Inflammation IV

General Pathology
Basic Principles
of Cellular and Organ Pathology
Inflammation - IV
CD3
Immune Disorders
Diseases
Jaroslava Dušková
Inst. Pathol. ,1st Med. Faculty, Charles Univ. Prague
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






Increased – Hypersensitivity –
Allergy
HIV-AIDS
neutropenia
leukemia
vascular - DM, ischemia –
atherosclerosis
malnutrition
aging
I.
II.
III.
IV.

anaphylactic
cytotoxic
immune complexes
cell mediated (delayed) Tcell mediated cytotoxicity
Self oriented – Autoimmune
Diseases



Autoimmunity – definition,
function
Mechanisms of autoimmune
reaction prevention
Autoimmune diseases –
representatives


systemic
organ related
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..

antimicrobial substances: lysozym, secretory IgA
Defenses Against Infection – 2/3

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, brain
Defenses Against Infection – 3/3

Immune response

humoral: B-cells, plasma cells, immunoglobulins

cell-mediated: T-cells, lymphokins
Immune Deficiency Diseases
 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
- DM, ischemia – atherosclerosis
 Malnutrition
 Aging
 Vascular
Immune Deficiency Diseases
- clinical manifestations

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






Increased susceptibility to
• infections
• tumours
HIV-AIDS
Neutropenia
Leukemia
Vascular - DM, ischemia – atherosclerosis
Malnutrition
Aging
Hypersensitivity - types
I.
anaphylactic
astma
II.
cytotoxic
III.
immune complexes SLE, GN, Ag+AB+C
IV.
cell mediated (delayed) tbc, contact
erythroblastosis
IgE
IgG, IgM
dermatitis – T-cell mediated cytotoxicity
Hypersensitivity - types
I.
anaphylactic (astma) Th2 activationproduction of IgE – degranulation of mast
cells – vasoactive amins- hypersensitivity
reaction
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
Hypersensitivity - types
III. immune complexes SLE, GN, polyarteritis
nodosa… Ag+AB+C

depositions in blood vesels

vascular complications
Hypersensitivity - types
IV. T -cell mediated (delayed) tbc, contact
dermatitis, RA, MS, DM I, HT,

cytokine mediatd inflammation - CD4 T cells
– delayed response, macrophages ar the
main effectors

direct cytolysis CD8 T cells
Contact
stomatitis
unknown allergen
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
Self x
non-self
Mechanisms Preventing Antiself
Reactivity:
clonal deletion - thymus
clonal anergy – APC „off signal“
peripheral suppresion – Ts CD8+
Protection from protectors….
Activation of Apoptosis
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
SLE - Lupus
erytematodes
disseminatus
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
SLE. Papillary necroses – vasculitis
(Bilddatenbank Basel)
SLE GN . Man 29.
(Bilddatenbank Basel)
Rheumatoid arthritis
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)
Amyloidosis renis
Amyloid Diagnosis
Immunohistochemistry
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,
sialoadenitis, 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
Sicca syndrome
meandr
scaning
FS ≥ 1
Focus Score morphometry result table
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 (& mucous membranes)
ANTIBODY
DISEASE
intercel. epith. matrix
pemphigus
(desmoglein 3)
basal membrane of
epidermis
pemphigoid
Pemphigus vulgaris
Pemphigus vulgaris
Systemic
Sclerosis
SS
Sclerodermia
SS
Sclerodermia
Inflammation – autoimmune
Organ autoimmune diseases – GIT
ANTIBODY against
DISEASE
mitochondrie
primary billiary
cirrhosis
membr. hct., cytosol
CAH
gliadin
gluten
enteropathy
Celiac Sprue
man 27 yrs
4 pieces from D3 announced
 3 pieces diam. 1-2mm found


clin. dg. susp. celiakia, diff. dg. lambliasis
CD 3
CD 3
CD 3
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
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

m. Crohn
m. Crohn
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
Thyroid
m.G-B
Hashimoto Thyroiditis
Hashimoto
Thyroiditis
Epinephritis chronica
Inflammation – autoimmune
Organ autoimmune diseases – CNS
ANTIBODY
DISEASE
acetylcholin rec.
myasthenia
gravis
disseminated
sclerosis
basic myelin protein
Sclerosis cerebrospinalis multiplex disseminata – multiple sclerosis - MS
chronic autoimmune demyelinating encephalitis
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….)
Sclerosis cerebrospinalis multiplex disseminata
- virusinfluence
infection influence
2.
MS – viral
(2)




Pathogenesis
infection of endothelia – microangiitis
blood-brain- barrier disorder
serum & CSF
CD4,
CD8
(miror image to AIDS)
Pons Varoli – lux. modř
Sclerosis
cerebrospinalis
multiplex disseminata
immobility/spasticity
 anesthesia
 sight disorders
 incontinence
 cognitive dysfunction
 pain
 depresssion

Immune Disorders Diseases
Morphology
 alteration up to necrosis
 NG + lymphoplasmocellular infiltration
 fibrosis
Prognosis
 important in terms of both morbidity and
mortality – possible lethal outcome
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- thrombosisischemia

indirect recognition by the host CD4+ T cells –
AB mediated
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
acute
chronic
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
