immunology

1. IMMUNOPATHOLOGY
HYPERSENSITIVITY
BY GOMATHI.M

2. IMMUNOPATHOLOGY
0 Defects or malfunction in either innate or acquired
immune response provokes the illness or disease.
0 Overactive immune response-Hypersensitivity
0 Inappropriate reaction to self-autoimmunity
0 Ineffective immune response-immunodeficiency

3. HYPERSENSITIVITY
0 Undesired immune response
0 Hypersensitivity 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.

5. HISTORY
0 2000 years ago, Lucretius states that “Differences are so
great that one man’s meat is another man’s poison”.
0 Paul 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.
0 Hence they coined this overreaction as anaphylaxis.
0 Awarded Noble Prize in physiology or medicine in 1913 .

6. 0 1st exposure-sensitization
0 2nd exposure- shocking dose
0 Anaphylaxis- without protection rather than an
anamnestic (non forgetting) protective response.
0 Anaphylaxis :
0 humoral immunity – immediate hypersensitivity
0 Cell- mediated immunity – delayed-type hypersensitivity.

7. CAUSES OF HP DISEASES
0 Reaction against environmental antigens – production
of IgE antibodies cause allergic reactions.
0 Reaction against microbes
0 Autoimmunity

8. CLASSIFICATION OF
HYPERSENSITIVITY
0 In 1960s Gell and Coombs classified it into 4 types .
0 Type I – Immediate anaphylaxis
0 Type II – antibody – dependent cytotoxic hypersensitivity
0 Type III – Immune complex-mediated cytotoxicity
0 Type IV – delayed type hypersensitivity

10. TYPE I HYPERSENSITIVITY
0 CHARACTERISTICS:
0 occur quickly after 2nd exposure to the antigen or allergen
0 Inflammation reaction consists of accumulation of basophils,
eosinophils, neutrophils, Th2 cells
0 IgE mediated response
0 Antigens – plants, foods, drugs, insect products, mold
spores, animal hair, foreign serum, vaccines
0 Atopy：the genetic predisposition to synthesize
inappropriate levels of IgE specific for external allergens

11. MECHANISM

13. Slow reacting substance of anaphylaxis

14. Degranulate and release the biological mediators
Preformed granule mediators
Histamine
New generated mediators
Bradykinin Leukotrienes Platelet activating factor Prostaglandin D2
Dilate capillaries,increase permeability, increase mucus secretion, contract smooth muscle
Systemic anaphylaxis
Skin
Respiratory tract
Degist tract

15. Treat target organs
Drug
therapy:
sodium
chromoglcate-stabilize PM &
inhibit degranulation
Antihistamine &
acetyl salicylic acid

16. TYPE II HYPERSENSITIVITY
0 CHARACTERISTICS:
0 Antibody dependent cell-mediated cytotoxicity (ADCC)
0 Antibody (IgM & IgG) activate the complement system which
lyse the cell and destroy it.

17. MECHANISM

18. Allergen
Stimulate
Antibody
Cell
A. Opsonic phagocytosis
Combined opsonic activities
D. ADCC of NK
C. Effect of complement
Cell injury ways of type II hypersensitivity

19. Antigen or hapten on cell
Antibody (IgG, IgM)
Activate complement
Lyse target cell
Opsonic phagocytosis
Destroy target cell
Target cell injury
NK , phagocyte
Stimulate / block
ADCC
Change the function ofTarget cell
Mechanism of Type II hypersensitivity

20. DISEASES
0 TRANSFUSION SYNDROME
0 ERYTHROBLASTOSIS FOETALIS
0 DRUG INDUCED AUTO HEMOLYTIC ANEMIA

21. TYPE III

22. TYPE III
Free Ag + Primed Ab
Larger immune complex
Deposit in tissue or blood vessel wall
Inflammation

23. 2、Mechanism of type III hypersensitivity
Formation of the intermediate immune complex
Deposition of the intermediate immune complex
Tissue injury by the immune complex

24. 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 capillariesEliminate by phogacytosis
Combine and activate complement system
Basophils and mast cells
C3a,C5a,C3b
Platelets
Infiltration of neutrophils
Release of vasoactive amine
Blood Clotting Mechanisms
Phagocytose complex
Release of vasoactive amine
Aggregation of platlets
Release the enzymes in lysosome
Increase vascular permeability
Edema
Tissue injury
Thrombus
Increase vascular permeability
Bleeding
Local or systemic immune complex diseases
Edema

25. 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

26. 5. Type IV hypersensitivity
1、characteristics of type IV hepersensitivity
2、 mechanism of type IV hepersensitivity
3、common diseases of type IV hepersensitivity

27. 1. Characteristics
Interaction of primed T cells and associated antigen
Infiltration of Mononuclear Cells, Inflammatory response

28. 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

29. Antigen
Induce
T cell
(CD4+,CD8+)
CD4+
T cell
Release
Secondary
contact
Primed T cell
CD8+
T cell
Cytokines
IL-2
TNF-b
INF-g
TF
MCF
MIF
MAF
SRF
Infiltration of
monocyte and Mf
Proliferation of T cell
Exudation and edema
Cytotoxicity
Directly kill target cells
Inflammation characterized by infiltration of Mf , monocyte,
And tissue injury
Mechanism of type IV hypersensitivity

30. 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

31. SUMMERY

33. THANK YOU……..

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