Immunopathology lec 2 By Dr. Mays Ibrahim - PowerPoint Presentation

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Immunopathology lec 2

By Dr. Mays Ibrahim

hypersensitivity type Ihypersensitivity

typre

IIhypersensitivity typre IIIhypersensitivity typre IV

Types of hypersensitivity reactions

Definition:

hypersensitivity reaction characterized by the formation of

in-situ or circulating

antibody-antigen

immune complexes, which deposit in tissue resulting in complement activation, inflammation and tissue injury.Examples:Serum sicknessSystemic lupus erythematosus(SLE)Glomerulonephritis

Type III hypersensitivity (immune complex disease)

Definition

: hypersensitivity reaction mediated by sensitized T lymphocyte

Delayed type

hypersensitivity

CD4+ T-cell lymphocyte mediated granuloma formationCytotoxic T cell mediatedCD8+ T cell lymphocyte destroy antigen-containing cellsExamples

PPD

skin test and tuberculosis

Viral infections, immune reaction to tumors, contact dermatitis, type 1 diabetes

Type IV hypersensitivity (cell mediated type)

is

an immune reaction to self-antigens result from loss of self-tolerance.

Self-tolerance: is the normal state of non-responsiveness to one’s own antigens.

The

mechanisms of self-tolerance can be either central or peripheral:Central Tolerance:This refers to the process by which T and B cells that recognize self antigens are either killed (negative selection) or rendered harmless.

Negative selection: T cell expressing TCR with

high affinity

for self-antigens undergo apoptosis. This happens in the thymic medulla.

Peripheral Tolerance

Auto-reactive cells that

escape central regulatory

mechanisms can be removed or inactivated in the periphery through Anergy: is irreversible functional inactivation of T cells when they recognize self-antigen

Autoimmune disease:

Definition

: chronic systemic autoimmune disease characterized by loss of self tolerance and production of autoantibodies.

Epidemiology

:

Female more than maleAge 20-45Types of Autoantibodies present:

Antinuclear antibody(ANA) (more than 95%)

Anti-

dsDNA (40-60%)Anti-Sm(20-30%)

Mechanism

of injury:

type II and III hypersensitivity reactions

Cell injury (e.g., UV light and other environmental insults) leads to apoptosis and an increased burden of nuclear antigens. Defective B and T-cell tolerance leads to autoantibodies directed against the nuclear antigens, with the resulting immune complexes being ingested by B cells and dendritic cells; subsequent TLR engagement causes further cellular activation, cytokine production, and augmented autoantibody synthesis, which causes more apoptosis in a self-amplifying loop.

Autoimmune diseases:

Systemic lupus

erythematosus

(SLE):

hematologic

Hemolytic anemia

Thrombocytopenia

Neutropenia

LymphopeniaArthritis: polyarthralgia and synovitis without joint deformity.

Skin:

Malar “butterfly” rash, sunlight exacerbates the lesions

Maculopapular rashKidney diseases:

glomerulonephritis

Heart

Libman

sacks endocarditis(no bacterial endocarditis): numerous small, warty vegetations (1 to 3 mm) on the inflow or outflow surfaces (or both) of the mitral and tricuspid valvesSerosal

surfaces: pericarditis,

pleuritis, and pleural effusions

CNS: focal neurologic symptoms, seizure, and psychosis.

Treatment: steroid and immunosuppressive agents.Prognosis:Chronic unpredictable course with remission and relapse.Death is frequently due to renal failure and infectioins

Distribution of the disease:

Definition

: autoimmune disorder characterized by

destruction

of the lacrimal and salivary glands resulting

in inability to produce tears and saliva.Epidemiology:Female more than male age range 30-50

Clinical

features:

dry eyes-keratoconjunctivitis sicca

dry mouth-

xerostomia

mikulicz

syndrome: enlargement of the salivary and lacrimal glands often associated with rheumatoid arthritis and other autoimmune diseaseanti-ribonucleoprotein

antibodies

SS-A(Ro)

SS-B(La)

Complication: increased risk of developing lymphoma. Sjo"gren Syndrome

Definition

: autoimmune disease characterized by triad of autoimmunity, non-inflammatory

vasculopathy and collagen deposition with

fibrosis(fibroblast

stimulation and deposition of collagen in the skin and internal organs)Female more than maleAge range 20-55

Pathogenesis:

Vascular damage:

microvascular injury is the hallmark of the systemic sclerosis it is thought to be due to chronic perivascular fibrosis or by direct autoimmune attack. The end process of repeated injuries lead to vascular lumen narrowing. activation of fibroblast by cytokines, interleukin-1(IL-1), platelet derived growth factor(PDGF), and /or fibroblast growth factor(FGF) leads to fibrosis.

Scleroderma(progressive systemic sclerosis)

Advanced systemic sclerosis. The extensive subcutaneous fibrosis has virtually immobilized the fingers, creating a

clawlike

flexion deformity. Loss of blood supply has led to cutaneous ulcerations

Systemic sclerosis. A, Normal skin. B, Skin biopsy from a patient with systemic sclerosis. Note the extensive deposition of dense collagen in the dermis with virtual absence of appendages (e.g., hair follicles) and foci of inflammation (arrow).

IT IS OF TWO TYPES

Diffuse scleroderma

:

characterized by

Anti-DNA topoisomerase I antibodies(Scl-70) 70%Widespread skin involovement of Early involvement of visceral organsEsophagus-dysphagia

GI tract-

malabsorption

Pulmonary fibrosis-dyspnea on exertionCardiac fibrosis-arrythmias

Kidney fibrosis-renal insufficiency

Localized scleroderma

:

characterized byAnti-centromere antibodies

Limited Skin involvement of the face and hand

Late

involovement

of visceral organsRelatively benign clinical courseCan ssociate with -CREST syndrome: Calcinosis, Raynaud phenomenon, E

sophageal dysmotility, S

clerodatyly

,

T

elangiectasia

Is

a chronic autoimmune inflammatory disease that affects mainly the joints, especially small joints (digits before wrist, ankles, elbows, and knees) in a bilaterally symmetric pattern), but can affect multiple tissues (blood vessels, skin, heart, lungs, and muscles).

RA

is caused by an autoimmune response against self-antigen(s), which leads to T cell reactions in the joint with production of cytokines that activate phagocytes that damage tissues and stimulate proliferation of synovial cells (

synovitis). Antibodies may also contribute to the disease. About 80% of patients have serum immunoglobulin M (IgM) (and, less frequently, IgA) autoantibodies that bind to the Fc portions of their own (self )

IgG

.

These autoantibodies are called rheumatoid factor. They may form immune complexes with self-IgG that deposit in joints and other tissues, leading to inflammation and tissue damageRheumatoid arthritis (RA)