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