AG 2022 Sem 2
LECTURE 4
MICROBIOLOGY ( IMMUNITY)
TREND COPY CENTER
Hypersensitivity
Definition:
Hypersensitivity refers to undesirable (damaging, discomfort-producing and sometimes
fatal) reactions produced by the immune system.
Classification:
Hypersensitivity reactions are classified into four types based on the mechanisms
involved and time taken for the reaction:
o Type I: immediate or anaphylactic hypersensitivity.
o Type II: cytotoxic hypersensitivity.
o Type III: immune complex hypersensitivity.
o Type IV: delayed type hypersensitivity.
1. Type I Hypersensitivity (anaphylaxis)
Type I hypersensitivity is also known as immediate or anaphylactic hypersensitivity.
Main components:
1) Allergens: 2) IgE
o Inhalants: Pollen grains, fungal allergens 3) Mast cells and basophils
4) Pharmacologically active mediators
o Injectants: Drugs
o Contact: Antiseptic spray, clothes
o Other: Food, animal hair, insects.
Page | 1
Manifestations:
o Systemic: anaphylaxis.
o Localized (Atopy):
▪ Skin (Atopic dermatitis).
▪ Eyes (conjunctivitis).
▪ Nasopharynx (rhinorrhea, allergic rhinitis “hay fever”).
▪ Broncho-pulmonary tissues (asthma).
▪ GI tract (food allergy).
Mechanism:
• Allergens enter the body for the first time and produce IgE.
• IgE has very high affinity for its receptors on mast cells and basophils and become
fixed on the surface of these cells within few weeks.
• A subsequent exposure to the same allergen, the allergen combines with IgE on the
surface of mast cells or basophils, cross links the cell-bound IgE, increase Ca++
influx and triggers the release of various pharmacologically active substances.
Page | 2
Pharmacologically active mediators of immediate hypersensitivity
A- Preformed mediators in granules:
Bronchoconstriction, mucus secretion, vasodilatation,
Histamine vascular permeability.
Tryptase Proteolysis.
ECF-A (Eosinophil
chemotactic factor-A) Attract eosinophil and neutrophils.
B- Newly formed mediators
Leukotriene B4 Basophil attractant.
Leukotriene C4,D4 Same as histamine but 1000x more potent.
Prostaglandin D2 Edema and pain.
Diagnostic tests for immediate hypersensitivity
• Skin (prick and intradermal) tests: ID injection of allergen leads to induration at
the site of injection within 15 minutes.
• Measurement of Total IgE and specific IgE antibodies: measured by ELISA.
Treatment
a) Avoidance of exposure.
b) Symptomatic treatment.
c) Immunotherapy.
d) Monoclonal antibodies.
Avoidance of exposure
• For dust mite allergens: Cover mattresses, pillows with dust mite resistant covers.
• For fungal allergens:
1. removing indoor plants (which promote mould growth)
2. drying or removing wet carpets.
Page | 3
Symptomatic treatment
1. Antihistamines which block histamine receptors.
2. Chromolyn sodium: inhibits mast cell degranulation, by inhibiting Ca++ influx.
3. Leukotriene receptor blockers: to block leukotrienes.
4. Bronchodilators (inhalers).
5. Steroids: systemic or local (topical, inhaled, intranasal)
6. Epinephrine: only in sever systemic anaphylaxis
Immunotherapy
✓ Definition: administration of gradually increasing doses of allergen extracts at regular
intervals over a period of years (starting with a very small dose), given to patients by SC
injection or drops/tablets under the tongue (sublingual).
✓ Mechanism: It is possible to teach the immune system to tolerate the allergen and
causes the production of 'regulatory' immune cells,
which:
o stop the production of IgE
o rise in allergen-specific IgG4 antibodies with blocking activity, bind and neutralize
much of the allergen preventing its binding to cell-bound IgE on the mast cells →
inhibition of release of inflammatory mediators from mast cells.
Monoclonal antibodies
• Made against the Fc portion of human IgE.
• Blocks the attachment of the IgE to the mast cells → prevents the subsequent
release of histamine by those cells upon exposure to allergen.
Page | 4
2. Type II hypersensitivity
• Also known as cytotoxic hypersensitivity and may affect a variety of organs and
tissues.
• The antigens are normally endogenous, although exogenous chemicals (haptens)
which can attach to cell membranes can also lead to type II hypersensitivity.
• Primarily mediated by IgM or IgG classes →
o Complement mediated lysis.
o Phagocytes and Killer cells may also play a role (ADCC).
Mechanism:
• The reaction time is minutes to hours.
• Type II hypersensitivity is primarily mediated by antibodies of the IgM or IgG
classes which will attach to antigen on the membrane of cells which may lead to:
o Complement → attached to antigen-antibody on the surface of these cells
leading to cell lysis.
o Phagocytes and killer cells may also lead to cell lysis.
Types:
A- RBCs lysis
B- WBCS lysis
C- Platelet destruction
Page | 5
RBCs lysis
1. Incompatible blood transfusion:
• ABO: Intravascular haemolysis (by complement).
Manifestations: nausea, fever, rigors, back pain.
• RH: extravascular haemolysis (by phagocytic cells).
2. Erythroblastosis fetalis:
• When mother (Rh negative) gives birth to Rh positive infant, at time of birth,
fetal blood may enter to maternal circulation and produce antibody against Rh
antigen.
• At 2nd pregnancy, the antibody will cross the placenta and become attached to
Rh antigen on the surface of RBCs of the fetus and extravascular haemolysis
occur and the infant show anemia and jaundice at first day then
hepatosplenomegally and bilirubin encephalopathy.
3. Autoimmune hemolytic disease.
WBCs lysis
1) Granulocytopenia: antibodies to neutrophils.
2) Systemic Lupus Erythematosus (SLE)
Platelet destruction:
• Idiopathic thrombocytopenic purpura (ITP)
Page | 6
3. Type III hypersensitivity
(Immune complex hypersensitivity)
• It is mediated by soluble immune complexes.
• They are mostly of the IgG class, rarely IgM.
• The antigen is soluble. It may be:
✓ exogenous (chronic bacterial, viral or parasitic infections),
✓ endogenous (self-antigen).
Mechanism:
• The antigen is soluble and not attached to the organ involved.
• Soluble antigen-antibody immune complexes → penetrate the endothelium of
blood vessels and deposited on the vascular basement membrane→ This will
stimulate the complement fixation releasing C3a, C4a and C5a portions→
attract neutrophils which will infiltrate the area → release lysosomal enzymes
leading to → destruction of the basement membrane→ interfering with the blood
supply to the target organ.
Clinical types:
1. Serum sickness.
2. Arthus reaction
3. Hypersensitivity pneumonitis.
4. Poststreptococcal glomerulonephritis
5. Autoimmune disease: Rheumatoid arthritis (RA), Systemic Lupus Erythematosus
(SLE).
Page | 7
4. Type IV hypersensitivity
• Type IV hypersensitivity is also known as cell mediated or delayed type
hypersensitivity.
• The classical example of this hypersensitivity is tuberculin (Mantoux) reaction
which peaks 48 hours after the injection of antigen (PPD or old tuberculin).
• The lesion is characterized by induration and erythema.
Mechanism:
• CD4+ helper T cells recognize antigen in a complex with Class II MHC.
• The antigen-presenting cells mainly the macrophages secrete cytokines as IL-12 to
stimulate the proliferation of CD4+ Th1 cells.
• CD4+ T cells secrete cytokines as IL-2 and interferon gamma, further inducing
the release of other Th1 cytokines, thus mediating the immune response:
Activated CD8+ T cells destroy target cells on contact.
Chemokines (such as IL-8), monocyte chemotactic and activating factor
(MCAF) that collectively lead to macrophage activation and production of
hydrolytic enzymes which lead to the development of a local tissue reaction
which is usually maximal in 48-72 h.
The classical examples of this hypersensitivity are:
• Tuberculin (Mantoux) reaction which peaks 48 hours after the injection of
antigen (PPD or old tuberculin).
• Chronic eczema.
Page | 8
Comparison between different types of hypersensitivity
Page | 9
