hypersensitivity reactions, pathology and microbiology

1. HYPERSENSITIVITY
REACTIONS

2. • Immunity – protective – overcome infectious agents (antigens)
and toxins Immune response – may also be injurious to host
• Sensitised individual respond to specific antigenic stimuli in an
inappropriate or exaggerated manner
• In protective part of immunity – antigen is the focus of attention
and what happens to it Example: Bacteriolysis, Toxin
neutralization

3. • In hypersensitivity antigens are of little concern and often
innocuous or bland substances such as serum proteins or
pollen
• Hypersensitivity is concerned with what happens to host
as a result of immune reaction

4. Essentials for Hypersensitivity
• Contact with allergen
• Sensitizing/priming dose
• Induction of AMI/CMI
• Shocking dose

5. • Injurious consequences in the sensitized host, following
contact with specific antigens.
• Deals with injurious aspect of heightened and exaggerated
immune response leading to tissue damage, disease or even
death
• Concerned with what happens to the host rather than what
happens to the antigen.

6. • TRADITIONAL CLASSIFICATION
• COOMB AND GELL (1963) CLASSIFICATION
• Traditional classification is based on the time required for a
sensitized host to develop clinical reactions on re-exposure to
the specific antigen
• Coomb and Gell classification is based on mechanism of
pathogenesis

7. • TRADITIONAL CLASSIFICATION
1. IMMEDIATE HYPERSENSITIVITY: (B cell or antibody mediated)
Anaphlaxis Atopy
Antibody mediated damage
Arthus phenomenon Serum sickness
2. DELAYED HYPERSENSITIVITY
Infection (Tuberculin) type Contact dermatitis type

9. COOMB AND GELL CLASSIFICATION(4 types)
1. Type l : IgE mediated
2. Type ll : Cytolytic & Cytotoxic
3. Type lll : Immune complex
4. Type lV : Delayed hypersensitivity

12. • IgE dependant/ Reagin , mediated
Occur in 2 forms:
1. Anaphylaxis – acute, potentially fatal, systemic form.
2. Atopy – chronic or recurrent, non fatal, localized form.

13. TYPE I HS
• Ana- without, Phylaxis-protection
Classical immediate hypersensitivity reaction
• Sensitization
1. Most effective when Ag is introduced parenterally
2. Minute quantities are enough
3. Interval of 2-3 weeks needed between sensitizing & shocking dose

14. • Once sensitized it remains so for long time
• Shocking dose most effective by IV route then IP, then SC
then ID
• The shocking Ag must be same or similar to Sensitizing
Ag
• Mechanism: Cytotropic IgE – IgE antibodies bound to
surface of mast cells and basophils FcER receptors
analogous to TCR is present in these cells

15. • Schultz Dale phenomenon:
• Intestinal or uterine muscle strips – from sensitized guinea pigs – kept
in a bath of ringer’s solution – contract vigorously on addition of
specific antiserum
• Primary mediators: Histamine, Serotonin, Chemotactic factors
• Secondary mediators: Prostaglanins and Leukotrienes, Platelet
activating factor (PAF) Others: anaphylatoxins, bradykinin
• Theobald-Smith phenomenon:
• Guinea pigs - Sublethal load of sea anemones – toxin - immune

17. • IMMEDIATE REACTION 1. Activation of TH2 Cells and Production of IgE Antibody

20. • In the late-phase reaction, eosinophils that are recruited amplify and
sustain the inflammatory response without additional exposure to the
triggering antigen
• TH2 cytokine IL-5 is the most potent eosinophil-activating cytokine
known
• Eosinophils liberate two unique proteins called major basic protein and
eosinophil cationic protein, which damage tissues
• Late-phase reaction is a major cause of symptoms allergic asthma
• Treatment of these diseases requires the use of steroids, rather than
anti-histamine drugs, which are of benefit in the immediate reaction

21. Humans –
Itching of scalp & tongue, flushing of skin, difficulty in
breathing, nausea, vomiting, diarrhoea, acute hypotension,
loss of consciousness, death (rare)
Causes - Serum therapy, antibiotics, insect stings
Treatment - Adrenalin 0.5 ml (1 in 1000 solution) SC/IM
repeated up to 2 ml in 15 min

23. CUTANEOUS ANAPHYLAXIS
• Follows I.D. injection (small shocking dose) – a local wheal & flare
response is seen.
• Wheal – central pale area of puffiness due to edema
• Flare - surrounds wheal, caused by hyperemia and subsequent
erythema.
• Uses - Testing for hypersensitivity
• Precaution – Keep adrenalin injection ready to combat severe fatal
reaction.

24. ATOPY
Refers to naturally occurring familial hypersensitivities of
human beings :
• Hay fever - Asthma
• Antigens involved in atopy can be 1. Inhalants – pollen,
house dust 2. Ingestants – eggs, milk 3. Contact
allergens.

25. DIAGNOSIS
1. Skin tests (ID injection ) - with allergens like pollen, cat or dust mite
• Children - 3x3 mm wheal Adults – 4x4 mm wheal +ve test takes 5 -15
mins to develop
• persist for 30 mins or more
IMMEDIATE RESPONSE.
2. Radioallergosorbent test (RAST) - to measure the levels of Ig E in
serum

26. TYPE 2 HS
• MECHANISMS 1. Opsonization and phagocytosis

27. INFLAMMATION

28. CELLULAR DYSFUNCTION

29. TYPE 2 CYTOTOXIC REACTIONS
• Involve activation of complement by IgG or IgM binding to an
antigenic cell. Antigenic cell is lysed.

30. TYPE 2 HYPERSENSITIVITY REACTIONS
Reactions against blood cells & platelets
1. Incompatible blood transfusion.
2. Hemolytic disease of the newborn.
3. Autoimmune hemolytic anemias,
4. thrombocytopenia.
Reactions against Tissue Antigens
1. Myasthenia gravis & LATS in Grave’s
2. Pemphigus vulgaris

33. TYPE 3 HYPERSENSITIVITY REACTIONS
• Involve reactions against soluble antigens circulating in serum.
• Antibody-Antigen immune complexes are deposited in organs,
activate complement, and cause inflammatory damage.
• Glomerulonephritis: Inflammatory kidney damage.
• Occurs when slightly high antigen-antibody ratio is present.

37. Results from repeated or prolonged exposure to an antigen Occurs in several
diseases, such as systemic lupus erythematosus (SLE), which is associated with
persistent antibody responses to autoantigens

38. SERUM SICKNESS
• Systemic form of type lll HS.
• Appears 7-12 days following the injection of large doses of foreign
serum (Diphtheria antitoxin).
• ICs are deposited on the endothelial lining of blood vessels in
various parts of the body.
• Features – fever, lymphadenopathy, splenomegaly, arthritis,
glomerulonephritis, endocarditis, rashes, abdominal pain, nausea &
vomiting.

40. ARTHUS REACTION
• Local reaction consisting of edema, induration & hemorrhage.
• Followed by repeated SC injection with a foreign serum/ normal
horse serum.
• Intense local reaction – edema, induration, hemorrhagic necrosis
Reaches peak after 4 - 10 hrs, disappears by 48 hrs.
• Takes more than 12 hrs to develop.
• Involve CMI reactions.

42. TYPE 4 HYPERSENSITIVITY REACTION
• Takes more than 12 hrs to develop.
• Involve CMI reactions.
• Provoked by intracellular microbial infections or haptens like simple
chemicals
Varieties of Delayed HS :
• 1. Contact 48-72 hrs
• 2. Tuberculin 48-72 hrs
• 3. Granulomatous 21-28 days

44. CONTACT DERMATITIS
Eczematous reaction at the point of contact with an allergen, like
1. Metals – nickel, chromium
2. Simple chemicals – dyes
3. Drugs – Penicillin
Cells involved in Contact HS
1. Langerhans cells
2. Keratinocyte

45. • Lesions – vary from macules & papules to vesicles that break
down leaving behind raw weeping areas
• Detected by ‘Skin Patch Test’
• Allergen is applied to the skin under an adherent dressing.
• Itching appears in 4- 5 hrs.
• Local reaction after 24- 48 hrs: Erythema to vesicle or blister
formation

47. TUBERCULIN TYPE HS
• Tuberculin type –
ID inoculation of PPD in sensitized individual leads to induration &
inflammation in 48-72 hrs.
This is not the same as skin test done for Type I hypersensitivity.
Used for diagnosis / exclusion of diagnosis of many bacterial / fungal /
parasitic / viral and autoimmune diseases.
Leprosy, Tuberculosis, Schistosomiasis, sarcoidosis, crohns disease

51. SCWARZTMANN REACTION
Not an immune reaction
Pertubation in factors affecting intravascular coagulation
Ex: Waterhouse Freiderichsen syndrome
Meningococcal septicemia

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