Igg and igm based immunopathological reaction reaction of hypersensitivity type ii
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IgG and IgM based immunopathological reaction (reaction of hypersensitivity type II). = antibody-dependent. antibodies produced by the immune response bind to antigens on the patient's own cell surfaces. intrinsic ("self" antigen, innately part of the patient's cells).

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IgG and IgM based immunopathological reaction (reaction of hypersensitivity type II).

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Igg and igm based immunopathological reaction reaction of hypersensitivity type ii

IgG and IgM based immunopathological reaction (reaction of hypersensitivity type II).

  • = antibody-dependent

  • antibodies produced by the immune response bind to antigens on the patient's own cell surfaces

  • intrinsic ("self" antigen, innately part of the patient's cells)

  • extrinsic (absorbed onto the cells during exposure to some foreign antigen, possibly as part of infection with a pathogen)

  • These cells are recognized by macrophages or dendritic cells which act as antigen presenting cells, this causes a B cell response where antibodies are produced against the foreign antigen.


Igg and igm based immunopathological reaction reaction of hypersensitivity type ii1

IgG and IgM based immunopathological reaction (reaction of hypersensitivity type II)

  • Autoimmune hemolytic anemia

  • Goodpasture's syndrome

  • Autoimmune pernicious anemia

  • Immune thrombocytopenia

  • Transfusion reactions

  • Myasthenia gravis

  • Rheumatic fever

  • Acute transplant rejection


Immun e complex based immunopathological reaction reaction of hypersensitivity type iii

Immune complex based immunopathological reaction (reaction of hypersensitivity type III)

  • occurs when antigens and antibodies are present in roughly equal amounts, causing extensive cross-linking

  • large immune complexes that cannot be cleared are deposited in vessel walls and induce an inflammatory response

  • the reaction can take hours, days, or even weeks to develop


Immun e complex based immunopathological reaction reaction of hypersensitivity type iii1

Immune complex based immunopathological reaction (reaction of hypersensitivity type III)

Some clinical examples:

  • Rheumatoid arthritis

  • Immune complex glomerulonephritis

  • Serum sickness

  • Subacute bacterial endocarditis

  • Systemic lupus erythematosus

  • Farmer's lung (Arthus-type reaction)

  • Polyarteritis nodosa


Primary immunodeficiency

PRIMARY IMMUNODEFICIENCY

clinical manifestactions

examples


Immunodeficiency

IMMUNODEFICIENCY

  • Primary immunodeficiencies

    - congenital, genetically defined disorders

    - onset of symptoms - predominantly at an early

    age

  • Secondary immunodeficiencies

    - caused by chronic infections, irradiation,

    injuries, immunosupression therapy, surgery,

    stress

    - disorders appear at any age


Immunideficiency

IMMUNIDEFICIENCY

  • Humoral deficiency disorders

    = the B cell deficiency disorders – the qualitative or quantitative defects of the B cells, present 70% of IDs

  • T cell deficiency disorders and the combined B-cell and T-cell deficiency disorders (20%) – group of the qualitative or quantitative defects of the T and B cells

  • Phagocytic celldisorders– group of the qualitative or quantitative defects of the fagocytic cells (10%)

  • Complement disorders – caused by the deficiency of the complement components or functions (<1%)


Major clinical features

MAJOR CLINICAL FEATURES

  • Humoral deficiency disorders - manifest as the recurrent bacterial sinopulmonary and gastrointestinal infections

    - caused by streptococcus, staphylococcus, haemophilus, begin when infants are 5-9 months of age

  • T cell disorders - manifest as the recurrent bacterial, fungal and viral respiratory and gastrointestinal infection

  • Complement disorders – are associated with increased incidence of the infections and autoimmune diseases and with edema in the case of hereditary angioedema

  • Phagocytic celldisorders – characterized by recurrent infections caused by various organisms incluging abscesses, purulent skin infections, granulomatousinflammations


Humoral deficiency disorders

HUMORAL DEFICIENCY DISORDERS

  • Bruton’s X-linkedhypogamaglobulinemia

  • CVID - Common Variable ImmunoDeficiency

  • Selective immunoglobulin A deficiency <0,07 g/l


Bruton s x linked hypogamaglobulinemia

Bruton’s X-linkedhypogamaglobulinemia

  • the genetic defect on the X chromosome leads to the defective function of a tyrosine kinase in the B cells

  • This defect result in a block of the pre-B cells maturation into the B cells with surface IgM

  • the immunologic findings: < 2% circulating B cells

    - low serum levels of all classes of immunoglobulins

    - number and function of T cells are intact

    - pre-B cells are in the bone marrow

  • features : begining from 5-9 months of age

    - manifests as recurrent bacterial sinopulmonary and gastrointestinal infection caused by streptococcus, staphylococcus, haemophilus, meningococcus, salmonella, campylobacter, giardia

  • Treatment consists of life-long intravenous pooled human gammaglobulin replacement and antibiotics.


Common variable immunodeficiency

Common VariableImmunoDeficiency

  • the B cell functional disorder characterized by the normal number

    of the B cells, low levels of IgG and IgA, a poor response to all

    vaccines and decrease of the T cells (CD4+) number and function

  • the symptom’s onset between 2ndand 3rddecade

  • the clinical features:

    - recurrent respiratory tract infections (pneumonia), cutaneous and

    gastrointestinal infection

    - disease is accompanied by occurrence of the granulomas,

    lymphadenopathy, splenomegaly

  • Treatment consist of the intramuscular or intravenous

    gammaglobulin replacement.


Selective deficiency of iga

Selective deficiency of IgA

  • level of IgA up to 0,05 g/l, age > 4 years

  • the most frequent primary ID

    - stem cell defect

    - repeated infections of respiratory tract

    - susceptibility to autoimmune disorders, malignant disorders, allergy

    - contra-indication of administration of drug with IgA


T cell deficiency disorders

T cell deficiency disorders

  • DiGeorge syndrome

    - the genetic defect on the chromosome 22 leads to disorder of

    development of 3rdand 4thbranchial pouch with congenital

    hypoplasia of both the thymus and parathyroid glands

    - patients suffer from disorder of pre-thymocytes maturation due to

    absence/hypoplasia of thymus

    - syndrome CATCH 22: cardiac defects, abnormal facies, thymic

    hypo/aplasia, cleft palate, hypocalcemia, deletion 22q11.2

    - the symptom’s onset soon after the birth – hypocalcemic spasms

    andmanifestations of congenital heart disease

    - treatment: symptomatic, transplantation of a thymus


Primary fagocytic cell defects

PRIMARY FAGOCYTIC CELL DEFECTS

Chronic granulomatous disease

- X- linked recesive disorder - leads to defect in neutrophilic cytochrome b with suppresion of intracellular killing of ingested microorganisms

- normal number of leucocytes

- infection of catalase-positive bacterias

- symptoms appear in the first year of age: pyogenic cutaneous

infections, abscesses, granulomas in many organs, pyogenic

lymphadenitis

- treatment: long-term ATB administration, interferon gamma,

corticosteroids


Complement deficiency

COMPLEMENT DEFICIENCY

  • C2, C3, C4 complement components deficiencies

    - lead to an impaired opsonization, susceptibility to infections,

    autoimune diseases

  • C6, C7, C8, C9complement components deficiencies

    - lead to the autoimmune diseases – SLE, RA, sclerodermia and to

    the neisserial infection

  • MBLdeficiencies

    - lead to the respiratory infections and susceptibility to the

    autoimune and allergy diseases

  • Treatment: vaccination, ATB


Hereditary angioedema

HEREDITARY ANGIOEDEMA

pathophysiology

clinical manifestations

treatment


Hereditary angioedema1

HEREDITARY ANGIOEDEMA

  • the congenital AD complement disorder cased by the defect on the chromosome 11

  • leads to absence orfunctional deficiency of C1-inhibitor

  • C4 a C2 complement components show a low level

    during atack

  • Type I - occurs in 85%

    - an absence of C1-inhibitor

  • Type II - occurs in 15%

    - a functional deficiency of C1-inhibitor

  • Secondary - SLE, lymfoma


Hereditary angioedema2

HEREDITARY ANGIOEDEMA

  • C1 esterase inhibitor deficiency leads to uncontrolled C1 activity and resultant production of a kinin that increases capillary permeability

  • Clinical feature: transient recurrent localized edema

  • the triggering factors: injuries or surgical/stomatological operations

  • more offen occures in pregnancy

  • laryngeal edema could be life-threatening, immediate treatment is necessary !


Treatment

TREATMENT

  • Preventive – consist of an administration of androgens, a-fibrinolytics

    - before operation is necessary C1-INH concentrate or a

    fresh frozen plasma administration

    - stomatology procedures are performed in hospital

  • Immediate - C1-INH concentrate or fresh frozen plasma administration

  • tracheotomy in severe larynx edema

  • treatment with ACE inhibitorsis contraindicated


Acquired immunodeficiencies

ACQUIRED IMMUNODEFICIENCIES

causes

mechanisms involved

AIDS


Acquired immunodeficiencies1

ACQUIRED IMMUNODEFICIENCIES

  • Acute and chronic viral infections – EBV, CMV, herpetic virus, influenza, HIV

  • Metabolic disorders– diabetes, renal failure, disorder of liver function

  • Autoimmune diseases– autoantibodies against immunocompetent cells (neutrophils, lymphocytes)

  • Allergic diseases

  • ChronicGIT diseases, nephrotic syndrome

  • Malignant diseases(leukemia, lymphoma, myeloma)

  • Hypersplenism/asplenia, splenectomy – deficiency in generation of antibodies against encapsulated microorganisms(Pneumococcus, Neisseria)

  • Burn, postoperative status, injuries

  • Severe nutritional disorders, chronic stress

  • Drug induced immunodeficiencies(chemotherapy), immunosupression

  • Chronic exposureto harmfulchemical substances, ionizing radiation


Igg and igm based immunopathological reaction reaction of hypersensitivity type ii

AIDS

  • Acquired ImmunoDeficiency Syndrom

    - caused by a retrovirus called human immunodeficiency virus

    - current incidence 40 mil.people, predominantly in central Africa, CZ – about 1000 infected people

  • viral transmission occurs through:

    - sexual intercourse

    - contact with blood

    - transplacentally, during the birth process or

    through a breast milk


Virus hiv 1

VIRUS HIV-1

  • virion is consisted of a capside with marrow protein - p24 and RNA

  • RNA is copied into double-stranded DNA using reverse transcriptase

  • virus integrates to the human cell genome and arise a provirus

  • an activation of provirus leads to the replication of viral nuclear acid and genesis of a virion that goes through the cell membrane and caused the lysis of cell


Primary infection

PRIMARY INFECTION

  • Infection - begins by HIV-1 with a tropism for macrofages:

    - the membrane molecules of dendritic cells bind

    glycoproteins on HIV-1 surface and transport viruses to the lymphatic nodes (LN), where activated T cells are infected viruses are replicated in the lymphatic nodes and transfer to the blood

  • features: malaise, fever, pain of muscles and joints, sweating, loss of appetite, vomiting, diarrhoea, rash, lymphadenopathy

  • Immunological findings: elevated C-reactive protein, lymphopenia, decrease of CD4+ cells

  • specific antibodies against HIV-1 don‘t generate

  • identification of viruses is performed by PCR or by the evidence of viral protein p24 presence


Asymptomatic periode

ASYMPTOMATIC PERIODE

  • asymptomatic period – HIVs-1 with a tropism for macrophages are changed into viruses with a tropism for T cells and demage T cells (CD4+)

  • viruses replicate in cell secondary lymphatic organs

    - the period can last a several years

  • lasting depends on:

    - virus doses and virulence

    - an individual condition of immune system an infected

    person

    - an acceleration occures by repeated infection of

    different HIVs


Igg and igm based immunopathological reaction reaction of hypersensitivity type ii

AIDS

  • AIDS- Related Complex (ARC) presents with lymphadenopathy and comes before fully developed AIDS

  • Clinical features of AIDS :

    - candidiasis of mouth and esophagous

    mucose, colpitis

    - oral leucoplakia, opportunistic infections

    - Kaposi sarcoma, non-Hodgkin‘s lymfoma


Vaccine

VACCINE

  • development of a vaccine is unsuccessful

    due to:

    - unsuccesful searching for a dominant viral antigen

    - variability of the viruses HIV-1 in the course of time

    - absence of an animal experimental model (even the

    primate‘s infection course isn‘t identical with human)


Treatment1

TREATMENT

  • Inhibitors of reverse transcriptase - 2 types

    +

  • Inhibitor of viral protease

    =

  • Therapy result to the inhibition of DNA synthesis, stop the progress of the disease and prolong the life of HIV infected persons


Immunoglobulin replacement therapy

IMMUNOGLOBULIN REPLACEMENT THERAPY

Indication

Contra-indication

Adverse reaction


Ivig is approved for treating

IVIG is approved for treating

  • X-linked Bruton agammaglobulinemia

  • Common Variable ImmunoDeficiency

  • others


Contra indications

CONTRA-INDICATIONS

  • Repeated severe side effects

  • Selective IgA deficiency with anaphylactic reaction to immunoglobuline

  • Severe acute infection


Ig administration

IG ADMINISTRATION

  • Intramuscullar – maximum dose 1,5 g IgG/ week

  • Subcutaneous – total dose/month 400mg/kg, administration every week

  • Intravenous - 400 mg/kg/month


Autoimmune disorders

AUTOIMMUNE DISORDERS

examples


Clinical categories

CLINICAL CATEGORIES

  • systemic

    - affect many organs and tissue

  • organ localised

    - affect predominantly one organ accompained by affection of other organs (nonspecific bowel diseases, celiatic disease, AI hepatitis, pulmonary fibrosis)

  • organ specific

    - affect one organ or group of organs connected withdevelopment or function


Examples of systemic autoimmune diseases

EXAMPLES OF SYSTEMIC AUTOIMMUNE DISEASES

examples

autoantibodies


Systemic autoimmune diseases

SYSTEMIC AUTOIMMUNE DISEASES

  • Systemic lupus erythematosus

  • Rheumathoid arthritis

  • Sjögren‘s syndrome

  • Dermatopolymyositis

  • Systemic sclerosis

  • Mixed connective tissue disease

  • Antiphospholipid syndrome

  • Vasculitis

  • Sarcoidosis


Systemic lupus erythematosus

SYSTEMIC LUPUS ERYTHEMATOSUS

  • chronic, inflammatory, multiorgan disorder

  • predominantly affects young women

  • autoantibodies react with nuclear material and attack cell function, immune complexes with dsDNA deposit in the tissue

  • general symptoms: include malaise, fever, weight loss

  • multiple tissueare involved including the skin, mucosa, kidney, joints, brain and cardiovascular system

  • characteristic features: butterfly rash, renal involvement, CNS manifestation, pulmonary fibrosis


Diagnostic tests

DIAGNOSTIC TESTS

  • a elevated ESR (erythrocyte sedimentation rate), low CRP, trombocytopenia, leukopenia, hemolytic anemia, depresed levels of complement (C4, C3), elevated serum gamma globulin levels


Autoantibodies

AUTOANTIBODIES

  • Autoantibodies: ANA, dsDNA (double-stranged), ENA (SS-A/Ro, SS-A/La), Sm, against histones, phospholipids


Rheumatoid arthritis

RHEUMATOID ARTHRITIS

  • chronic, inflammatory joint disease with systemic involvement

  • predominantly affects women

  • characterized by an inflammatory joint lesion in the synovial membrane, destruction of the cartilage and bone, results in the joint deformation

  • clinical features: arthritis, fever, fatigue, weakness, weight loss

  • systemic features: vasculitis, pericarditis, uveitis, nodules under skin, intersticial pulmonary fibrosis

  • diagnostic tests: elevated C- reactive protein

    and ESR, elevated serum gammaglobulin levels

    - autoantibodies against IgG = rheumatoid factor

    (RF), a-CCP (cyclic citrulline peptid), ANA

    - X-rays of hands and legs- show a periarticular

    porosis, marginal erosion


Antiphospholipid syndrome

Antiphospholipid syndrome

  • autoimmune disease characterized by vein and arterial thrombosis, repeated abortions

  • accompanied by anti-phospholipid autoantibodies (APA) and antibodies against β2-glykoprotein I


Examples of organ specific autoimmune diseases

EXAMPLES OF ORGAN- SPECIFIC AUTOIMMUNE DISEASES

diseases

autoantibodies


Organoleptic autoimmune diseases

ORGANOLEPTIC AUTOIMMUNE DISEASES

  • Ulcerative colitis

  • Crohn‘s disease

  • Coeliac disease

  • Autoimmune hepatitis

  • Primary biliary cirhosis

  • Primary sclerotic cholangoitis

  • Pulmonary fibrosis


Ulcerative colitis

Ulcerative colitis

  • chronic inflammation of the large intestine mucose and submucose

  • features: diarrhea mixed with blood and mucus

  • extraintestinal features (artritis, uveitis)

  • autoantibodies against pANCA, a- large intestine


Crohn s disease

Crohn‘s disease

  • the granulomatous inflammation of all intestinal wall with ulceration and scarring that can result in abscess and fistula formation

  • the inflammation of Crohn's disease the most commonly affects the terminal ileum, presents with diarrhea and is accompanied by extraintestinal features - iridocyclitis, uveitis, artritis, spondylitis

  • antibodies againstSaccharomyces cerevisiae (ASCA), a- pancreas


Coeliac disease

Coeliac disease

  • a malabsorption syndrome characterized by marked atrophy and loss of function of the villi of the jejunum

  • inflammatory bowell disease arise from gliadin exposition

  • autoantibodies against endomysium, the most specific = tissue transglutaminaze; antibodies against gliadin are nonspecific

  • biopsy of the jejunum with findings of the villi atrophy


Organ specific autoimmune diseases

ORGAN SPECIFIC AUTOIMMUNE DISEASES

  • Autoimmune endocrinopathy

  • Autoimmune neurological diseases

  • Autoimmune cytopenia

  • Autoimmune cutaneous diseases

  • Autoimmune eye diseases


Autoimmune endocrinopathy

AUTOIMMUNE ENDOCRINOPATHY

  • Hashimoto‘s thyroiditis

  • Graves-Basedow disease

  • Postpartum thyroiditis

  • Diabetes mellitus I. type

  • Addison‘s disease

  • Autoimmune polyglandular syndrome

  • Pernicious anemia


Hashimoto s thyroiditis

Hashimoto‘s thyroiditis

  • thyroid disease result to hypothyroidism on the base of lymphocytes and plasma cells infiltrate

  • autoantibodies against thyroidal peroxidase (a-TPO) and/or against thyroglobulin (a-TG)


Grave s disease

Grave‘s disease

  • thyrotoxicosis from overproduction of thyroid hormone (patient exhibit fatigue, nervousness, increased sweating, palpitations, weight loss,

    exophtalmos)

  • autoantibodies against thyrotropinreceptor,

    autoantibodies cause thyroid cells proliferation


Diabetes mellitus insulin dependent

Diabetes mellitus (insulin- dependent)

  • characterized by an inability to process sugars in the diet, due to a decrease in or total absence of insulin production

  • results from immunologic destruction of the insuline- producing β-cells of the islets of Langerhans in the pancreas

  • autoantibodies against GAD- glutamic acid decarboxylase = primary antigen), autoantibodies anti- islet cell, anti- insulin

  • islets are infiltrated with B and T cells


Autoimmune neuropathy

AUTOIMMUNE NEUROPATHY

  • Guillain-Barré syndrome (acute idiopathic polyneuritis)

  • Myasthenia gravis

  • Multiple sclerosis


Myasthenia gravis

Myasthenia gravis

  • chronic disease resulting from faulty neuromuscular transmission

  • characterized by muscle weakness and fatigue

  • the muscle weakness and neuromuscular dysfunction result from blockage and depletion of acetylcholin receptors at the myoneural junction

  • immunological findings: autoantibodies against Ach receptors

  • ptosis of the eye


Multiple sclerosis

Multiple sclerosis

  • chronic demyeline disease with abnormal reaction T cells to myeline protein on the base of mimicry between a virus and myeline protein

  • features: weakness, ataxia, impaired vision, urinary bladder dysfunction, paresthesias, mental abberations

  • autoantibodies against MOG (myelin-oligodendrocyte glycoprotein)

  • Magnetic resonance imaging of the brain and spine shows areas of demyelination

  • The cerebrospinal fluid is tested for oligoclonal bands, can provide evidence of chronic inflammation of the central nervous system


Immunosupression

IMMUNOSUPRESSION

non-specific treatment

examples of drugs

indication

risks


Immunosuppressants

Immunosuppressants

  • are drugs that inhibit or prevent activity of the immune system

  • They are used in immunosuppressive therapy to:

  • Prevent the rejection of transplanted organs and tissues

  • Treat autoimmune diseases

  • Treat some other non-autoimmune inflammatorydiseases (allergic asthma, atopic eczema)


Glucocorticoids

Glucocorticoids

  • suppress the cell-mediated immunity

  • cytokine production

  • suppress the humoral immunity

  • side-effects: hypertension, dyslipidemia, hyperglycemia, peptic ulcers, osteoporosis, disturbed growth in children


Igg and igm based immunopathological reaction reaction of hypersensitivity type ii

Drugs affecting the proliferation of both T cells and B cells - Cyclophosphamide, Methotrexate, Azathioprine, Mycophenolate mofetil

Drugs blocking the activation of lymphocytes – Tacrolimus, Sirolimus, Cyclosporin A

Monoclonal antibodies - Daclizumab


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