Immunology Lecture Notes by MK Alex (PHD Fellow-Mak)

IMMUNOLOGY LECTURE NOTES
BY MK ALEX (PhD Fellow- Mak)

 Hypersensitivity refers to a condition in which an immune response results in
exaggerated or inappropriate reactions that are harmful to the host.
 Immune response mobilizes effector molecules to remove an antigen (Ag) by
various mechanisms.
 These molecules induce localized inflammatory response to eliminates Ag
without extensive damage to host’s tissue.
 However, under certain conditions, this response may have deleterious
effects/tissue damage.
 These reactions typically occur after the second contact with a specific antigen
(allergen).
 The first contact is a necessary preliminary event that induces sensitization to
that allergen
 There are four main types of hypersensitivity reactions.
 Type I. Immediate Hypersensitivity
 Type II. Hypersensitivity
 Type III. Hypersensitivity
 Type IV. Hypersensitivity
 Types I, II, and III are antibody mediated, and type IV is T-cell mediated.

 Induced by allergens(antigens),
 Allergen induce antibody response.
 In this Ab response, the plasma cells produce IgE.
 IgE binds with high affinity Fc receptors on Mast cells and
Basophils.
 Subsequent exposure to the same allergen cross-links the
membrane bound IgE on the sensitized cells causing them to
degranulate.
 Released ‘active mediators’ ’act on the surrounding tissue casuing
‘vasodilation and smooth muscle contraction’ (systemic or
localized).
Allergen (antigen)
Antigen-presenting cell (APC)

phagocytizes and processes
THE MECHANISMS antigen.
OF A TYPE I
HYPERSENSITIVITY
REACTION: APC presents
SENSITIZATION epitope to Th2 cell.
Th2 cell
IL-4 IL-4 from Th2
cell stimulates selected
B cell B cell clone.
B cells become plasma cells

that secrete IgE.
Plasma
cell
IgE against allergen
IgE stem binds to

mast cells, basophils,
and eosinophils.
IgE
Mast cell Basophil Eosinophil
BY MK ALEX (PhD Fellow- Mak) Sensitization
THE MECHANISMS OF A TYPE I
HYPERSENSITIVITY
Subsequent exposure
to allergen
Sensitized mast cell,

basophil, or eosinophil
Histamines, kinins,
proteases, leukotrienes,
prostaglandins, and other
inflammatory molecules
Degranulation

 Involve antibody-mediated destruction of cells
 Occurs when IgG or IgM are produced against surface antigens on body cells
 These Abs can trigger either by activating complement system which create pores in the
membrane of foreign cell (e.g. autoimmune hemolytic anemia) or mediate cell destruction by
antibody-dependent cell-mediated cytotoxicity (ADCC) by facilitating the binding of NK cells.
 Cytotoxic cells with Fc receptors bind the Fc region of the antibody on the target cells and
promote the killing of the cells.
 Antibody binds to foreign cell, serve as an opsonin, enabling phagocytic cells with Fc or C3b
receptors to bind and phagocytose the antibody-coated cell.

• Blood transfusion reactions
• Hemolytic disease of the newborn (Rh disease)
• Autoimmune hemolytic anemias
• Drug reactions
• Drug-induced loss of self-tolerance
• Hyperacute graft rejection
• Myasthenia gravis (acetylcholine receptor)
• Sensitivity to tissue antigens

Blood type Natural Abs Can donate Can receive
present to: from:
A Anti-B A, AB A, O
B Anti-A B, AB B, O
AB none AB A,B,AB,O
O Anti-A All O
Anti-B
Type II hypersensitivity
 The ABO system and transfusion reactions
 Blood group antigens are surface molecules of red

blood cells
 Each person’s red blood cells have A antigen, B
antigen, both antigens, or neither antigen
 Transfusion reaction can result if individual receives
different blood type
 Donor’s blood group antigens may stimulate the
production of antibodies in the recipient
 Causes destruction of the transfused cells

 The ABO system and transfusion reactions
 Recipient has preexisting antibodies to foreign

blood group antigens
 Immediate destruction of donated blood cells
can occur
 Recipient has no preexisting antibodies to foreign
blood group antigens
 Transfused cells initially circulate and function
normally
 Eventually recipient’s immune system destroys
foreign antigens

EVENTS LEADING TO
HEMOLYSIS
Type A antigens on red
blood cells of patient
Donated red blood cells
with B antigen
Anti-B
antibody
Transfusion
Complement
Hemoglobin
Agglutination and
complement binding
Hemolysis

 The Rh system and hemolytic disease of the newborn
 Rh antigen
 Common to red blood cells of humans and
rhesus monkeys
 About 85% of humans are Rh positive (Rh+)
 Rh– woman carrying an Rh+ fetus may be at risk
for hemolytic disease
 RhoGAM administered to prevent hemolytic
disease of the newborn

Hemolytic Disease of the New Born
RhD-ve mother
Anti-RhD Abs
RhD +ve fetus

IMMUNOLOGY LECTURE NOTES RhD +ve fetus
Hemolytic disease of the new born
‘A’ blood group
mother
Anti-B Abs
‘B’ blood group fetus

Treatment (RhoGAM)
Anti-RhD Abs
RhD-ve mother
RhD +ve fetus RhD +ve fetus
Mid-term injection of RhoGAM and a second

injection within a few days of delivery
Treatment
Inject Anti-RhD Abs mothers

immediately after delivery
Prevents sensitization

EVENTS IN THE
DEVELOPMENT
OF HEMOLYTIC
DISEASE OF THE
NEWBORN-
OVERVIEW

 Antibody and soluble antigen reaction generates immune complexes
 Ag/Ab complexes facilitate the clearance Ag by phagocytic cells
 Large amount and distribution of immune complexes can lead to tissue damage
 Deposition of immune complexes near the site of Ag entry lead to localized reactions.
 Complexes are usually deposited on blood vessel walls, synovial membrane joints, glomerular
and choroid plexus of the brain.
 Immune complex deposits lead to the recruitment of neutrophils at the site of Ag entry. Injury
is due to enzymes released from neutrophil granules.
 Immune complex can activate complement system to cause more tissue injury.

 Usually occurs when slightly high antigen-
antibody ratio is present.
 Glomerulonephritis: Inflammatory kidney
damage.
 Systemic lupus erythematosus (SLE),
 Serum sickness

IMMUNE COMPLEX MEDIATED
HYPERSENSITIVITY

Antigens combine with
antibodies to form
antigen-antibody complexes.
THE MECHANISM Antigen
OF TYPE III Antibody (IgG)

Antigen-antibody complex
(IMMUNE-
COMPLEX Phagocytes remove most
of the complexes, but
MEDIATED) some lodge in the walls
of blood vessels.
HYPERSENSITIVITY
-OVERVIEW
There the complexes
activate complement.
Inactive complement
Active complement
Antigen-antibody complexes
and activated complement
attract and activate
neutrophils, which release
inflammatory chemicals.
Neutrophil
Inflammatory chemicals
Inflammatory chemicals
damage underlying
blood vessel wall.

Type III (Immune
complex)
Hypersensitivity

“Immune complex
disease”
Soluble Ag/IgG or IgM
 high titers of each
required
Immune processes
involved:
 classical complement
pathway
 phagocytic cells
 When some subpopulations of activated TH cells encounter certain Ag(s), they secrete
cytokines that induce a localized inflammatory reaction (DTH).
 Characterized by large influxes of nonspecific inflammatory cells, e.g.macrophages.
 DTH was first described by Robert Koch in 1880, when he worked on MTB.
 Response plays an important role in defense against intracellular pathogen.
 In DTH the reaction is delayed and macrophages are recruited , unlike neutrophils in Type III
Hypersensitivity.

• An exaggerated interaction between antigen and normal CMI-
mechanisms
• Requires prior priming to antigen
• Memory T-cells recognize antigen together with class II MHC molecules
on antigen-presenting cells
• Blast transformation and proliferation
• Stimulated T-cells release soluble factors (cytokines)
• Cytokines
• attract and activate macrophages and/or eosinophils
• help cytotoxic T-cells become killer cells, which cause tissue damage

Delayed Reaction maximal reaction time
Jones-Mote 24 hours
Contact 48-72 hours
tuberculin 48-72 hours
granulomatous at least 14 days
QN read and make brief notes on each

• Viruses (destructive skin rashes)
• smallpox
• measles
• herpes simplex
• Fungi
• candidiasis
• dematomycosis
• coccidioidomycosis
• histoplasmosis
• Parasites (against enzymes from the eggs lodged in liver)

• leishmaniasis
• schistosomiasis

Mediated by T cells
Delayed, takes 24-48 hours
Examples: contact Hypersensitivity:
Nickel
 Chromate
 Poison Ivy

Contact Dermatitis

poison Ivy
skin
Mo
urushiol
serum protein
Inflammation
APC Th1

Tuberculosis Patient
PPD(Ag derived from M.tuberculosis)
Erythema & Induration

Used as a diagnostic Test
 Not accurate.

 Type V Stimulatory Hypersensitivity
 Interaction of autoantibodies with cellular receptors
 Antibody binding mimics receptor-ligand interaction
 Examples
 thyroid stimulating antibody (mimics thyroid stimulating hormone [TSH] of pituitary binds to thyroid
cell receptor
 activation of B-cell by anti-immunoglobulin

Immunology, 7th edition by Kuby (2013).
Immunology, 6th edition by David male, Ivan Roitt, David B Roth and
Jonathan Brostoff (2006).
Dr. Prakash Nagarkatti (2012).Hypersensitivity.
www.pathmicro.med.sc.edu/...immppt/19-20-hyp


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IMMUNOLOGY LECTURE NOTES

BY MK ALEX (PhD Fellow- Mak)