Inflammation

Mononuclear-Phagocyte System (Reticuloendothelial System)

This cell system includes cells derived from 2 sources with common morphology, function and
origin. These are as under:
Blood monocytes. These comprise 4-8% of circulating leucocytes.
Tissue macrophages. These include the following cells in different tissues:
i) Macrophages in inflammation.
ii) Histiocytes which are macrophages present in connective tissues.
iii) Kupffer cells are macrophages of liver cells.
iv) Alveolar macrophages (type II pneumocytes) in lungs.
v) Macrophages/histiocytes of the bone marrow.
viii) Osteoclasts in the bones.
ix) Microglial cells of the brain.
x) Langerhans’ cells/dendritic histiocytes of the skin.
The mononuclear phagocytes are the scavenger cells of the body as well as participate in
immune system of the body; their functions in inflammation are as under:
Role of macrophages in inflammation.
i) Phagocytosis (cell eating) and pinocytosis (cell drinking).
ii) Macrophages on activation by lymphokines released by T lymphocytes or by
non-immunologic stimuli elaborate a variety of biologically active substances as under:
● Proteases like collagenase and elastase which degrade collagen and elastic tissue.
● Plasminogen activator which activates the fibrinolytic system.
● Products of complement.
● Some coagulation factors (factor V and thromboplastin) which convert fibrinogen to
fibrin.
● Chemotactic agents for other leucocytes.
● Metabolites of arachidonic acid.
● Growth promoting factors for fibroblasts, blood vessels and granulocytes.
● Cytokines like interleukin-1 and TNF-.
● Oxygen-derived free radicals.
Role of lymphatics in inflammation/ morphology of inflammatory cells
 Healing

Healing of fracture of bone

Healing of fracture by callus formation depends upon some clinical considerations whether the
fracture is:
traumatic (in previously normal bone),
or pathological (in previously diseased bone);
complete or incomplete like green-stick fracture; and simple (closed), comminuted (splintering
of bone), or compound (communicating to skin surface).

Primary union of fractures occurs in a few special situations when the ends of fracture are
approximated as is done by application of compression clamps. In these cases, bony union
takes place with formation of medullary callus without periosteal callus formation. The patient
can be made ambulatory early but there is more extensive bone necrosis and slow healing.
Secondary union is the more common process of fracture healing and is described under the
following 3 headings:
i) Procallus formation
ii) Osseous callus formation
iii) Remodelling
PROCALLUS FORMATION.
Haematoma forms due to bleeding from torn blood vessels, filling the area surrounding the
fracture.
Local inflammatory response occurs at the site of injury with exudation of fibrin, polymorphs and
macrophages. The macrophages clear away the fibrin, red blood cells, inflammatory exudate
and debris.
Ingrowth of granulation tissue begins with neovascularisation and proliferation of mesenchymal
cells from periosteum and endosteum. A soft tissue callus is thus formed which joins the ends of
fractured bone without much strength.
Callus composed of woven bone and cartilage starts within the first few days. The cells of inner
layer of the periosteum have osteogenic potential and lay down collagen as well as osteoid
matrix in the granulation tissue
The osteoid undergoes calcification and is called woven bone callus. At times, callus is
composed of woven bone as well as cartilage, temporarily immobilising the bone ends. This
stage is called provisional callus or procallus formation

OSSEOUS CALLUS FORMATION.

The procallus acts as scaffolding on which osseous callus composed of lamellar bone is formed.
The woven bone is cleared away by incoming osteoclasts and the calcified cartilage
disintegrates. In their place, newly-formed blood vessels and osteoblasts invade, laying down
osteoid which is calcified and lamellar bone is formed by developing Haversian system
concentrically around the blood vessels.

REMODELLING.
During the formation of lamellar bone, osteoblastic laying and osteoclastic removal are taking
place remodelling the united bone ends. The external callus is cleared away, compact bone
(cortex) is formed in place of intermediate callus and the bone marrow cavity develops in
internal callus.

COMPLICATIONS OF FRACTURE HEALING. These are as under:

1. Fibrous union may result instead of osseous union if the immobilisation of fractured bone is
not done.
2. Non-union may result if some soft tissue is interposed between the fractured ends.
3. Delayed union may occur from causes of delayed wound healing in general such as infection,
inadequate blood supply, poor nutrition, movement and old age.

Healing of Nervous Tissue

CENTRAL NERVOUS SYSTEM.
The nerve cells of the brain, spinal cord and ganglia once destroyed are not replaced. Axons of
CNS also do not show any significant regeneration. The damaged neuroglial cells, however,
may show proliferation of astrocytes called gliosis.
PERIPHERAL NERVOUS SYSTEM.
In contrast to the cells of CNS, the peripheral nerves show regeneration, mainly from
proliferation of Schwann cells and fibrils from distal end. Briefly, it consists of the following:
Myelin sheath and axon of the intact distal nerve undergo Wallerian degeneration up to the next
node of Ranvier towards the proximal end. Degenerated debris are cleared away by
macrophages. Regeneration in the form of sprouting of fibrils takes place from the viable end of
axon. These fibrils grow along the track of degenerated nerve so that in about 6-7 weeks, the
peripheral stump consists of tube filled with elongated Schwann cells

Healing of SKELETAL MUSCLE.

The regeneration of striated muscle is similar to peripheral nerves. On injury, the cut ends of
muscle fibres retract but are held together by stromal connective tissue.
The injured site is filled with fibrinous material, polymorphs and macrophages.
After clearance of damaged fibres by macrophages, one of the following two types of
regeneration of muscle fibres can occur:
If the muscle sheath is intact, sarcolemmal tubes containing histiocytes appear along the
endomysial tube which
If the muscle sheath is damaged, it forms a disorganised multinucleate mass and scar
composed of fibrovascular tissue e.g. in Volkmann’s ischaemic contracture.

Immunity

IMMUNODEFICIENCY DISEASES
Failure or deficiency of immune system, which normally plays a protective role against
infections, manifests by occurrence of repeated infections in an individual having
immunodeficiency diseases. Traditionally, immunodeficiency diseases are classified into 2
types:
A. Primary immunodeficiencies are usually the result of genetic or developmental abnormality of
the immune system.
B. Secondary immunodeficiencies arise from acquired suppression of the immune system.

Primary Immunodeficiency Diseases:

​ Severe Combined Immunodeficiency (SCID): A group of rare, inherited disorders

characterized by severe deficiencies in both T cells and B cells, leaving
individuals highly susceptible to infections.
​ Common Variable Immunodeficiency (CVID): This is a primary immunodeficiency
characterized by low levels of serum immunoglobulins (antibodies) and an
increased susceptibility to recurrent infections.
​ DiGeorge Syndrome: Caused by a chromosomal deletion, this syndrome results
in underdeveloped thymus and parathyroid glands, leading to T cell deficiencies
and susceptibility to infections.
​
Secondary Immunodeficiency Diseases:

​ HIV/AIDS (Human Immunodeficiency Virus/Acquired Immunodeficiency

Syndrome): HIV attacks and destroys CD4 T cells, weakening the immune system
and making the individual susceptible to various infections and cancers.
​ Chronic Lymphocytic Leukemia (CLL): A type of cancer that affects B cells, often
leading to a weakened immune system as the cancerous cells overcrowd the
bone marrow.
​ Chemotherapy-Induced Immunodeficiency: Cancer treatments such as
chemotherapy can suppress the immune system, making patients more
susceptible to infections.
​ Corticosteroid-Induced Immunodeficiency: Prolonged use of corticosteroids can
suppress the immune system, increasing the risk of infections.
​ Malnutrition-Induced Immunodeficiency: Inadequate nutrition can compromise
the immune system, leading to increased vulnerability to infections.

Hypersensitivity reactions
The lesions of hypersensitivity are a form of antigen-antibody reaction. These lesions are
termed as hypersensitivity reactions or immunologic tissue injury, of which 4 types are
described: type I, II, III and IV
"ADCC" stands for Antibody-Dependent Cell-Mediated Cytotoxicity*

Examples
Type I Hypersensitivity:

● Allergic Rhinitis
● Anaphylaxis

Type II Hypersensitivity:

● Autoimmune Hemolytic Anemia

● Drug-Induced Hemolytic Anemia

Type III Hypersensitivity:

● Systemic Lupus Erythematosus (SLE)

● Serum Sickness

Type IV Hypersensitivity:

● Contact Dermatitis
● Tuberculin Skin Test (Mantoux Test)
AUTOIMMUNE DISEASES

Autoimmunity is a state in which the body’s immune system fails to distinguish between ‘self’
and ‘non-self’ and reacts by formation of autoantibodies against one’s own tissue antigens. In
other words, there is loss of tolerance to one’s own tissues; autoimmunity is the opposite of
immune tolerance

Mechanism

​ Loss of Immune Tolerance:

● The immune system typically distinguishes between self and non-self antigens.
● In autoimmune diseases, there is a breakdown in immune tolerance, leading to
the recognition of self-antigens as foreign.
​ Activation of Immune Response:
● Activation of immune cells, such as T cells and B cells.
● Release of autoantibodies (antibodies targeting self-antigens) and inflammatory
mediators.
​ Tissue Damage and Inflammation:
● Autoantibodies and immune cells target specific tissues or organs.
● Inflammation and damage to the affected tissues.
● Chronic inflammation may contribute to the development of symptoms and
complications.
​ Variability in Target Organs:
● Autoimmune diseases can affect various organs and tissues, leading to a wide
range of symptoms.
● Examples include joints (Rheumatoid Arthritis), pancreas (Type 1 Diabetes),
nervous system (Multiple Sclerosis), thyroid (Hashimoto's Thyroiditis), and
others.
​ Immune Complex Formation:
● Formation of immune complexes (antigen-antibody complexes) in the
bloodstream.
● Deposition of immune complexes in tissues contributes to inflammation and
organ damage (e.g., Systemic Lupus Erythematosus).
​ Chronic Nature:
● Autoimmune diseases often have a chronic course, with periods of exacerbation
and remission.
● Progressive tissue damage may occur over time, leading to long-term
complications.

TYPES AND EXAMPLES OF AUTOIMMUNE DISEASES

Depending upon the type of autoantibody formation, the autoimmune diseases are broadly
classified into 2 groups:

1. Organ specific diseases. In these, the autoantibodies formed react specifically against an
organ or target tissue component and cause its chronic inflammatory destruction. The tissues
affected are endocrine glands (e.g. thyroid, pancreatic islets of Langerhans, adrenal cortex),
alimentary tract, blood cells and various other tissues and organs.

2. Organ non-specific (Systemic) diseases. These are diseases in which a number of

autoantibodies are formed which react with antigens in many tissues and thus cause systemic
lesions. The examples of this group are various systemic collagen diseases.

Organ-Specific Autoimmune Diseases:

● Hashimoto's Thyroiditis
● Type 1 Diabetes
● Multiple Sclerosis (MS)

Non-Organ-Specific Autoimmune Diseases:

● Rheumatoid Arthritis
● Systemic Lupus Erythematosus (SLE)
● Scleroderma