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KUSMARDILAB. OF IMMUNOPATHOLOGY
DEPT. OF ANATOMICAL PATHOLOGY
FACULTY OF MEDICINE
UNIVERSITY OF INDONESIA
KUSMARDILAB. OF IMMUNOPATHOLOGY
DEPT. OF ANATOMICAL PATHOLOGY
FACULTY OF MEDICINE
UNIVERSITY OF INDONESIA
THE SCOPE OF IMMUNOPATHOLOGY
I. ESSENTIAL IMMUNOLOGY
II. HYPERSENSITIVITY
III. IMMUNODEFICIENCY
IV. AUTOIMMUNE DISEASE
AntigenTISSUES
CELLS --------Tumour
--------Parasitic
--------Fungi
--------Bacteria
--------Virus
--------Molecules-----Protein
-----Carbohydrate
-----Lypoprotein
THE COMPONENT OF THE IMMUNE SYSTEMCELLULAR
LYMPHOCYTES MACROPHAGES
K (NK) CELLS
POLYMORPHS
SOLUBLE HUMORAL IMMUNOGLOBULIN
COMPLEMENT LYMPOKIN
THE ORIGIN OF THE CELLULAR COMPONENT OF THE IMMUNE SYSTEM
STEMCELLS
LYMPHOID
B CELLS
T CELLS
TH
TS
TDTH
TC
MYELOID
MACROPHAGESMONO
HISTI
GRANULOCYTES EO
NET
BA
MAST
THE CHARACTERISTIC OF IMMUNE RESPONSE
1. SELF RECOQNATION
2. SPECIFICITY
3. MEMORY
NATURAL IMMUNITY
IMMUNITY NONSPECIFIC PHYSICAL LYSOZYME
CHEMICAL COMPLEMENT
SPECIFIC INTERFERON
CELLULER 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
Ag
MHC II
APC Ag TH
TH TH
memory
IL-2R
B
Plasma cellIL-2
Tc
BCGF
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 response
a. Phagocytic activity
b. Complement activitation
Phagocytic activity
AgAg Ag Ag
Ag/Ab macrophage Efficient 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 effect
Bacterium
Punched out holes in
terget cell membrane RBC
Cytolytic 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 Ag
Fixation of IgE to mast cells and basophils by Fc fragment
Degranulation
of mast cell
Release of mediators and
vasoactive subtances
Ag/Ab reaction on surface of mast cell
Type 1 Anaphylaxis, atopy, allergy
Antigens and ‘allergens’
most potent antigen
very large molecules
molecular weights from 15 to 40,000
common allergens : ATS, Penc, Bee venom, etc.
Antibody
IgE
Plasma 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 reaction
Anaphylactic shock Hay Fever Asthma
1st 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 bronchi
2nd injection 2nd contact 2nd contact
bronchial irritation of Bronchial constriction
constriction conjunctiva difficult breathing
perhaps a skin rash
may be fatal
Ag (cell surface) specific Ab combination produces
Complement Increased phagocytic Increased
activation activity (opsonic effect) “killer”cell
activity
DESTRUCTION OF CELL
Type III- Immune complex (Arthus) type Vasoactive amines Effect on
Ag/Ab Complement (anaphilatoxin) vessel wall
activation Polymorphs
(chemotaxis)
Platelet Thrombosis
aggregation
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 humoral
cell-mediated
(2) THE NON-SPESIFIC SYSTEM phagosytes
complement
Primary (inhereted) deficiencies
B cell, T cell,
B and T cell deficits associated with recurring infections
Secondary deficiencies
T cell activity
B cell deficit
Malnutrition-
particularly with protein deficiency
Latrogenic effect -
e.g. immunosuppressorrs : cytotoxics
corticosteroids
Infections -
acute viral, chronic bacterial
chronic protozoal, e.g. malaria
Chronic debilitating disease -
e.g. renal failure : diabetes millitus
Malignant disease -
e.g. lymphoma, Hodkin’s disease
IMPAIRED IMMUNITY
INFECTION
often OPPORTUNISTIC
common predisposing conditions
AGAMAGLOBULINEMIA (PENY. BRUTON)X-LINKEDHAMPIR SLL PD PRIABELUM JELAS HINGGA 6 BLN (Ig ibu <<)DEF PRIMER TERBANYAK PRELIMFOSIT B TIDAK BISA MATURE infeksi bakteri sering kambuh faringitis, sinusitis, bronkitis, pneumonia, hepatitis
.limfosit B (-) dlm sirkulasi, prelimfosit B (N) pd sstl
.KGB, tonsil (-/rudimenter)
.Sel plasma (-) dlm sirkulasi
.Limfosit T dan CMI (N)I
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-AIDS
Infection Latent stages Stages of opportunistic
No initial (months-years) infection and tumours
symptoms (1-2 years)
Virus present in Infection opportunistic
limphoncytes others
- no signs malignant Kaposi’s
- persistent limph tumours sarcoma
node enlargement lymphomas
Simplified Life Cycle of the Human Immunodeficiency Virus
AIDS - ASSOCIATED DISEASE
1. Brain Tumours
Inflamation
2. Mouth, Trachea, Oesophagus Candidiasis
3. Lung Pneumocystis carinii infection
Fungal infections, Tuberculosis
4. Intestines Protozoal, Salmonella infection
5. Skin Kaposi’s sarcoma, Fungal infections,
Herpes Zoster
BLOOD CHANGES OF AIDS
Immunoglobulin may be elevated in the early stages
T4 (helper) lymphocytes are severely reduced
T4/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. Unknown
2. Multifactors
Figure 1. 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 antigen
II. Homeostatic disturbance
I. Expose of sequested antigenI. Expose of sequested antigen
isolated antigenisolated antigen
(e.g. sperm, lens)(e.g. sperm, lens)
nonself antigennonself antigen
Ig antispermIg antisperm
Ig antilensIg 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
Grave’s tyrotoxicosis
1. TYROID CELL Hashimoto’s, Grave’s disease
2. PARIETAL CELLS of stomach Pernicioous anaemia
3. RBC Haemolitic anaemia
4. PANCREATIC CELL Type I DM
5.ADRENAL CORTICAL CELLS Addison’s disease
6. PARATHYROID CELLS Primary hypoparathyroidism
7. ACETYLCHOLINE RECEPTOR Myasthenia gravis
1. MITOCHONDRIA of liver => Prim. Biliary cirrhosis
2.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 tulang
Misal: reticulin fibrosis, myelofibrosis, dll
2. Pada sel darah Misal: anemia
SEL DARAH MERAHberbentuk bulat, bikonkaf shg dapat
menampung oksigen sebanyak banyaknya.
tidak berintidiameter 8 µmtebal 2 µmbanyak 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) Patologis
1. 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) Patologis
2. 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) Patologis
3. 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) Patologis
4. Fibrosis Retikulin Peningkatan jumlah retikulin (kolagen tipe III).
5.MyelofibrosisPeningkatan jumlah kolagen
6. OsteosklerosisProliferasi jaringan tulang
AnemiaKeadaan dimana jumlah RBC total berkurang
Patofisiologi:1. Kebanyakan karena hipoproliferasi RBC,
menyebabkan gangguan bentuk dan jumlah.
1. Sedikit karena destuksi RBC berlebihan, biasanya jumlah normal tapi cepat lisis (hemolitik), akibat infeksi Plasmodium (malaria), cacing pita.
AnemiaPengaruh anemia: Anoksia, hipoksia
1. Perubahan metabolisme aerob menjadi anaerob ATP sedikit letih/lesu.
1. Banyakdihasilkan radikal bebas.
2. Dihasilkan asam laktat pegal, letih.
Kompensasi tubuh melawan anemia:
1. Penurunan afinitas Hb-O2 DeoksiHb produksi 2,3 difosfogliserat.
1. Redistribusi aliran darah: vasokontriksi pembuluh darah pada organ yang tidak vital, untuk mensuplai darah pada organ yang vital.
1. 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/ sitometrik
A. normokrom pada normositik anemiaB. hipokrom pada mikrositik anemiaC. Normokromik pada makrositik anemia2. Eritrokinetik
A. hemolisis B. Hemoragi3. Biokimia
1. Bentuk Sel/ sitometrikA. normokrom normositik anemia
Warna, 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 anemia
Warna sel normal, bentuk sel membesar, jumlah RBC normal.
Hb normal.Tjd pada: anemia defisiensi vit B12, anemia
defisiensi folat.
2. Eritrokinetik A. Hemolisis
Destruksi RBC berlebihan krn infeksi (co: cacing, malaria)
B. HemoragiKehilanagn RBC dari pembuluh darah krn perdarahan akibat faktor mekanik/ kecelakaan.
3. Biokimia A. 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/µl abnormal:<100.00U/ µl causes:
1. production defects such as marrow injury (drugs, irradiation) 2. marrow failure (aplastis anemia) 3. splenomegaly 4. accelerated destruction: thiazide, ethanol, sulfa, etc
Platelet Disorders2. ThrombocytosisPlatelet count > 350.000 /ulcause : iron deficiency B 12 deficiency drugs (vincristine,efinefiin, etc)
3. Disorders of Platelet Function
defect is in platelet adhesion, aggregation,or granule release
cause : drugs (aspirin,NSAID) uremia,cirrhosis, etc.
4. Disorders of Blood Coagulation
Congenital DisordersHemophilia Aincidence 1:10,000‘sex linked recessive dificiency of factor VIII
5. Acquired DisordersVitamin K deficiency impairs production of factors II (prothrombin ) VII,IX,and X.