Immunologic Diseases - Delta University - Fall 2024-2025 PDF

The immune system A multifaceted system whose main function is protection against infection The immune system must be able to Generate produce a variety Detect antigens activation of effector...

The immune system A multifaceted system whose main function is protection against infection The immune system must be able to Generate produce a variety Detect antigens activation of effector Down regulate the as foreign signals proteins that inflammatory neutralize process once the pathogens or foreign agent is activate other eliminated cells,  The immune system innate immunity adaptive immunity innate immunity physical barrier the skin or mucosa circulating cells complement  Adaptive – acquired Immunity Highly specific immune response Antibody (Humoral Immunity) Cell-Mediated Immunity B- Cells T- Cells adaptive – acquired immune response Primary Secondary  Immunologic diseases  When the immunologic system couses undesirable consequences react against the body tissues in one of three ways Immunodeficiency Auto immunity Hypersensitivity ▪ Ineffective immune ▪Inappropriate ▪ Overactive immune response reaction to self response ▪ Any part of the ▪ The immune ▪ Reaction out of individual immune system react against proportion or system is defective self component ▪ Reaction against harmless antigens  immunodeficiency diseases Secondary Primary -When the immune system is - Inborn defct in immune system weakened by another treatment or - Manifest it self at birth or shortly illness after - Decreased numbers or function of the various components of the immune system, leading to increased incidence of infections.  Primary immunodeficiency diseases Deficiencies in Innate Deficiencies in Adaptive Immunity Immunity Defect in phagocytes Combined B-and B cell T cell defects deficiencies T cell functions deficiencies  Deficiencies in Innate Immunity Defect in phagocytes functions Chemotaxis Phagocytosis Killing Lazy leukocyte syndrome: Defect in movement Chediack Higashi Syndrome: Defect in phagocytosis  Recurrent infections mainly with Candida, and other fungi  Deficiencies in Adaptive Immunity Combined B and T B cell defects cell defects T cell defects Combined B & T- cell Deficiencies The basic defect involve the lymphoid stem cell. Lymphocyte precursor cells are improperly formed result in decreased B- and T-cell counts and/ or functions, as the development of these cells is impaired  B & T cell deficiency Severe combined Wiskot –Aldrich Immunodeficiency with Immunodeficiency ataxia telangectasia syndrome ▪Begins in the first few weeks of ▪Ocular and facial ▪Affect B & T cell and life, it includes bacterial, viral, telangiectasia platelets fungal infections.(localized or ▪petechiae, bruising, and ▪Continued ataxia bloody diarrhea systemic candidiasis ) ▪ Varied immunodeficiency ▪otitis media, pneumonia and ▪Cutaneous granulomas. skin infections are frequent problems. ▪The patient die from massive infection during the 1st year of life.  B- cell Deficiencies - Inability to produce a single class of antibody, Most commonly Ig A - Decreasing in certain classes of - lack the ability of immunoglobulins producing sufficient amount of all B-Cell immunoglobulins Deficiencies - A gammaglobulinemia. Lack the ability of producing all immunoglobulins T- cell deficiencies T- cell deficiencies Quantitative Qualitative Bare lymphocyte syndrome DiGeorge’ Syndrome - Genetic abnormality of MHC molecule Genetic abnormality of Humoral Cell- immune Thymus The great mediated responses. Parathyroid immune vessels of gland responses the heart T cells fail to Absent T- Inadequate activate B lymphocyte Hypocalcemia cells T cells response and tetany activation Oral manifestation of primary immune disorders (PID) :  Patients with T-lymphocytes abnormalities have more oral disease than patients with B-lymphocytes disorders T-lymphocytes disorders lead to: Chronic fungal and viral infections which occurs in oral more than bacterial infection. (Chronic oral candidiases, herpes simplex virus infections.)  The infection may be localized to the mouth but frequently disseminated.  Mucosal and skin telangiectasis of ataxia telangiectasia.  Cleft palate with thymic hypoplasia, bifid uvula micrognathia and short philtrum of the upper lip.   The major sign in B-cell abnormality: Recurrent bacterial infections as chronic maxillary sinusitis. (Referred pain in upper anterior teeth and first molars) Dental management  Dental treatment for (PID) primary immune disorders must minimize the chances of local infection  Antifungal therapy prior to dental treatment especially in patients with decrease T-cell function and oral candidiasis  Dental infections: Culture for bacteria & fungi, sensitivity test before giving antibiotic therapy.  Immunoglobulin therapy  Patient with B-cell abnormalities are usually given monthly therapy with concentrated human gammaglobulin  Prior dental treatment, the gammaglobulin level should checked, at least 200 mg/dl.  When oral surgery is necessary an extra dose of gammaglobulin should be administered the day before surgery in a dose between 100 and 200mg/kg of body weight.  Blood transfusion Those patients lack Ig and have weaken immune system Ig depleted blood (to prevent antigen antibody reaction) Fresh blood with destroyed lymphocytes (to prevent graft versus host reaction).  Secondary Immunodeficiencies Innate Adaptive system immunity decrease T-cell number and/or Humoral Cellular Complement function. immunity - cancer - Advanced liver - Gastrointestinal losses chemotherapy - Treatment with malabsorption/protein-losing disease. - Stem cell anti-tumor enteropathy), Malignancies. transplantation. necrosis factor - Nephrotic syndrome, - Aplastic anemia. - Hematologic malignancy, - Autoimmune - Medication: neutropenia. (immunosuppressives, such as corticosteroids and chemotherapy)  Autoimmune diseases immune response against self  May be due to either antibodies (autoantibodies) or immune cells (autoreactive lymphocytes)  A common characteristic is the presence of a lymphocytic infiltration in the target organ.  A common mechanism is a failure of peripheral tolerance systems that normally control autoreactive lymphocytes.  immune tolerance, or immunological tolerance  Means forgiveness, adaptation, unresponsiveness,  How to produce the forgiveness of the immune cells with self antigens, how to make the immune cells harmless or inactive against self antigens (cells education).  This can be produced by several mechanisms in the thymus and bone marrow for T and B cells respectively and this is what is known by central tolerance  In the lymph nodes and tissues this is what is called peripheral tolerance  Deleting auto-reactive lymphocyte clones before they develop into fully immunocompetent cells. (induction of apoptosis)  induction of anergy a state of non-activity.  The cytotoxic cells and other immune cells escape this tolerance start to be activated against self antigens and produce what is called autoimmune diseases Lymphocyte fetal development is most active in development and education continues as the thymus degenerates and the as immature slowing as lymphocytes bone marrow shrinks are generated, in adult life Terminologies Autoimmune disease - Reaction against self antigens Connective tissue diseases - Involve connective tissue Collagen disease - Involving mainly collagen Collagen vascular disease, - Involving the blood vessels Hyper immune disease -Hyper activity of immune system - Ag – Ab connection leads to Immune complex fixation of the complement  Autoimmune Diseases Scleroderma Lupus erthymatosis Rheumatoid arthritis Rheumatoid Arthritis (RA)  Arthritis of small and large joints  The target organ is the synovial tissue and the cartilage of the joint.  In which Rheumatic Factor (RF) is the most important and common type of auto antibodies  B cells, which can differentiate into plasma cells, are also found within the synovial infiltrate  There are frequent extra-articular manifestations. affects other organs including muscles and the hematopoietic system  Affects all age groups highest incidence in women from 30 to 50 years of age Clinical Manifestations  RA is a symmetric polyarthritis  All joints may be involved, including the temporomandibular joint  Affected joints develop redness, swelling, and warmth, with eventual atrophy of the muscle around the involved area  Joint destruction and deformity with time, including ▪ subcutaneous nodules ▪ swan-neck deformities. ▪ cervical spine disease may cause C1–C2 subluxation ▪ spinal cord compression.  Rheumatoid nodules may develop in the lungs, pleura, pericardium, sclerae, and, rarely, the heart, eyes, or brain.  Medical treatment and side effects  Methotrexate and other antirheumatic agents, such as d-penicillamine and NSAIDs, can cause stomatitis.  Minocyline may cause hyperpigmentation intraorally.  Cyclosporine can produce Gingival overgrowth  prednisone or TNF-a-blocking therapy may predispose patients to the development of opportunistic infections Associated Oral Manifestations  Sjogren's syndrome, a common complication of rheumatoid arthritis.  Side effects of the drugs used for treatment  Involvement of TMJ Dental Management  Hyperextension of the neck must be avoided.  Prolonged morning stiffness is common in RA, so late-morning appointments may be best  Patients with severe RA who have prosthetic joints may require prophylactic antibiotic therapy  It is imperative that the dentist understand the mechanism of action of the patient’s current medications, their possible side effects, and their potential interactions with drugs commonly used in dentistry.  Lupus Erythrymatosis Autoimmune inflammatory disorder Discoid Systemic Confined to the skin and mucosa Multisystem involvement mostly face and scalp and oral mucosa - The specific etiology of SLE is not known with certainty suggested - Associated factors: Genetic, Endocrine disorder, Viral infection - Serum antibodies and immune complexes are detected mainly autoantibodies against DNA (anti nuclear antibodies ANA) in addition to autoantibodies directed against nucleoprotein, erythrocytes, leukocytes, platelets, coagulation factors, and liver, kidney, or heart tissue. - Affect both children and older individuals, peak incidence is the 20- to 40-year-old age range, more frequently in females.  Clinical manifestations Skin: up to 85% of SLE patients are affected. Butte fly rash Cutaneous lupus can occur without Bollus multisystem involvement (discoid LE) Acute Erythematous papules Specific - Sub- Annular- diagnostic polycystic Skin acute lesions papulo-squamous Chronic - Alopecia - Photo sensitivity. Non -specific - Urticaria , erythema, telangiectasis - Cutaneous vasculitis.  A-specific cutaneous features : 1-Acute cutaneous lupus. occurs in 85% of patients with SLE I- Butter fly rashes: form, mask shaped erythemetous eruption, sparing the nasolabial fold, malar area and nose bridge. II- Bollus form. III- Erythematous papules form 2-Subacute: occurs in 10-15% of patients  Annular- polycystic eruption  papule-squamous. usually on the trunk and arms ( psoriasis form) 3-chronic cutaneous lupus: occur in 15-20% of cases. affect face skin or scalp in about 80% of cases. B- Non-specific cutaneous lesions: - Alopecia - Photo sensitivity. - Urtiacaria ,erythema, telengiectases - cutaneous vasculitis. Oral lesions: There are 2 predominant types: 1- discoid lesions:  Appear as whitish striae radiated from the central erythematous area (brush border)  Atrophy and telangiectasis.  Affect buccal and labial mucosa, gingiva and palate. 2- oral ulcerations: – Non-specific: can not be easily clinically distinguished from other oral ulcers (e.g. aphthous ulcers) – Histologically: lymphocytic infiltration (perivascular and at the ulcer base). Oral lesions of SLE Systemic manifestations Renal: - Proteinourea to rapidly progressive glomerulonephritis. Musculo-skeletal: - Arthritis, Fixed joints deformity, TMJ invovement. Myalgias and myositis, Avascular necrosis (associated with corticosteroid therapy). Central nervous system: - Cerebral vasculitis or direct neuronal damage. psychosis, stroke, seizures Cardiovascular: - Vasculitis, pericarditis, endocarditis - Defect in blood co-agulation pathway - Decrease in anticoagulant proteins Diagnosis 1-lupus band test deposits of immunoglobulin and C3 in the basement membrane zone. shows Ig deposits at two different places The first is a band like deposit along the epidermal basement membrane ("lupus band test" is positive); the second is within the nuclei of the epidermal cells (antinuclear antibodies are present). 2- The inflammatory infiltrate in oral lesions of LE consists primarily of helper/inducer T lymphocytes. 3-Antinuclear antibodies (ANA) are of major diagnostic importance in LE and include 4-Other features Aneamia, leukopenia (neutropenia and lymphopenia) and thrombocytopenia Treatment  Corticosteroids remain the cornerstone of therapy in SLE and are especially useful for controlling disease flares in addition to immunosuppressive drugs  Dental management: Risk of infection: – CBC Elective oral surgical procedures with the potential for bacteremia should be delayed if the ANC (Absolute neutrophil count) is near 1,000 cells/mm3, – Prophylactic antibiotic are often recommended Risk of bleeding. – Platelet transfusion in surgical patients with platelet count below 50,000/mm3. – Check the INR Value before any oral surgery Adrenal suppression.  Any patient treated with supra-physiologic doses of corticosteroids (7.5mg/day or higher prednisone for 2 weeks or longer is at risk for adrenal suppressions.  The duration of adrenal suppression is dependant on both the dose and duration of treatment.  Abnormal adrenal response observed ranging from about a week (20mg for 5 days prednisone) to up to a year after long term high dose steroid administration  older guidelines recommended routine doubling of the steroid dose in patients at risk of adrenal suppression undergoing surgical procedures,  current recommendations are based on the rational approach  Guidelines for Supplementation of Patients at Risk of Adrenal Insufficiency Undergoing Dental Surgery A- ▪ Routine dental procedures No supplementation ▪ Current Topical Use B- Minor oral surgery lasting 1 h  50 –100 mg of hydrocortisone equivalent the day of surgery, with continuation of the dose for an additional day dependent on the amount of blood loss, the presence of infection, and the length of the surgery D- Major oral surgery with general anesthesia lasting >1 h having significant blood loss, such as cancer or orthognathic surgery  Usual daily dose before surgery and of 50 mg hydrocortisone equivalent intravenously during surgery and every 8 h after the initial dose for up to 72  Scleroderma  A disease affects connective tissue and blood vessels and leads to :  fibrosis hardening  tightening of the skin and mucosa.  Etiology and Pathogenesis  The exact etiology is unclear suggested factors: Genetics, exposure to chemicals, viral infection.  pathogenesis is characterized by vascular damage and accumulation of collagen and other extracellular matrix components at the involved sites (microvasculature changes & narrows small arteries) Clinical Manifestations Types progressive systemic Localized form sclerosis (PSS), involving the skin, with minimal systemic features. skin and internal organs are involved. localized form (scleroderma primarily) Linear scleroderma Morphea en coup de sabre guttate morphea When affect the head and face larger lesions that coalesce Morphea ▪Indurate violaceous ▪lose hair and then Progress That sweat gland to skin patches function hyperpigmented area depressed below the level of the skin Linear scleroderma  A band of sclerotic induration and hyperpigmentation. that may run the entire length of an extremity, involving underlying muscle, bones, and joints  When affects one side of the face. result in hemiatrophy.  progressive systemic sclerosis (PSS), limited cutaneous diffuse cutaneous skin thickening limited to the widespread skin thickening (progressing from hands the fingers to the trunk (previously called CREST syndrome for) Calcinosis cutis: calcium deposits form in the skin. Raynaud’s phenomenon Esophageal dysmotility Fibrosis of esophageal muscules Scleroductility "skleros" meaning hard and "daktylos" meaning a finger or toe – "hard fingers or toes". Telangiectasia May be detected on the skin of the face and on oral mucosa Raynaud’s Phenomenon.  Most common initial finding of PSS.  Marked intimal hyperplasia of the digital arteries of scleroderma patients narrows the vessels.  Stimuli such as cold that normally stimulate vasoconstriction can cause complete obstruction of the blood flow to the fingertips  Digital cyanosis, numbness, and blanching found  Digital pitting scars, nail fold infarcts, or ulcers that occasionally cause loss of the digit internal organ involvement  Generalized arthralgias and morning stiffness  Pulmonary hypertension  ischemic, fibrotic, and inflammatory lesions cardiac lesions and “Patchy fibrosis of cardiac muscles.  Hypertension, dysrhythmias, conduction disturbances, and left ventricular hypertrophy  GIT disorders of motility  “Scleroderma renal crisis” which is a syndrome characterize by malignant hypertension, renal insufficiency, hyperreninemia, evidence of microangiopathic hemolysis  Oral Findings *Rigid lips, Narrow mouth aperture *Mask like face due to loss of skin folds *Hard and rigid tongue making speaking and swallowing difficult. *Involvement of the esophagus causes dysphagia. *Restricted mouth opening due to involvement the soft tissues around the TMJ causing a pseudoankylosis. *Dental radiographic findings include uniform thickening of the periodontal membrane, especially around posterior teeth * calcinosis of the soft tissues around the jaws. The areas of calcinosis will show up on dental films and may be misinterpreted as radiographic intr-abony lesions. *Extensive involvement of facial tissues and muscles of mastication pressure that will cause resorption of the mandible especially at the angle of the mandible at the attachment of the masseter muscle. *The coronoid process, condyle, and area of muscles attachment may also be damaged by the continual pressure. *Patients may also have oral disease secondary to drug therapy or xerostomia. Xerostomia from associated Sjogren's syndrome results in an increased susceptibility to dental caries and periodontal disease. *Gingival hyperplasia may result from calcium channel blockers; and pemphigus, blood dyscrasias, or lichenoid reactions. Dental Management  The most common problem in the dental treatment of scleroderma patients is the physical limitation caused by the narrowing of the oral aperture and rigidity of the tongue.  The oral opening may be increased an average of 5 mm by stretching exercises. One particularly effective technique is the use of an increasing number of tongue blades between the posterior teeth to stretch the facial tissues.  Customized toothbrush handles should be provided for patients who cannot grip an ordinary toothbrush.  When treating a patient with diffuse scleroderma, the extent of the heart, lung, or kidney involvement should be considered, and appropriate alterations should be made before, during, and after treatment.  Patients with extensive resorption of the angle of the mandible are at risk of developing pathologic fractures from minor trauma, Dr. Reda Saber