Course: ImmunologyLecturer : Dr. W eam Saad
HypersensitivityAllergy is inappropriate or disturbing immune response against certain antigens.
Hypersensitivities are immunological reactions; they were classified for the first
time by the scientists Gell and Coombs into four major types according to their
1. Type I: Immediate Hypersensitivi ty.
2. Type II: Cytotoxic Hypersensitivity.
3. Type III: Immune complex Hypersensitivity.
4. Type IV: Delayed type Hypersensitivity .
Type I Hypersensitivity:Usually called immediate , anaphylactic or atopic allergy. Has 3 arms or
components; IgE/Mast cells/Allergen.
Allergen : is an antigen that stimulates Hypersensitivity, it is commonly
innocuous environmental antigen (not harmful for normal peoples).
1. Causes or Motives:1) Genetic susceptibility, this type of Hypersensitivity is usually hereditary.
2) Re -exposure to the same allergen.
2. Target :Soluble Ag or allergen. Some of them are able to induce allergy directly after
exposure e.g. house dusts and grass pollens. Other allergens need to combine
with certai n body proteins (act like hapte ns) e.g. pencillin antibiotic. While
others may be changed inside human body and turn to aller gic Ag like some
foods after di gestion.
3. Immunological Mechanisms:First exposure or previous exposure:
1) Allergen (Ag) processed by APCs and certain Ags wi ll be
expressed on APCs surface.
2) B -cells response to APCs by producing specific IgE antibodies
against that allergic Ag.
3) Binding of these IgE to the Fc reseptors of mast cells (or basophils).
Second exposure or re -exposure:When the same Ag or allergen enters the body again; it will bind to the specific
IgE on mast cells surface that stimulate the degranulation process to release the
vasoactive and inflammatory mediators after series intracellular signal. The
granules contain the mediators:
Eosinophils chemotactic factor ECF
These mediators will be released to the neighboring tissues and fluids afterdegranulation. Then clinical signs appear depending on alle rgen type and
allergic resp onse either systemic or local. e .g. in asthma the symptoms or signs
are: nausea, sneezing, hard to breath , asphyxia coughing, tearing eyes and
others. (Figure 1 )
Mast cells : they are basophils with more specification found in muc osa of
airways and gut as well as in connective tissues. They have specialized surface
receptors for the Fc portion of IgE antibodies.
4.Characteristics of this type of allergy :Acute allergic reaction, starts immediately after exposure to allergen (wi thin
minutes) and lasts for 4 -5 hrs.
Cause Eosinophilia (incre ase E osinophil s number in blood) and IgE levelsincrease.
Severity depends on the type of allergen, dose of exposure and immune system
state. Most of these allergy kinds are seasonal e.g. Hey fever.
Food and drugs Allergy
A systemic sever type I hypersensitivity, life threatening condition. Occurs
when the allergy mediators are relea sed in high amounts and mixed to form
leukotrines mixture SRS -A (slow - reacting substance of anaphylaxis). This
mixture is 1000 times powerful than histamine or prostaglandins in contracting
This response physiological symptom starts with sudden anaphylactic shock,
hard to breath , abdominal cramps (some time ), diarrhea, vomiting and may end
with death because of respiratory and cardiac failure.
Rapid administration of adrenaline (epinephrine) can stop shock progress.
Epinephrin e raises blood pressure and reverses the action of SRS -A (SRS -A
drops down blood pressure), then restore respiratory and heart function. The
important exampleis the systemic anaphylaxis that occurs after drugs like
penicillin and bees biting. Blood pressur e drops due to vasodilation after
mediators’ release . Also occurs in animals after injection with prepared Ags
during immunization experiments.
Type II HypersensitivityIt is usually called Antibody -Mediated or antibody -dependent cytotoxic
1. Causes or Motives:Combination of surface Ag of the cell with specific Abs (IgG, IgM classes),
resulting in the death of that cell by stimulating phagocytic attack or starting the
complement pathway that leads to cell lysis. These cells are usually foreign cells
e.g. RBCs during blood transfusion.
2. Target :Antigens on cell surface (part of the cell membrane), not against soluble Ag.
3. Immunological Mechanisms:When IgG or IgM antibodies bind to cell surface antigen forming Ag -Ab
complex, this will cause cellular damage by many ways:
1) Activation of complement system (classical pathway).C3b deposition with
anaphylatoxins C3a, C4a and C5a. then membrane attack complex
formation which cause lysis of target cell.
2) Antibody -dependant cell -mediated cytotoxicity occurs when the Abs (Fabportion) bound to the surface Ag of the target cell. Then this bound Ab
will also bind to the phagocytic cells and natural killer cells (NK) by Fc
portion. Here the antibody works as a bridge between target cells and
effector cells of the immune system. (Figure 2)
4. Characteristics of this type of allergy :1) Clinical signs depend on the type of the cell that has the target
antigen which induced this type of allergy. e.g. blood group
hyperse nsitivity differ from graft rejection.
2) Need specific immune response and specific antibody.
3) Cause necrosis because of cells lysis.
4) Life threatening some times.
Examples: Blood grouping compatibility.
Newborn hemolytic di sease
Clinical Example :Hemolytic disease of newborn:
Rh incompatibility occurs when Rh - negative mother and Rh+ father. When the
first fetus is Rh+ and during giving b irth; the mother will expose to the Rh
antigens of the fetus. During second child Rh+ ; the anti -Rh antibodies (IgG) that
formed after the first child will cross the placenta and attack the Rh+ cells
(RBCs) of the fetus. After birth the infant develops Jaundice or hemolytic
disease of newborn. Before birth mothers liver filters the fetus bloo d. The
treatment is by remove fetal Rh+ blood and replaced by Rh - blood to stop
reaction between child Rh+ and antibodies of mother in child circulating blood
that crossed placenta.
Mothers with Rh - negative avoid these cases by passive artificial immuniz ation
with Rhogam injections (anti -Rh antibodies commertialy called Anti -D). That to
avoid memory immune response in mothers' blood.
Type III Hypersensitivity:Called immune complex hypersensitivity. Results after some infections e.g.
bacteria and duri ng autoimmune diseases.
1. Causes or Motives :1) High antigen load.
2) Weak or ineffective immune response.
3) Not enough function of macrophage to remove immune complexes
The antigen -antibody complex (Ag -Ab complex) which escape or avoid clear
(engulfment) by macrophages and deposite d in body tissues.
3. Immunological Mechanisms:1) This type is also mediated by Abs(IgG or IgM) after forming, they bind to
soluble Ag(resulting from bacterial infection for example).
2) Ag -Ab complex that formed will be cleared by MФ.
3) Excess complex will deposit in any tissue and accumulate there.
4) Deposited complex will induce a number of inflammatory pathways or
reactions to clear tissues like attraction of PMNLs, releasing of proteolytic
enzymes causing local necrosis, vascular damage, odema, redness and
attraction of more PMNLs because of activation of complement system
which release of C3a, C4a and C5a anaphyla toxins, all these reactions end
with tissues necrosis.
4. Characteri stics of this type of allergy :1) The painful inflammatory lesions will appear during this type of
hypersensitivity in any tissue or organ that Ag -Ab complex deposited.
That will lead to this organ disorder within 7 -10 days after exposure to
2) Abs in t his type formed during normal immune response against either
exogenic Ag ( infectious or environmental) or endogenic Ag (self Ag in
Rheumatoid Arthritis (Joints)
Lymphodenitis (Lymph Nodes)
Vasculitis (Blood Vessels)
Clinical Example :Serum Sickness:
A disease occur because of type III hypersensitivity when a person get larg
doses of foreign serum e.g. horse serum antitoxins to protect against Tetanus
and Diphtheria .
Type IV Hypersensitivity:Called Delayed type or cell -mediated type. Caused by a type of T -cells(CD4+)
Lymphocytes which called T DTH (Delayed Type Hypersensitivity ). This type is
classified according to the clinical manifestations or signs and the body site that
1. Causes or Motives :Cell mediated immune response against certain Ags resulting from lon g
standing infections or poisons exposure.
2. Target :Ag coated cells of the body, the Ags are:
1) Natural products, mostly Haptens of low molecular weight, like poisons
(ivy and oak) or industrial agents (Nickel compounds).
2) Prolonged infections (long standing) Ags like Leprosy, Tuberculosis,
Brucellosis and fungal infections.
3. Immunological Mechanisms :1) Need first exposure and second exposure to form memory T -cells.
2) Engulfment, processing and presenting allergic or foreign Ag.
3) Sensitization and activation of T DTH and the production of cytokines or
lymphokines that i nvolved in CMI e.g. Macrophage -activating factor
4) MФ response and destroy Ag coated cells causing inflammation and
4. Characteristics of this type of allergy :1) It is called dela yed because it occurs after 24 -48 hr after exposure to
2) Cell -mediated immune response involving MФ, T -lymphocytes (TDTH ) and
3) Cause Eosinophilia.
Examples:Contact Dermatitis (Eczema)
Clinical Example s: Contact Dermatitis:
When allergic compounds penetrate to skin (Hapten) , they will bind to self
protein and become immunogenic Ag , then expressed on APCs surface
(langerhance). During second exposure to same Ag it will induce t ype 4
hypersensitivity causing i tching, redness, rash and swallow of skin site of
Mycobacterium tuberculosis infection is long s tanding intracellular infection .
When the Ag persist for long time, Granuloma will be formed. It’s the most
sever type of type 4 hypersensitivity. It is a type of chronic inflammation that
involves tissues transformation or damage. Leprosy infections are the same .
It is a cyst include phagocytic cells which turned to Giant cells(large
multinucleus MФ ) , and intracellular pathogen with some epithelial cells. This
can occur in lungs, heart and kidneys and cause tissues damage because of high
amounts of lysosomal enzymes released to surrounding tissues.