inflammation - iv · immune disorders diseases –table of contents immune deficiency diseases...
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General Pathology
Basic Principles of Cellular and Organ Pathology
Inflammation - IV
Jaroslava Dušková
Inst. Pathol. ,1st Med. Faculty, Charles Univ. Prague
CD3
Immune Disorders
Diseases Jaroslava Duško
vá
Immune Disorders Diseases – table of contents
Immune Deficiency Diseases primary – inborn
NG disorders
thymic hypoplasia
T-lymphopenia
Bruton´s agamaglobulinemia
isolated IgA deficiency
complement deficiency
secondary – acquired HIV-AIDS
neutropenia
leukemia
vascular - DM, ischemia –atherosclerosis
malnutrition
aging
Increased – Hypersensitivity –Allergy
I. anaphylactic
II. cytotoxic
III. immune complexes
IV. cell mediated (delayed) T-cell mediated cytotoxicity
Self oriented – Autoimmune Diseases Autoimmunity – definition,
function
Mechanisms of autoimmune reaction prevention
Autoimmune diseases –representatives systemic
organ related
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Defenses Against Infection – 1/3
Surface
barriers: skin, conjunctiva, mucous membranes
mechanical removal: shedding, tears, mucus,
ciliary action, coughing, salivation, swallowing,
urination, defecation
normal bacterial flora
chemical inhibitors: gastric acid, lactic acid, fatty
acids,bile salts, Tamm- Horsfall protein..
antimicrobial substances: lysozym, secretory IgA
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Defenses Against Infection – 2/3
Nonspecific resistance factors fever, interferon, complement, lysozyme, C-reactive
protein, lactoferrin, α1- antitrypsin
Inflammation- soluble factors clotting system –Hageman fc. (XII)
complement system: chemotactic fc, anaphylatoxins
kinin system: bradykinin
Inflammation- phagocytes circulating: neutrophils, eosinophils, monocytes, macrophages
fixed: alveoli, spleen, liver, bone marow, brain
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Defenses Against Infection – 3/3
Immune response
humoral: B-cells, plasma cells, immunoglobulins
cell-mediated: T-cells, lymphokinsJaroslava Duško
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Primary – inborn - genetically determined
NG disorders
Thymic hypoplasia – Di George syndrome
T-lymphopenia
Bruton´s agamaglobulinemia (X-linked, BTK)
Isolated IgA deficiency
Complement deficiency
Secondary – acquiredHIV-AIDS
Neutropenia
Leukemia
Vascular - DM, ischemia – atherosclerosis
Malnutrition
Aging
Immune Deficiency Diseases
Jaroslava Duško
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Primary – inborn - genetically determined
NG disorders
Thymic hypoplasia – Di George syndrome
T-lymphopenia
Bruton´s agamaglobulinemia (X-linked, BTK)
Isolated IgA deficiency
Complement deficiency
Secondary – acquired HIV-AIDS
Neutropenia
Leukemia
Vascular - DM, ischemia – atherosclerosis
Malnutrition
Aging
Immune Deficiency Diseases
- clinical manifestations
Increased susceptibility to
• infections
•tumoursJaroslava Duško
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Hypersensitivity - types
I. anaphylactic astma IgE
II. cytotoxic erythroblastosis IgG, IgM
III. immune complexes SLE, GN, Ag+AB+C
IV. cell mediated (delayed) tbc, contact
dermatitis – T-cell mediated cytotoxicityJarosla
va Dušková
Hypersensitivity - types
I. anaphylactic (astma) Th2 activation-
production of IgE – degranulation of mast
cells – vasoactive amins- hypersensitivity
reaction
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Hypersensitivity - types
II. cytotoxic erythroblastosis, pemphigus
vulgaris, myasthenia gravis, DM I, pernicious
anemia… IgG, IgM
target antigens on cell surface
destruction of cells
derangement of function
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Hypersensitivity - types
III. immune complexes SLE, GN, polyarteritis
nodosa… Ag+AB+C
depositions in blood vesels
vascular complicationsJarosla
va Dušková
Erythema multiforme
J.P.Sapp et al. Contemporary maxillofacial pathology.
2nd ed. Mosby 2004
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J.P.Sapp et al. Contemporary maxillofacial pathology.
2nd ed. Mosby 2004
Erythema multiforme
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Hypersensitivity - types
IV. T -cell mediated (delayed) tbc, contact
dermatitis, RA, MS, DM I, HT,
cytokine mediated inflammation - CD4 T
cells – delayed response, macrophages are
the main effectors
direct cytolysis CD8 T cells
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Contact
stomatitis
unknown allergen
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Autoimmunity
lack of self-tolerance
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Autoimmunity
constant activity in
organogenesis
regeneration
metalaxiaJarosla
va Dušková
Autoimmune Diseases
Def.:
loss of self-tolerance
resulting into damage
of organ /tissueJarosla
va Dušková
Self x Non-SelfMechanisms Preventing Antiself
Reactivity:
clonal deletion - thymus
clonal anergy – APC „off signal“
peripheral suppresion – Ts CD8+
Protection from protectors….
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Activation of Apoptosis
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Inflammation – autoimmuneSystemic autoimmune diseases
DISEASE
SLE
RA
Sjögren dis.
Syst. sclerodermia
Dermato–polymyositis
Prim. vasc. syndromes
ANTIBODY
ANA, ENA
collag. II, Fc –Ig
(rheum. factor)
ANA,ENA
ENA (Scl–70)
ENA (Jo–1)
ANCA
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SLE - Lupus
erytematodes
disseminatus
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Lupus erytematodes disseminatus
VASCULITIS
skin – butterfly rash, discoid erythema
mucose membranes ulcers
heart- Libman-Sacks endocarditis
arthritis
serositis
hemopoietic disorders – hemolytic anemia, leuco-lympho- thrombocyto- penia
kidney – glomerulonephritis
CNS – seizures, psychosis (vascular etiology?)
SLE
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SLE. Papillary necroses – vasculitis (Bilddatenbank Basel)
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SLE GN . Man 29. (Bilddatenbank Basel)
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Rheumatoid arthritis
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Rheumatoid arthritis- polyarthritis progressiva primaria chronica
adult women mainly
small joints
morning stiffness
dysfigering, pain, ankylosis
+ tendovaginitis, iridocyclitis, vasculitis, lung fibrosis
serum rheumatoid factor – IgM x Fc IgG –immunocomplexes
complication (potentially killing)
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Amyloidosis renis
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Amyloid Diagnosis Immunohistochemistry
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Def.:
a group of autoimmune conditions
characterized by T-lymphocyte
mediated sialo- & dacryoadenitis
----------
women predilection
sicca (dry) syndrome
Sjögren´s syndrome
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Classification:
primary: keratoconjunctivitis sicca,
sialoadenitis, no co-existing systemic a-i
diseases
secondary: accompanying rheumatoid
arthritis, SLE, dermatomyositis….
Sjögren´s syndrome
Jaroslava Duško
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T.E.Daniels, Th.B. Aufdemorte, J.S.Greenspan:
Histopathology
of Sjögren´s syndrome.
s. 41-52, in:
N. Talal, H.M. Moutsopoulos, S.S.Kassan:
Sjögren´s syndrome. Clinical and
immunological aspects. Springer Vrlg, Berlin, Heidelberg, New York, London, Paris, Tokyo 1987, 299ss.
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Focus Score
Morphometric representation of focally
accented chronic sialoadenitis
focus – agregate of 50 and more
lymphocytes (defined 1968) Jarosla
va Dušková
Sicca syndrome
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meandr
scaning
FS ≥ 1
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Focus Score morphometry result table
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Lichen planus
J.P.Sapp et al. Contemporary maxillofacial pathology.
2nd ed. Mosby 2004
Jaroslava Duško
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Lichen planus
fibrinogen Ab in BM
Mucous Membrane
Pemphigoid IgG, C3 along BM
Pemphigus vulgaris IgG
Erythema multiforme IgM,C3
deep dermis - perivascular
J.P.Sapp et al. Contemporary maxillofacial pathology.
2nd ed. Mosby 2004
Jaroslava Duško
vá
Inflammation – autoimmune: Organ autoimmune diseases
Skin (& mucous membranes)
ANTIBODY
intercel. epith. matrix(desmoglein 3)
basement membrane
of epidermis
DISEASE
pemphigus
pemphigoidJarosla
va Dušková
Mucous membrane
pemphigoid
J.P.Sapp et al. Contemporary maxillofacial pathology.
2nd ed. Mosby 2004
Jaroslava Duško
vá
Pemphigus vulgaris
J.P.Sapp et al. Contemporary maxillofacial pathology.
2nd ed. Mosby 2004
Jaroslava Duško
vá
Pemphigus vulgaris
Jaroslava Duško
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Pemphigus
vulgaris
J.P.Sapp et al. Contemporary maxillofacial pathology.
2nd ed. Mosby 2004
Jaroslava Duško
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Pemphigus vulgaris
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Sclerodermia
Systemic
Sclerosis
SS
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SS
Sclerodermia
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Sclerodermia - vasculitis
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Inflammation – autoimmuneOrgan autoimmune diseases – GIT
ANTIBODY against
mitochondrie
membr. hct., cytosol
gliadin
DISEASE
primary billiary
cirrhosis
CAH
gluten
enteropathy
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Celiac Sprue
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man 27 yrs B 2138/06
4 pieces from D3 announced
3 pieces diam. 1-2mm found
clin. dg. susp. celiakia, diff. dg. lambliasis
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CD 3
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CD 3
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CD 3
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Histopathology Report
mild shortening & widening of villi
intraepit. lymphocytes > 40/100 enterocytes
lamblie not found
Conclusion: histopathology changes
supporting clinical dg. suggested - celiac
sprue - type 3a of Marsh´ - Oberhuber´s
classification
Jaroslava Duško
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Marks, DJB, Harbord, MWN, Mac Allister R. et al.:
Impotent immune System: An Underlying
Problem in Crohn´s Disease. Lancet 2006, 367, 668-78
in patients with Crohn´s an impaired acute
inflammatory response – 79% reduction in
the number of neutrophils and interleukin 8
in ulcerative colitis initiation of inflammation
normal, resolution delayedJarosla
va Dušková
m. Crohn
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m. Crohn
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Inflammation – autoimmuneOrgan autoimmune diseases – endocrine
ANTIBODY
TGB, microsomes
pancreas cells
insulin
ins. receptors
adrenal microsomes
TSH rec.
DISEASE
GB, HT
DM I
I–res. DM
I–res. DM
Adison dis.
GB
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Thyroid m.G-B
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Hashimoto Thyroiditis
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Hashimoto
Thyroiditis
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Epinephritis chronica
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m. Adisoni
atrophy
tbc
tumour
Jaroslava Duško
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Inflammation – autoimmuneOrgan autoimmune diseases – CNS
ANTIBODY
acetylcholin rec.
basic myelin protein
DISEASE
myasthenia
gravis
disseminated
sclerosisJaroslava Duško
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Sclerosis cerebrospinalis multiplex disseminata – multiple sclerosis - MS
chronic autoimmune demyelinating encephalitis
Jaroslava Duško
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Sclerosis cerebrospinalis multiplex disseminata- virus infection influence (morbilli, herpes, EB)
…bacteria?...
Pathogenesis
interaction of the macroorganism
and virus – limited antibody production
(only 10-20% produced viruses are virulent)
virus mutation & immunosupresion
(age, pregnancy, stress, other diseases….)
Jaroslava Duško
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MS – viral influence (2)
Pathogenesis
infection of endothelia – microangiitis
blood-brain- barrier disorder
serum & CSF CD4, CD8
(miror image to AIDS)
Sclerosis cerebrospinalis multiplex disseminata
- virus infection influence 2.
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Sclerosis
cerebrospinalis
multiplex disseminata
immobility/spasticity
anesthesia
sight disorders
incontinence
cognitive dysfunction
pain
depresssion
Pons Varoli – lux. modř
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Immune Disorders Diseases
Morphology
alteration up to necrosis
NG + lymphoplasmocellular infiltration
fibrosis
Prognosis
important in terms of both morbidity and
mortality – possible lethal outcome
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Rejection of Transplants - pathways
Allografts – MHC molecules recognized
mainly on the graft DCs:
direct recognition by the host CD8+T cells –endothelial damage - acute fibrinoid necrosis- thrombosis-
ischemia
indirect recognition by the host CD4+ T cells –
AB mediated
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Rejection of Transplants - effectors
hyperacute - hours – pre-existing ABs
acute – days to weeks CD4+ and CD8+
T cells
chronic – months – productive
endarteritis – T cell secretion of cytokins
chronic
acute
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Graft Versus Host Disease - GVHD
cause - immunocompetent donor T cells in:
hematopoietic stem cell transplantation
organs rich in lymphoid cells – liver
non-irradiated blood transfusion
manifestation: acute – days to weeks – epithelial necroses –
GIT, skin – potentially lethal
chronic – months - syst. sclerosis - like skin
lesions, autoimmune disorders
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