Inflammation
1. Inflammation: local defensive response resulted by
damage to body tissue.
1. Causative agents: microbial infection physical
agents (heat, radiant agents, electricity, and sharp
objectives) chemical agents (acids, basis, and gases).
2. Signs: redness pain heat swelling
3. (and sometimes) loss of function.
Inflammation
3. Functions of inflammation:
 To destroy the injurious agent, if possible, and to
remove it and its by-products from the body.
 If destruction is not possible, to limit the effects on
the body by confining or walling off the injurious
agent and it's by products.
 To repair or replace tissue damaged by the injurious
agent and it's by products.
Inflammation
4. Stages of infection:
A. Vasodilatation and increase permeability of blood vessels: this is
caused by chemical released by cells of damaged tissue listed in table (3-1)
Chemical
Histamine
2
Kinins
4
5
Function
mast cell
1
3
Produced by
basophilesplatelets
By liver and present in blood
plasma
Prostaglandi
Cells of damaged area
ns
mast cell of (skin, respiratory
Leukotrienes system, blood vessels)
basophiles
Cytokines:
IL-1, IL-6,
Macrophages (fig. 3-1)
IL-8, IL-12,
and TNF-α
Vasodilatation
Vasodilatation, Chemotaxis
for granulocytes
Vasodilatation, help
phagocytes move through
capillary wall.
Increase permeability of
blood vessels, help attack
phagocytes to pathogen
Vasodilatation, increase
permeability of blood vessels,
Chemotactic factors
Activated macrophages secret
a range of cytokines
Local effects
Activates vascular
endothelium ,
activates lymphocytes,
local tissue destruction,
increase access of
effector cells
Activates vascular
endothelium, and increase
vascular permeability
which leads to increase
entry of
IgG, complement and cells
to tissue and increase fluid
drainage to lymph nods
Lymphocyte
activation,
increase
antibody
production
Systemic effects
Fever
Production of
IL-6
Fever, Moblization
of metabolite shoks
Fever, induce
acute- phase protein
production
Chemotactic
factor recruits
neutrophils,
basophile and T
cells to site of
infection
Activates NK cells
induces the
differentiation of
CD4 T cells into
TH1
Inflammation
B. Phagocyte migration and phagocytosis: PMNs and
monocytes leave the blood and migrate to sites of
infection in a multistep process mediated through
adhesive interactions that are regulated by
macrophage-derived cytokines and chemokines.
1. The first step (Rolling adhesion) involves the
binding of leukocytes to vascular endothelium
through interactions between E-selectins on the
endothelium and their carbohydrate ligands on the
leukocyte sialyl-LewisX moiety (s-LeX)
Inflammation
2.
The Tight binding does, however, allow stronger interactions, which
occur as a result of the induction of intercellular adhesion molecules
ICAM-1 on the endothelium and the activation of its receptors
leukocyte functional antigens LFA-1 on the leukocyte by contact with
a chemokine like IL-8and its receptor.
3. This binding allows the leukocyte to squeeze between the endothelial
cells forming the wall of the blood vessel leading to diapedesis and
migration toward the source of chemokines.
Rolling adhesion
Tight binding
Diapedesis
Blood
stream→
s-LeX
IL-8 receptor
LFA-1
E-selectins
ICAM-1
Vascular
endothelium
→
chemokine
Tissue
→
IL-8
Migration
Inflammation
4.The invading microbes were eliminated by
phagocytosis of PMNs other phagocytes start
establishes for adaptive immune response.
5.The pain is caused by
nerve damage
pressure of edema
irritation by toxins.
Inflammation
3. Tissue repair: the process in which tissue replace dead or
damaged tissue.
1. Skin has a high capacity for regeneration, whereas, cardio
muscular does not.
2. Some microbes evade phagocytosis and cause chronic
inflammation like Mycobacterium tuberculosis, such away
lead to continuous production of cytokines and induce
fibroblast in the site of infection to synthesis collagen fiber
which leads to fibrosis.
Fever
Fever : abnormally high body temperature
1. The most causes of fever are bacteria, toxin, and viruses.
2. Bacterial endotoxin (LPS) bound to CD14 on macrophage. This then
triggers the membrane protein Toll Like Receptor 4 (TLR4) to
signal to the nucleus, activating the transcription factor, which in
turn activates genes involved in production cytokines IL1(endogenous pyrogen) and TNF-α
3. These cytokines cause the hypothalamus to release prostaglandin
that reset the hypothalamic thermostat at high temperature, thereby
causing fever.
Fever
4. A high body temperature is caused by constriction of blood
vessels, increase rate of metabolism, and shivering.
5. Fever is considered defense against disease according to:
 IL-1 helps to activate T-cells and so on adaptive immunity.
 High body temperature intensifies the effect of antiviral
interferon.
 Increase production of transferrins that decrease the iron
availability to microbes.
 High body temperatures increase speed of body reactions and
help tissue repair.
Antimicrobial substances
Antimicrobial substances: Complement system.
Complement is a system of more than 30 plasma proteins
that activates a cascade of proteolytic reactions on microbial
surfaces but not on host cells, coating these surfaces with
fragments that are recognized and bound by phagocytic
receptors on macrophages. The cascade of reactions also
releases small peptides that contribute to inflammation and
cytolysis (fig. 3-3).
Complement
Complement activation can
occur on three pathways according
to activation manner:
A. Classical pathway: this
pathway is initiated by an
antigen-antibody reaction.
The splitting of C3 into C3a
and C3b starts a cascade that
result in cytolysis,
inflammation, and
opsonization. (fig 3-4)
Complement
B. Alternative pathway: this
pathway is activated by contact
between certain complement
protein (C3 and factors B, D, and
P) and pathogen there are no
antibody involved. Once C3a
and C3b are formed they
participate in cytolysis,
inflammation, and opsonization.
(fig 3-5)
Complement
C. Lectin pathway: when the
plasma protein mannosebinding lectin (MBL) binds to
mannose sugar on the surface of
microbes. MBL function as an
opsonin that enhance
phagocytosis and splitting of C3
into C3a and C3b starts a
cascade that result in cytolysis,
inflammation, and opsonization.
(fig 3-6)


Thank you for lesson







