Applied Bioscience for Health Instability 2
Module Notes
Acute inflammation
• Inflammation is one of the main components of innate immunity.
• Inflammation is a rapid and nonspecific protective response to cellular injury from any cause. It can
occur only in vascularised tissue.
• The hallmarks of acute inflammation are localised vasodilation, increased vascular permeability
and diapedesis.
• The macroscopic manifestations of inflammation are redness, swelling, heat, pain and loss of
function of the inflamed tissues.
Cellular components of inflammation
• Many different types of cells are involved in the inflammatory process, including neutrophils,
monocytes and macrophages, eosinophils and platelets.
• The most important activator of the inflammatory response is the mast cell, which initiates
inflammation by releasing biochemical mediators (histamine, chemotactic factors) from preformed
cytoplasmic granules and producing other mediators (prostaglandins, leukotrienes) in response to a
stimulus.
• Phagocytic cells (neutrophils and macrophages) engulf and destroy microorganisms by enclosing
them in phagocytic vacuoles, within which toxic products and degradative lysosomal enzymes kill
and digest the microorganisms.
• Polymorphonuclear neutrophils, the predominant phagocytic cells in the early inflammatory
response, exit the circulation by diapedesis through the retracted endothelial cell junctions and
move to the inflammatory site by chemotaxis.
• The macrophage, the predominant phagocytic cell in the late inflammatory response, is highly
phagocytic, is responsive to cytokines and promotes wound healing.
• Eosinophils release products that control the inflammatory response and are the principal cell that
kills parasitic organisms.
• Platelets interact with proteins of the clotting system to stop bleeding and release a number of
mediators that promote and control inflammation.
• Phagocytosis is a multistep cellular process for the elimination of pathogens and foreign debris.
The steps include recognition and attachment, engulfment, containment of the foreign debris or
pathogen inside a vacuole and finally destruction of pathogens or foreign debris.
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Inflammatory mediators
• Histamine is the major vasoactive amine released from mast cells. It causes constriction of vascular
smooth muscles in the lungs, dilation of capillaries and retraction of endothelial cells lining the
capillaries, which increases vascular permeability.
• Chemotactic factors are released from mast cell granules, forming a chemical gradient to attract
inflammatory cells towards the site of inflammation.
• Leukotrienes produce histamine-like effects, smooth muscle contraction and increased vascular
permeability. The biological activity of platelet-activating factor is virtually identical to that of
leukotrienes.
• Nitric oxide is released from the endothelium and causes vasodilation by inducing relaxation of
vascular smooth muscle. It may suppress mast cell release of inflammatory molecules.
• Prostaglandins cause increased vascular permeability, neutrophil chemotaxis and pain by direct
effects on nerves.
• Cytokines are responsible for mediating responses in both the innate and the adaptive immune
systems. They are also either pro-inflammatory or anti-inflammatory and include interleukins and
interferons.
• Tumour necrosis factor-alpha induces a multitude of pro-inflammatory effects, including
enhancement of endothelial cell adhesion molecule expression, which results in increased
adherence of neutrophils. It is also a strong mediator of fever.
Plasma protein systems
• Inflammation is mediated by three key plasma protein systems: the complement system, the
coagulation system and the kinin system. The components of all three systems are a series of
inactive proteins that are activated sequentially.
• The complement system can be activated by antigen–antibody reactions (through the classical
pathway) or by other products, especially bacterial polysaccharides (through the lectin pathway or
the alternative pathway), resulting in the production of biologically active fragments that cause cell
lysis.
• The most biologically potent products of the complement system are C3b (opsonin), C3a
(anaphylatoxin) and C5a (anaphylatoxin, chemotactic factor).
• Opsonins, such as antibody and complement component C3b, coat microorganisms and make
them more susceptible to phagocytosis by binding them more tightly to the phagocyte.
• The coagulation system stops bleeding, localises microorganisms and provides a meshwork for
repair and healing.
• Bradykinin is the most important product of the kinin system and causes vascular permeability,
smooth muscle contraction and pain.
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Chronic inflammation
• Chronic inflammation can be a continuation of acute inflammation that lasts 2 weeks or longer. It
also occurs as a distinct process without much preceding acute inflammation.
• Chronic inflammation is characterised by a dense infiltration of lymphocytes and macrophages.
The body may wall off and isolate the infection to protect against tissue damage by formation of a
granuloma.
Clinical manifestations of inflammation
• Local manifestations of inflammation are the result of the vascular changes associated with the
inflammatory process, including vasodilation and increased capillary permeability. The symptoms
include redness, heat, swelling and pain.
• The functions of the vascular changes are to dilute toxin molecules produced by dying cells or
contaminating microorganisms, carry plasma proteins and leucocytes to the injury site, carry debris
away from the site and initiate healing and repair.
• The principal systemic effects of inflammation are fever and increases in levels of circulating
leucocytes and plasma proteins (acute phase reactants).
Fever
• Temperature regulation is achieved through precise balancing of heat-production and heat-loss
mechanisms. Body temperature is maintained in a narrow range between approximately 36.2°C and
37.7°C.
• Temperature regulation is mediated by the hypothalamus through thermoreceptors in the skin,
hypothalamus, spinal cord and abdominal organs.
• Heat is produced through chemical reactions of metabolism, skeletal muscle contraction, chemical
thermogenesis and conserved through vasoconstriction and voluntary mechanisms.
• Heat is lost through radiation, conduction, convection, vasodilation, decreased muscle tone,
evaporation of sweat, increased respiration and voluntary mechanisms.
• Hyperthermia (an increase in core temperature above normal) can produce nerve damage,
coagulation of cell proteins and death.
• Hypothermia (a decrease in core temperature below normal) slows the rate of chemical reaction
(tissue metabolism), increases the viscosity of the blood, slows blood flow through the
microcirculation, facilitates blood coagulation and stimulates profound vasoconstriction.
• Fever is triggered by the release of pyrogens from bacteria, leucocytes and other cells involved in
the immune response. Fever is both a normal immunological mechanism and a symptom of a
disease.
• Fever involves an increase in the interthreshold zone mediated via prostaglandin E2 production.
When the fever breaks, body temperature returns to normal.
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• Fever aids responses to infection. Higher temperatures kill many microorganisms and decrease
serum levels of iron, zinc and copper, which are needed for bacterial replication.
Wound healing
• Damaged tissue proceeds to restoration of the original tissue structure and function if little tissue
has been lost or the injured tissue is capable of regeneration. This is called healing by primary
intention.
• Tissues that sustained extensive damage or those incapable of regeneration heal by the process of
repair resulting in the formation of a scar. This is called healing by secondary intention.
• Wound healing occurs in two separate phases: the reconstructive phase in which the wound
begins to heal; and the maturation phase in which the healed wound is remodelled.
• Dysfunctional wound healing can occur as a result of abnormalities in either the inflammatory
response or the reconstructive phase of resolution and repair.
Hypersensitivity reactions
• Hypersensitivity is an inappropriate immune response misdirected against the host’s own tissues
or directed against beneficial foreign tissues, such as transfusions or transplants; or it can be an
exaggerated response against environmental antigens (allergy).
• Mechanisms of hypersensitivity are classified as type I IgE-mediated hypersensitivity reactions,
type II tissue-specific hypersensitivity reactions, type III immune complex–mediated hypersensitivity
reactions and type IV cell-mediated hypersensitivity reactions.
• Hypersensitivity reactions can be immediate (developing within seconds or hours) or delayed
(developing within hours or days).
• Anaphylaxis, the most rapid immediate hypersensitivity reaction, is an explosive reaction that
occurs within minutes of re-exposure to the antigen and can lead to cardiovascular shock.
• Allergens are antigens that cause allergic responses.
• Type I hypersensitivity reactions occur after antigen reacts with IgE on mast cells, leading to mast
cell degranulation and the release of histamine and other inflammatory substances.
• Type II hypersensitivity reactions are caused by four possible mechanisms: complement-mediated
lysis; opsonisation and phagocytosis; antibody-dependent cell-mediated cytotoxicity; and
modulation of cellular function.
• Type III hypersensitivity reactions are caused by the formation of immune complexes that are
deposited in target tissues, where they activate the complement cascade, generating chemotactic
fragments that attract neutrophils into the inflammatory site.
• Type IV hypersensitivity reactions are caused by specifically sensitised T cells, which either kill
target cells directly or release lymphokines that activate other cells, such as macrophages.
• Allergies can be mediated by any of the four mechanisms of hypersensitivity.
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• Clinical manifestations of allergic reactions are usually confined to the areas of initial intake or
contact with the allergen. Ingested allergens induce gastrointestinal symptoms, airborne allergens
induce respiratory or skin manifestations and contact allergens induce allergic responses at the site
of contact.
Transplantation
• Transplantation of organs into a host causes an immune response. A transplant rejection can be
hyperacute, acute or chronic, depending on the amount of time that elapses between
transplantation and rejection.
The ABO blood group system
• There are four ABO blood groups: O, A, B and AB.
• Individuals have naturally occurring antibodies to ABO blood group antigens in their plasma
according to their ABO blood group.
• Because administration of an incompatible ABO blood transfusion is potentially fatal, the ABO
blood group system is the most clinically important.
• The Rh system is the second most clinically important blood group system.
• Blood group O Rh-negative is known as the universal donor as it can be safely transfused to
individuals of any ABO and Rh blood group.
Autoimmune diseases
• Autoimmunity is a disturbance in the immunological tolerance of self-antigens. The immune
system is normally able to distinguish the individual’s own antigens against foreign antigens.
• The exact mechanisms for autoimmune diseases are unknown.
Immune deficiencies
• Immunodeficiency is the failure of mechanisms of self-defence to function in their normal capacity.
• Immunodeficiencies are either primary (congenital) or secondary (acquired). Primary
immunodeficiencies are caused by genetic defects that disrupt lymphocyte development, whereas
acquired immunodeficiencies are secondary to disease or other physiological alterations.
• The clinical hallmark of immunodeficiency is a propensity to unusual or recurrent severe infections.
The type of infection usually reflects the immune system defect.
• The most common infections in individuals with defects of cell-mediated immune response are
fungal and viral, whereas infections in individuals with defects of the humoral immune response or
complement function are primarily bacterial.
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• Severe combined immunodeficiency is a total lack of T cell function and a severe (either partial or
total) lack of B cell function.
• Defects in B cell function are diverse, ranging from a complete lack of the human bursal equivalent,
the lymphoid organs required for B cell maturation, to deficiencies in a single class of
immunoglobulins.
• Acquired immunodeficiencies are caused by superimposed conditions, such as malnutrition,
medical therapies, physical or psychological trauma or infections.
• Acquired immunodeficiency syndrome (AIDS) is an acquired dysfunction of the immune system
caused by a retrovirus (human immunodeficiency virus (HIV)) that infects and destroys CD4+ cells
(helper T cells).
• Therapy for HIV infection consists of a combination of drugs to control the virus. Supportive
therapy (e.g. antibiotics) is prescribed when individuals contract AIDS infections and malignancies.
References
Craft, J., Gordon, C., Huether, S., McCance, K., & Brashers, V. (2020). Understanding Pathophysiology
(4th ed). Elsiver.
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