4th SEMESTER PHARM.

D
SESSION (2007-2012)
Defense against microbes is mediated
by:
Innate immunity
Early reactions
Also called natural or native immunity
Adaptive immunity
Late responses
High specificity
Memory
Adaptive immunity
Is important for host defense against microbial
infections
Can cause tissue injury and disease
Hypersensitivity diseases
Disorders caused by immune responses
A common cause of hypersensitivity
disease is failure of self-tolerance
Property of the immune system that
ensures that individuals do not respond to
their own antigens
Disorders caused by failure of self-
tolerance are called autoimmune
diseases
 Hypersensitivity diseases may also
result from uncontrolled or excessive
responses against foreign antigens
Microbes
Noninfectious environmental antigens
TYPES, MECHANISMS AND DIAGNOSTIC TESTS
The term hypersensitivity is used to
describe immune responses which
are damaging rather than helpful
to the host.
 Nearly 45 years ago Gell and
Coombs proposed a classification
scheme which defined 4 types of
hypersensitivity reactions.
 The four types of hypersensitivity are:
Type I Hypersensitivity- IgE mediated
Type II Hypersensitivity- Antibody
mediated
Type III Hypersensitivity- immune
complex
Type IV Hypersensitivity- cell
mediated

The first three are mediated by antibody,

THE “IMMEDIATE” ALLERGIC REACTION
 A hypersensitivity due to excessive
production of the class of antibody
known as IgE. Reactions between
allergens and IgE bound to mast cells
and basophils cause a greatly
heightened inflammatory response.
 May vary from minor inconvenience
to death
Usually take 10 to 30 mins to appear
after exposure to antigen
Sometimes delayed onset of reaction
(10-12h)
BASIC ELEMENTS ARE:

MEDIATOR = IgE
PRIMARY CELLULAR COMPONENT =
MAST CELL AND BASOPHILS
AMPLIFIER = PLATELETS,
NEUTROPHILS AND EIOSINOPHILS
STEP 1:
EXPOSURE OF ANTIGEN TO ANTIGEN
PRESENTING CELL
STEP 2:
RECOGNITION BY T- HELPER CELLS

ACTIVATION OF B-CELLS INTO PLASMA

AND MEMORY CELLS

SECRETION OF ANTIBODIES (IgE)

STEP 3:
IgE BINDS TO HIGH AFFINITY RECEPTORS
(FC EPSILONRI)
ON THE SURFACE OF MAST CELLS
STEP 4:
SUBSEQUENT EXPOSURE OF ANTIGEN

ANTIGEN BINDS WITH IgE ON THE

SURFACE OF MAST CELLS
STEP 5:
RELEASE OF PRIMARY INFLAMMATORY
METABOLTES

ACTIVATION OF SECONDARY
METABOLITES
 MOLECULE EFFECTS
PRIMARY MEDIATORS
HISTAMINE VASCULAR PERMEABILITY, SMOOTH MUSCLE CONTRACTION

SEROTONIN VASCULAR PERMEABILITY, SMOOTH MUSCLE CONTRACTION

ECF-A EOSINOPHIL CHEMOTAXIS

NCF-A NEUTROPHIL CHEMOTAXIS
PROTEASES MUCUS SECRETION, CONNECTIVE TISSUE DEGRADATION

SECONDARY MEDIATORS
LEUKOTRIENES VASCULAR PERMEABILITY, SMOOTH MUSCLE CONTRACTION

PROSTAGLANDINS VASCULAR PERMEABILITY, SMOOTH MUSCLE CONTRACTION

AND PLATELET ACTIVATION

BRADYKININ VASCULAR PERMEABILITY, SMOOTH MUSCLE CONTRACTION

CYTOKINES NUMEROUS EFFECTS INC. ACTIVATION OF VASCULAR

ENDOTHELIUM, EOSINOPHIL RECRUITMENT AND ACTIVATION
The reactions, mediated by agents
without IgE-allergen interaction, are
not hypersensitivity reactions
although they produce the same
symptoms. 
1. Anaphylaxis
2. Asthma
3. Allergic Rhinitis
4. Food Allergy
1. PRICK TEST
2. TRANSDERMAL TEST
3. ELISA
1. ANTIHISTAMINES
2. Chromolyn sodium
3. leukotriene receptor blockers
4. use of IgG antibodies
THE CYTOTOXIC HYPERSENSITIVITY
Definition
A hypersensitivity resulting from
antibodies mistakenly reacting with normal
self antigens on body cells. Binding of the
antibodies to these normal cells results in
immune destruction.
 IgG OR IgM
IN THIS CASE

MADE AGAINST SELF ANTIGENS

ATTACH TO THE SURFACES OF CELLS HAVING

SELF EPITOPS

SELF ANTIGEN=Any constituent of the body's

own tissues capable of stimulating
autoimmunity
FAILURE IN IMMUNE TOLERANCE

ENTERANCE OF FOREIGN ANTIGEN

RESEMBLING SOME MOLECULE ON THE
SURFACE OF HOST CELLS

'IMMUNE TOLERANCE' is the process by

which the immune system does not attack an
antigen
THESE FACTORS LEAD TO:

3. OPSONIZATION

4. MAC LYSIS
5. ADCC
DEFINITION:
The attachment of microbes and other
foreign cells to phagocytes by
antibody molecules such as IgG and
complement proteins such as C3b.
Also called enhanced attachment or
immune adherence.
MECHANISM
THE OPSONIZATION IS OF THE HOST CELL

PHAGOCYTES STICK TO MEMBRANES OF

HOST CELL

VIA IgG, C3B, C4B

PHAGOCYTES DISCHARGE THEIR

LYSOSOMES
RESULT:
LYSIS OF HOST CELL
DEFINITION

A protein complex produced during the

complement pathways. C5b6789 (MAC
or membrane attack complex) puts
pores into lipid bilayer membranes of
human cells to which antibodies have
bound. This results in cell lysis.
MECHANISM
IgG / IgM

BINDS WITH EPITOPS ON CELL SURFACES

ACTIVATE CLASSICAL PATHWAY OF

COMPLEMENT SYSTEM

MAC CAUSES LYSIS OF CELL

MECHANISM
DEFINITION

The process of NK cells binding to the

Fc portion of antibodies that have
bound to epitopes of cells recognized
as nonself such as infected cells and
tumor cells. Once bound to the Fc
portion of the antibody, the NK cell will
then lyse that cell with perforins.
MECHANISM
IgG / IgM

BINDS WITH EPITOPS ON CELL SURFACES

NK CELLS ATTACH TO THE Fc PORTION OF

IgG/IgM

RELEASE OF PERFORINS AND GRANZYMES BY NK

APOPTOSIS
MECHANISM
MECHANISM
AB AND RH BLOOD GROUP REACTIONS;
AUTOIMMUNE DISEASES SUCH AS:
RHEUMATIC FEVER where antibodies result in
joint and heart valve damage;
IDIOPATHIC THROMBOCYTOPENIA PURPURA
where antibodies result in the destruction of
platelets;
MYASTHENIA GRAVIS where antibodies bind to
the acetylcholine receptors on muscle cells
causing faulty enervation of muscles;
GOODPASTURE'S SYNDROME where
antibodies lead to destruction of cells in the
kidney;
SOME DRUG REACTIONS.
TYPE II HYPERSENSITIVITY ALSO
PARTICIPATES IN EARLY TRANSPLANT
REJECTIONS.
1. DETECTION OF CIRCULATING
ANTIBODY AGAINST THE TISSUES
INVOLVED

3. THE PRESENCE OF ANTIBODY AND

COMPLEMENT IN THE LESION (BIOPSY)
BY IMMUNOFLUORESCENT STAINING
(PATTERN = LINEAR).
ANTI-INFLAMMATORY DRUGS

IMMUNOSUPPRESSANT DRUGS
THE IMMUNE COMPLEX HYPERSENSITIVITY
Definition :
A hypersensitivity resulting from large
quantities of soluble antigen-antibody
complexes passing between endothelial
cells of the blood vessels and becoming
trapped on the surrounding basement
membrane.
 1. SELF OR NON-SELF ANTIGEN

3. ANTIBODIES
MOSTLY IgG
RARELY IgM

PATHOLGY OCCURS AT THE SITE OF

DEPOSITION
NORMALLY
SOLUBLE ANTIGEN-ANTIBODY COMPLEX
FORMATION

REMOVED BY MACROPHAGES IN SPLEEN

AND LIVER
ABNORMALLY
INCREASED SOLUBLE ANTIGEN-ANTIBODY
COMPLEX FORMATION

NOT ALL REMOVED BY MACROPHAGES IN

SPLEEN AND LIVER

DEPOSITION OF COMPLEXES VIA BLOOD

VESSELS
STEP 1
Large quantities of soluble antigen-antibody
complexes form in the blood and are not completely
removed by macrophages.
STEP 2
These antigen-antibody complexes lodge in the blood
vessels between the endothelial cells and the
basement membrane.
STEP 3
These antigen-antibody complexes
activate the classical complement
pathway leading to vasodilation
STEP 4
The complement proteins and antigen-
antibody complexes attract leukocytes
to the area.
STEP 5
The leukocytes discharge their killing
agents and promote massive
inflammation. This can lead to tissue
death and hemorrhage.
1. SERUM SICKNESS, A COMBINATION
TYPE I AND TYPE III HYPERSENSITIVITY
2. AUTOIMMUNE ACUTE
GLOMERULONEPHRITIS
3. RHEUMATOID ARTHRITIS
4. SOME CASES OF CHRONIC VIRAL
HEPATITIS
Examination of tissue biopsies for
deposits of immunoglobulins and
complement by immunofluorescence
(pattern = granular)
The presence of immune complexes in
serum
Depletion in the level of complement
ANTI-INFLAMMATORY DRUGS
THE CELL MEDIATED OR DELAYED TYPE HYPERSENSITIVITY
Definition:
A hypersensitivity resulting from cell-
mediated immunity (cytotoxic T-
lymphocytes and cytokines) causing
harm to the body.
 CAUSED BY T-CELLS
T-HELPER CELLS BY SECRETION OF
CYTOKINES
MAINLY BY CYTOTOXIC T-CELLS BY
DIRECT DAMAGE
STEP 1
ANTIGEN ENTERS THE BODY

ENGULFED BY MACROPHAGES

PRESENTED TO T-H CELLS

T-H CELLS BECOMES ACTIVATED AND

INCREASED IN NUMBER
STEP 2
SECOND EXPOSURE

ENGULFED BY MACROPHAGES

PRESENTED TO T-H CELLS

T-H CELLS RELEASE CYTOKINES

STEP 1
ANTIGEN BINDS TO NORMAL CELL

EPITOPE PRESENTED WITH MHC-1

CTL ATTACHED BY TCR/CD8+

ACTIVATION OF T-CELL
STEP 2

ACTIVATION OF CYTOTOXIC T-CELL

RELEASE OF
7. PORE-FORMING PROTEINS CALLED
PERFORINS
8. PROTEOLYTIC ENZYMES CALLED GRANZYMES
9. CHEMOKINES
STEP 3

PERFORINS FORM PORES

GRANZYMES PASS THROUGH PORES

ACTIVATE ENZYMES OF CELLS

APOPTOSIS
THE CELL OR TISSUE DAMAGE done
during diseases like tuberculosis,
leprosy, smallpox, measles, herpes
infections.
THE SKIN TEST REACTIONS seen for
tuberculosis and other infections
CONTACT DERMATITIS like poison ivy
TYPE -1 INSULIN-DEPENDENT DIABETES
where CTLs destroy insulin-producing
cells
1. IN VIVO
Mantoux test
Patch test
2. INVITRO
1. Lympho-cytotoxicity
2. IL-2 production
Corticosteroids and other
immunosuppressive agents
CHARACTE type-I type-II type-III type-IV
RISTICS (anaphylacti (cytotoxic) (immune (delayed
c) complex) type)
ANTIBODY IgE IgG, IgM IgG, IgM None

ANTIGEN exogenous cell surface soluble tissues &

organs
RESPONSE 15-30 minutes- 3-8 hours 48-72 hours
TIME minutes hours
APPEARANC weal & flare lysis and erythema and erythema
E necrosis edema, and
necrosis induration
HISTOLOGY basophils and antibody complement monocytes
eosinophil and and and
complemen neutrophils lymphocytes
TRANSFERRE antibody antibody antibody T-cells
t
D WITH
EXAMPLES allergic Erythro- Farmer's lung tuberculin
asthma, hay blastosis disease test, poison
fever fetalis, ivy,
granuloma