KUSMARDILAB. OF IMMUNOPATHOLOGYDEPT. OF ANATOMICAL PATHOLOGYFACULTY OF MEDICINE UNIVERSITY OF INDONESIA

KUSMARDILAB. OF IMMUNOPATHOLOGYDEPT. OF ANATOMICAL PATHOLOGYFACULTY OF MEDICINE UNIVERSITY OF INDONESIA

THE SCOPE OF IMMUNOPATHOLOGY

I. ESSENTIAL IMMUNOLOGYII. HYPERSENSITIVITYIII. IMMUNODEFICIENCYIV. AUTOIMMUNE DISEASE

AntigenTISSUESCELLS --------Tumour --------Parasitic --------Fungi --------Bacteria --------Virus --------Molecules-----Protein -----Carbohydrate -----Lypoprotein

THE COMPONENT OF THE IMMUNE SYSTEMCELLULAR LYMPHOCYTES MACROPHAGES K (NK) CELLS POLYMORPHSSOLUBLE HUMORAL IMMUNOGLOBULIN COMPLEMENT LYMPOKIN

THE ORIGIN OF THE CELLULAR COMPONENT OF THE IMMUNE SYSTEM

STEMCELLSLYMPHOIDB CELLS T CELLSTHTSTDTHTCMYELOIDMACROPHAGESMONOHISTIGRANULOCYTESEONETBAMAST

THE CHARACTERISTIC OF IMMUNE RESPONSE

1. SELF RECOQNATION

2. SPECIFICITY

3. MEMORY

NATURAL IMMUNITY

IMMUNITYNONSPECIFICPHYSICAL LYSOZYMECHEMICAL COMPLEMENTSPECIFIC INTERFERONCELLULER POLYMORPS MO

THE SPECIFIC IMMUNE RESPONSEPRIMARY RESPONSE ANTIGEN DISEASE (FIRST ATTACK) IMMUNE SPECIFIC REACTION IMMUNE RESPONSE

RECOVERY DESTRUCTION SPECIFIC OF ANTIGEN IMMUNE STATE

SECONDARY RESPONSE(SUBSEQUENT CONTACT) ANTIGEN SPECIFIC MEMORY AND RECOGNITION OF ANTIGEN

ALMOST IMMEDIATE RAPID ACTIVATION OF IMMUNE REACTION IMMUNE RESPONSE

NON DISEASE VERY RAPID DESTRUCTION SPECIFIC IMMUNE OF ANTIGEN STATE ENHANCED

APC AgMHC II APC Ag TH TH THmemoryIL-2R BPlasma cellIL-2 TcBCGF BCDF

IMMUNE REACTION

1. PRECIPITATION of a soluble Ag

2. AGGLUTINATION of a particulate Ag (e.g. bacteria)

3. ANTITOXIC EFFECT:The Ag/Ab combination neutralised the toxic activity Toxic molecule Anti-toxin(Ig)4. ENHANCEMENT of the nonspecific immune responsea. Phagocytic activityb. Complement activitation

Phagocytic activity Ag

AgAgAgAg/AbmacrophageEfficient phagocytosis

COMPLEMENT ACTIVATIONActivation-classical pathway Ag/Ab

1 2 3 4 5 6 7 8 9 Fc(IgM or Ig G)Activation-alternate pathway,endotoxin

Bactericidal effectBacteriumPunched out holes interget cell membraneRBCCytolytic effect

HYPERSENSITIVITY

TYPE I

ANAPHYLACTIC/ALLERGY

ASMA, RINITIS, URTIKARIA

IgE

TYPE II

CYTOTOXIC

RX TRANFUSI, Rh, OBAT

IgG, IgM

TIPE III

RX KOMPLEKS IMUN

GLOMERULONEFRITIS

IgG

TIPE IV

TIPE LAMBAT, DELAYED TYPE, CELL MEDIATED IMMUNITY

DERMATITIS KONTAK, TUBERKULIN, GRANULOMA

LIMFOSIT T

Such cross-linking leads to rapid degranulation (60-300 secs) of the mast cells and the release of primary inflammatory mediators stored in the granules. These mediators cause all the normal consequences of an acute inflammatory reaction - increased vascular permeability, smooth muscle contraction, granulocyte chaemotaxis and extravasation etc. Mast cell activation via Fc epsilonRI also leads to the production of two other type of mediators. These secondary mediators, unlike the stored granule contents, must be synthesised de novo and comprise arachadonic acid metabolites (prostaglandins and leukotrienes) and proteins (cytokines and enzymes).

HIPERSENSITIVITAS TIPE I

IgE = REAGIN, AFINITAS vs MAST & BASOFIL

IgG4, AFINITAS RENDAH vs MAST & BASOFIL

First exposure Formation to Ag of Ig E

Second exposure to AgFixation of IgE to mast cells and basophils by Fc fragmentDegranulation of mast cellRelease of mediators and vasoactive subtancesAg/Ab reaction on surface of mast cellType 1 Anaphylaxis, atopy, allergy

Antigens and allergensmost potent antigenvery large molecules molecular weights from 15 to 40,000common allergens : ATS, Penc, Bee venom, etc.AntibodyIgEPlasma cells forming Ig E : tonsil, adenoid, bronchi, GI tract, Urinary Bladder.Mast cells In the same areas the IgE-producing plasma cells, plus skin, uterus and synovial membranes

Clinical example of type I reactionAnaphylactic shock Hay Fever Asthma1st injection of horse serum 1st contact with 1st contact(ATS), penc bee sting grass pollen horse mite dust General sensitivition local sensitivition animal dander conjunctiva and local sensitivition passage of bronchi2nd injection 2nd contact 2nd contactbronchial irritation of Bronchial constrictionconstriction conjunctiva difficult breathingperhaps a skin rashmay be fatal

Ag (cell surface) specific Ab combination produces

Complement Increased phagocyticIncreasedactivation activity (opsonic effect) killercell activity

DESTRUCTION OF CELL

Type III- Immune complex (Arthus) type Vasoactive amines Effect on Ag/Ab Complement (anaphilatoxin) vessel wall activationPolymorphs(chemotaxis)Platelet Thrombosisaggregation destruction of renal glomeruli IgG or IgM

Type IV-Cell-mediated (delayed)

Usually local

Sensitised T cells

Skin reaction to chemical contact dermatitis

IMMUNE DEFICIENCY STATES(1) THE SPESIFIC SYSTEM humoralcell-mediated(2) THE NON-SPESIFIC SYSTEM phagosytescomplementPrimary (inhereted) deficienciesB cell, T cell, B and T cell deficits associated with recurring infectionsSecondary deficienciesT cell activityB cell deficit

Malnutrition- particularly with protein deficiencyLatrogenic effect - e.g. immunosuppressorrs : cytotoxics corticosteroidsInfections - acute viral, chronic bacterial chronic protozoal, e.g. malariaChronic debilitating disease - e.g. renal failure : diabetes millitusMalignant disease - e.g. lymphoma, Hodkins disease IMPAIRED IMMUNITYINFECTION often OPPORTUNISTICcommon predisposing conditions

AGAMAGLOBULINEMIA (PENY. BRUTON)

X-LINKEDHAMPIR SLL PD PRIABELUM JELAS HINGGA 6 BLN (Ig ibu

The gene Bruton's tyrosine kinase (Btk) plays an essential role in the maturation B cells in the bone marrow, and when mutated, immature pre-B lymphocytes are unable to develop into mature B cells that leave the bone marrow into the blood stream.

SINDROME DiGEORGE, HIPOPLASIA TIMUS

KANTONG FARING III & IV (-) TIMUS & PARATIROID (-)

TIMUS (-/RUDIMENTER) LIMFOSIT T(-/ )

INFEKSI JAMUR, VIRUS,BAKTERI

PARATIROID (-) HIPOKALSEMIA TETANI

TANSPLANTASI TIMUS

IMMUNE DEFICIENCY STATES-AIDSInfection Latent stagesStages of opportunistic No initial (months-years) infection and tumours symptoms (1-2 years) Virus present in Infection opportunistic limphoncytes others - no signs malignant Kaposis - persistent limph tumours sarcoma node enlargement lymphomas

Simplified Life Cycle of the Human Immunodeficiency Virus

AIDS - ASSOCIATED DISEASE

1. Brain Tumours Inflamation2. Mouth, Trachea, Oesophagus Candidiasis3. Lung Pneumocystis carinii infection Fungal infections, Tuberculosis4. Intestines Protozoal, Salmonella infection5. Skin Kaposis sarcoma, Fungal infections, Herpes Zoster

BLOOD CHANGES OF AIDS

Immunoglobulin may be elevated in the early stagesT4 (helper) lymphocytes are severely reducedT4/T8 ratio reversed

Human Immunodeficiency Virus Infection. A 7-year-old girl with human immunodeficiency virus (HIV) infection and a Kaposi sarcoma lesion.

ETIOLOGY

1. Unknown2. Multifactors

Figure1.Requirements for the development of an autoimmune disease. The immune response of a genetically predisposed individual to an environmental pathogen, in association with defects in immunoregulatory mechanisms, can lead to the development of an autoimmune disease. The importance of the single components represented in this Venn diagram may vary between individuals and diseases. However, the appearance of an autoimmune disease requires the convergence of all three components. T, T cell; B, B cell; DC, dendritic cell.Bob Crimi

I. Expose of sequested antigenII. Homeostatic disturbance

I. Expose of sequested antigenisolated antigen(e.g. sperm, lens)

nonself antigen

Ig antispermIg antilens

virus A. self antigen self antigen modification neo-Ag failure of Th recognation autoactivity autoimmune diseases

B. Nonself Ag (Streptococcus ~myocard cells )

anti myocard

MHC II normal: *on the cell surface of: mo, B cell, T cell, dendritic, langerhans*in the cytoplasm of: other cells Patologic:MHC on the surface of tyroid cells vs anti HLA_DR

Graves tyrotoxicosis

1. TYROID CELL Hashimotos, Graves disease2. PARIETAL CELLS of stomach Pernicioous anaemia3. RBC Haemolitic anaemia4. PANCREATIC CELL Type I DM5.ADRENAL CORTICAL CELLS Addisons disease6. PARATHYROID CELLS Primary hypoparathyroidism7. ACETYLCHOLINE RECEPTOR Myasthenia gravis

1. MITOCHONDRIA of liver => Prim. Biliary cirrhosis2.SMOOTH MUSCLE of liver =>Chronic active hepatitis (CAH)3.NUCLEAR CONSTITUENT of liver => CAH of skin &muscle =>conn. Tissue dis.4. Ig in the kidney, blood vessel, joint => RA, SLE

GANGGUAN HEMATOPOETIC

Hematopoesis:

proses pembentukan sel darah dan pematangannya.

Ganguan Hematopoesis :gangguan pada proses pembentukan sel darah maupun proses pematangannya, meliputi sel darah merah, sel darah putih, sistem koagulasi

gangguan hematopoetik:1. Pada sumsum tulangMisal: reticulin fibrosis, myelofibrosis, dll

2. Pada sel darah Misal: anemia

SEL DARAH MERAHberbentuk bulat, bikonkaf shg dapat menampung oksigen sebanyakbanyaknya.tidak berintidiameter 8 mtebal 2 mbanyak mengandung haemoglobin (02 berikatan dengan Hb lbh banyak di bagian tepi daripada bagian tengah. Hb memberikan warna merah pacla sel darah.

SEL DARAH MERAHFungsinya:1. Alat transport yang membawa zat yang cliperlukan oleh sel/jaringan, mis: oksigen, makanan, dan vitamin.

2. Membawa zat-zat yang tidak diperlukan tubuh untuk dikeluarkan dari tubuh, misal COz, senyawa nitrogen, dan racun.

3. Perbaikan saluran-saluran

Sumsum Tulang (Non) Patologis1. Hipersellular

peningkatan bentuk (membesar) salah satu atau lebih sel.

Contoh: Granolocytic hyperplasia non patologi sediaan hapus darah tepi, bentuk sel granulosit menjadi lebih besar daripacla normal sebagai respon karena memfagositosis mikroorganisme.

Sumsum Tulang (Non) Patologis2. Aplasia atau hipoplasia

Kekurangan/ketiadaan bentuk (mengecil) salah satu atau lebih sel.

Penyebab: idiopatik (tdk diketahui pasti)Latrogenik (salah penatalaksanaan)Obat-obatan

Sumsum Tulang (Non) Patologis3. Folikel Limfoid

Pembentukan folikel di dalam limfoid, terjadi pada orang dewasa.

Penyebab: konsumsi obat yang berpengaruh pada sumsum tulang spt antikanker (siklofosfamid), kloramfenikol

Sumsum Tulang (Non) Patologis4. Fibrosis Retikulin Peningkatan jumlah retikulin (kolagen tipe III).

5.MyelofibrosisPeningkatan jumlah kolagen

6. OsteosklerosisProliferasi jaringan tulang

AnemiaKeadaan dimana jumlah RBC total berkurang

Patofisiologi:Kebanyakan karena hipoproliferasi RBC, menyebabkan gangguan bentuk dan jumlah.

Sedikit karena destuksi RBC berlebihan, biasanya jumlah normal tapi cepat lisis (hemolitik), akibat infeksi Plasmodium (malaria), cacing pita.

AnemiaPengaruh anemia: Anoksia, hipoksia

Perubahan metabolisme aerob menjadi anaerob ATP sedikit letih/lesu.

Banyakdihasilkan radikal bebas.

Dihasilkan asam laktat pegal, letih.

Kompensasi tubuh melawan anemia:

Penurunan afinitas Hb-O2 DeoksiHb produksi 2,3 difosfogliserat.

Redistribusi aliran darah: vasokontriksi pembuluh darah pada organ yang tidak vital, untuk mensuplai darah pada organ yang vital.

Peningkatan curah jantung.

Tanda dan Gejala AnemiaKehilangan 20% darah dari vol. total.Sulit nafas krn oksigen kurang.Letih/lesu karena metabolisme anaerob.Sakit kepala krn darah ke otak kurang.Hypotensi.Syncope (sempoyongan).Takikardi (denyut jantung meningkat).Pucat pada kulit, kuku, wajah krn sekresi bilirubin meningkat.

Klasifikasi Anemia1. Bentuk Sel/ sitometrikA. normokrom pada normositik anemiaB. hipokrom pada mikrositik anemiaC. Normokromik pada makrositik anemia2. EritrokinetikA. hemolisis B. Hemoragi3. Biokimia

1. Bentuk Sel/ sitometrikA. normokrom normositik anemiaWarna, bentuk, jumlah RBC normal.Hb normal.Penderita menunjukkan gejala anemia spt lelah, pucat, lemah, sakit kepala, hipotensi.Tjd pada: anemia penyakit kronik, anemia hemolitik spt pad mens, anemia akut krn perdarahan, anemia aplastis.

1. Bentuk Sel/ sitometrikB. hipokrom pada mikrositik anemia Warna sel pudar, bentuk sel mengecil, jumlah RBC berkurang.Hb berkurang.Tjd pada: anemia defisiensi Fe, Thalasemia, anemia krn penyakit kronis.

1. Bentuk Sel/ sitometrik C. Normokromik pada makrositik anemiaWarna sel normal, bentuk sel membesar, jumlah RBC normal.Hb normal.Tjd pada: anemia defisiensi vit B12, anemia defisiensi folat.

2. Eritrokinetik Hemolisis Destruksi RBC berlebihan krn infeksi (co: cacing, malaria)

B. HemoragiKehilanagn RBC dari pembuluh darah krn perdarahan akibat faktor mekanik/ kecelakaan.

3. Biokimia Kekurangan enzim glukosa 6 fosfat dehidrogenase.

Orang negro dg infeksi sal kemih + kloramfenikol/sulfonamid ggn sintesis DNA anemia hemolitik.B. Kekurangan kofaktor spt Fe, Vit B12

Bleeding and thrombotic disordersBleeding may result from abnormalities:

Platelets Blood vessels walls Coagulation

Platelet Disorders1. Trombocytopenia normal : 150.000-350.000/l abnormal:

Platelet Disorders2. ThrombocytosisPlatelet count > 350.000 /ulcause : iron deficiency B 12 deficiency drugs (vincristine,efinefiin, etc)

3. Disorders of Platelet Functiondefect is in platelet adhesion, aggregation,or granule release

cause : drugs (aspirin,NSAID) uremia,cirrhosis, etc.

4. Disorders of Blood Coagulation

Congenital DisordersHemophilia Aincidence 1:10,000sex linked recessive dificiency of factor VIII

5. Acquired DisordersVitamin K deficiency impairs production of factors II (prothrombin ) VII,IX,and X.

*