allergy, hypersensitivity, types of allergy

1. Topic: 'Hyper sensitivity'
Presented by: Sadya Laraib
6th semester (A)
Roll no. 30.

2. 1. Definition:
 It is excessive immune response which leads
to undesirable consequences, i.e. tissue or
organ damage/ dysfunction.
 immune responses which are damaging
rather than helpful to the host.
 Excessive immune response in a
sensitized individual (atopic) leading to
tissue damage.

3. Why hypersensitivity occurs in some
people? (not all)
 Allergins
 Low immunity from childhood
 Host factors include heredity, gender, race, and
age, with heredity being by far the most significant.
 However, there have been recent increases in the
incidence of allergic disorders that cannot be
explained by genetic factors alone.
 Four major environmental candidates are
alterations in exposure to infectious diseases during
early childhood, environmental pollution, allergen
levels, and dietary changes.

4. Types of Hypersensitivity:
Nearly 45 years ago Gell and
Coombs proposed a classification
scheme which defined 4 types of Hypersensitivity type I
hypersensitivity reactions.
Ab mediated: type:Ⅰ, Ⅱ, Ⅲ Hypersensitivity type II
(Immediate)
T-cell mediated: type Ⅳ (Delayed)
Hypersensitivity type III
Hypersensitivity type IV

6. Hyper sensitivity type I:
IgE mediated, immediate
hypersensitivity/ allergy
Major features:
React and disappear quickly
on re-exposure to Ag
Dysfunction rather than
severe tissue and cell damage
occurs
Obvious individual
difference and genetic
correlation
By mast cells and basophils

7. MECHANISM OF ACTION
BASIC ELEMENTS ARE:
1. MEDIATOR = IgE
2. PRIMARY CELLULAR COMPONENT = MAST
CELL AND BASOPHILS
3. AMPLIFIER = PLATELETS, NEUTROPHILS
AND EIOSINOPHILS

8. MECHANISM OF ACTION

9. MECHANISM OF ACTION
STEP 1:
EXPOSURE OF ANTIGEN TO ANTIGEN
PRESENTING CELL

11. MECHANISM OF ACTION
STEP 2:
RECOGNITION BY T- HELPER CELLS
ACTIVATION OF B-CELLS INTO PLASMA AND
MEMORY CELLS
SECRETION OF ANTIBODIES (IgE)

13. MECHANISM OF ACTION
STEP 3:
IgE BINDS TO HIGH AFFINITY RECEPTORS
(FC EPSILONRI)
ON THE SURFACE OF MAST CELLS

15. MECHANISM OF ACTION
STEP 4:
SUBSEQUENT EXPOSURE OF ANTIGEN
ANTIGEN BINDS WITH IgE ON THE SURFACE
OF MAST CELLS

16. Mechanism of action

17. MECHANISM OF ACTION
STEP 5:
RELEASE OF PRIMARY INFLAMMATORY
METABOLTES
ACTIVATION OF SECONDARY METABOLITES

18. SYMPTOMS
1. May vary from minor inconvenience to
death
2. Usually take 10 to 30 mins to appear after
exposure to antigen
3. Sometimes delayed onset of reaction (10-
12h)

19. MECHANISM OF ACTION
MOLECULE EFFECTS
PRIMARY MEDIATORS
HISTAMINE VASCULAR PERMEABILITY, SMOOTH MUSCLE CONTRACTION
SEROTONIN VASCULAR PERMEABILITY, SMOOTH MUSCLE CONTRACTION
ECF-A EOSINOPHIL CHEMOTAXIS
NCF-A NEUTROPHIL CHEMOTAXIS
PROTEASES MUCUS SECRETION, CONNECTIVE TISSUE DEGRADATION
SECONDARY MEDIATORS
LEUKOTRIENES VASCULAR PERMEABILITY, SMOOTH MUSCLE CONTRACTION
PROSTAGLANDINS VASCULAR PERMEABILITY, SMOOTH MUSCLE CONTRACTION
AND PLATELET ACTIVATION
BRADYKININ VASCULAR PERMEABILITY, SMOOTH MUSCLE CONTRACTION
CYTOKINES NUMEROUS EFFECTS INC. ACTIVATION OF VASCULAR ENDOTHELIUM,
EOSINOPHIL RECRUITMENT AND ACTIVATION

20. CLINICAL"a serious allergic reaction that is rapid
Anaphylaxis is defined as
DISEASES
in onset and may cause death". It typically results in a number of
symptoms including an itchy rash, throat swelling, and low blood
pressure. Common causes include insect bites, foods, and
medications. Anaphylaxis
Asthma (from the Greek, "panting") is the
common chronic inflammatory disease of
the airways characterized by variable and recurring
symptoms, reversible airflow obstruction, etc
Allergic rhinitis is an allergic inflammation of the nasal airways. It Asthma
occurs when an allergen, such as pollen, dust or animal dander
(particles of shed skin and hair) is inhaled by an individual with a
sensitized immune system.
The protein in the food is the most common allergic component.
These kinds of allergies occur when the body's immune system
mistakenly identifies a protein as harmful. Some proteins or Allergic Rhinitis
fragments of proteins are resistant to digestion and those that
are tagged by the IgE. The immune system, thinking the
organism (the individual) is under attack, triggers an allergic
reaction. These reactions can range from mild to severe. Allergic
responses include dermatitis, gastrointestinal and respiratory
distress, including such life-threatening anaphylactic
responses and vasodilation; these require immediate emergency
intervention. Individuals with protein allergies commonly avoid
contact with the problematic protein. Some medications may
prevent, minimize or treat protein allergy reactions. injectable
form of epinephrine such as an EpiPen

21. DIAGNOSTIC TESTS
1. PRICK TEST
2. TRANSDERMAL TEST
3. ELISA

22. TREATMENT
1. ANTIHISTAMINES
2. Chromolyn sodium
3. leukotriene receptor blockers
4. use of IgG antibodies

23. Hyper sensitivity type II:
Definition:
A hypersensitivity resulting from
antibodies mistakenly reacting with
normal self antigens on body cells.
Binding of the antibodies to these
normal cells results in immune
destruction.

24. MEDIATORS
IgG OR IgM
IN THIS CASE
1. MADE AGAINST SELF ANTIGENS
2. ATTACH TO THE SURFACES OF CELLS HAVING
SELF EPITOPS
SELF ANTIGEN=Any constituent of the body's own
tissues capable of stimulating autoimmunity

25. FACTORS FOR RELEASE OF
MEDIATORS
1. FAILURE IN IMMUNE TOLERANCE
2. ENTERANCE OF FOREIGN ANTIGEN
RESEMBLING SOME MOLECULE ON THE
SURFACE OF HOST CELLS
 'IMMUNE TOLERANCE' is the process by which
the immune system does not attack an antigen

26. MECHANISM OF ACTION
THESE FACTORS LEAD TO:
1. OPSONIZATION
2. MAC LYSIS
3. ADCC

27. 1- OPSONIZATION
DEFINITION:
The attachment of microbes and other foreign
cells to phagocytes by antibody molecules such
as IgG and complement proteins such as C3b.
Also called enhanced attachment or immune
adherence.

28. OPSONIZATION
MECHANISM
THE OPSONIZATION IS OF THE HOST CELL
PHAGOCYTES STICK TO MEMBRANES OF HOST
CELL
VIA IgG, C3B, C4B
PHAGOCYTES DISCHARGE THEIR LYSOSOMES

29. OPSONIZATION
RESULT:
LYSIS OF HOST CELL

30. 2- MAC LYSIS
DEFINITION
A protein complex produced during the
complement pathways. C5b6789 (MAC or
membrane attack complex) puts pores into
lipid bilayer membranes of human cells to
which antibodies have bound. This results in
cell lysis.

31. MAC LYSIS
MECHANISM
IgG / IgM
BINDS WITH EPITOPS ON CELL SURFACES
ACTIVATE CLASSICAL PATHWAY OF
COMPLEMENT SYSTEM
MAC CAUSES LYSIS OF CELL

32. MAC LYSIS
MECHANISM

33. 3-ANTI-BODY DEPENDENT
CYTOTOXICITY (ADCC)
DEFINITION
The process of NK cells binding to the Fc
portion of antibodies that have bound to
epitopes of cells recognized as nonself such
as infected cells and tumor cells. Once bound
to the Fc portion of the antibody, the NK cell
will then lyse that cell with perforins.

34. ADCC
MECHANISM
IgG / IgM
BINDS WITH EPITOPS ON CELL SURFACES
NK CELLS ATTACH TO THE Fc PORTION OF IgG/IgM
RELEASE OF PERFORINS AND GRANZYMES BY NK
APOPTOSIS

35. ADCC
MECHANISM

36. ADCC
MECHANISM

37. EXAMPLES OF TYPE 2
HYPERSENSITIVITY
 AB AND RH BLOOD GROUP REACTIONS;
 AUTOIMMUNE DISEASES SUCH AS:
 RHEUMATIC FEVER where antibodies result in joint and
heart valve damage;
 IDIOPATHIC THROMBOCYTOPENIA PURPURA where
antibodies result in the destruction of platelets;
 MYASTHENIA GRAVIS where antibodies bind to the
acetylcholine receptors on muscle cells causing faulty
enervation of muscles;
 GOODPASTURE'S SYNDROME where antibodies lead to
destruction of cells in the kidney;

38. EXAMPLES OF TYPE 2
HYPERSENSITIVITY
 SOME DRUG REACTIONS.
 TYPE II HYPERSENSITIVITY ALSO
PARTICIPATES IN EARLY TRANSPLANT
REJECTIONS.

39. DIAGNOSTIC TESTS
1. DETECTION OF CIRCULATING ANTIBODY
AGAINST THE TISSUES INVOLVED
2. THE PRESENCE OF ANTIBODY AND
COMPLEMENT IN THE LESION (BIOPSY) BY
IMMUNOFLUORESCENT STAINING
(PATTERN = LINEAR).

40. TREATMENT
 ANTI-INFLAMMATORY DRUGS
 IMMUNOSUPPRESSANT DRUGS

41. Hyper sensitivity type III:
(THE IMMUNE COMPLEX HYPERSENSITIVITY)
Definition:
A hypersensitivity resulting from
large quantities of soluble antigen-
antibody complexes passing
between endothelial cells of the
blood vessels and becoming trapped
on the surrounding basement
membrane.

42. COMPOSITION OF IMMUNE
COMPLEX
1. SELF OR NON-SELF ANTIGEN
2. ANTIBODIES
MOSTLY IgG
RARELY IgM
 PATHOLGY OCCURS AT THE SITE OF
DEPOSITION

43. CAUSE OF TYPE 3 HYPERSENSITIVITY
NORMALLY
SOLUBLE ANTIGEN-ANTIBODY COMPLEX
FORMATION
REMOVED BY MACROPHAGES IN SPLEEN
AND LIVER

44. CAUSE OF TYPE 3 HYPERSENSITIVITY
ABNORMALLY
INCREASED SOLUBLE ANTIGEN-ANTIBODY
COMPLEX FORMATION
NOT ALL REMOVED BY MACROPHAGES IN
SPLEEN AND LIVER
DEPOSITION OF COMPLEXES VIA BLOOD
VESSELS

45. MECHANISM OF ACTION
STEP 1
Large quantities of soluble antigen-antibody complexes
form in the blood and are not completely removed by
macrophages.

46. MECHANISM OF ACTION
STEP 2
These antigen-antibody complexes lodge in the blood
vessels between the endothelial cells and the basement
membrane.

47. MECHANISM OF ACTION
STEP 3
These antigen-antibody complexes activate the
classical complement pathway leading to
vasodilation

49. MECHANISM OF ACTION
STEP 4
The complement proteins and antigen-
antibody complexes attract leukocytes to the
area.

51. MECHANISM OF ACTION
STEP 5
The leukocytes discharge their killing agents
and promote massive inflammation. This can
lead to tissue death and hemorrhage.

53. EXAMPLES OF TYPE 3
HYPERSENSITIVITY
1. SERUM SICKNESS, A COMBINATION TYPE I
AND TYPE III HYPERSENSITIVITY
2. AUTOIMMUNE ACUTE
GLOMERULONEPHRITIS
3. RHEUMATOID ARTHRITIS
4. SOME CASES OF CHRONIC VIRAL
HEPATITIS

54. DIAGNOSTIC TESTS
1. Examination of tissue biopsies for deposits of
immunoglobulins and complement by
immunofluorescence (pattern = granular)
2. The presence of immune complexes in serum
3. Depletion in the level of complement

55. TRAETMENT
 ANTI-INFLAMMATORY DRUGS

56. Hyper sensitivity type IV:
(THE CELL MEDIATED OR DELAYEDTYPE HYPERSENSITIVITY)
Definition:
A hypersensitivity resulting from
cell-mediated immunity (cytotoxic
T-lymphocytes and cytokines)
causing harm to the body.

57. CAUSE OF TYPE 4 HYPER-
SENSITIVITY
 CAUSED BY T-CELLS
1. T-HELPER CELLS BY SECRETION OF
CYTOKINES
2. MAINLY BY CYTOTOXIC T-CELLS BY
DIRECT DAMAGE

58. MECHANISM OF ACTION
T-H CELLS INDUCED
STEP 1
ANTIGEN ENTERS THE BODY
ENGULFED BY MACROPHAGES
PRESENTED TO T-H CELLS
T-H CELLS BECOMES ACTIVATED AND
INCREASED IN NUMBER

59. MECHANISM OF ACTION
T-H CELLS INDUCED
STEP 2
SECOND EXPOSURE
ENGULFED BY MACROPHAGES
PRESENTED TO T-H CELLS
T-H CELLS RELEASE CYTOKINES

61. MECHANISM OF ACTION
T-H CELLS INDUCED
STEP 3 T-H 2 CELLS RELEASE
T-H 1 or TD CELLS IL-4 AND IL-5
RELEASE CYTOKINES
ATTRACTION FOR MORE PROMOTE
MACROPHAGES AT THE EXTRACELLULAR
SITE OF ATTACK KILLING BY
EOSINOPHILS
MORE INFLAMMATION
TISSUE DAMAGE
SKIN LESIONS

63. MECHANISM OF ACTION
CTOTOXICT CELLS INDUCED
STEP 1
ANTIGEN BINDS TO NORMAL CELL
EPITOPE PRESENTED WITH MHC-1
CTL ATTACHED BY TCR/CD8+
ACTIVATION OF T-CELL

64. MECHANISM OF ACTION
CTOTOXICT CELLS INDUCED
STEP 2
ACTIVATION OF CYTOTOXIC T-CELL
RELEASE OF
1. PORE-FORMING PROTEINS CALLED
PERFORINS
2. PROTEOLYTIC ENZYMES CALLED
GRANZYMES
3. CHEMOKINES

66. MECHANISM OF ACTION
CTOTOXICT CELLS INDUCED
STEP 3
PERFORINS FORM PORES
GRANZYMES PASS THROUGH PORES
ACTIVATE ENZYMES OF CELLS
APOPTOSIS

67. MECHANISM OF ACTION
CTOTOXICT CELLS INDUCED

68. EXAMPLES OF TYPE 4
HYPERSENSITIVITY
 THE CELL OR TISSUE DAMAGE done during
diseases like tuberculosis, leprosy, smallpox,
measles, herpes infections.
 THE SKIN TEST REACTIONS seen for
tuberculosis and other infections
 CONTACT DERMATITIS like poison ivy
 TYPE -1 INSULIN-DEPENDENT DIABETES
where CTLs destroy insulin-producing cells

69. DIAGNOSTIC TESTS
1. IN VIVO
1. Mantoux test
2. Patch test
2. INVITRO
1. Lympho-cytotoxicity
2. IL-2 production