KUSMARDI
LAB. OF IMMUNOPATHOLOGY DEPT. OF ANATOMICAL PATHOLOGY FACULTY OF MEDICINE
UNIVERSITY OF INDONESIA
II.
III.
HYPERSENSITIVITY
IMMUNODEFICIENCY
IV.
AUTOIMMUNE DISEASE
Antigen
TISSUES CELLS --------Tumour --------Parasitic
--------Fungi
--------Bacteria --------Virus --------Molecules-----Protein -----Carbohydrate -----Lypoprotein
NATURAL IMMUNITY
IMMUNITY NONSPECIFIC PHYSICAL LYSOZYME COMPLEMENT INTERFERON
CHEMICAL SPECIFIC
CELLULER
POLYMORPS
MO
RESPONSE
RECOVERY
DESTRUCTION OF ANTIGEN
SECONDARY RESPONSE (SUBSEQUENT CONTACT) ANTIGEN SPECIFIC MEMORY AND RECOGNITION OF ANTIGEN
ALMOST IMMEDIATE
RAPID ACTIVATION OF
IMMUNE REACTION
IMMUNE RESPONSE
NON DISEASE
Ag
TH BCDF
TH memory
Tc
IMMUNE REACTION
1. PRECIPITATION of a soluble Ag
3. ANTITOXIC EFFECT:The Ag/Ab combination neutralised the toxic activity Toxic molecule Anti-toxin(Ig)
Phagocytic activity Ag
Ag
Ag
Ag
Ag/Ab
macrophage
Efficient phagocytosis
COMPLEMENT ACTIVATION
Activationclassical pathway Ag/Ab
1 Fc (IgM or Ig G) 2 3 4 5 6 7
Cytolytic effect
RBC
Bacterium
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 (60300 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,
BASOFIL
AFINITAS vs MAST
&
IgG4,
& BASOFIL
Second exposure to Ag
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 1st injection of horse serum (ATS), penc bee sting General sensitivition Hay Fever 1st contact with grass pollen local sensitivition Asthma 1st contact horse mite dust animal dander
conjunctiva and
passage 2nd injection bronchial constriction perhaps a skin rash may be fatal 2nd contact irritation of conjunctiva
local sensitivition
of bronchi 2nd contact Bronchial constriction difficult breathing
Ag (cell surface)
Complement
Increased phagocytic
Increased
activation
killercell
activity
DESTRUCTION OF CELL
Effect on
vessel wall
Sensitised T cells
contact dermatitis
Malnutritionparticularly 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, Hodkins disease INFECTION often OPPORTUNISTIC IMPAIRED IMMUNITY
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.
IMMUNE DEFICIENCY STATES-AIDS Infection No initial symptoms Virus present in Latent stages (months-years) Stages of opportunistic infection and tumours (1-2 years) Infection opportunistic
limphoncytes
- no signs - persistent limph node enlargement malignant tumours
others
Kaposis sarcoma lymphomas
Immunodeficiency Virus
1. Brain
Tumours Inflamation
Candidiasis
3. Lung
4. Intestines 5. Skin
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
isolated antigen
(e.g. sperm, lens) nonself antigen
Ig antisperm
Ig antilens
virus A. self antigen self antigen modification neo-Ag failure of Th recognation autoactivity autoimmune diseases
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
4. PANCREATIC CELL
Type I DM
Addisons
Primary
1. MITOCHONDRIA of liver => Prim. Biliary cirrhosis 2.SMOOTH MUSCLE of liver =>Chronic active hepatitis (CAH) 3.NUCLEAR CONSTITUENT of liver => CAH =>conn. Tissue dis. of skin &muscle
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
menampung oksigen sebanyakbanyaknya. tidak berinti diameter 8 m tebal 2 m banyak mengandung haemoglobin (02 berikatan dengan Hb lbh banyak di bagian tepi daripada bagian tengah. Hb memberikan warna merah pacla sel darah.
tubuh untuk dikeluarkan dari tubuh, misal COz, senyawa nitrogen, dan racun.
3. Perbaikan saluran-saluran
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.
Kekurangan/ketiadaan bentuk (mengecil) salah satu atau lebih sel. Penyebab: idiopatik (tdk diketahui pasti) Latrogenik (salah penatalaksanaan) Obat-obatan
Anemia
Keadaan 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.
Anemia
Pengaruh anemia: Anoksia, hipoksia
1.
Perubahan metabolisme aerob menjadi anaerob ATP sedikit letih/lesu. Banyakdihasilkan radikal bebas. Dihasilkan asam laktat pegal, letih.
1. 2.
DeoksiHb
produksi
1.
Redistribusi aliran darah: vasokontriksi pembuluh darah pada organ yang tidak vital, untuk mensuplai darah pada organ yang vital. Peningkatan curah jantung.
1.
bilirubin meningkat.
Klasifikasi Anemia
1. Bentuk Sel/ sitometrik
A. normokrom pada normositik anemia B. hipokrom pada mikrositik anemia C. Normokromik pada makrositik anemia
pucat, lemah, sakit kepala, hipotensi. Tjd pada: anemia penyakit kronik, anemia hemolitik spt pad mens, anemia akut krn perdarahan, anemia aplastis.
berkurang. Hb berkurang. Tjd pada: anemia defisiensi Fe, Thalasemia, anemia krn penyakit kronis.
RBC normal. Hb normal. Tjd pada: anemia defisiensi vit B12, anemia defisiensi folat.
2. Eritrokinetik
A.
Hemolisis
3. Biokimia
A.
Orang negro dg infeksi sal kemih + kloramfenikol/sulfonamid ggn sintesis DNA anemia hemolitik. B. Kekurangan kofaktor spt Fe, Vit B12
Platelet Disorders
1. Trombocytopenia normal : 150.000-350.000/l abnormal:<100.00U/ l
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 Disorders
2. Thrombocytosis Platelet count > 350.000 /ul cause : iron deficiency B 12 deficiency drugs (vincristine,efinefiin, etc)
5. Acquired Disorders
Vitamin K deficiency