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Immunopathology and
Immunotherapeutics
By Dr. Sheeba Murad Mall
• Course Contents:
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The basis of immunology, Antigen recognition and response of immune system
Tolerance: immunological principles of tolerance: central versus peripheral tolerance,
role of regulatory T cells, natural killer T cells, dendritic cells
Innate immune barriers and there disruption
Immune responses against common infections (common viral, bacterial and parasitic
infections)
Immune evasion mechanisms in infections
Primary immunodeficiencies of lymphocytes, phagocyte disorders, complement
disorders , Proliferation disorders of immunologic cells
Allergy and asthma
Allergic diseases: asthma, anaphylactic syndrome, insect venom allergy, rheumatoid
arthritis, systemic lupus erythematosus, rheumatic fewer and other conditions due to
hypersensitivity
Autoimmune response and immune tolerance
Immune mediated inflammatory disorders
Immunotherapy: overview of cuttent ongoing research related to immunotherapies
(small molecules, biologicals)
Solid Tumor Immunology
Recommended Books
 Understanding Immunology by Peter Wood,
2006
 Cellular and Molecular Immunology, 2012
 Essentials of Clinical Immunology by Helen
Chapel, Mansel Haeney, Siraj Misbah and Neil
Snowden
 Immunology by Kuby, 2011
 Basics in Immunology by Lichtmann and Abdul
Abbass, 2006
• First sessional 20%
• Second sessional 20%
• Quiz and Assignment 10%
• Terminal 50%
• How will you define
– Immunity?
– Immunology?
– Immunopathology?
• What is the importance of
studying this subject?
• Why are you studying
Immunopathology?
Terms in relation to Immunopathology
Immunopathology
•Immunity
•is defined as resistance to disease
“Immunity” derives from the latin word immunitas, meaning
exemption from military service, tax payments or other public
services
The state of exemption or protection from infectious disease
•Pathology
•The scientific study of the nature of disease and its causes,
processes, development, and consequences. Also called
pathobiology.
•The anatomic or functional manifestations of a disease: the
pathology of cancer.
•A departure or deviation from a normal condition
Immunopathology
• The study of disease processes that have an
immunologic cause
• Injury induced by antibodies or other products of
an immune response
• The branch of biomedical science concerned with
immune reactions associated with disease, whether
the reactions be beneficial, without effect, or
harmful
• The structural and functional manifestations
associated with immune responses to disease
• The collection of cells, tissues and molecules
that mediate resistance to infections or an
immune response is called an immune system
• The coordinated reaction of the cells and
molecules comprising immune system against
infectious microbes is the immune response
Question!!
Can only infectious agents
initiate an immune response?
The physiologic function of the
immune system is defense against
infectious microbes,
However,
even noninfectious foreign substances
can elicit immune responses!!!!
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Mechanisms that normally protect
individuals from infection and eliminate
foreign substances are also capable of
causing tissue injury and disease
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Thereby leading to autoimmune diseases
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The importance of education of immune
system against self and non-selfphenomenon of tolerance
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immune response is a reaction to
components of microbes as well as to
macromolecules, such as
– proteins and
– polysaccharides,
– and small chemicals that are recognized as
foreign, regardless of the physiologic or
pathologic consequence of such a reaction
Two arms of immunity
natural or native immunity
RESPONSE
oreign invaders - viruses, bacteria, allergens, toxins and
IMMUNE
arasites- constantly
bombard SYSTEM
our body.
Innate or non specific
- generalized
- early, limited specificity
- the first line of defense
Adaptive or specific
- variable
- later, highly specific
- memory
Innate immunity
(natural or native immunity)
• The innate immune system is what we are born with and it is nonspecific;
all antigens are attacked pretty much equally
• It is genetically based and we pass it on to our offspring.
• Physical and chemical barriers, such as
– epithelia
– antimicrobial chemicals produced at epithelial surfaces
• phagocytic cells
– (neutrophils, macrophages)
– Dendritic cells
– and natural killer (NK) cells
• blood proteins, including
– members of the complement system
– and other mediators of inflammation i.e. proteins called cytokines that
regulate and coordinate many of the activities of the cells of innate
immunity
– The mechanisms of innate immunity are specific for structures that are
common to groups of related microbes and may not distinguish fine
differences between microbes
Epithelial barriers
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The first and, arguably, most important barrier is the skin
Acid pH (< 7.0) of skin secretions inhibits bacterial growth
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"The skin is the largest organ in the body: 12-15% of body weight, with a
surface area of 1-2 [square] meters.“
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Skin protects body tissues against injuries
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helps regulate body temperature
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One square inch (6.5 square centimeters) of skin contains up to 4.5 m of
blood vessels
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The nerves in skin receive the stimuli that are then interpreted by the
brain as touch, heat, and cold
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Intact epithelial membranes- especially the stratified squamous epithelial
surfaces such as skin constitute an extremely effective barrier to infection
• Skin is composed of
three layers:
– Epidermisimpervious layer of
stratified squamous
epitheial layer of
cells
– Dermis- vascular
connective tissue
– subcutaneous fatty
tissue
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The interface between the epidermis
and dermis is extremely irregular and
consists of a succession of papillae, or
fingerlike projections- smallest where
the skin is thin and longest in the skin
of the palms and soles
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The skin varies in thickness from
0.5 mm on the eyelids to 4 mm or more
on the palms and soles
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Hair follicles secrete sebum that
contains lactic acid and fatty acids both
of which inhibit the growth of some
pathogenic bacteria and fungi
Areas of the skin not covered with hair,
such as the palms and soles of the feet,
are most susceptible to fungal
infections e.g. athlete's foot
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Subcutaneous fatty tissue:
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is the deepest layer of the skin
It is composed of connective tissue,
blood vessels, and fat cells
This layer binds the skin to underlying
structures,
insulates the body from cold,
and stores energy in the form of fat
Surface Barriers or Mucosal Immunity
• Sticky mucus in respiratory and
gastrointestinal tracts traps many
microorganisms
• Mechanically, pathogens are expelled from
the lungs by ciliary action as the tiny hairs
move in an upward motion
– coughing and sneezing abruptly reject both
living and nonliving things from the respiratory
system
– the flushing action of tears, saliva, and urine
also force out pathogens
– as does the sloughing off of skin
Pathology of cystic fibrosis
• Saliva, tears, nasal secretions, and
perspiration contain lysozyme, an enzyme
that destroys Gram positive bacterial cell
walls causing cell lysis
• The stomach’s mucosa secrete hydrochloric
acid (0.9 < pH < 3.0, very acidic) and proteindigesting enzymes that kill many pathogens
Normal flora
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Normal flora are the microbes, mostly bacteria, that live in and on
the body with, usually, no harmful effects to us
We have about 1013 cells in our bodies and 1014 bacteria, most of
which live in the large intestine
There are 103–104 microbes per cm2 on the skin (Staphylococcus
aureus, Staph. epidermidis, diphtheroids, streptococci, Candida, etc.)
Various bacteria live in the nose and mouth. Lactobacilli live in the
stomach and small intestine
– The upper intestine has about 104 bacteria per gram;
– the large bowel has 1011 per gram, of which 95–99% are anaerobes
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Normal flora fill almost all of the available ecological niches in the
body and produce bacteriocidins, defensins, cationic proteins, and
lactoferrin all of which work to destroy other bacteria that compete
for their niche in the body
The resident bacteria can become problematic when they invade
spaces in which they were not meant to be as examples:
– (a) staphylococcus living on the skin can gain entry to the body
through small cuts/nicks.
Various Dermatological pathologies
MACROSCOPIC TERMS USED IN
DERMATOLOGY
1. MACULE
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circumscribed lesion of up to 5mm* in diameter
characterized by flatness and usually distinguished
from surrounding skin by its coloration
e.g. vitiligo, freckles
Vitiligo is a disease in which the pigment cells of the
skin, melanocytes, are destroyed in certain areas.
Simple freckles are usually tan, round, and small -about the size of a common construction nail head.
Sunburn freckles are often darker, have irregular
jagged borders, and may be larger than a pencil eraser.
* Some sources use 10mm as the size boundary between different lesions
Macule
Patch
• Circumscribed lesion
of more than 5mm in
diameter characterized
by flatness and usually
distinguished from
surrounding skin by its
coloration.
3. PAPULE
– elevated dome-shaped or flat –topped lesion < 5 mm
across
– e.g. warts, nevi, dermal tumor, acne vulgaris
4. NODULE
– elevated lesion with spherical
contour
> 5 mm across
– e.g. keratoacanthoma,
Keratoacanthoma (KA) is a common
low-grade (unlikely to metastasize or
invade) skin tumour that is believed
to originate from the neck of the hair
follicle.
– Many pathologists consider it to be a
form of squamous cell carcinoma
(SCC)
– appendage tumor
Nodule
5. PLAQUE
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Elevated flat-topped
area, usually > 5 mm
across
e.g. psoriasis,
seborrheic keratosis
(is a noncancerous
benign skin growth
that originates in
keratinocytes),
mycosis fungoides
Plaque
6. VESICLE
– Fluid-filled raised
area < 5mm
– e.g. herpes zoster,
chicken pox,
eczematous
dermatitis
• 7. BULLA
– fluid-filled raised
area >5 mm across
– e.g. pemphigus
• is a rare group of
blistering autoimmune
disease that affect
skin and mucous
membrane
MACROSCOPIC TERMS USED IN
DERMATOLOGY
8. BLISTER
– Common term used for vesicle or bulla
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A blister is a small pocket of fluid within the
upper layers of the skin, typically caused by
forceful rubbing , burning, freezing, chemical
exposure or infection
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Most blisters are filled with a clear fluid called
serum or plasma
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However, blisters can be filled with blood
(known as blood blisters or with pus (if they
become infected)
9. PUSTULE
– discrete, pus-filled, raised area
– e.g. impetigo (It is primarily caused by Staphylococcus
aureus, and sometimes by Streptococcus pyogenes)
– acne vulgaris
Pustule
10. WHEAL
– Itchy, transient,
elevated areas with
variable blanching and
erythema formed as a
result of dermal
edema
– e.g. urticaria/allergy,
insect bites
10.
WHEAL
Wheal
11. SCALE
– dry, horny, platelike
excrescenses
– e.g. psoriasis, tinea
infection (capitis,
corpora)
Scale
12. LICHENIFICATION
– thickened and rough
skin characterized by
prominent skin
markings
– e.g. lichen simplex,
eczematous
dermatitis
Lichenification
13. EXCORIATION
– traumatic lesion
characterized by
breakage of the
epidermis
– e.g. body louse
infestation
Excoriation
14. ONYCHOLYSIS
– loss of integrity of nail substance
– e.g. psoriasis
Onycholysis