General Pathology

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General Pathology

• Basic Principles of Cellular and Organ Pathology
• Inflammation - IV

http//www1.lf1.cuni.cz/jdusk/
Jaroslava Dušková Inst. Pathol. ,1st Med.
Faculty, Charles Univ. Prague
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Inflammation

• Definition
• complex reaction of organism to damage
• (aim homeostasis maintenance)

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Inflammation - Causes

• nonliving
• physical
• chemical

• living
• viral
• bacterial
• mycotic
• parasitic
• AUTOIMMUNE

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Inflammation immunity

• Nonspecific antibodies
• imunocomplexes on dendritic cells
• long lasting antigen presentation

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Mechanisms of Immune Response

• antigen specific
• humoral B lymphocytes
• cellular T lymphocytes
• INTERACTION
• B-lymphoTh affinity maturation plasmocyte

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Autoimmunity

• lack of self-tolerance

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Autoimmunity

• constant activity in
• organogenesis
• regeneration
• metalaxia

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Autoimmune Diseases

• Def.
• loss of self-tolerance resulting into damage of
  organ /tissue

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Mechanisms Preventing Antiself Reactivity

• clonal deletion (thymus)
• clonal anergy (thymus)
• peripheral clonal supression by
  Tsupressor cells ( B,T helpers)

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Inflammation autoimmune Systemic autoimmune
diseases

• DISEASE
• SLE
• RA
• Sjögren dis.
• Syst. sclerodermia
• Dermatopolymyositis
• Prim. vasc. syndromes

• ANTIBODY
• ANA, ENA
• collag. II, Fc Ig
• (rheum. factor)
• ANA,ENA
• ENA (Scl70)
• ENA (Jo1)
• ANCA

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Sjögrens syndrome

• Def.
• a group of autoimmune conditions characterized
  by T-lymphocyte mediated sialo- dacryoadenitis
• ----------
• women predilection
• sicca (dry) syndrome

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Sjögrens syndrome

• Classification
• primary keratoconjunctivitis sicca, no
  co-existing systemic a-i diseases
• secondary accompanying rheumatoid arthritis,
  SLE, dermatomyositis.

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• T.E.Daniels, Th.B. Aufdemorte, J.S.Greenspan
  Histopathology
• of Sjögrens syndrome.
• s. 41-52, in
• N. Talal, H.M. Moutsopoulos, S.S.Kassan
  Sjögrens 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)

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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
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Inflammation autoimmune Organ autoimmune
diseases skin

• ANTIBODY
• intercel. epith. matrix
• basal membrane of epidermis

• DISEASE
• pemphigus
• pemphigoid

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Inflammation autoimmune Organ autoimmune
diseases GIT

• ANTIBODY against
• mitochondrie
• membr. hct., cytosol
• gliadin

• DISEASE
• prim. bill. cirrhosis
• CAH
• gluten enteropathy

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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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Histopathology Report

• mild shortening widening of villi
• intraepit. lymphocytes gt 40/100 enterocytes
• lamblie not found
• Conclusion histopathology changes supporting
  clinical dg. suggested - celiac sprue - type 3a
  of Marsh classification

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Marks, DJB, Harbord, MWN, Mac Allister R. et al.
Impotent immune System An Underlying Problem in
Crohns Disease. Lancet 2006, 367, 668-78

• in patients with Crohns an impaired acute
  inflammatory response 79 reduction in the
  number of neutrophils and interleukin 8
• in ulcerative colitis initiation of inflammation
  normal, resolution delayed

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Inflammation autoimmune Organ autoimmune
diseases endocrine

• ANTIBODY
• TGB, microsomes
• pancreas ? cells
• insulin
• ins. receptors
• adrenal microsomes
• TSH rec.

• DISEASE
• GB, HT
• DM I
• Ires. DM
• Ires. DM
• Adison dis.
• GB

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Inflammation autoimmune Organ autoimmune
diseases CNS

• ANTIBODY
• acetylcholin rec.
• basic myelin protein

• DISEASE
• myasthenia gravis
• disseminated sclerosis

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Hypersensitivity

1. anaphylactic astma IgE
2. cytotoxic erythroblastosis IgG, IgM
3. immune complexes SLE, GN AgABC
4. cell mediated (delayed) tbc, contact dermatitis
   T-cell mediated cytotoxicity

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Defenses Against Infection 1.

• 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..
• antimicrobial substances lysozym, secretory IgA

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Defenses Against Infection 2.

• Nonspecific resistance factors
• fever, interferon, complement, lysozyme,
  C-reactive protein, lactoferrin, a1- 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

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Defenses Against Infection 3.

• Immune response
• humoral B-cells, plasma cells, immunoglobulins
• cell-mediated T-cells, lymphokins