Immunology Flashcards


INFLAMMATION

NORMAL RESPONSE OF LIVING TISSUE TO A SUBLETHAL INJURY. A reaction of
the microcirculation. An attempt to localize and eliminate bacteria,
foreign particles or antigens. Composed of vascular alterations and
cellular phenomena.(occurs in all tissues;not specific to oral
tissues) The reason redness and edema are produced when specific oral
bacteria react with host tissues to produce acute gingivitis and
periodontitis. The first phase is a non-adaptive, non-specific, innate
response. (Phagocytic cells= monocytes, macrophages, and neutrophils)
The natural history of inflammation actually starts before an
irritant exists, with the transendothelial migration of resident
leukocytes, especially the mast cell. Mast cells are among the most
effective cells in alerting the endothelium of a local problem.
Mast cell interaction with the vascular system leads to erythema and
edema, which are two of the five cardinal signs of inflammation.
Mast cells also signal the endothelial cells to recruit
inflammatory leukocytes
. The inflammatory leukocytes are active in phagocytosis,
killing, antigen processing and presentation, specific immune
responses, and tissue remodeling. They cause the infiltrated area to
lose function (the fifth cardinal sign of inflammation) as a side
effect of their intense focus on resolving the problem and remodeling
the tissue. Also depicted are the complement metabolites, iC3b, C3a,
and C5a. These molecules are important in allowing the immune system
to �see� substances for which they do not possess receptors. TNF-?,
Tumor necrosis factor alpha; IL-8, interleukin-8; SRS-A, slow-reacting
substance of anaphylaxis.


Initial events in inflammation


mediated by leukocytes and mast cells


Injurious stimuli (physical, chemical or
bacterial)

Transient vasoconstriction of arterioles

Hyperemia (dilation of capillaries and venules due to
mediator response)

Increased vascular permeability- endothelial changes-
accumulation of inflammatory exudate (polymorphonuclear
leukocytes, macrophages and lymphocytes) - Inflammatory cells
migrate to area.

Neutralization, dilution and destruction of
irritant

Containment of inflammation

Initiation of repair

If infection not completely removed acute inflammation will
progress to chronic inflammation. May get more extensive
involvement of immune system in reactions to eliminate
infectious agent.


Plasma -derived vasoactive mediators


Plasma contains 3 major
enzyme cascades in an inactive state, each of which is
composed of a series of sequentially activated proteases.
These inter related systems include the coagulation cascade, kinin
generation, and complement
. These systems evolved as a means of the organism as a whole to
respond to foreign and toxic substances. Also
have acute-phase proteins, and interferons. These soluble
factors have a wide range of activity. Basically, complement and
acute-phase proteins function intrinsically against bacteria and
fungi, whereas interferons defend against viral infections.

Complement System

consists of a group of 30 plasma proteins and membrane associated
cell receptors. ( about 5% of soluble serum components) In addition to
being a source of vasoactive mediators, components of the complement
system are an integral part of the immune system and play an important
role in the host defense against bacteria. Enables endothelium and
leukocytes to recognize and bind foreign substances for which they
lack receptors. Most important component of complement is C3.

. Compliment is the fire of the immune system. It enhances
the inflammatory response and enables the endothelium and
leukocytes to see and find the problem. The complement system
additionally facilitates phagocytosis and destruction of foreign
substances or direct destruction of cells or microorganisms via the
membrane attack complex.

Complement: Classical Pathway


Classical Pathway:
Activators = Immune complexes (IgM, IgG), aggregated antibody,
proteases, polyanions (polynucleotides)-Activated by factors
causing an immune reaction.

Complement: alternative pathway

(Probably most active in periodontal disease): Activators =
derivative products of infectious organisms and by foreign
materials; i.e. endotoxins, polysaccharides, fungi, viruses- Fast
acting system- acts even if substances do not cause immune response

-Activation of either pathway
-anaphylatoxins
-Kinin-like C2a (vasoactive substance)
-IC3b opsonin


Activation of either pathway leads to formation of
a membrane attack complex capable of inducing cell lysis in invading
bacteria or host and generation of the biologically active
anaphylatoxins C3a and C5a Anaphylatoxins (C3a, C4a, C5a)
increase vascular permeability; induce degranulation of mast cells
and basophiles. C5a also chemotaxic factor for neutrophils,
monocytes, esinophils and basophiles (attracts leukocytes and
stimulates phagocyte secretion) Produces a vasoactive
substance termed kinin-like, C2a, which induces pain, and
increases vascular permeability and dilation. Produces
an opsonin, iC3b which binds to molecular aggregates, particles
or cell which enable phagocytes to ingest them.

Bacterial activation of complement system


Bacterial activation of complement system can
occur by direct activation of alternative system or activation of
classical pathway by antibody binding to the surface of the
organism. Bacteriolysis may occur by action of the membrane
attack complex or enhanced bacterial clearance following
opsonization. (Gram �ve bacteria= bacteriolysis
).

Bacterial opsonization = Specific molecules e.g. IgG, C3b bind
to surface of bacteria and enhances phagocytosis by enabling
receptors on the phagocyte cell membrane to recognize and bind to the
oposinized bacterium. (Gram +ve=

Phagocytosis)

membrane attack complexes


C5b, C6, C7, C8, C9 (The terminal complement components)


Cellular elements involved in Inflammatory response
-origins of cellular elements

A. Origins of cellular elements: Bone marrow source of pluripotent
hematopoietic stem cell

Bone marrow

common lymphoid progenitor

blood = B cell (liver, spleen, and bone)

effector cell = Plasma cell
Bone marrow

common lymphoid progenitor

blood
= T cell (thymus)

effector cell = Activated T cell
Bone Marrow

myeloid progenitor

Blood

Polymorphonuclear leukocytes (basophil, eosinophil,
neutrophil, and monocytes)
Bone marrow

myeloid progenitor

Blood

monocyte

tissues

Macrophage, Mast cells)

and peripheral dendritic cells (Langerhans cells)
which originate from peripheral dendritic cell in
blood.
Myeloid progenitor

megakaryocyte

Blood

Platelets
Myeloid progenitor

erythroblast

blood

Erythrocytes

Neutrophil dysfunction/ periodontal disease


Periodontal disease in some individuals may be due to
neutrophil dysfunction or the ability of some bacteria to evade
neutrophil activity. A.a produces an exotoxin which stimulates
release of leukotoxin which kills PMN�s and monocytes i.e.
possible cause of juvenile periodontitis.
Invitro studies have shown that gingivalis
impedes transepithelial migration of neutrophils and prevents
secretion of IL-8 by epithelial cells.

Another possibility is that
Rather than a protective role, it is proposed that neutrophil
actions result in local tissue injury and thus have a primary role in
the immunopathogenesis of at least some forms of periodontal disease.
The basic paradigm shift is that in some cases, PMNs do not exhibit a
decrease in function, but rather they become hyperactive and
are primed for actions that result in tissue break-down.