This document discusses different types of hypersensitivity and immune responses. It covers: 1. The four main types of hypersensitivity reactions (Type I-IV) based on their immune mechanisms, examples of each type, and their characteristic features. 2. Details on Type I immediate hypersensitivity and anaphylaxis, including primary and secondary mediators, mast cell activation, and atopic susceptibility. 3. Type II antibody-mediated hypersensitivity, examples like hemolytic anemia, and mechanisms of tissue damage. 4. Type III immune complex-mediated hypersensitivity, examples like SLE, and mechanisms of inflammation and tissue damage. 5. Type IV delayed hypersensitivity, using tuberculosis as an

1. Immunity and
Hypersensitivity
• Faculty- Dr. Shefali Goyal
(Pathology)

2. Type I (Immediate
Hypersensitivity)
Anaphylaxis, Allergy, Atopy,
Asthma
Type II (Antibody
mediated)
Auto Immune Hemolytic
Anemia, Good Pasture
syndrome
Type III (Immune
complex mediated)
SLE, Serum sickness, Arthus
reaction
Type IV (Delayed
Hypersensitivity)
Contact dermatitis, Multiple
sclerosis, Type I DM,
CLASSIFICATION BASED ON
IMMUNE MECHANISMS

3. MECHANISMS OF
HYPERSENSITIVITY RN:
Type I: Immediate
hypersensitivity:
• Production of IgE antibody, release of
vasoactive amines and other mediators
from mast cells; recruitment of other
inflammatory cells (late phase reaction).
• Pathologic lesions: Vascular dilatation,
edema, smooth muscle contraction, mucus
production, inflammation.

4. Immediate (type I) hypersensitivity:
• Rapidly developing reaction
• Occurring within minutes, a state of shock is
produced; may be fatal.
• In individuals previously sensitized.
1. Immediate response: vasodilatation,
vascular leakage, smooth muscle spasm,
glandular secretions.
2. Late phase: infiltration of tissue by
eosinophils, basophils, monocytes; tissue
destruction, mucosal epithelium damage.

5. Prototype disorders:
• Anaphylaxis
• Allergies (food allergy, allergic rhinitis and
conjunctivitis)
• Asthma (Bronchial)
• Atopic forms (Hay fever)

6. Mast cells:
• BM derived cells, widely distributed in
tissues.
• Cytoplasm bound granules+ve
(metachromatic dye); contain
1. Histamine,
2. Enzymes (protease, acid hydrolase),
3. Proteoglycans (Heparin, chondratin
sulphate).
• ACTIVATION OF ANAPHYLOTOXINS: (C5a
and C3a).

8. Never forget:
1. Dendritic cells—capture antigens
2. T cells differentiate to TH-2 cells
3. IL 4 activates B cells to produce Ig E
4. Ig E attracts mast cells
(Mast cells and basophils express Ig E
receptors).
5. IL 5 activates eosinophils
6. IL 13 activates epithelial cells to produce
mucous.

9. PRIMARY MEDIATORS OF
ALLERGY
• Histamine
• Adenosine
• Heparin
• Tryptase
• Kinins
• Complements

10. Primary mediators:
• Biogenic amines: Histamine: smooth muscle
contraction, increased vascular permeability.
• Enzymes: Protease (chymase, tryptase) acid
hydrolases : tissue damage.
• Proteoglycans: Heparin (anticoagulant) &
Chondratin sulphate.

11. SECONDARY MEDIATORS OF
ALLERGY
• Lipid mediators:: Leukotrienes- LTC4,
LTD4; Prostaglandins- PGD2
• Cytokines:: PAF, TNF, IL-1, 4, 5, 6. Eotaxin
• IL-4 is mast cell regulator; released by T
cells.

12. Secondary mediators:
• Arachidonic acid derivatives: Leukotriens B4,
C4, D4—bronchial smooth muscle spasm,
vasodilatation, chemotactic for neutrophils,
eosinophils.
• Prostaglandin D2: intense bronchospasm,
mucous secretion.
• PAF (Platelet Activating Factor): platelet
aggregation, bronchospasm, vasodilatation.
• Cytokines

13. Susceptibility: Genetically
determined
• ATOPY: predisposition to develop
immediate hypersensitivity reaction to a
variety of inhaled and ingested allergens.
• Atopic individuals have increased serum
levels of Ig E levels, and more IL 4
producing TH 2 cells.

14. Systemic Anaphylaxis:
• C/F: Vascular shock, wide spread edema,
difficulty in breathing, laryngeal edema,
vomiting diarrhea, even may die.
• Occur after antisera, drugs (penicillin),
hormones, enzymes.
• Previous history of allergy is important.

15. ANTIBODY MEDIATED
(TYPE II) HYPERSENSITIVITY:

16. Mechanism:
• Antibodies are directed against antigens
present on cell surface or extracellular
substances.
• Three different mechanisms:
1. Opsonization & compliment & Fc-receptor –
mediated phagocytosis.
2. Compliment and Fc receptor mediated
inflammation.
3. Antibody mediated cellular dysfunction.

17. Type II hypersensitivity:
• O: Autoimmune hemolytic anemia, ATP,
Transfusion rn, erythroblastosis fetalis.
• C: Vasculitis, Goodpasture syndrome, ARF,
glomerulonephritis.
• A: Myasthenia Gravis, Grave’s disease, insulin
resistant DM, Pernicious anemia, Pemphigus
vulgaris.

18. EXAMPLES OF TYPE II
REACTION
• Transfusion reaction
• Erythroblastosis fetalis
• Autoimmune hemolytic anemia,
leukopenia, thrombocytopenia
• Drug reactions: Hemolysis following
Penicillin
• Phemphigus vulgaris
• Myasthenia gravis, Graves disease (Ab
mediated cellular dysfunction)

19. Type III hypersensitivity:
• IMMUNE COMPLEX MEDIATED: Ag-Ab
complexes produces tissue damage mainly
by eliciting inflammation at the site of
deposition.
• Circulating immune complexes are
deposited typically in vessel wall.
• It represents normal mechanism of Ag
removal.
• Two types: Systemic/ Localized.

20. Immune complex mediated:
• SP-PARAS:
• S: Systemic lupus erythematosis (SLE)
• P: Polyathritis nodosa (PAN)
• P: Post-streptococcal GN
• A: Acute GN (AGN)
• R: Reactive Arthritis
• A: Arthus reaction
• S; Serum sickness

21. Mechanisms:
• Phase I: Immune complex
formation
• Phase II: Immune complex
deposition
• Phase III: Immune complex
mediated inflammation

22. Factors influencing:
• Size of immune complexes: larger complexes –
rapidly removed. So relatively harmless; smaller
–circulate longer—dangerous.
• Functional status of mononuclear phagocytic
system: intrinsic dysfunction of phagocytic
system—persistence of immune complexes in
circulation.
• Charge, affinity, structure, hemodynamic
factors…,etc.

23. CELL MEDIATED (type IV)
Hypersensitivity:
• Types:
1. Delayed- type hypersensitivity: CD4
+ T- cell mediated toxicity.
2. Direct T- cell mediated cytolysis:
CD 8 + T- cells.

24. Delayed Type Hypersensitivity:
• Classic E.g..is Tuberculosis reaction:
tuberculin injection-intracutaneous-
reddening and induration appear in 8-12
hours; reaches peak by 24 –72 hours;
thereafter gradually subsides.
• Morphology: perivascular mononuclear
cells cuffing.

25. DELAYED HYPERSENSITIVITY
Tuberculin reaction
• To identify susceptible persons in the
population prone for tuberculosis
• Screening procedure; not diagnostic of
disease.
• Performed in family members of patient
with open tuberculosis
• To know the family members who can get
afflicted, who are already exposed and
Immune.

26. TUBERCULIN TEST
• Procedure: Intracutaneous Inj. of Protein
Lipopolysaccharide (LPS) extract of
Tubercle bacillus (0.1ml)
• Mark the skin site (Volar aspect of
forearm)
• Read the result after 8 to 12 hrs
• Erythema, induration appear and peak by
24 to 72 hrs
• Response measured on size of

27. • Persons are categorized as Mild, Severe
and No reaction
• Persons who are immune and
sensitized show mild reaction::::
Normal.
• Persons who are not Immune, Immune
suppressed, Immune deficient show--No
response
• Persons who are Very sensitive are more
susceptible show Severe reaction.
• Conversion of Negative to Positive
Tuberculin is more significant.

28. • This test is not used to detect tuberculosis
• Done to see susceptible persons who are
around a case of Tuberculosis
• Persons who show No reaction and
Severe reaction----- need Anti Tb
prophylaxis
• Mild reaction persons need not be given
prophylaxis.
• Persons with No reaction: Immune
suppression to be ruled out.

29. • Microscopy: Perivascular (Cuffing)
accumulation of CD4+ helper T cells,
Macrophages
• Dermal edema, Fibrin deposition
• Pathogenesis of Tuberculin Reaction:
- First exposure.. The CD 4+ T cells are
formed and stay in circulation as memory T
cells
- Subsequent exposure there is response
of memory T cells to antigens

30. TUBERCULOSIS

31. TUBERCULOSIS
Infects one third of the Worlds
population
Kills about 3 million patients each year
Single most infectious cause of death on
Earth

32. Etiology
• Mycobacterium tuberculosis
• Mycobacterium bovis
• Mycobacterium avium
• Mycobacterium intracellulare
Mycobacteria - aerobic , non-spore bearing,
non-motile , waxy coat, AFB – positive;

33. Caseation
• Lysis of Macrophages
• Direct toxicity of mycobacteria to
macrophages
• Cytokines released by macrophages such
as TNF
• Inadequate blood supply
Mycobacteria cannot grow in this acidic
environment lacking oxygen & so infection
is controlled

34. Types
• PRIMARY
• SECONDARY
• PROGRESSIVE PULMONARY
- Cavitary Fibrocaseous Tuberculosis
- Miliary Tuberculosis
- Tuberculous Bronchopneumonia

35. TRANSPLANT REJECTION
• Complex phenomenon
• Both Cell and Ab mediated immune
response
• Renal, Hepatic, Cardiac, Bone marrow
• Recognition of graft as Foreign is by Direct
& Indirect pathway
• Damage is mediated by parenchymal &
endothelial cell disruption
• Cytokine, Microvascular injury, Ischemia

36. Transplant Rejection
• Graft rejection is an immunological
response mediated primarily by T-cells
• Major antigens involved : MHC complex
• Minor antigens: Minor H antigens
– Variable non-MHC proteins
– Presented via MHC I molecules
– Rejection is slower

37. MORPHOLOGY OF GRAFT
REJECTION
• Hyperacute, Acute Cellular, Acute Humoral,
Chronic
• HYPERACUTE: Preformed Anti donor Ab are
present in circulation.
• Rejection occurs within minutes (On table)
• Graft is Cyanotic, Mottled, Flaccid.
• Widespread Acute arteritis, thrombosis,
necrosis
• Can be avoided by screening Antibodies and
Cross reaction methods

38. Hyperacute Graft Rejection
• Donor has preexisting ABO antibodies
– Previous blood transfusions
– ABO antigens also present on leukocytes, endothelial
cells
• During surgery antibodies bind to endothelial
vessels of graft
• Immediate activation of complement, blood
clotting
• Can be prevented by cross matching donor and
recipient

39. • ACUTE REJECTION: Days to weeks to
months
• Both Humoral & Cellular rejection.
• Can be delayed by Immunosuppression
• Humoral rejection Vasculitis
• Cellular rejection  Edema, parenchymal
damage

40. • CHRONIC REJECTION: Months to
years
• There is vascular damage, loss of
parenchyma, interstitial fibrosis
• Compromised blood supply, chronic
healing, effects of immunosuppressant
on parenchyma, hyalinization, fibrosis,
atrophy

41. METHODS TO INCREASE GRAFT
SURVIVAL
• HLA matching of donor & recipient
• Cross matching
• Autograft, Isograft, Allograft, Xenograft
• Immunosuppression of recipient.
• Azathioprine, Corticosteroids,
Cyclosporine, Anti lymphocyte globulins
• More Immunosuppression is not
advisable

42. GRAFT Vs HOST DISESE
• Seen commonly in Allogenic bone marrow
transplants
• Recipient is Immunosuppressed. Donor
gives immunocompetent cells
(Transplanted)
• Donor cells recognize host tissue as
foreign and cause T cell dependant injury
(delayed hypersensitivity & CTL response)

43. MORPHOLOGY OF GVHD
• Acute GVHD: Days to weeks
• Epithelial necrosis in Skin, Liver, GIT
• Jaundice, Mucosal ulceration, Diarrhea,
Rash
• Chronic GVHD: Skin lesions resemble
systemic sclerosis
• Can avoid GVHD by depleting Donor T
cells, Irradiation of graft