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Immunological
DiseaseDisease
Dr. Deepak K. Gupta
Syllabus
• Immuno deficiency disorders
– a brief knowledge of various types of immuno deficiency
disorders
– A sound knowl...
Immunodeficiency disordersImmunodeficiency disorders
Introduction
• A state in which the immune system's ability
to fight infectious disease is compromised or
entirely absent....
Primary Immunodeficiency Disease
• Myeloid lineage
– Congenital agranulocytosis
– Leukocyte-adhesion deficiency
• Lymphoid...
Symptoms
• Recurrent respiratory infections.
• Persistent bacterial infections →sinusitis, otitis and
bronchitis.
• Increa...
Aetiology
• Aetiology associated with
–Genetic defects of missing enzymes.
–Specific development impairment (pre-B-
cell f...
Severe combined immunodeficiency
(SCID)
• Various genetic defects
• No TCR or defective TCR
• Defective cell signaling
• D...
Secondary Immunodeficiency
• Drug related
• Disease related
– Cancer
– AIDS– AIDS
• HIV
• T helper cell as target
Acquired Immunodeficiency
Syndrome/AIDSSyndrome/AIDS
Introduction
• Caused by Human
Immunodeficiency
Virus (HIV)
• Human immune• Human immune
system are unable to
overcome the...
Introduction
• A weak immune system can no longer effectively
defend the body resulting to
– The body becomes vulnerable t...
Acquired Immunodeficiency
Syndrome (AIDS)
• A “syndrome” is a group of symptoms & signs
associated with the same underlyin...
PREVALENCE
• HIV infection – global pandemic
• Worldwide 40.3 million infected people,
– Among adults 15 - 49 yrs. , 1.1%
...
History
• 1979 – Increased Kaposi sarcoma and
Pneumocystis carinii infections in
homosexuals noted in Africa.
• 1981 – Fir...
HIV VIROLOGY
• It is RNA virus, in the group of lenti virus.
– Subfamily of retrovirus.
• It contains two copies of single...
HIV VIROLOGY
HIV Pathophysiology
• Penetration of virus in to
host plasma membrane
results into virion
• Reverse transcriptase and
inte...
Transmission
It can be transmitted through the following body fluids:
• Blood
• Semen
• Vaginal fluid
• Breast milk
HIV ca...
Concentration in Human Body FluidsConcentration in Human Body Fluids
 Blood
 Semen
 Milk
 Saliva
 Vaginal secretion
CLASSIFICATION
CLASSIFICATION
• CDC classifies HIV infection into 3 categories, as
follows:
– Category A: Asymptomatic HIV infection with...
CLASSIFICATION
• These 3 categories are further subdivided on
the basis of the CD4+ T-cell count, as follows:
1. > 500/µL:...
SIGNS AND SYMPTOMS
• The patient with HIV may present with signs and symptoms
of any of the stages of HIV infection.
• No ...
SIGNS AND SYMPTOMS
• HIV infection can cause
some sequelae,
• Including AIDS-associated
dementia/encephalopathy
• HIV wast...
SIGNS AND SYMPTOMS
HIV Screening & Diagnosis
• Antibody detection:
– Blood donors screening,
– ELISA, Western-Blot (Confirmatory)
• Antigen d...
Oral Manifestation of HIV
• Oral conditions associated with HIV infection are divided into five major
groups:
-Microbiolog...
TREATMENT
• Highly active antiretroviral therapy (HAART) is the
principal method for preventing immune deterioration.
• Cl...
Hypersensitivity reactions
An exaggerated or inappropriate state ofAn exaggerated or inappropriate state of
normal immune ...
Hypersensitivity reactions
• The lesions of hypersensitivity are a form of
antigen - antibody reaction.
• Subdivided into ...
TYPE I HYPERSENSITIVITY
• A state of rapidly
developing or
anaphylactic type of
immune response to an
antigen (i.e. allerg...
TYPE I
HYPERSENSITIVITY
• First contact of the host with the antigen,
sensitisation takes place.
• In response to initial ...
Clinical and Pathologic Manifestations
• Generalized manifestation
– Itching, urticaria (hives), and skin erythema
– Follo...
Clinical and Pathologic Manifestations
• Systemic anaphylaxis
– Administration of antisera e.g. anti-tetanus serum (ATS)
–...
Hypersensitivity Type II
TYPE II HYPERSENSITIVITY
• Cytotoxic type reaction
• Reactions by humoral antibodies that attack
cell surface antigens on ...
ETIOLOGY AND PATHOGENESIS
• Participation by complement system,
• Tissue macrophages, platelets, natural killer
cells, neu...
Clinical Manifestation
• Cytotoxic antibodies to blood cells
– Autoimmune haemolytic anaemia
– Transfusion reactions
– Hae...
Hypersensitivity Type III
Type III hypersensitivity is also known as immune
complex hypersensitivity.
The reaction may take 3 - 10 hours after exp...
Mechanism of Type III Hypersensitivity
 Antigens combines with antibody within circulation and form
immune complex
 Wher...
Pathogenesis of
TYPE III
Antigens combine with
antibodies to form
antigen-antibody complexes.
Antigen
Antibody (IgG)
Antig...
Type III (ICM) Hypersensitivity
Hypersensitivity Type III Reactions
Systemic ReactionsLocal Reactions
 Arthus Reaction:
...
Immune Complex Diseases:
 Hypersensitivity Pneumonitis
 Glomerulonephritis
Type III Hypersensitivity: Clinical
Manifesta...
Hypersensitivity pneumonitis
 Inhalation of antigens into lungs stimulates antibody
production
Type III Hypersensitivity:...
Glomerulonephritis
 Immune complexes in the blood are deposited in
glomeruli
 Damage to the glomerular cells impedes blo...
Rheumatoid arthritis
 Immune complexes deposited in the joint
» Results in release of inflammatory chemicals
» The joints...
The crippling distortion of joints characteristic of rheumatoid arthritis
Systemic lupus erythematosus
Autoantibodies against DNA result in immune complex
formation
Many other autoantibodies can...
The characteristic facial rash of systemic lupus
erythematosus
Hypersensitivity Type IV
 Delayed hypersensitivity is a function of T Lymphocytes, not antibody.
 It starts hours (or Days) after contact with th...
The tuberculin response
• An injection of tuberculin beneath the skin causes
reaction in individual exposed to tuberculosi...
A positive tuberculin test
Allergic contact dermatitis
• Cell-mediated immune response
• Results in an intensely irritating skin rash
Type IV Hyperse...
Allergic contact dermatitis
Graft rejection
• Rejection of tissues or organs that have been transplanted
• Grafts perceived as foreign by a recipient ...
Types of grafts
Autograft
Isograft Allograft Xenograft
Genetically identical
sibling or clone
Genetically different
member...
Summary
Auto-immune Disease
The state in which the body’s immune systemThe state in which the body’s immune system
fails to distin...
Auto-immune Disease
• Theories of Autoimmunity
– Immunological factors
– Genetic factors
• increased expression of Class I...
ORGAN NON-SPECIFIC - SYSTEMIC
• Systemic lupus erythematosus
• Rheumatoid arthritis
• Scleroderma (Progressive systemic sc...
ORGAN SPECIFIC - LOCALISED
• ENDOCRINE GLANDS
– Hashimoto’s
(autoimmune) thyroiditis
– Graves’ disease
– Type 1 diabetes m...
Systemic Lupus Erythematosus (SLE)
• Classical example of systemic autoimmune or
collagen diseases
• 2 forms of lupus eryt...
Systemic Lupus Erythematosus (SLE)
Systemic Lupus Erythematosus (SLE)
Scleroderma (Progressive Systemic
Sclerosis)
• Skin disease
characterised by
progressive fibrosis
• 2 main types
• Diffuse...
Scleroderma-
Diffuse scleroderma
Sjogren’s syndrome
• Sicca syndrome
• Gougerot-sjorgen syndrome
• Triad
– Keratonjuctivitis sicca– Keratonjuctivitis sicca...
Clinical features
• 0.5-1% of population
• Female >40 yrs, F:M = 10:1
• Children or young may be affected
• Dryness of mou...
Clinical presentation
• Oral mucosa
– Parchment like appearance –
red, dry, tendered, smooth
glazed
– Difficulty in wearin...
Radiographic features
• Sialography
– Punctate
– Cavitary defect – filled
with radioopaque
contrast media
• ‘Cherry blosso...
Treatment
• No satisfactory t/t
• SYMPTOMATICALLY treated
• Keratoconjuctivitis
– Occular lubricant – artificial tears lik...
HLA complex
• Human Leucocyte Antigens
• Determine one’s own tissue from non-self
- histocompatibility
• Immense importanc...
HLA complex
• Class I MHC antigens
– HLA-A, HLA-B and HLA-C
– CD8+ i.e. T suppressor
lymphocytes carry receptors
for class...
Clinical Importance: HLA complex
• Organ transplantation
• Regulation of the immune system
– Class I: function of cytotoxi...
Transplant Rejection
• According to the genetic relationship between donor and
recipient, transplantation of tissues is cl...
Transplant Rejection
• The greater the genetic disparity between donor and
recipient in HLA system - stronger and more rap...
Mechanisms of Graft Rejection
• Except for autografts and isografts, an immune
response against allografts is inevitable.
...
HYPERACUTE REJECTION
• Within minutes to hours of placing the transplant
and destroys it.
• Humoral antibody against donor...
ACUTE REJECTION
• Within a few days to a few months of transplantation
• It may be
– Acute humoral rejection: Extensive in...
CHRONIC REJECTION
• Repeated attacks of acute rejection
• May develop slowly over a period of months to a
year
• Immunolog...
Immunological disease
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Immunological disease

Immunological disease

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Immunological disease

  1. 1. Immunological DiseaseDisease Dr. Deepak K. Gupta
  2. 2. Syllabus • Immuno deficiency disorders – a brief knowledge of various types of immuno deficiency disorders – A sound knowledge of immunodeficiency disorders relevant to dentistry. • Hypersensitivity reactions• Hypersensitivity reactions • Autoimmune disorders – Basic knowledge of various types – sound knowledge of autoimmune disorders of oral cavity and related structure • Immunology of Transplantation and Malignancy • Immunehaematology
  3. 3. Immunodeficiency disordersImmunodeficiency disorders
  4. 4. Introduction • A state in which the immune system's ability to fight infectious disease is compromised or entirely absent. • It may be 2 types• It may be 2 types – Primary: Usually congenital, resulting from genetic defects in some components of the immune system. – Secondary (Acquired): as a result of other diseases or conditions such as HIV infection, malnutrition, immunosuppression
  5. 5. Primary Immunodeficiency Disease • Myeloid lineage – Congenital agranulocytosis – Leukocyte-adhesion deficiency • Lymphoid lineage – Severe combined immunodeficiency (SCID) – B cells Agammaglobulinemia• Agammaglobulinemia • Hypogammaglobulinemia • Specific Ig Deficiencies – T cells • DiGeorge Syndrome • Wiskott Aldrich Syndrome • Complement system deficiency • Disorder of Phagocytosis : chronic granulomatous disease
  6. 6. Symptoms • Recurrent respiratory infections. • Persistent bacterial infections →sinusitis, otitis and bronchitis. • Increased susceptibility to opportunistic infections (OIs) and recurrent fungal yeast infections.and recurrent fungal yeast infections. • Skin and mucous membrane infections. • Resistant thrush, oral ulcers and conjunctivitis. • Diarrhoea and malabsorption. • Failure to thrive and delayed or incomplete recovery from illness.
  7. 7. Aetiology • Aetiology associated with –Genetic defects of missing enzymes. –Specific development impairment (pre-B- cell failure).cell failure). –Infections, malnutrition and drugs
  8. 8. Severe combined immunodeficiency (SCID) • Various genetic defects • No TCR or defective TCR • Defective cell signaling • Defective IL 2• Defective IL 2 • Recurrent infections • Death at early age
  9. 9. Secondary Immunodeficiency • Drug related • Disease related – Cancer – AIDS– AIDS • HIV • T helper cell as target
  10. 10. Acquired Immunodeficiency Syndrome/AIDSSyndrome/AIDS
  11. 11. Introduction • Caused by Human Immunodeficiency Virus (HIV) • Human immune• Human immune system are unable to overcome the infection. • The person becomes “immunodeficient”
  12. 12. Introduction • A weak immune system can no longer effectively defend the body resulting to – The body becomes vulnerable to a variety of infections & cancers.cancers. – Infections that take advantage of a weakened immune system are “opportunistic infections”. – Eventually the immune system is so weak that the body is overwhelmed by infections and/or cancers, and the person dies.
  13. 13. Acquired Immunodeficiency Syndrome (AIDS) • A “syndrome” is a group of symptoms & signs associated with the same underlying condition. • Classified in 2-type• Classified in 2-type – HIV-1: predominantly found in East, Central, South Africa and other parts of the world – HIV-2 reported mainly in W. Africa.
  14. 14. PREVALENCE • HIV infection – global pandemic • Worldwide 40.3 million infected people, – Among adults 15 - 49 yrs. , 1.1% – 4.1 million death – 4.5 million new cases/ year– 4.5 million new cases/ year – 14,000 new infections/ day • 2.40 million Indians are living with HIV – 83% are the in age group 15-49 years – 39% (930,000) are among women – Andhra Pradesh, Maharashtra, Karnataka , Tamil Nadu – account for 55% – (UNAIDS 2006 )
  15. 15. History • 1979 – Increased Kaposi sarcoma and Pneumocystis carinii infections in homosexuals noted in Africa. • 1981 – First case in California.• 1981 – First case in California. • > 30 million in world – 1999 – increasing
  16. 16. HIV VIROLOGY • It is RNA virus, in the group of lenti virus. – Subfamily of retrovirus. • It contains two copies of single stranded Ribonucleic Acid (RNA). • Viral RNA is surrounded by a capsid made from viral• Viral RNA is surrounded by a capsid made from viral proteins • This is enclosed in a viral envelope formed from the cellular membrane of the host cell. • Primary targets CD4+T lymphocytes • Over time, CD4 cell counts decline and results in a poorly functioning immune system
  17. 17. HIV VIROLOGY
  18. 18. HIV Pathophysiology • Penetration of virus in to host plasma membrane results into virion • Reverse transcriptase and integrase molecules get attached to viral RNA.attached to viral RNA. • These helps in the synthesizes of DNA copies of RNA. – Integrase catalyses their insertion into the host DNA chromosome in the nucleus.
  19. 19. Transmission It can be transmitted through the following body fluids: • Blood • Semen • Vaginal fluid • Breast milk HIV can’t be transmitted through the following :HIV can’t be transmitted through the following : • Saliva • Tears • Urine • Mosquitoes • Toilet Seats • Kissing • Hugging
  20. 20. Concentration in Human Body FluidsConcentration in Human Body Fluids  Blood  Semen  Milk  Saliva  Vaginal secretion
  21. 21. CLASSIFICATION
  22. 22. CLASSIFICATION • CDC classifies HIV infection into 3 categories, as follows: – Category A: Asymptomatic HIV infection without a history of symptoms or AIDS-defining conditions Category B: HIV infection with symptoms that are– Category B: HIV infection with symptoms that are directly attributable to HIV infection (or a defect in T-cell–mediated immunity) or that are complicated by HIV infection – Category C: HIV infection with AIDS-defining opportunistic infections
  23. 23. CLASSIFICATION • These 3 categories are further subdivided on the basis of the CD4+ T-cell count, as follows: 1. > 500/µL: Categories A1, B1, C1 2. 200-400/µL: Categories A2, B2, C22. 200-400/µL: Categories A2, B2, C2 3. < 200/µL: Categories A3, B3, C3
  24. 24. SIGNS AND SYMPTOMS • The patient with HIV may present with signs and symptoms of any of the stages of HIV infection. • No physical findings are specific to HIV infection; • The physical findings are those of the presenting infection or illness. • Manifestations include the following:• Manifestations include the following: – Acute seroconversion manifests as a flulike illness, consisting of fever, malaise, and a generalized rash – The asymptomatic phase is generally benign – Generalized lymphadenopathy is common and may be a presenting symptom – Recurrent, severe, and occasionally life-threatening infections or opportunistic malignancies
  25. 25. SIGNS AND SYMPTOMS • HIV infection can cause some sequelae, • Including AIDS-associated dementia/encephalopathy • HIV wasting syndrome• HIV wasting syndrome (chronic diarrhea and weight loss with no identifiable cause)
  26. 26. SIGNS AND SYMPTOMS
  27. 27. HIV Screening & Diagnosis • Antibody detection: – Blood donors screening, – ELISA, Western-Blot (Confirmatory) • Antigen detection – Blood donors screening, diagnostic– Blood donors screening, diagnostic – ELISA • Nucleic Acid Testing (DNA, RNA): – Blood donors screening (on pools), diagnostic, follow up – Lymphocyte culture • Tests for defects in immunity • CD4+ T cell counts
  28. 28. Oral Manifestation of HIV • Oral conditions associated with HIV infection are divided into five major groups: -Microbiological infections (fungal, bacterial, viral) -Oral neoplasias -Neurological conditions -Lesions of uncertain aetiology-Lesions of uncertain aetiology -Oral conditions associated with HIV treatment. • Other co-infections and conditions associated with HIV infection, which are significant to dentists are: -Syphilis -Tuberculosis -Persistent generalised lymphadenopathy -Gastro-oesophageal reflux disease (GORD).
  29. 29. TREATMENT • Highly active antiretroviral therapy (HAART) is the principal method for preventing immune deterioration. • Classes of antiretroviral agents include the following: – Nucleoside reverse transcriptase inhibitors (NRTIs) – Protease inhibitors (PIs)– Protease inhibitors (PIs) – Nonnucleoside reverse transcriptase inhibitors (NNRTIs) – Fusion inhibitors – CCR5 co-receptor antagonists (entry inhibitors) – HIV integrase strand transfer inhibitors
  30. 30. Hypersensitivity reactions An exaggerated or inappropriate state ofAn exaggerated or inappropriate state of normal immune response with onset of adverse effects on the body
  31. 31. Hypersensitivity reactions • The lesions of hypersensitivity are a form of antigen - antibody reaction. • Subdivided into four types; – Type I hypersensitivity – Type II hypersensitivity – Type III hypersensitivity – Type IV hypersensitivity • First three are variations on antibody-mediated (Immediate type) injury, whereas the fourth is cell mediated (delayed type)
  32. 32. TYPE I HYPERSENSITIVITY • A state of rapidly developing or anaphylactic type of immune response to an antigen (i.e. allergen) toantigen (i.e. allergen) to which the individual is previously sensitised. • The reaction appears within 15-30 minutes of exposure to antigen
  33. 33. TYPE I HYPERSENSITIVITY • First contact of the host with the antigen, sensitisation takes place. • In response to initial contact with antigen, circulating B lymphocytes get activated • And it differentiate to form IgE-secreting plasma cells.plasma cells. • IgE antibodies so formed bind to the Fc receptors present on the surface of mast cells and basophils • During the second contact with the same antigen • The combination sets in cell damage – Membrane lysis, – Influx of sodium and water – degranulation of mast cells-basophils
  34. 34. Clinical and Pathologic Manifestations • Generalized manifestation – Itching, urticaria (hives), and skin erythema – Followed in short order by profound respiratory difficulty • Pulmonary bronchoconstriction • Accentuated by hypersecretion of mucus. – Laryngeal edema may cause upper airway obstruction – Musculature of the entire gastrointestinal tract– Musculature of the entire gastrointestinal tract • Resultant vomiting • Abdominal cramps • Diarrhea – systemic vasodilation with fall in blood pressure – may progress to circulatory collapse and death within minutes • Local reactions – Skin (contact, causing urticaria), – Gastrointestinal tract (ingestion, causing diarrhea) – Lung (inhalation, causing bronchoconstriction)
  35. 35. Clinical and Pathologic Manifestations • Systemic anaphylaxis – Administration of antisera e.g. anti-tetanus serum (ATS) – Administration of drugs e.g. penicillin – Sting by wasp or bee • Local anaphylaxis• Local anaphylaxis – Hay fever: pollen – Bronchial asthma – Food allergy to ingested allergens like fish, cow’s milk, eggs etc. – Cutaneous anaphylaxis – Angioedema
  36. 36. Hypersensitivity Type II
  37. 37. TYPE II HYPERSENSITIVITY • Cytotoxic type reaction • Reactions by humoral antibodies that attack cell surface antigens on the specific cells and tissues and cause lysis of target cellstissues and cause lysis of target cells • Within 15-30 minutes after exposure to antigen
  38. 38. ETIOLOGY AND PATHOGENESIS • Participation by complement system, • Tissue macrophages, platelets, natural killer cells, neutrophils and eosinophils • Main antibodies are IgG and IgM• Main antibodies are IgG and IgM
  39. 39. Clinical Manifestation • Cytotoxic antibodies to blood cells – Autoimmune haemolytic anaemia – Transfusion reactions – Haemolytic disease of the newborn (erythroblastosis foetalis) – Idiopathic thrombocytopenic purpura (ITP) – Leucopenia with agranulocytosis– Leucopenia with agranulocytosis – Drug-induced cytotoxic antibodies • Cytotoxic antibodies to tissue components – Graves’ disease – Myasthenia gravis – Male sterility – Type 1 diabetes mellitus – Hyperacute rejection reaction
  40. 40. Hypersensitivity Type III
  41. 41. Type III hypersensitivity is also known as immune complex hypersensitivity. The reaction may take 3 - 10 hours after exposure to the antigen (as in Arthus reaction). The reaction may be general (e.g., serum sickness) or Type III (ICM) Hypersensitivity The reaction may be general (e.g., serum sickness) or may involve individual organs including or other organs. Antigens causing immune complex mediated injury are: Exogenous Endogenous
  42. 42. Mechanism of Type III Hypersensitivity  Antigens combines with antibody within circulation and form immune complex  Wherever in the body they deposited  They activate complement system Type III (ICM) Hypersensitivity  They activate complement system  Polymorphonuclear cells are attracted to the site  Result in inflammation and tissue injury
  43. 43. Pathogenesis of TYPE III Antigens combine with antibodies to form antigen-antibody complexes. Antigen Antibody (IgG) Antigen-antibody complex Phagocytes remove most of the complexes, but some lodge in the walls of blood vessels. There the complexes activate complement. Inactive complement TYPE III Hypersensitivity Inactive complement Active complement Antigen-antibody complexes and activated complement attract and activate neutrophils, which release inflammatory chemicals. Neutrophil Inflammatory chemicals Inflammatory chemicals damage underlying blood vessel wall.
  44. 44. Type III (ICM) Hypersensitivity Hypersensitivity Type III Reactions Systemic ReactionsLocal Reactions  Arthus Reaction: It is named for Dr. Arthus. Inflammation caused by the deposition of immune complexes at a localized site. Clinical Manifestation is : Hypersensitivity Pneumonitis  Serum Sickness: Systemic inflammatory response to deposited immune complexes at many areas of body. Few days to 2 weeks after injection of foreign serum or drug it results in : Fever, Urticaria, Artheralgia, Eosinophila, Spleenomegally, and Lymph adenopathy
  45. 45. Immune Complex Diseases:  Hypersensitivity Pneumonitis  Glomerulonephritis Type III Hypersensitivity: Clinical Manifestation  Glomerulonephritis  Rheumatoid Arthritis  Systemic Lupus Erythematosus
  46. 46. Hypersensitivity pneumonitis  Inhalation of antigens into lungs stimulates antibody production Type III Hypersensitivity: Clinical Manifestation  Subsequent inhalation of the same antigen results in formation of immune complexes » Activates complement
  47. 47. Glomerulonephritis  Immune complexes in the blood are deposited in glomeruli  Damage to the glomerular cells impedes blood Type III Hypersensitivity: Clinical Manifestation  Damage to the glomerular cells impedes blood filtration  Kidney failure and, ultimately, death result
  48. 48. Rheumatoid arthritis  Immune complexes deposited in the joint » Results in release of inflammatory chemicals » The joints begin to break down and become Type III Hypersensitivity: Clinical Manifestation » The joints begin to break down and become distorted  Trigger not well understood  Treated with anti-inflammatory drugs
  49. 49. The crippling distortion of joints characteristic of rheumatoid arthritis
  50. 50. Systemic lupus erythematosus Autoantibodies against DNA result in immune complex formation Many other autoantibodies can also occur Type III Hypersensitivity: Clinical Manifestation Many other autoantibodies can also occur » Against red blood cells, platelets, lymphocytes, muscle cells Trigger unknown  Immunosuppressive drugs reduce autoantibody formation Glucocorticoids reduce inflammation
  51. 51. The characteristic facial rash of systemic lupus erythematosus
  52. 52. Hypersensitivity Type IV
  53. 53.  Delayed hypersensitivity is a function of T Lymphocytes, not antibody.  It starts hours (or Days) after contact with the antigen and often lasts for days.  Principal pattern of immunologic response to variety of intra cellular microbiologic agents i.e.: Mycobacterium Tuberculosis Viruses Type IV (Cell Mediated) Hypersensitivity Viruses Fungi Parasites Mechanism • Activation of T Lymphocytes • Release of cytokines and macrophage activation • T-cell mediated cytotoxicity
  54. 54. The tuberculin response • An injection of tuberculin beneath the skin causes reaction in individual exposed to tuberculosis or tuberculosis vaccine Type IV Hypersensitivity: Clinical Manifestation • Used to diagnose contact with antigens of M. tuberculosis » No response when individual not infected or vaccinated » Red, hard swelling develops in individuals previously infected or immunized
  55. 55. A positive tuberculin test
  56. 56. Allergic contact dermatitis • Cell-mediated immune response • Results in an intensely irritating skin rash Type IV Hypersensitivity: Clinical Manifestation • Triggered by chemically modified skin proteins that the body regards as foreign • Acellular, fluid-filled blisters develop in severe cases • Can be treated with glucocorticoids
  57. 57. Allergic contact dermatitis
  58. 58. Graft rejection • Rejection of tissues or organs that have been transplanted • Grafts perceived as foreign by a recipient undergo rejection Type IV Hypersensitivity: Clinical Manifestation rejection • Immune response against foreign MHC on graft cells • Rejection depends on degree to which the graft is foreign to the recipient » Based on the type of graft
  59. 59. Types of grafts Autograft Isograft Allograft Xenograft Genetically identical sibling or clone Genetically different member of same species
  60. 60. Summary
  61. 61. Auto-immune Disease The state in which the body’s immune systemThe state in which the body’s immune system fails to distinguish between ‘self’ and ‘non-self’ and reacts by formation of autoantibodies against own tissue.
  62. 62. Auto-immune Disease • Theories of Autoimmunity – Immunological factors – Genetic factors • increased expression of Class II HLA antigens • Evidence from increased familial incidence• Evidence from increased familial incidence – Microbial factors • Infection with microorganisms, particularly viruses (e.g. EBV infection), and less often bacteria (e.g. streptococci, Klebsiella) and mycoplasma • Types of Autoimmunity – Organ Specific – Organ non-specific
  63. 63. ORGAN NON-SPECIFIC - SYSTEMIC • Systemic lupus erythematosus • Rheumatoid arthritis • Scleroderma (Progressive systemic sclerosis) • Polymyositis-dermatomyositis• Polymyositis-dermatomyositis • Polyarteritis nodosa (PAN) • Sjögren’s syndrome • Reiter’s syndrome • Wegener’s granulomatosis
  64. 64. ORGAN SPECIFIC - LOCALISED • ENDOCRINE GLANDS – Hashimoto’s (autoimmune) thyroiditis – Graves’ disease – Type 1 diabetes mellitus – Idiopathic Addison’s • BLOOD CELLs – Autoimmune haemolytic anaemia – Autoimmune thrombocytopenia – Pernicious anaemia– Idiopathic Addison’s disease • ALIMENTARY TRACT – Autoimmune atrophic gastritis in pernicious anaemia – Ulcerative colitis – Crohn’s disease – Pernicious anaemia • OTHERS – Myasthenia gravis – Goodpasture’s syndrome – Primary biliary cirrhosis – Lupoid hepatitis – Membranous glomerulonephritis
  65. 65. Systemic Lupus Erythematosus (SLE) • Classical example of systemic autoimmune or collagen diseases • 2 forms of lupus erythematosus • Systemic or disseminated form – Acute and chronic inflammatory lesions widely scattered in the bodybody – Presence of various nuclear and cytoplasmic autoantibodies in the plasma • Discoid form – chronic and localised skin lesions – involving the bridge of nose and adjacent cheeks – Without any systemic manifestations. – Rarely, discoid form may develop into disseminated form.
  66. 66. Systemic Lupus Erythematosus (SLE)
  67. 67. Systemic Lupus Erythematosus (SLE)
  68. 68. Scleroderma (Progressive Systemic Sclerosis) • Skin disease characterised by progressive fibrosis • 2 main types • Diffuse scleroderma• Diffuse scleroderma – Skin shows widespread involvement – May progress to involve visceral structures • CREST syndrome
  69. 69. Scleroderma- Diffuse scleroderma
  70. 70. Sjogren’s syndrome • Sicca syndrome • Gougerot-sjorgen syndrome • Triad – Keratonjuctivitis sicca– Keratonjuctivitis sicca – Xerostomia – Rheumatoid arthritis • Along with SLE, polyarthritis nodosa, polymyositis or scleroderma Primary Sjorgen’s syndrome or SICCA complex Secondary Sjorgen’s Syndrome
  71. 71. Clinical features • 0.5-1% of population • Female >40 yrs, F:M = 10:1 • Children or young may be affected • Dryness of mouth and eyes – hypofunction of• Dryness of mouth and eyes – hypofunction of salivary gland and lacrimal glands • Painful, burning sensation of oral mucosa • Nose, larynx, pharynx, tracheobronchial tree and vagina additionally involved
  72. 72. Clinical presentation • Oral mucosa – Parchment like appearance – red, dry, tendered, smooth glazed – Difficulty in wearing dentures • Saliva – frothy • Angular cheilitis• Angular cheilitis • Disturbances of taste senation • Recurrent candidiasis – dorsum of tongue – red & atrophic mucosa – fissuring and labulations on surface (COBBLE-STONE) • Acute bacterial sialadenitis
  73. 73. Radiographic features • Sialography – Punctate – Cavitary defect – filled with radioopaque contrast media • ‘Cherry blossom’ or ‘branchless fruit laden‘branchless fruit laden tree’ – Contrast media extravasates through weakened salivary gland – Poor elimination of contrast media – over a month
  74. 74. Treatment • No satisfactory t/t • SYMPTOMATICALLY treated • Keratoconjuctivitis – Occular lubricant – artificial tears like methyl cellulose • Xerostomia• Xerostomia – Salivary subsitute • Extensive dental caries • Fluoridation and oral prophylaxis is indicated • Surgery not indicated unless the disease is cause discomfort to p/t • Radiotherapy – not recommended
  75. 75. HLA complex • Human Leucocyte Antigens • Determine one’s own tissue from non-self - histocompatibility • Immense importance so they are called• Immense importance so they are called major histocompatibility complex (MHC) or HLA complex • Most of MHC are located on a portion of chromosome 6 of all nucleated cells of the body and platelets
  76. 76. HLA complex • Class I MHC antigens – HLA-A, HLA-B and HLA-C – CD8+ i.e. T suppressor lymphocytes carry receptors for class I MHC • Class II MHC antigens: HLA-• Class II MHC antigens: HLA- D • Class III MHC antigens: complement system (C2 and C4) coded on HLA complex • not associated with HLA expression
  77. 77. Clinical Importance: HLA complex • Organ transplantation • Regulation of the immune system – Class I: function of cytotoxic T cells (CD8+ subpopulation) – Class II: function of helper T cells (CD4+ subpopulation). • Association of diseases• Association of diseases – Inflammatory disorders e.g. ankylosing spondylitis. – Autoimmune disorders e.g. rheumatoid arthritis, insulin dependent diabetes mellitus. – Inherited disorders of metabolism e.g. idiopathic haemochromatosis
  78. 78. Transplant Rejection • According to the genetic relationship between donor and recipient, transplantation of tissues is classified into 4 groups: – Autografts: donor and recipient is the same individual – Isografts: donor and recipient of the same genotype.– Isografts: donor and recipient of the same genotype. – Allografts: donor is of same species but of a different genotype. – Xenografts: donor is of a different species from that of the recipient • For transplant to be successful there must be matching of HLA complex
  79. 79. Transplant Rejection • The greater the genetic disparity between donor and recipient in HLA system - stronger and more rapid will be the rejection reaction • Besides the rejection reaction, a peculiar problem occurring especially in bone marrow transplantation is Graft-versus- host (GVH) reactionhost (GVH) reaction – Fever, – Weight loss & anaemia – Dermatitis, – Diarrhoea, – Intestinal malabsorption – Pneumonia – Hepatosplenomegaly
  80. 80. Mechanisms of Graft Rejection • Except for autografts and isografts, an immune response against allografts is inevitable. • Immunosuppressive drugs: survival of allografts in recipients possible. • Rejection of allografts involves both cell-• Rejection of allografts involves both cell- mediated and humoral immunity. • Types of Rejection Reactions – Hyperacute rejection – Acute rejection – Chronic rejection
  81. 81. HYPERACUTE REJECTION • Within minutes to hours of placing the transplant and destroys it. • Humoral antibody against donor-antigen • Cross-matching of the donor’s lymphocytes with• Cross-matching of the donor’s lymphocytes with those of the recipient before transplantation- reduced the frequency of hyperacute rejection. • Organ becomes swollen, oedematous, haemorrhagic, purple and cyanotic rather than gaining pink colour.
  82. 82. ACUTE REJECTION • Within a few days to a few months of transplantation • It may be – Acute humoral rejection: Extensive infiltration of lymphocytes (mainly T cells), a few plasma cells, monocytes and a few polymorphspolymorphs • damage to the blood vessels and there are foci of necrosis in the transplanted tissue – Acute cellular rejection • Poor response to immunosuppressive therapy, • Acute rejection vasculitis and foci of necrosis in small vessels
  83. 83. CHRONIC REJECTION • Repeated attacks of acute rejection • May develop slowly over a period of months to a year • Immunologic or ischaemic• Immunologic or ischaemic • Ex: Renal transplant - rising serum creatinine levels – intimal fibrosis – interstitial fibrosis and tubular atrophy – may develop glomerulonephritis

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