflammation, vascular leakage, tissue repair and remodeling

Is an inflammatory mediator

Question 9

What are local effects of prostoglandins ?

Answer 9

Increase blood flow and vascular permeability, chemotactic, pain sensitisation, smooth muscle effects

Inflammatory mediator

Question 10

What do leukotrienes do ?

Answer 10

Bronchoconstrictions (asthma), inflammation and chemoattractant, mucus secretion, increase vascular permeability

Inflammatory mediator

Question 11

What are examples of cytokines ?

Answer 11

TNF alpha, Il-1, IL-4, IL-5, IL-6, IL-13, IL-18 and TGF beta

all but TGF beta are inflammatory mediators

Question 12

What does a high dose of intravenous allergen lead to ?

Answer 12

Connective tissue mast cells affected
-General release of histamine and systemic anaphylaxis

Question 13

What does a low dose of subcutaneous allergen lead to ?

Answer 13

Connective tissue mast cells affected
-Local release of histamine, urticaria

Question 14

es a

What does a low dose of allergen inhalation lead to ?

Answer 14

Mucosal mast cells affected
-Increased mucous production and nasal irritation causes allergic rhinitis in upper airway
-Increase mucous secretion and bronchial smooth muscle contraction cause asmtha in lower airway

Question 15

What does ingestion of an allergen cause ?

Answer 15

Mucosal mast cells affected
-Contraction of intestnal smooth muscle causes vomiting
-Outflow of fluid into gut causes dioreehea
-Antigen moves into blood; urticaria or anaphylaxis

Question 16

What is Type II (cytotoxic) hypersensitivity?

Answer 16

Antibody-mediated reaction
-IgG or IgM binds to antigens on cell surfaces or tissues; cell destruction or dysfunction.
-Onset: up to 8 hours (2–24 hours)
-Type II hypersensitivity is an autoimmunity

Autoimmunity

Question 17

How does Type II hypersensitivity cause tissue damage?

Answer 17

1) IgG/IgM bind to cell-surface or membrane antigens.

2) Activate complement (C’) → opsonization, inflammation, cell lysis.

3) Recruit immune cells (e.g., neutrophils, macrophages).

4) ADCC by NK cells may occur.
→ Results in inflammation, cytotoxicity, or functional alteration.

ADCC = Antibody dependant cellular cytotoxicity (ADCC)

Question 18

What are the main effects of Type II hypersensitivity?

Answer 18

Cytotoxic effects: Cell death via complement or ADCC.

Functional disruption: Antibodies alter receptor activity (e.g., stimulate or block signaling).

Autoimmunity and inflammation in affected tissues.

NK cells are main mediators of ADCC

Question 19

What diseases are caused by Type II hypersensitivity?

Answer 19

On cells (cytotoxic)
-Autoimmune hemolytic anemia
-Erythroblastosis fetalis (hemolytic disease of newborn)

On tissues (destructive):
-Goodpasture’s syndrome
-Hyperacute transplant rejection
-Addison’s disease

Receptor alteration (functional):
-Graves’ disease (stimulation of TSH receptor, hyperthyroidism)
-Myasthenia gravis (blockage of ACh receptor, muscles weakened and tire quickly)

Question 20

What is a Type 3 hypersensitivity ?

Answer 20

Immune complex–mediated reaction
-IgG and IgM antibodies form soluble immune complexes with antigens which deposit in tissues; triggers inflammation and tissue damage.
-Onset: 3–12 hours after exposure.

Biggest immune complexes removed by spleen, medium sized deposit, small stay dissolved and in circulation

Question 21

How does Type III hypersensitivity cause tissue damage?

Answer 21

1) IgG and IgM bind to soluble antigens → form immune complexes.

2) Complexes deposit in tissues (vessels, joints, kidneys, lungs).

3) Complement activation occurs → C3a, C5a generation.

4) Neutrophil recruitment → inflammation and tissue damage.

5) Results in vasculitis, arthritis, nephritis, and rash.

Question 22

What are the clinical features and pathological outcomes of Type III hypersensitivity?

Answer 22

1) Inflammation and damage due to immune complex deposition.

2) Symptoms: fever, vasculitis, arthritis, nephritis, and rash.

3) Tissue injury caused by neutrophils and complement activation.

4) Severity depends on complex size (medium-sized complexes deposit most easily).

Question 23

Give examples of Type III hypersensitivity diseases.

Answer 23

Systemic lupus erythematosus (SLE)

Post-streptococcal glomerulonephritis (PSGN)

Serum sickness

Cryoglobulinaemia (Type II/III overlap)

Hypersensitivity pneumonitis (e.g. bird fanciers lung)

Question 24

Compare relative levels of antigens, antibodies and complexes as a type III hypersensitive reaction progresses

Answer 24

In blue zone is when complex deposition occurs and when symptoms happen
-small spaces and blood vessels affected as there can be deposition and damage gere, need to think about where complexes will go as this is where will be affeced. Deposition doesn’t occur in large spaces like big vessels
-paghoytic cells e.g. neutrohpils and macrophages remove complexes from deposition sites which is where inflammationa ndf stuff comes from

Question 25

What is Type IV hypersensitivity?

Answer 25

A cell-mediated, antibody-independent hypersensitivity reaction -Controlled by T cells and cellular mediators. -Onset: 24–72 hours (delayed). -Also called: Delayed-type hypersensitivity (DTH). | Second most common hypersensitivity reactions

Question 26

How does Type IV hypersensitivity occur?

Answer 26

1) Sensitized T cells (Th1, Th2, Th17, CD8⁺ CTLs) recognize antigen presented by APCs. 2) Release of cytokines recruits macrophages, eosinophils, and neutrophils. 3) Leads to inflammation, granuloma formation, and tissue destruction. 4) Can involve hapten–carrier complexes (e.g., nickel in contact dermatitis).

Question 27

Which cells mediate Type IV hypersensitivity and what are their effects?

Answer 27

Th1 + macrophages - type IVa: inflammation, granuloma, organ and cellular destruction → Type 1 diabetes, contact dermatitis Th2 + eosinophils - type IVb: chronic allergic inflammation → Persistent asthma, atopic dermatitis CD8⁺ T cells (CTLs) - type IVc: direct cytotoxicity → Stevens–Johnson syndrome, toxic epidermal necrolysis (TEN) Th17 + neutrophils - type Ivd: acute neutrophilic inflammation → Acute generalized exanthematous pustulosis (AGEP), Behçet’s disease

Question 28

What are key clinical manifestations of Type IV hypersensitivity?

Answer 28

Delayed onset (24–72 hours) after exposure. Rash, granuloma, ulcers, organ/tissue inflammation, organ/cellular destruction Diseases: -Contact dermatitis -Type 1 diabetes mellitus -Persistent asthma -Atopic dermatitis -Stevens–Johnson syndrome (SJS) -Toxic epidermal necrolysis (TEN) -Acute generalized exanthematous pustulosis (AGEP) -Behçet’s disease | Tuberculin ## Footnote Rash can be ulcerating

Question 29

What is a hapten ?

Answer 29

A small molecule (hapten), such as nickel, cannot by itself trigger a Type IV hypersensitivity reaction. When it binds to a self-protein, it forms a hapten–carrier complex. This complex is then recognized as foreign by T cells, which become activated and cause a cell-mediated inflammatory response. Example: Nickel contact dermatitis, where nickel acts as a hapten

Question 30

What is needed for mast cell degranulation in a type I hypersensitivity

Answer 30

A thresholf amount of IgE production and binding onto mast cells is required for degranulation -If enough receptors cross link with IgE there will be degranulation

Question 31

What is the body attempting to do with an allergic response ?

Answer 31

Tying to prevent/remove parasite infection - would be good at fighting parasite

Question 32

What tends to cause anaphylaxis more ?

Answer 32

Allergen needs to be systemic for anaphylaxis - bee/wasp stings go into blood, antibiotics (penicillin), IV drugs, food anaphylaxis is very rare but is really bad, insects/venoms/drug indued much more common

Question 33

Which subtype of type IV hypersensitivity causes granulomas ?

Answer 33

Granulomas form in Type IVa hypersensitivity reactions, which are Th1- and macrophage-mediated delayed-type hypersensitivity responses. -Evil antigens (actuallt evil or pretend evil) persist inside of macrophages which body doesn't like