Download Inflammation - allergy & autoimmunity

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
Inst. Pathol. ,1st Med. Faculty,
Charles Univ. Prague
Inflammation
Definition:
complex reaction of
organism to damage
(aim: homeostasis maintenance)
Inflammation - Causes


nonliving
physical
chemical
living
viral
bacterial
mycotic
parasitic
AUTOIMMUNE
Inflammation – immunity
Nonspecific antibodies


imunocomplexes on
dendritic cells
long lasting antigen
presentation
Mechanisms
of Immune Response
antigen specific



humoral B– lymphocytes
cellular T– lymphocytes
INTERACTION
B-lympho–Th – affinity maturation – plasmocyte
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
Sjögren´s syndrome
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….
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
– agregate of 50 and more
lymphocytes
(defined 1968)
 focus
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
DISEASE
intercel. epith. matrix
pemphigus
basal membrane of
epidermis
pemphigoid
Inflammation – autoimmune
Organ autoimmune diseases – GIT
ANTIBODY against
DISEASE
mitochondrie
prim. bill.
cirrhosis
membr. hct., cytosol
CAH
gliadin
gluten
enteropathy
man 27 yrs
B 2138/06
4 pieces from D3 announced
 3 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
DISEASE
TGB, microsomes
pancreas  cells
insulin
ins. receptors
adrenal microsomes
TSH rec.
GB, HT
DM I
I–res. DM
I–res. DM
Adison dis.
GB
Inflammation – autoimmune
Organ autoimmune diseases – CNS
ANTIBODY
DISEASE
acetylcholin rec.
myasthenia
gravis
disseminated
sclerosis
basic myelin protein
Hypersensitivity
1.
anaphylactic
astma
2.
cytotoxic
3.
immune complexes SLE, GN
4.
cell mediated (delayed) tbc, contact
erythroblastosis
IgE
IgG, IgM
Ag+AB+C
dermatitis – T-cell mediated cytotoxicity
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
Defenses Against Infection – 2.

Nonspecific resistance factors


Inflammation- soluble factors




fever, interferon, complement, lysozyme, C-reactive
protein, lactoferrin, α1- antitrypsin
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 response

humoral: B-cells, plasma cells, immunoglobulins

cell-mediated: T-cells, lymphokins