inst. pathol, 1st med. faculty, charles univ., prague general pathology basic principles of cellular...
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Inst. Pathol, 1st Med. Faculty, Charles Univ., PrInst. Pathol, 1st Med. Faculty, Charles Univ., Pragueague
General Pathology Basic Principles
of Cellular and Organ Pathology
Inflammation - IV
Jaroslava Dušková
Inst. Pathol. ,1st Med. Faculty, Charles Univ. Prague
http://www1.lf1.cuni.cz/~jdusk/
InflammationDefinition:
complex reaction of organism to damage
(aim: homeostasis maintenance)
Inflammation - Causes
nonlivingphysical
chemical
livingviral
bacterial
mycotic
parasitic
AUTOIMMUNE
Inflammation – immunity
Nonspecific antibodies imunocomplexes on
dendritic cells long lasting antigen
presentation
antigen specific humoral B– lymphocytes cellular T– lymphocytes
INTERACTIONB-lympho–Th – affinity maturation – plasmocyte
Mechanisms of Immune
Response
Autoimmunity
lack of self-tolerance
Autoimmunity
constant activity in organogenesis regeneration metalaxia
Autoimmune Diseases
Def.:
loss of self-tolerance resulting into damage of organ /tissue
Mechanisms Preventing Antiself Reactivity:
clonal deletion (thymus)
clonal anergy (thymus)
peripheral clonal supression by
Tsupressor cells ( B,T helpers)
Inflammation – autoimmune Systemic 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
Def.:
a group of autoimmune conditions characterized by T-lymphocyte mediated sialo- & dacryoadenitis
----------women predilection
sicca (dry) syndrome
Sjögren´s syndrome
Classification: primary: keratoconjunctivitis sicca, no co-
existing systemic a-i diseases
secondary: accompanying rheumatoid arthritis, SLE, dermatomyositis….
Sjögren´s syndrome
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.
Focus Score
Morphometric representation of focally accented chronic sialoadenitis
focus – agregate of 50 and more lymphocytes (defined 1968)
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
Inflammation – autoimmune Organ autoimmune diseases – skin
ANTIBODY
intercel. epith. matrix
basal membrane of epidermis
DISEASE
pemphigus
pemphigoid
Inflammation – autoimmune Organ autoimmune diseases – GIT
ANTIBODY against
mitochondrie
membr. hct., cytosol
gliadin
DISEASE
prim. bill. cirrhosis
CAH
gluten enteropathy
man 27 yrs B 2138/06
4 pieces from D3 announced3 pieces diam. 1-2mm found
clin. dg. susp. celiakia, diff. dg. lambliasis
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´ classification
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 delayed
Inflammation – autoimmune Organ 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
Inflammation – autoimmune Organ autoimmune diseases – CNS
ANTIBODY
acetylcholin rec.
basic myelin protein
DISEASE
myasthenia gravis
disseminated sclerosis
Hypersensitivity
1. anaphylactic astma IgE
2. cytotoxic erythroblastosis IgG, IgM
3. immune complexes SLE, GN Ag+AB+C
4. cell mediated (delayed) tbc, contact
dermatitis – T-cell mediated cytotoxicity
Defenses Against Infection – 1.
Surfacebarriers: 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
Defenses Against Infection – 2.
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
Defenses Against Infection – 3.
Immune responsehumoral: B-cells, plasma cells, immunoglobulins
cell-mediated: T-cells, lymphokins