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Home , Transplant rejection

AUTOIMMUNITY Transplant rejection AIDS

P. Babál ÚPA LFUK

Allergy - reaction to an allergen from the environment Autoimmunity- immune mechanisms oriented against components of self tissues Ehrlich: “horror autotoxicus” - reparative processes - frequently accompanied by against altered tissues (faster removal of these tissues) - if autoantibodies persist permanently -> autoimmunity - specific - systemic

MECHANISMS BY WHICH AUTOIMMUNITY DEVELOPS

Release of sequestered Ag - spermatozoa, lens, myelin

Abnormal T-cell function: - Systemic erythematodes, diminished Ts function other AI diseases

Enhanced Th cell function - hemolytic anemias

Polyclonal activation - SLE, EBV-induced anti-DNA Ab GENETIC FACTORS in autoimmunity

HLA system of genes - regulates immune responses = individuals with certain HLA genes expression are at higher risk to develop AI disease

Ankylotic spondyllitis B27 87.4 % Autoimmune thyreotoxicosis DR3 3.7 Hashimoto thyroiditis DR5 3.2 Diabetes mellitus II. DR3 3.3 Sclerosis multiplex DR2 4.1 Goodpasture sy. DR2 15.9 Autoimmune diseases of NERVE SYSTEM

Systemic polyradiculoneuropathy (Guillain-Barre sy.) - 3/4 weeks after viral infection = demyelinization of motor neurons … anti-myelin Ab

Myastenia gravis autoAb reacting with receptors for ACH at the neuro-muscular disc (block, destruction) -> weakness. Result of Ts failure to suppress autoimmune B-cell clones

Acute allergic encephalomyelitis - 2 weeks after viral infection, usually measles (morbilli) typical perivascular demyelinization

Sclerosis multiplex = diffuse demyelinization of CNS cell-mediated immunity against basic myelin Myastenia gravis

Thymus Autoimmune diseases of THYROID GLAND

Autoimmune thyrotoxicosis IgG Ab against TSH on thyriod gland cells

- binding of anti-TSH Ab = stimulation of proliferation and T4 secretion -> struma - Exophtalmus ... Ab against TSH receptors on ophtalmic muscles

Hashimoto struma thyroglobuline - sequestered Ag ? … NO ! it is drained by lymphatics - accumulation of lymphoid tissue -> autoAb against thyroid cells (autoreactive Th, not controlled by Ts)

DIABETES MELLITUS I. = “autoimmune ß-cell insufficiency”, =juvenile diabetes (genetic basis) Starting stimulus - usually viral infection mediated by autoreactive Tc COLLAGENOSES

= systemic autoimmune diseases with collagen damage - “fibrinoid necrosis” = mediated by immunocomplex mechanism with complement action Systemic lupus erythematodes - serum Ab against different cell components, especially nucleus Ag-Ab complexes -> tissue damage, prevalently glomeruli (membranous glomerulonephritis), arteries (arteriolitis, periarteriolar ) -> lead to tissue damage (parenchymatous organs, dermis, epidermis, CNS)

Rheumatoid arthritis = symetrical disease of joints (knees, small joins of the hand) Hyperplastic synovial membrane, destruction of cartillage. Start = pathologic IgG synthesis against some Ag (EBV ?!), “antiglobuline” synthesis = rheumatoid factor (IgM). Immune complexes destroyed in circulation, in synovial fluid … attract PMN -> damage COLLAGENOSES cont.

Polyarteriitis nodosa - similar to arteritis in serum disease. Starting factor - viral infection, medicines…, immune Ag-Ab complexes are deposited in arterial walls -> fibrinoid necrosis, thrombosis. Sclerodermia (progressive systemic sclerosis) - sclerosis, perivascular mononuclear infiltration -> skin, synovia, mucosas Ab against different

Dermatomyositis dominant symptoms = muscle weaknes, skin erythema Autoreactive T infiltration of muscles and dermis, different autoreactive antibodies -> sclerosis of dermis, dystrophy/necrosis of muscles PERNICIOUS ANEMIA

- serum autoAb against binding locus of B12 vitamin on intrinsic factor of parietal cells of gastric mucosa. Ab sythetized by plasma cells in gastric mucosa in chronic atrophic gastritis.

Other autoimmune diseases:

PRIMARY BILIARY CIRRHOSIS BULLOUS SKIN DISEASES - PEMPHIGUS - PEMPHIGOID PSORIASIS ERYTHEMA NODOSUM GLOMERULONEPHRITIS GOODPASTURE SYNDROMA INSULINE RESISTANT DIABETES SJÖGREN SYNDROMA

IgG

C3

*

* * C3

* IgG

TRANSPLANTATION REJECTION

Based on genetic relation between donor and recipient - transplantations Classify into 4 groups: 1. (autofraft), donor and recipient are the same organism. 2. Isotransplantation (isograft), donor and recipient are the same genotype. 3. Alotransplantation (allograft), donor is from the same species, with different genotype. 4. (xenograft), donor is from different species than recipient.

Most frequent transplantations: Skin, , heart, lung, liver, pancreas, and bone marrow

Successful transplantation w/out immunological rejection - pared HLA antigens of donor and recipient

Particular problem in cases of bone marrow transplantation, -versus-host (GVH) reaction Mechanisms of graft rejection

1. CELL-MEDIATED REJECTION. - mediated by T-cells: - cytotoxic T-cells (CD8+) - reaction iniciated by T helper cells (CD4+)

2. -MEDIATED REACTIONS. - present circulating antibodies in recipient as consequence of pre- sensibilisation of recipient before transplantation, e.g. transfusion of blood, pregnancy; - in non-sensibilised individuals it may be complement-mediated , antibody-related cell cytotoxicity and formation of -antibody complexes. Types of rejection reactions hyperacute, acute and chronic

1. HYPERACUTE REJECTION. - minutes to hours after introduction of transplanted organ (mediated by circulating antibodies of recipient against antigens of the donor: lymphocyte cross test of donor and recipient) hyperacute rejection is noticed immediately after vascular linking - organ usually swells, becomes hemorrhagis, pink to dark blue instead of rose. -fibrin-platelets thrombi plug capillaries, vascular wall may necrotize... necrosis and focal hemorrhage. Types of rejection reactions

2. ACUTE REJECTION. - days to months after transplantation - rejection of graft is caused by cell-mediated or antibody reaction

Acute cell-mediated rejection - infiltration intersticium of transplanted tissue by lymphocytes (mainly T-cells), damage cells and vessel walls in transplantate.

Akútna humorálna rejekcia sa objaví pri nedostatočnej odpovedi na imunosupresívnu terapiu - charakteristická vaskulitídou a fokálnou nekrózou malých ciev AKÚTNA REJEKCIA

Ly Typy rejekčných reakcií

3. CHRONICKÁ REJEKCIA.

- sa vyvinie postupne v priebehu mesiacov až rokov. - imunologické a ischemické mechanizmy

-postupná fibróza intimy ciev, interstíciová fibróza a atrofie parenchýmových buniek . (V renálnom alogénnom štepe sa môže vyvinúť glomerulonefritída prenesením z príjemcu alebo zriedka vznikne glomerulonefritída de novo). Graft-versus-host reakcia --- črevo cieva----

HE HE

CD8 CD8 Graft-versus-host reakcia --- pečeň

HE

CD8