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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)

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