I. Type hypersensitivity reaction
I. Type hypersensitivity reaction
I. Type hypersensitivity reaction
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Immunpathology<br />
Immunpathology<br />
Immunpathology<br />
Immunpathology<br />
Dr. Tímár T r József J zsef
I. I. I. I. I. <strong>Type</strong> <strong>Type</strong> <strong>Type</strong> <strong>Type</strong> <strong>Type</strong> <strong>hypersensitivity</strong><br />
<strong>hypersensitivity</strong><br />
<strong>hypersensitivity</strong><br />
<strong>hypersensitivity</strong><br />
<strong>hypersensitivity</strong><br />
<strong>reaction</strong> <strong>reaction</strong> <strong>reaction</strong> <strong>reaction</strong> <strong>reaction</strong> (allergy) (allergy)<br />
(allergy)<br />
(allergy)<br />
(allergy)<br />
1st exposure to Antigene (AG) IgE production<br />
2nd Ag (allergene) exposure IgE production/binding<br />
(mast cell, basophylic leukocyte FcεR + )<br />
DEGRANULATION<br />
LTB4 histamine histamine<br />
Chemotactic factors PAF LTD4<br />
Cytokines PGE2 PE<br />
LTD4E4 PAF<br />
Chemotaxis/exsudation vasodilatation smooth muscle-spasm<br />
permeability<br />
Neutrophyl leukocyte<br />
Eosinophyl leukocyte<br />
Makrophage oedema
ACTIVATION OF MAST CELLS IN TYPE I<br />
HYPERSENSITIVITY REACTION<br />
EO-Leu
PATOGENESIS OF<br />
TYPE I<br />
HYPERSENSITIVITY<br />
REACTION<br />
Mucosal<br />
lining<br />
Pollen
Allergy<br />
Allergy<br />
Allergy<br />
Allergy<br />
�� Local: rhinitis, asthma, conjunctivitis<br />
�� skin: urticaria, ekzema, angioneurotic<br />
oedema,<br />
�� Systhemic: anaphylactic shock<br />
�� (adrenalin: smooth muscle cell relax, no<br />
vasospasm)
Allergy, Allergy, Allergy, Allergy, macroscopy<br />
macroscopy<br />
macroscopy<br />
macroscopy
Generalizált anaphylacticus reakció<br />
Glottis oedema
II. II. II. II. II. <strong>Type</strong> <strong>Type</strong> <strong>Type</strong> <strong>Type</strong> <strong>Type</strong> <strong>hypersensitivity</strong><br />
<strong>hypersensitivity</strong><br />
<strong>hypersensitivity</strong><br />
<strong>hypersensitivity</strong><br />
<strong>hypersensitivity</strong><br />
<strong>reaction</strong> <strong>reaction</strong><br />
<strong>reaction</strong><br />
<strong>reaction</strong>A.<br />
Complement-dependent <strong>reaction</strong><br />
AB binds target cell<br />
C5-9 C1423<br />
Complement-dependent opsonization/fagocytosis<br />
cellular cytotoxicity<br />
B. AB-dependent cellular cytotoxicity<br />
Target cell binds AB (Fc exposition)<br />
FcR+ effector cell-binding (NK cell macrophage)<br />
Target cell death<br />
C. Anti-surface receptor AB mediated<br />
Anti-receptor-AB production<br />
AB binds target cell<br />
- +<br />
Receptor-block Receptor-activation<br />
(AchR, myasthenia) (TSHR, hyperthyreosis)
Myastenia gravis
Basedov-Graves kór
II. type hypersensitivty (cytotoxic)
Hydrops foetus<br />
universalis<br />
Rh<br />
incompatibility
G<br />
Lung haemorrhage. Goodpasture<br />
syndrome
III. III. III. III. <strong>Type</strong> <strong>Type</strong> <strong>Type</strong> <strong>Type</strong> <strong>hypersensitivity</strong><br />
<strong>hypersensitivity</strong><br />
<strong>hypersensitivity</strong><br />
<strong>hypersensitivity</strong><br />
<strong>hypersensitivity</strong><br />
2nd antigene-exposition AG/AB complex generation (Ge)<br />
immunocomplex deposition<br />
(kidney, skin, serous membranes, vessel wall)<br />
vasodilatation neutrophyl migration thrombocyte aggregation<br />
degranulation microthrombus<br />
oedema ischemia<br />
tissue-necrosis
pathomechanism<br />
pathomechanism<br />
pathomechanism<br />
pathomechanism<br />
�� Acute:<br />
�� AG/AT complex (Se), organic deposition,<br />
inflammation…..C3b<br />
inflammation ..C3b<br />
(phagocytosis)C5b,6/7: chemotaxis,<br />
(inflammation), C5-9membrane<br />
C5 9membrane-attack attack<br />
complex…cell complex cell death<br />
�� Fibronoid necrosis, vasculitis (neu)
necrotising vasculitis
Pathomechanism<br />
Pathomechanism<br />
Pathomechanism<br />
Pathomechanism<br />
�� Chronic: persistent antigen<br />
�� causes: „autoimmune autoimmune disease” disease<br />
�� Antisera-snake, Antisera snake, mouse anti-hum anti humán n T cell<br />
antibody, bacterial streptokinase, iv.<br />
penicillin
IV.<strong>Type</strong> IV.<strong>Type</strong> IV.<strong>Type</strong> IV.<strong>Type</strong> <strong>hypersensitivity</strong><br />
<strong>hypersensitivity</strong><br />
<strong>hypersensitivity</strong><br />
<strong>hypersensitivity</strong><br />
A. Late type <strong>hypersensitivity</strong><br />
2nd antigene exposition + dendritic cell – T cell association (IL-2, TNFα, IFNγ)<br />
lymphocyte accumulation fibroblast-proliferation macrophage-activation<br />
angiogenesis epitheloid cells<br />
giant cells<br />
(Langhans, foreign Ag)<br />
B. T-cell mediated cytotoxicity<br />
Target cell expose foreign Ag (viral infected cell, allograft)<br />
CD8 + T cell activation<br />
Cell/tissue damage necrosis
Granuloma formation
TBC-lung<br />
A<br />
B<br />
C
Transplantation Transplantation Transplantation Transplantation pathology<br />
pathology<br />
pathology<br />
pathology<br />
�� Host-versus Host versus graft: organ transplant<br />
�� Graft-versus Graft versus host (bone marrow trpl)
ejection
Acute Acute Acute Acute rejection<br />
rejection<br />
rejection<br />
rejection
Kidney Kidney Kidney Kidney transplant transplant transplant transplant transplant rejection<br />
rejection<br />
rejection<br />
rejection<br />
�� Acute, humoral (preformed or newly formed anti-HLA anti HLA<br />
antibodies) 0-7 0 7 days<br />
�� Vasculitis (glomerulare, intertubulare): Neu, microthrombi,<br />
fibrinoid necrosis: Ig+, C+<br />
�� Tubulare hypoxia, necrosis: epithelial C4D+<br />
�� Multiple infarcts<br />
�� Acute, cellulare: 0-3 0 3 month<br />
�� tubulitis (ly, MPH), epithel HLA-DR+ HLA DR+<br />
intimal arteritis (a. interlobulare): cortical hypoxia,<br />
infarct
Kidney Kidney Kidney Kidney Kidney transplant transplant transplant transplant rejection,<br />
rejection,<br />
rejection,<br />
rejection,<br />
chronic chronic chronic chronic chronic (month/years)<br />
(month/years)<br />
(month/years)<br />
(month/years)<br />
�� Transplant arteriopathy (a.inl, a. arc)<br />
�� Progressing intimal fibrosis<br />
�� Active: ly, MPH infiltrate<br />
�� Secundary ischemic lesions<br />
�� Interstitial fibrosis<br />
�� Glomerulosclerosis<br />
�� Tubular atrophy<br />
�� Transplant glomerulopathy<br />
�� Capillary wall + mesangial proliferation<br />
�� Transplant capillaropathy (peritubular)<br />
�� Aspecific tubular lesions
Chronic Chronic Chronic Chronic rejection<br />
rejection<br />
rejection<br />
rejection
Hereditary Hereditary Hereditary Hereditary Hereditary immune immune<br />
immune<br />
immune<br />
immune<br />
disorders, disorders, disorders, disorders, humoral<br />
humoral<br />
humoral<br />
humoral<br />
�� X-linked linked hypogammaglobulinaemia (Bruton), BTK deff, propreB<br />
cells only,<br />
Enteral infections (vírus, (v rus, Giardia, Mycopl)<br />
�� Transient hypogammaglobulinaemia (T helper)<br />
�� Hyper-IgM Hyper IgM (CD40L deff)<br />
No isotype switch, switch,<br />
CD4+T cell problem (IgA, IgE IgG deff), path IgM,<br />
LND: no centr. germ….. germ ..<br />
�� Variable hypogammaglobulinaemia (B and T cell problem)<br />
�� Szelektív Szelekt v IgA deff (most frequent)<br />
C4A-del, C4A del, CD8+T problem, isotype switch : skin, GI infections…<br />
infections<br />
�� 5’-nukleotidase nukleotidase deff: perB only…… only……
Hereditary Hereditary Hereditary Hereditary Hereditary immune immune<br />
immune<br />
immune<br />
immune<br />
defficiency, defficiency, defficiency, defficiency, defficiency, cellular<br />
cellular<br />
cellular<br />
cellular<br />
�� Di-George Di George (thymus aplasia, 22q11del)<br />
Heart defect+ hypoparathyr, defect:(3/4<br />
pharyngeal), preT only<br />
�� Chr mucocutaneous candidiasis
Hereditary<br />
Hereditary<br />
Hereditary<br />
Hereditary<br />
Hereditary<br />
immunodefficiency, immunodefficiency, immunodefficiency, immunodefficiency, mixed<br />
mixed<br />
mixed<br />
mixed<br />
�� SCID: cytokineR γ- mutation<br />
predom T problem (X-linked, (X linked, male)<br />
�� Adenozin deaminase defficiecy (au-rec) (au rec)<br />
dATP toxic for T cells….DNA cells .DNA damage!!!<br />
�� Purine nucleotide phosphorylase-deff phosphorylase deff (dGTP toxic, T, DNA!!!)<br />
�� Wiskott-Adrich Wiskott Adrich sy (X-linked, (X linked, males)<br />
Xp1123 gén g n defficiency<br />
Opp infections, thrombocytopenia, ekzema<br />
�� Ataxia teleangiectasia .<br />
Thymus hyoplasia, LND atrophy, T+IgG/IgA deff (DNA repair gene)<br />
�� Reticular dysgenesis (myel, ly stem cell problem)<br />
�� Nude ly sy (HLA-II (HLA II deff), CD4T probleme: CIITA, RFX transcription<br />
factor disorder<br />
�� low HLA-I HLA I expression (peptide-transporter (peptide transporter problem) CD8 function<br />
distorted
Acquired Acquired Acquired Acquired immunodefficiency<br />
immunodefficiency<br />
immunodefficiency<br />
immunodefficiency<br />
immunodefficiency<br />
syndrome, syndrome, syndrome, syndrome, AIDS<br />
AIDS<br />
AIDS<br />
AIDS<br />
�� HIV1/2 infection: selective loss of CD4+<br />
cells<br />
�� Sex, blood, transplacental infections<br />
�� Target1: CD4+T (gp120HIV), citotoxic<br />
�� target2: macrophage (non toxic,<br />
rezervoár) rezervo r)….endothelial .endothelial cell?<br />
�� Soluble gp120+CD4T/anti-gp120 gp120+CD4T/anti gp120 ADCC
A<br />
B C<br />
CD4/CD8 ratio: 2-4/1 2 4/1<br />
HIV infection: decreased/reverted
HIV-1
Course Course Course Course Course of of of of AIDS<br />
AIDS<br />
AIDS<br />
AIDS<br />
�� LND: follicular hyperplasia (B), HIV+T zóne, z ne,<br />
CD4->5OO<br />
CD4 >5OO/ul,, /ul,, p24+<br />
�� Follicular involution (dendritic cell problem),<br />
latent AIDS:CD4T down, silent virus<br />
�� Opportunistic infections: crysis, viraemia,<br />
CD4T
Opportunistic Opportunistic Opportunistic Opportunistic Opportunistic infections infections infections infections infections in in<br />
in<br />
in<br />
in<br />
AIDS AIDS<br />
AIDS<br />
AIDS<br />
Helminthiasis<br />
Protozoonok<br />
Gombák<br />
Baktériumok<br />
Vírusok<br />
Strongyloides gastroenteritis, sepsis<br />
Pneumocystis carinii pneumonia<br />
Toxoplasma gondii encephalitis, disseminalt forma<br />
Cryptosporidium enteritis<br />
Isospora belli enteritis<br />
Candida albicans oesophagitis<br />
Cryptococcus meningitis<br />
Histoplasmosis disseminalt forma<br />
Coccidiomycosis disseminalt forma<br />
Mycobacterium avium disseminalt forma<br />
Mycobacterium kansasii<br />
Mycobacterium bovis extrapulmonáris tuberculosis<br />
Salmonella septicaemia<br />
Bacterialis pneumonia recidivans<br />
Herpes simplex mucocutan<br />
Bronchialis<br />
Oesophagealis<br />
CMV disseminalt<br />
Prion vCJ betegség leucoencephalopathia
Mycobacterium Avium (atypic MB)
CMV<br />
Pneumocytis carini
CANDIDIASIS az<br />
OESOPHAGUSBAN
PAS- candida, oesophagus<br />
CANDIDIASIS OESOPHAGUSBAN ( PAS reakció)