IMMUNOPATHOLOGYHYPERSENSITIVITY

BY GOMATHI.M

IMMUNOPATHOLOGY

0Defects or malfunction in either innate or acquired immune response provokes the illness or disease.

0Overactive immune response-Hypersensitivity0 Inappropriate reaction to self-autoimmunity0 Ineffective immune response-immunodeficiency

HYPERSENSITIVITY

0Undesired immune response

0Hypersensitivity is a state existing in a previously sensitized individual which leads to tissue damage on later exposure to the allergen.

0 It depends on the individual.

HISTORY02000 years ago, Lucretius states that “Differences are so

great that one man’s meat is another man’s poison”.

0Paul Poiter and Charles Richet- Pysalia the jelly fish- aqueous glycine extract administered to 5 dogs but they didn’t die. But after the second dose immediately reacted with illness, vomiting, diarrhea, asphyxia and died within few minutes.

0Hence they coined this overreaction as anaphylaxis.0Awarded Noble Prize in physiology or medicine in 1913 .

01st exposure-sensitization02nd exposure- shocking dose 0Anaphylaxis- without protection rather than an

anamnestic (non forgetting) protective response.

0Anaphylaxis :0 humoral immunity – immediate hypersensitivity0Cell- mediated immunity – delayed-type hypersensitivity.

CAUSES OF HP DISEASES

0Reaction against environmental antigens – production of IgE antibodies cause allergic reactions.

0Reaction against microbes

0Autoimmunity

CLASSIFICATION OF HYPERSENSITIVITY

0 In 1960s Gell and Coombs classified it into 4 types .

0Type I – Immediate anaphylaxis 0Type II – antibody – dependent cytotoxic hypersensitivity0Type III – Immune complex-mediated cytotoxicity0Type IV – delayed type hypersensitivity

TYPE I HYPERSENSITIVITY0CHARACTERISTICS: 0occur quickly after 2nd exposure to the antigen or allergen 0 Inflammation reaction consists of accumulation of basophils,

eosinophils, neutrophils, Th2 cells0 IgE mediated response0Antigens – plants, foods, drugs, insect products, mold

spores, animal hair, foreign serum, vaccines0Atopy ： the genetic predisposition to synthesize

inappropriate levels of IgE specific for external allergens

MECHANISM

Slow reacting substance of anaphylaxis

Degranulate and release the biological mediators

Preformed granule mediators New generated mediators

Histamine Bradykinin Leukotrienes Platelet activating factor Prostaglandin D2

Dilate capillaries,increase permeability, increase mucus secretion, contract smooth muscle

Systemic anaphylaxis Skin Respiratory tract Degist tract

Drug therapy: sodium chromoglcate-stabilize PM & inhibit degranulation

Antihistamine & acetyl salicylic acid

Treat target organs

TYPE II HYPERSENSITIVITY0CHARACTERISTICS:

0Antibody dependent cell-mediated cytotoxicity (ADCC)

0Antibody (IgM & IgG) activate the complement system which lyse the cell and destroy it.

MECHANISM

Allergen

Stimulate

Antibody

A. Opsonic phagocytosis

D. ADCC of NK

C. Effect of complement

Combined opsonic activities

Cell injury ways of type II hypersensitivity

Cell

Antigen or hapten on cell

Antibody (IgG, IgM)

Activate complement

Lyse target cell

Opsonic phagocytosis NK , phagocyte Stimulate / block

Destroy target cell ADCC

Target cell injury Change the function ofTarget cell

Mechanism of Type II hypersensitivity

DISEASES

0TRANSFUSION SYNDROME

0ERYTHROBLASTOSIS FOETALIS

0DRUG INDUCED AUTO HEMOLYTIC ANEMIA

TYPE III

Free Ag + Primed Ab Larger immune complex

Deposit in tissue or blood vessel wall  

Inflammation

TYPE III

2 、 Mechanism of type III hypersensitivity

Formation of the intermediate immune complex

Deposition of the intermediate immune complex

Tissue injury by the immune complex

Soluble antigen Body Antibody

Immune complex

Small molecular soluble Immune complex

intermediate molecular soluble Immune complex

Large molecular insoluble Immune complex

Deposit on the basement of capillaries

Combine and activate complement system

C3a,C5a,C3b

Infiltration of neutrophils

Phagocytose complex

Release the enzymes in lysosome

Tissue injury

Eliminate by phogacytosis

Platelets

Thrombus

Aggregation of platlets

Blood Clotting MechanismsRelease of vasoactive amine

Increase vascular permeability

Bleeding Edema

Basophils and mast cells

Release of vasoactive amine

Increase vascular permeability

Edema

Local or systemic immune complex diseases

3. common disease of type III hypersensitivity 1. Local immune complex disease

Arthus reaction ： Experimental local reaction, Necrotic vasculitis vasculitis, Ulcer

Human local reaction: insulin-dependent diabetes mellitus (IDDM) 2. Acute systemic immune complex disease

   serum sickness  Anti-serum Ab+Ag systemic tissue injury ,fever, arthritis, skin rash Pinicillin、 Sulfanilamide

Acute immune complex glomerulonephritis : Streptococcus infection

3. Chronic immune complex disease

SLE Rheumatoid arthritis ： RF+IgG Deposit on synovial membrane

5. Type IV hypersensitivity

1 、 characteristics of type IV hepersensitivity

2 、 mechanism of type IV hepersensitivity

3 、 common diseases of type IV hepersensitivity

1. Characteristics

Interaction of primed T cells and associated antigen

Infiltration of Mononuclear Cells, Inflammatory response

2. Mechanism of type IV hypersensitivity

Formation of effector and memory T cells

Inflammation and cytotoxicity caused by effector T cells

1) Inflammation and tissue injury mediated by CD4+Th1

Release chemokines and cytokines

Immune injury mainly caused by infiltration of mononuclear cells and

lymphocytes

2) Cytotoxicity of CD8+CTL

Antigen T cell(CD4+,CD8+)

Secondary contact

Induce

Primed T cell

CD4+ T cell

CD8+ T cell

ReleaseCytokines

IL-2TNF-bINF-g

TFMCFMIFMAFSRF

Directly kill target cells

Infiltration of monocyte and Mf

Proliferation of T cell

Exudation and edema

Cytotoxicity

Inflammation characterized by infiltration of Mf , monocyte, And tissue injury

Mechanism of type IV hypersensitivity

3. Common disease of type IV hypersensitivity

1) Infectious delayed type hypersensitivity

OT( Old Tuberculin ) test

2) Contact dermatitis :

Paint, drug red rash, papula, water blister, dermatitis

3) Acute rejection of allogenic transplantation and

immune response in local tumor mass

Same disease (SLE), multiple immune injury ,hypersensitivity involved

Same drug (penicillin), several types of hypersensitivity

SUMMERY

THANK YOU……..

0 Immunopathology, diagnosis, and management of hypersensitivity pneumonitis.0 Abstract0 Hypersensitivity pneumonitis (HP) is an inflammatory interstitial lung disease caused by a wide variety of organic

particles and certain small-molecular weight chemical compounds that provoke an exaggerated immune response in susceptible individuals. The clinical manifestations are heterogeneous and have been classically described as acute, subacute and chronic. The chronic form has an insidious onset over a period of months or years, with progressive dyspnea and often evolves to fibrosis. The pathology is characterized by a bronchiolocentric interstitial mononuclear cell infiltration, nonnecrotizing poorly formed granulomas, cellular pneumonitis and variable degrees of fibrosis. However, morphological diagnosis of HP is complicated because the subacute/chronic forms may be difficult to distinguish from idiopathic pulmonary fibrosis/usual interstitial pneumonia and nonspecific interstitial pneumonia. In general, diagnosis of HP represents a challenge for clinicians that need to weigh a constellation of clinical, laboratory, radiographic and (when available) pathological evidence for each patient to assess the certainty of the diagnosis. The cornerstone of therapy is antigen avoidance. Although clinical trials are scanty, corticosteroids are usually indicated based upon expert opinion. In this review we summarize the current evidence regarding the diagnostic criteria and therapeutic strategies as well as the immunopathological mechanisms putatively implicated in the development of the disease.

0 Arch Pathol Lab Med. 2008 Feb;132(2):204-5. doi: 10.1043/1543-2165(2008)132[204:HPAIR]2.0.CO;2.0 Hypersensitivity pneumonitis: an immunopathology review.0 Woda BA.0 Source0 Department of Pathology, University of Massachusetts Medical School, Worcester, USA. wodab@ummhc.org