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Protection and Hypersensitivity Mechanism Which Manifest On Skin
Protection and Hypersensitivity Mechanism Which Manifest On Skin
HYPERSENSITIVITY MECHANISM
WHICH MANIFEST ON SKIN
FK UNIB 2013
PROTECTION
INNATE IMMUNITY
INFLAMMATION:
ADAPTIVE IMMUNITY
HYPERSENSITIVITY MECHANISM
Infectious
Non infectious
NATURAL/NONSPECIFIC/
INHERENT/INNATE IMMUNITY
Integumentary System
(skin)
All multicellular organisms have defense mechanisms
Functions of skin
Protection
Excretion (salts, water, wastes)
Maintenance of body temperature
Metabolism (Vitamin D3)
Storage (lipids, blood reserve)
Detection of sensation
Note: skin keeps water in as well as keeping
it out
Hair shaft
Pore
Dermal papillae
(papillary layer
of dermis)
Epidermis
Meissner's corpuscle
Free nerve ending
Reticular layer of dermis
Sebaceous (oil) gland
Arrector pili muscle
Dermis
Artery
Hypodermis
(superficial
fascia)
Hair root
Hair follicle
Eccrine sweat
gland
Vein
Adipose tissue
Hair follicle receptor
(root hair plexus)
Figure 5.1
Figure 5.2b
Inner dermis:
connective tissues (what are they?)
Innate Immunity:
An Evolutionary View
All multicellular organisms have defense mechanisms
2.
3.
4.
5.
6.
7.
Recognition mechanisms of
innate immunity
Microbes evolve rapidly, so innate immunity
or mast cell
Inflammatory mediators:
Cytokines, chemokines
and lipids
TNF
Inflammation
A local physiological response to tissue
injury
It is not in itself a disease, but is usually a
manifestation of disease.
May have beneficial effects:
destruction of invading microorganisms
and walling of an abscess cavity,
prevention infection spreading.
Classified into:
Acute: initial and often transient series of
tissue reaction to injury
Chronic: subsequent and prolonged tissue
reaction following initial response
Sign of inflammation
1.
2.
3.
4.
5.
Inflammation
Acute
Initial response to tissue injury
Vascular component: dilatation of vessels
Exudative component: vascular leakage to protein-rich
fluid
Neutrophil polymorph is the characteristic cell
recruited to the tissue
Outcome may be resolution, suppuration (abscess),
organisation/progression to chronic inflammation
rich-fluid
Cellular component recruitment of
Early stages
oedema fluid, fibrin and pmn in extracellular
Involves 3 processes
(1) Changes in vessel calibre flow
(2) vascular permeability n formation of
exudate
(3) Formation of cellular component
emigration of
pmn into extravascular space
Vascular dilatation
Normal: most of
capillary bed closed
down
Acute inflammation:
sphincters open,
causing blood to flow
through all capillaries
Vascular changes:
Alteration in vessel calibre (transient
Cellular events :
emigration of pmn from microcirculation and
accumulation in the focus of injury (cellular
recruitment and activation)
Margination and rolling
Adhesion and transmigration,
Chemotaxis and activation (later stage)
Phagocytes
Macrophages are the chief phagocytic cells
Free macrophages wander throughout a region in
search of cellular debris
Kupffer cells (liver) and microglia (brain) are
fixed macrophages
Figure 21.2a
Mechanism of Phagocytosis
Microbes adhere to the phagocyte
Pseudopods engulf the particle (antigen) into a
phagosome
Phagosomes fuse with a lysosome to form a
phagolysosome
Invaders in the phagolysosome are digested by
proteolytic enzymes
Indigestible and residual material is removed by
exocytosis
Lysosome
Phagocytic vesicle
containing antigen
(phagosome).
3 Phagocytic vesicle is
fused with a lysosome.
Phagolysosome
Acid
hydrolase
enzymes
(b)
Figure 21.2b
Later stages
Chemotaxis of neutrophils (pmn)
Chemical mediator of acute inflammation
Plasma factors
Coagulation system (Hageman factor/F. XII)
Kinin system
Fibrinolytic system
Complement system
Mediators of Inflammation
Pro-inflammatory cytokines (TNF, IL-1) signal to
Mediators
Can be circulating in plasma or produced locally
Plasma derived mediator: complement, kinin, coagulation
Newly synthesized
Prostaglandins (leukocytes, platelets, ECs)
Leukotrienes (leukocytes)
Platelet activating factors (leukocytes, EC)
Activating oxygen species (leukocytes)
Nitric oxide (macrophages)
Cytokines (lymphocytes, macrophage, ECs)
Systemic mediators
(plasma)
Factor XII (Hageman factor) activation
Kinin system (bradykinin)
Coagulation/fibrinolysis system
Complement activation
C3a (anaphylatoxin)
C5a (anaphylatoxin)
C3b
C5b-9 (membrane attack complex)
Complement system
A cascade of enzymatic proteins. Can be
cells
During infection:
activate complement
Acute dermatitis
Role of tissue
macrophages
Secrete numerous chemical mediators
Most important: IL-1 and TNF-
Role of lymphatics
Lymphatic channels dilated (drain away
Role of neutrophil
polymorph
Movement
Adhesion to micro-organisms
Phagocytosis
Intracellular killing of micro-organism
Oxygen dependent mechanims
Release of lysosomal products
mediator
cellulitis
Skin (lateral part): red (erythema) due to
Chronic inflammation
Implies the process has extended oer a long
period of time
Cellular reactions acute
Lymphocyte, plasma cells and macrophage
predominate
Granulation or scar tissue also formed
Cause:
Primary chronic inflammation: transplant
rejection
Progression from acute inflammation
Recurrent episodes of acute inflammation
Local inflammation:
acute and chronic
Acute
Stimulus: transient
Duration: brief
Phagocyte: neutrophils
Characterized by
heat, redness,
swelling and pain
Formation of pus
Chronic
Stimulus: persistent
Duration: prolonged
Phagocyte:
macrophages
Characterized by cell
proliferation
Formation of
granuloma,
macrophage, fibrotic
wall
Chronic inflammation
Inflammation of prolonged duration in which active inflammation,
tissue destruction and attempts at repair occur simultaneously
Causes
Persistent damage
Persistent infection
Prolonged
exposure to toxic
agent
Autoimmunity
Significant damage
Key cells are different
MACROPHAGES
LYMPHOCYTES
NO exudate
Special types
GRANULOMATOUS
Granulomatous inflammation
What is a
granuloma? - an
aggregate of
macrophages
What causes
granulomatous
inflammation?
Infection TB
Foreign material
Reaction to tumours
Immune diseases
(sarcoid, crohns)
eczema
eczema
Inflammatory skin condition have a great variety
of precipitating factors
A reaction pattern, not a single disease, several
causes, varied clinical pattern, swelling of
epidermis, characterised by inflammation and
spongiosis (due to separation of keratinocytes and
fluid accumulation
NON-INFECTIOUS
INFLAMMATORY DISEASES
Urticaria
psoriasis
Strong genetic tendency, silvery scales of
psoriasis
Acanthotic, dermal papillae onlly covered by thin
Lichen planus
Violaceous, flat-topped and polygonal. White lines
Lupus erithematosus
Lupus erithematosus
Tuberculosis cutis
Tuberculosis cutis
Type I (IgE-mediated)
Type II (Fc and complement-mediated)
Type III (Immune complex-mediated)
Type IV (Delayed-type hypersensitivity)
Histamine
Produced almost exclusively by basophils and
mast cells (3-8 pg/cell)
Immediate pharmacologic effects:
pruritus (H1)
vascular permeability/vasodilatation
(H1)
smooth muscle contraction (H1)
gastric acid secretion (H2)
Injection of Histamine in
the Skin: The Triple
Local erythema - H (and some H )-mediated
Response
arteriolar dilatation
1
bronchodilators
Nose/eyes: erythema, congestion, burning
Therapy of Allergic
Disease
Inhibition of IgE synthesis: Immunotherapy
Inhibition of IgE binding to receptor:
Antihistamines
Leukotriene receptor antagonists
Topical and systemic corticosteroids
Type II Hypersensitivity
Examples of Type II HS:
Transfusion reactions
To ABO blood groups
To other RBC blood groups
(erythroblastosis fetalis)
Drug-induced hemolytic anemia (penicillin)
activation
Type IV Hypersensitivity
Delayed type hypersensitivity (DTH)
TH cells that have been sensitized by an
Immunopathology
Definition: Type IV reaction
The Type IV (delayed-type) reaction
does not require antibody.
Macrophages (epithelioid histiocytes) present antigen to
T-cells. The activated T-cells then release cytokines (IL12), which cause cell proliferation and recruit additional
inflammatory cells to the site.
Type IV Hypersensitivity
(Delayed)
CD4+ T lymphocytes
mediated
- Granulomatous
diseases
- Tuberculin skin reactions
- Transplant rejection
- Contact dermatitis
Cytotoxic T lymphocyte
(CTL) mediated
- Neoplastic cell lysis
- Transplant rejection
- Virus-infected cell lysis