There are four types of hypersensitivity reactions: Type I, II, III, and IV. Type I is an immediate, antibody-mediated reaction involving IgE antibodies and mast cells/basophils. Type II involves antibody binding to cells and tissues. Type III occurs when antigen-antibody complexes deposit in tissues. Type IV is a delayed, cell-mediated response involving antigen-specific T cells.

1. Hypersensitivity Reactions
• Four types.
• Three are antibody-mediated
injury.
• The fourth is cell mediated.

2. • Type I disease results from IgE
antibodies adsorbed on mast
cells or basophils are cross linked
by an antigen.

3. • Type II disorders are caused by
humoral antibodies that bind to
fixed tissue or cell surface antigen
and cause a pathologic process
by predisposing cells to
phagocytosis or to complement-
mediated lysis.

4. • Type III disorders are "immune complex
diseases“.
• antigen-antibody complexes precipitate
in vascular beds and activate
complement.
• The immune complexes and
complement activation fragments also
attract neutrophils.

5. • Type IV disorders ("delayed-type
hypersensitivity")
• Are cell-mediated immune
responses where antigen-specific
T lymphocytes are the ultimate
cause of the cellular and tissue
injury.

6. Type I hypersensitivity
• Is a tissue response that occurs
rapidly (within minutes) after the
interaction of allergen with IgE
antibody previously bound to the
surface of mast cells and
basophils in a sensitized host.

7. • 2 types:
–local reaction (e.g., seasonal
rhinitis, or hay fever, asthma)
–systemic disorder (anaphylaxis).

8. localized type I reactions
• Two well-defined phases:
–(1) the initial response,
•vasodilation,
•vascular leakage, and
•smooth muscle spasm,

9. •5 to 30 minutes after
exposure to an allergen and
subsiding by 60 minutes; and
•Mediated by mediators
released from mast cell
granules.

10. –(2) late-phase reaction
•sets in 2 to 8 hours later and lasts
for several days.
•intense infiltration with eosinophils
and other inflammatory cells, tissue
destruction.
•Mediated by the cytokines and lipid
mediators.

11. • occur at the route of exposure,
–skin (contact, causing urticaria),
–gastrointestinal tract (ingestion,
causing diarrhea), or
–lung (inhalation, causing
bronchoconstriction).

12. • Examples of localized anaphylactic
reactions.
–skin allergy
–food allergies,
–hay fever, and
–asthma

13. • Susceptibility to localized type I reactions
appears to be genetically controlled.
• Atopy is used to imply familial
predisposition to localized reactions.
• Patients who suffer from nasobronchial
allergy often have a family history of
similar conditions.

14. Systemic anaphylaxis
• Systemic (parenteral) administration of
protein antigens or drugs (e.g., bee venom
or penicillin).
• Within minutes of an exposure in a
sensitized host,
– itching,
– urticaria (hives), and
–skin erythema,
–respiratory difficulty

15. • Gastrointestinal tract - vomiting,
abdominal cramps, and diarrhea.
• Without immediate intervention ->
systemic vasodilation (anaphylactic
shock) - > circulatory collapse and
death within minutes.

16. • Mast cells and basophils are central
to the development of type I
hypersensitivity.

17. The sequence of events
• initial exposure to certain antigens
(allergens).
• stimulates the induction of CD4+ T cells
of the TH2 type.
• cytokines (IL-4 and IL-5)
• IgE production by B cells, growth factors
for mast cells, and recruit and activate
eosinophils.

18. • IgE antibodies bind to Fc receptors on
mast cells and basophils
• Re-exposure to the same antigen
• Cross-linking of the cell-bound IgE
• Cascade of intracellular signals
• The release of several powerful
mediators.

19. • Mast cell degranulation with
discharge of preformed or primary
mediators;
–Histamine
–Adenosine

20. 20

21. Histamine
–increased vascular permeability,
–vasodilation,
–bronchoconstriction, and
–increased secretion of mucus.

22. • Type I hypersensitivity plays an
important protective role in parasitic
infections.
• IgE antibodies are produced in response
to many helminthic infections, serve to
direct damage to schistosome larvae by
recruiting inflammatory cells and
causing antibody-dependent cell-
mediated cytotoxicity.

24. Type II hypersensitivity
• is mediated by antibodies directed
against target antigens on the
surface of cells or other tissue
components.
• The antigens may be normal
molecules intrinsic to cell
membranes or extracellular matrix,
or adsorbed exogenous antigens.

25. Three different mechanisms
1. COMPLEMENT-DEPENDENT REACTIONS
• Complement can mediate type II
hypersensitivity via two mechanisms:
• Direct lysis by membrane attack
complex.
• Opsonization followed by phagocytosis.

27. Clinical situations
• Transfusion reactions,
• Erythroblastosis fetalis
• Autoimmune hemolytic anemia,
• agranulocytosis, or
• Thrombocytopenia

28. 2. ANTIBODY-DEPENDENT CELL-
MEDIATED CYTOTOXICITY (ADCC)
• killing via cell types that bear
receptors for the Fc portion of IgG;
• Targets coated by antibody are lysed
without phagocytosis or complement
fixation .

30. • Mediated by leukocytes,
–Neutrophils,
–Eosinophils,
–Macrophages, and
–NK cells.

31. • ADCC is typically mediated by IgG
antibodies.
• In certain instances IgE antibodies
are used.
–Eosinophil-mediated killing of
parasites.

32. 3. ANTIBODY-MEDIATED CELLULAR
DYSFUNCTION
• antibodies directed against cell
surface receptors impair or
dysregulate function without causing
cell injury or inflammation.

33. Clinical situations
• Myasthenia gravis
– antibodies against
acetylcholine receptors in the
motor end-plates of skeletal
muscles impair neuromuscular
transmission with resultant
muscle weakness.

35. • Graves disease.
– antibodies against the thyroid-
stimulating hormone receptor
stimulate thyroid epithelial cells
and result in hyperthyroidism.

36. Type III hypersensitivity
• mediated by the deposition of
antigen-antibody (immune)
complexes, followed by
complement activation and
accumulation of
polymorphonuclear leukocytes.

37. • Immune complexes
–exogenous antigens( bacteria and
viruses)
–endogenous antigens(DNA).

38. • Immune complex-mediated injury
–systemic when complexes are formed
in the circulation and are deposited in
multiple organs or
–localized to particular organs (e.g.,
kidneys, joints, or skin) if the
complexes are formed and deposited
in a specific site.

39. SYSTEMIC IMMUNE COMPLEX DISEASE
• The pathogenesis - three phases:
• (1) formation of antigen-antibody
complexes in the circulation and
• (2) deposition of the immune
complexes in various tissues,
• (3) an inflammatory reaction in
various sites throughout the body.

41. Acute serum sickness
• prototype of a systemic immune
complex disease.
• when large amounts of foreign
serum were administered for passive
immunization (e.g., horse
antitetanus serum).

42. • First phase - 5 days after a foreign
protein is injected, specific
antibodies are produced-> react
with the antigen in the circulation
-> antigen-antibody complexes

43. • Second phase
–antigen-antibody complexes
formed in the circulation deposit in
various tissue beds.

44. Third phase - inflammatory reaction.
• 10 days after antigen administration.
• clinical features such as fever,
urticaria, arthralgias, lymph node
enlargement, and proteinuria.

45. • The favored sites of immune
complex deposition are kidney,
joints, skin, heart, serosal surfaces,
and small blood vessels.
• Localization in the kidney - filtration
function of the glomerulus.

46. • complexes leave the circulation and
deposit within or outside the vessel
wall, an increase in vascular
permeability.
–vasoactive mediators and/or
permeability-increasing cytokines
released by inflammatory cells.

47. Pathogenesis of tissue injury
• Complement activation by immune complexes
is central to the pathogenesis of injury.
• Anaphylatoxins (C3a and C5a) - increase
vascular permeability and are chemotactic for
polymorphonuclear leukocytes.
• Platelet aggregation and hagman factor
activation -> microthrombi formation and
inflammation.

48. • Phagocytosis of immune complexes by
the accumulated neutrophils -> the
release of proinflammatory
substances(prostaglandins, vasodilator
peptides, and chemotactic substances,
lysosomal enzymes, toxic oxygen radicals
-> digestion of basement membrane,
collagen, elastin, and cartilage.

49. The resultant pathologic lesion:
• vasculitis - blood vessels.
• glomerulonephritis - renal glomeruli.
• arthritis -joints, and so on.

50. Type IV Hypersensitivity (Cell-Mediated)
• Cell-mediated immunity - intracellular
pathogens Mycobacterium tuberculosis
and viruses, as well as extracellular
agents such as fungi, protozoa, and
parasites.
• can lead to cell death and tissue injury.
–contact skin sensitivity (e.g., poison )
and graft rejection.

51. • type IV hypersensitivity is mediated by
specifically sensitized T cells.
• two types:
• (1) delayed-type hypersensitivity,
initiated by CD4+ T cells, and
• (2) direct cell cytotoxicity, mediated by
CD8+ T cells.

52. • In delayed hypersensitivity, TH1-type
CD4+ T cells secrete cytokines, leading
to recruitment of other cells, especially
macrophages, which are the major
effector cells.
• In cell-mediated cytotoxicity, cytotoxic
CD8+ T cells assume the effector
function.

53. • T-CELL-MEDIATED CYTOTOXICITY
• sensitized CD8+ T cells kill antigen-
bearing target cells.
• The CD8+ effector cells, called cytotoxic T
lymphocytes (CTLs) -> critical role in
resistance to virus infections.
• CTLs also be involved in tumor immunity.

54. Our body immune defects
Primary defects
• Genetically or inborn defects
• Can be only B cell
• Only T cell
• Or sever combined B and T cell defects

55. • Secondary or acquired immune defects
• Which are after birth and can be due to
• Infectious agents eg?????
Non infectious
Chronic disease like