Immunology & Immunotechnology

Immunology & Immunotechnology
(Biot-3111) Lecture -11
1
11.2. Type II Hypersensitivity
• Also called Antibody-Mediated Cytotoxic

Hypersensitivity
• Antibody can activate:
• The complement system, creating pores in the membrane

of a foreign cell or
• It can mediate cell destruction by antibody dependent cell-

mediated cytotoxicity (ADCC)
2
11.2. Type II Hypersensitivity …
• Three examples:
• Transfusion Reactions
• Hemolytic Disease of the Newborn
• Drug-Induced Hemolytic Anemia
3
Transfusion Reactions
• The ABO Blood Group System
Cells of blood type O lack both A and B antigens 4

• A transfusion is incompatible (a transfusion reaction)

• When type B blood is transfused into a person with type A
blood
• The antigens on the type B blood cells will react with anti-B
antibodies in the recipient’s serum
• Usually of the IgM class
• This Ag-Ab reaction activates
• Complement mediated lysis, which causes lysis of the donor’s

RBCs as they enter the recipient’s system
5
• Clinical manifestations:
• Immediate hemolytic transfusion reactions
• Within hours, free hemoglobin can be detected in the plasma
• It is filtered through the kidneys, resulting in hemoglobinuria
• Symptoms include:
• Fever, chills, nausea, clotting within blood vessels, pain in the
lower back, and hemoglobin in the urine 6
• Treatment involves:
• Prompt termination of the transfusion and
• Maintenance of urine flow with a diuretic, because the

accumulation of hemoglobin in the kidney can cause acute
tubular necrosis
7
• Antibodies to other blood group antigens may result

from repeated blood transfusions
• ABO-compatible blood that is incompatible for other

blood group antigens
• Because minor allelic differences in these antigens can

stimulate antibody production
• These antibodies are usually of the IgG class
8
• Clinical manifestations:
• Delayed hemolytic transfusion reactions
• Develop between 2 and 6 days after transfusion, reflecting

the secondary nature of these reactions
• IgG is less effective than IgM in activating complement

• For this reason:
• Complement-mediated lysis of the transfused RBCs is incomplete
• Many of the transfused cells are destroyed at extravascular sites by

agglutination, opsonization, and subsequent phagocytosis by
macrophages 9
• Symptoms include:
• Fever, low hemoglobin, increased bilirubin, mild jaundice,

and anemia
• Free hemoglobin is usually not detected in the plasma or

urine in these reactions because RBC destruction occurs in
extravascular sites
10
Hemolytic Disease of the Newborn
• When maternal IgG antibodies specific for fetal blood

group antigens cross the placenta and destroy fetal red
blood cells
• The consequences of such transfer can be:
• Minor, serious, or lethal
11
• Severe hemolytic disease of the newborn, called

erythroblastosis fetalis
• Most commonly develops when an Rh+ fetus expresses an

Rh antigen on its blood cells that the Rh– mother does not
express
12
• Also
13
Rh– mother carrying
her first Rh+ fetus. Rh In response to If the woman
Rh+ father the fetal becomes pregnant
antigens from the
developing fetus can Rh antigens, the with another Rh+
enter the mother's mother fetus, her anti-Rh
blood during delivery will produce antibodies will cross
anti-Rh the placenta and
antibodies damage fetal red
Figure. Hemolytic disease of the newborn blood cells
14
• During the 1st pregnancy small amounts of fetal blood

pass through the placenta but not enough to induce a
responses
• During delivery larger amounts of fetal blood cross the

placenta causing an activation of B-cells that are Rh
antigen specific thus, leading to memory B-cells (anti-Rh
antibodies)
• The IgM antibody clears the Rh+ cells from the mother
15
• In subsequent pregnancies with an Rh+ fetus, the Rh+

RBC cross the placenta activating the memory B-cells
• These in turn cross the placenta and damage the fetal RBC
because they are seen as “foreign”
• This type of reaction can be prevented by administering

antibodies against the Rh antigen within 24-48 hours after
the 1st delivery
16
• Rhogam-is the antibody that is injected
• It will bind to the fetal RBC that enter the mother’s

circulation and facilitate the clearance of them before B-cell
activation
• In subsequent pregnancies the mother is unlikely to produce

IgG anti-Rh antibodies
• If the mother doesn’t receive this injection there are other

ways to treat this, depending on the severity
17
• For a severe reaction:
• The fetus can be given an intrauterine blood-exchange

transfusion to replace fetal Rh+ RBCs with Rh– cells
• These transfusions are given every 10–21 days until

delivery
18
• In less severe cases

• In fact exposed to low levels of UV light
• To break down the bilirubin and prevent cerebral damage
• Plasmapheresis to mother
• To separate the mother’s blood into two fractions:
• Blood cells
• Plasma
19
• The majority of cases (65%) of hemolytic disease of the

newborn have minor consequences and are caused by
ABO blood-group incompatibility between the mother and
fetus
• Type A or B fetuses carried by type O mothers most

commonly develop these reactions
20
Drug-Induced Hemolytic Anemia
• Certain antibiotics can adsorb nonspecifically to proteins

on RBC membranes
• E.g., penicillin, cephalosporin, and streptomycin
• Forming a complex similar to a hapten-carrier complex
21
• Such drug-protein complexes induce formation of

antibodies
• Which then bind to the adsorbed drug on RBCs, inducing

complement mediated lysis
• Thus, progressive anemia
• When the drug is withdrawn
• The hemolytic anemia disappears

22
11.3. Type III Hypersensitivity
• Also called Immune complex Mediated Hypersensitivity
• The reaction of Ab with Ag generates immune

complexes
• Generally, this complexing of Ag with Ab facilitates the

clearance of antigen by phagocytic cells
• In some cases, large amounts of immune complexes can

lead to tissue-damaging type III hypersensitive reactions
23
11.3. Type III Hypersensitivity …
• The magnitude of the reaction depends on:
• The quantity of immune complexes
• The immune complex distribution within the body
• Immune complexes form only when certain ratios of Ag and Ab

occur
• The antibodies involved are usually IgG
• When a certain Ag:Ab ratio exists, usually with a slight excess of

Ag
• The soluble complexes that form are small  escape phagocytosis
24
• Larger immune complexes
• are deposited on the basement membrane of blood vessel

walls or kidney glomeruli
• Smaller immune complexes
• may pass through the basement membrane and be deposited

in the subepithelium
25
Localized type III reaction

• Injection of an Ag intradermally or subcutaneously into an
animal that has high levels of circulating Ab specific for that
Ag leads to formation of localized immune complex
• Injection of an Ag:
• Can lead to an acute Arthus reaction within 4-8 hours
• Localized tissue and vascular damage result from accumulation of

fluid (edema) and RBC (erythema)
• Severity can vary from mild swelling to redness to tissue necrosis

26
• Insect bite:
• May first have a rapid type I
reaction
• Some 4-8 hours later a
typical Arthus reaction
develops
27
Generalized Type III Reactions
• When large amounts of Ag enter the bloodstream and bind

to Ab, circulating immune complexes can form
• If Ag is in excess, small complexes form
• Because these are not easily cleared by the phagocytic cells,

they can cause tissue-damaging type III reactions at various
sites
28
• E.g. Serum sickness

• Infectious Diseases
• Meningitis
• Hepatitis
• Mononucleosis
• Drug Reactions
• Allergies to penicillin and sulfonamides
• Autoimmune Diseases
• Systematic lupus erythematosus
• Rheumatoid arthritis
29
Figure. Immune complex–mediated hypersensitivity

30
11.4. Type IV Hypersensitivity
• Also called Cell Mediated Hypersensitivity/ Delayed

type hypersensitivity (DTH)
• Are caused mainly by T cells
• An important part of host defense against

intracellular parasites and bacteria
• Occurs within a day or more after a sensitized

individual is again exposed to an Ag 31
11.4. Type IV Hypersensitivity …
• A major factor in the delay is:
• The time required for the participating T cells and

macrophages to migrate to and accumulate near the Ags
• Phases of the DTH Response
• Sensitization phase
• Effector phase
32
Sensitization phase
• Occurs 1-2 weeks after primary contact with Ag
• TH cells are activated and clonally expanded by Ag

presented together with MHC class II on an appropriate
APC
• Generally CD4+ cells of the TH1 subtype are activated

during sensitization and designated as TDTH cells
33
34
Effector phase
• TDTH cells secrete a variety of cytokines and chemokines
• Which recruit and activate macrophages
• Macrophage activation
• Promotes phagocytic activity and increased concentration of
lytic enzymes for more effective killing
• Activated macrophages
• Are also more effective in presenting Ag and function as the
primary effector cell
35
• TH1 memory cells (TDTH cells) are activated and produce

cytokines:
• IFN-γ, TNF-α, and TNF-β
• Cause tissue destruction, inflammation
• IL-2 - activates T cells and CTLs.
• Chemokines - macrophage recruitment
• IL-3, GM-CSF - increase monocyte/macrophage production

36
37
• If the DTH response is prolonged
• A granuloma develops
• Continuous activation of macrophages induces the

macrophages to:
• Adhere closely to one another, assuming an epithelioid shape

and
• Sometimes fusing together to form giant, multinucleated cells

38
39
Skin test for tuberculosis

• Because Mycobacterium tuberculosis is often located within
macrophages
• It stimulates a delayed cell-mediated immune response
• As a screening test, protein components of the bacteria

(PPD) are injected into the skin
• If the recipient has (or has had) a previous infection by

tuberculosis bacteria
• An inflammatory reaction to the injection of these antigens will
appear on the skin in 2 to 3 days
40
Allergic contact dermatitis

• Is usually caused by haptens that combine with proteins
in the skin of some people to produce an immune response
• Reactions to poison ivy, cosmetics, and the metals in

jewelry (especially nickel) are familiar examples of these
allergies
Allergic contact dermatitis

Caused by wearing latex
surgical gloves
41
Pentadecacatechol Skin
Molecules from the protein
poison ivy plant
7–10 days 1-2 days
T cells: T memory cells: Many active T cells: Disease

Sensitization step Immune response
Primary contact Secondary contact

Figure . The development of an allergy (allergic contact dermatitis) to catechols from the poison ivy plant.
42
Summary
Type of Time Characteristics Examples
Reaction
Type I <30 IgE binds to mast cells or Anaphylactic shock from
(Anaphylactic) min basophils; causes degranulation drug injections and insect
these cells and release of reactive venom; common allergic
substances such as Histamine. conditions, such as hay
fever, asthma
Type II 5–12 Antigen causes formation of IgM Transfusion reactions, Rh
(Cytotoxic) hours and IgG antibodies that bind to incompatibility
target cell; when combined with
action of complement, destroys
target cell.
Type III 3–8 Antibodies and antigens form Arthus reactions, serum
(Immune hours complexes that cause damaging sickness
Complex) inflammation.
Type IV 24–48 Antigens activate TC that kill Rejection of transplanted
(Delayed hours target cell. tissues; contact dermatitis,
Hypersensitivit such as poison ivy; certain
y) chronic diseases, such as
tuberculosis 43

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(Biot-3111) Lecture -11

• Also called Antibody-Mediated Cytotoxic

• Antibody can activate:

• The complement system, creating pores in the membrane

• It can mediate cell destruction by antibody dependent cell-

• Hemolytic Disease of the Newborn

• Drug-Induced Hemolytic Anemia

Cells of blood type O lack both A and B antigens 4

• A transfusion is incompatible (a transfusion reaction)

• This Ag-Ab reaction activates

• Complement mediated lysis, which causes lysis of the donor’s

• Immediate hemolytic transfusion reactions

• Within hours, free hemoglobin can be detected in the plasma

• It is filtered through the kidneys, resulting in hemoglobinuria

• Prompt termination of the transfusion and

• Maintenance of urine flow with a diuretic, because the

• Antibodies to other blood group antigens may result

• ABO-compatible blood that is incompatible for other

• Because minor allelic differences in these antigens can

• These antibodies are usually of the IgG class

• Develop between 2 and 6 days after transfusion, reflecting

• IgG is less effective than IgM in activating complement

• Many of the transfused cells are destroyed at extravascular sites by

• Fever, low hemoglobin, increased bilirubin, mild jaundice,

• Free hemoglobin is usually not detected in the plasma or

Hemolytic Disease of the Newborn

• When maternal IgG antibodies specific for fetal blood

• The consequences of such transfer can be:

• Minor, serious, or lethal

• Severe hemolytic disease of the newborn, called

• Most commonly develops when an Rh+ fetus expresses an

• During the 1st pregnancy small amounts of fetal blood

• During delivery larger amounts of fetal blood cross the

• In subsequent pregnancies with an Rh+ fetus, the Rh+

• This type of reaction can be prevented by administering

• Rhogam-is the antibody that is injected

• It will bind to the fetal RBC that enter the mother’s

• In subsequent pregnancies the mother is unlikely to produce

• If the mother doesn’t receive this injection there are other

• For a severe reaction:

• The fetus can be given an intrauterine blood-exchange

• These transfusions are given every 10–21 days until

• In less severe cases

• To break down the bilirubin and prevent cerebral damage

• The majority of cases (65%) of hemolytic disease of the

• Type A or B fetuses carried by type O mothers most

Drug-Induced Hemolytic Anemia

• Certain antibiotics can adsorb nonspecifically to proteins

• E.g., penicillin, cephalosporin, and streptomycin

• Forming a complex similar to a hapten-carrier complex

• Such drug-protein complexes induce formation of

• Which then bind to the adsorbed drug on RBCs, inducing

• Thus, progressive anemia

• When the drug is withdrawn

• The hemolytic anemia disappears

• Also called Immune complex Mediated Hypersensitivity

• The reaction of Ab with Ag generates immune

• Generally, this complexing of Ag with Ab facilitates the

• In some cases, large amounts of immune complexes can

• The magnitude of the reaction depends on:

• The quantity of immune complexes