Hypersensitivity and its causes and effects.ppt

Hypersensitivity and its causes and effects

1. Immune Disorder
-Hypersensitivity
Prof. S. Antwi-Baffour
SBAHS

2. Hypersensitivity Reactions
A state of altered reactivity in which the
body reacts with an exaggerated
immune response to a foreign agent.

12. Hypersensitivity Reactions

13. Type I
Hypersensitivity

14. Type I Hypersensitivity
classic allergic reactions
allergens–Ags that trigger HS-I reactions
atopicpeople tend to mount IgE responses
get hay fever, asthma, etc.
mast cells / basophilsare major effectors
have high-affinity Fc receptors for IgE
granules contain mediators of HS-I reaction

15. Sensitized phase

16. Activation phase

17. Type I (Anaphylactic) Reactions
Occur within minutes of exposure to antigen
Antigens combine with IgE antibodies
IgE binds to mast cells and basophils,
causing them to undergo degranulationand
release several mediators:
Histamine:Dilates and increases permeability of
blood vessels (swelling and redness), increases
mucus secretion (runny nose), smooth muscle
contraction (bronchi).
Prostaglandins:Contraction of smooth muscle of
respiratory system and increased mucus secretion.
Leukotrienes:Bronchial spasms.
Anaphylactic shock: Massive drop in blood
pressure. Can be fatal in minutes.

18. Figure 10-1

19. Type I Hypersensitivity
Primary mediatorsin mast / baso granules
histamine–↑ permeability of the capillaries
serotonin ~ vaso-constriction
heparin –anticoagulant
chemotactic factors recruit eos, neutrophils
Secondary mediatorsmade later
arachidonic acid metabolites (PG, LT)
platelet activ. factors (PAF)
bradykinins

20. Type I Hypersensitivity
Cytokinescontribute to HS-I response
mast cells secrete IL-4, IL-5, IL-6, TNF-α
IL-4 helps activate B cells; increases IgE prod
IL-5 recruits eosinophils
IL-6, TNF contribute to inflamm. (fever, etc.)
Eosinophilsincreased in atopic individuals
have low-affinity FcR for IgE
degranulation → PAF, PG, LT
important in late-phase asthma

21. Type I Hypersensitivity
Sensitizationphase: IgE produced in response to
allergen
IgE binds to FcR on mast cells / basophils
mast cells sensitized
Activationphase: on next encounter with allergen
allergen cross-links IgE receptors on mast cell → immediate
degranulation
(mast cell degran. can also occur w. some chemicals, or C’
-anaphylatoxins C3a, C5a)
Effectorphase: tissue Rx to degranulation
vasc. perm. , mucous secretions, influx of eos, neuts, etc.

22. Biologic effects of mediators

23. Type I HS Reactions
Localizedanaphylaxis (atopy)
cutaneous anaphylaxis –wheal & flare
Urticaria (skin rash)
allergic rhinitis (hay fever)
food allergies
atopic dermatitis (allergic eczema)
asthma (lower resp. tract)

24. Type I HS Reactions
Systemicanaphylaxis worst case
anaphylactic shock
mast cells degran. all over body
3 potentially fatal Rx
laryngeal edaema–fluid leaking out → swelling
bronchiole constriction→ suffocation
peripheral edema→ shock from fluid loss
2°mediators cause prolonged effects later
late phase reaction

25. Figure 10-12

26. Identifying HS-I: Allergy Testing
skin test: small doses of allergen
look for wheal & flare
measure IgE levels

27. Treatment for HS-I Disorders
avoid allergen (Rx can get worse each time
drugs
anti-histamines(not Abs) compete w. histamine for
receptors
epinephrine–best immediate trt for anaphyl. shock
reverses effects of granules (vasoconstriction, relaxes
muscles)
quick acting, but short duration
cortisone –blocks histamine synthesis.

28. Treatment for HS-I Disorders
Immunological treatment
hyposensitization–rpt injections of allergen
may work by shifting from IgE to IgG production
MAb anti-IgEthat binds mIgE on B cells
(if binds IgE on mast cells → degranulation)

29. Type II
Hypersensitivity

30. Type II Hypersensitivity
Ab-mediated cytotoxicity
Abs vs. cell surface Ags → C’lysis or ADCC
Most common HS-II Rx involve rbc
transfusion Rx
haemolytic disease of the newborn (HDN)
autoimmune haemolytic anaemia (AIHA)

31. Antibody Dependent Cellular Cytotoxicity (ADCC)

32. Type II (Cytotoxic) Reactions
Involve activation of complementby IgG or IgM
binding to an antigenic cell.
Antigenic cell is lysed.
Transfusion reactions:
ABO Blood group system: Type O is universal
donor. Incompatible donor cells are lysed as
they enter bloodstream.
Rh Blood Group System: 85% of population is
Rh positive. Those who are Rh negative can be
sensitized to destroy Rh positive blood cells.
Haemolytic disease of newborn: Fetal cells
are destroyed by maternal anti-Rh antibodies
that cross the placenta.

33. Type II Hypersensitivity Rx
Haemolytic Transfusion Rx
ABO incompatible transfusion can → immediate
disaster
IgM isohaemagglutinins bind rbc → activate C’
rapid intravascular lysis, agglut.
renal failure, death
Dx: detection of haemoglobinuria, haemolysis
Trt: stop TF; diuretics
Prevent by crossmatch:
patient serum (Abs) + donor rbc (Ags)

34. Haemolytic Disease of Newborn (HDN)
involves Rh blood group system
3 genes C, D, E: Dmost immunogenic
get Rh Abs only by exposure to Ags
Abs mostly IgG
HDN (erythroblastosis fetalis)
Rh(D) negative mom with Rh+ fetus makes Abs
vs baby rbc that enter mom circ. at birth
next pregnancy: IgG Abs cross placenta, destroy
fetal rbc → jaundice, brain damage

36. HDN
Prevent HDN by giving mom RhoGAM after birth
anti-Rh Abs that lyse baby rbc in mom circ.
Abs also prevent sensitization (activ. of B cells)
Dx HDN in baby with Coombs test
detects Abs already on baby rbc
add Coombs rgt (anti-IgG) to baby / cord blood
look for clumping

37. Type II Hypersensitivity
Other HS-II Rx = autoimmune haemolytic
anaemia (AIHA)
autoAbs can result from drugs (e.g., penicillin)
that stick to rbc → Abs → C’activation
E

38. End of Part I
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39. Type III
Hypersensitivity

40. Type III (Immune Complex) Reactions
Involve reactions against solubleantigens
circulating in serum.
Usually involve IgA antibodies.
Antibody-Antigen immune complexes are
deposited in organs, activate complement,
and cause inflammatory damage.
Glomerulonephritis: Inflammatory kidney
damage.
Occurs with slightly high antigen-antibody
ratio present.

44. Type III Hypersensitivity
immune complex reactions
2 types of harmful Rx
Arthus Rx from localized immune complexes
serum sickness from circulating complexes

45. Arthus Rx
intradermalinjection of Ag
complexes deposit on blood vessel walls, kidney, etc
damage mech: C’activ. → inflammation
C3a / C5a chemotactic for neutrophils, cause
degranulation of mast cells
“frustrated phagocytes”–neuts. bind C3b on
complexes -can’t phago →dump granules on
complexes in tissues → damage
examples of Arthus-type Rx
insect bite
pneumonitis / farmer’s lung (dust from moldy hay)
d’se.

46. Arthus Reaction

47. Serum Sickness
generalized HS-III –circulating immune complexes
induced by injection of foreign proteins
complex deposit in capillary beds
SS: vasculitis–rash, fever, joint pain, etc.
damage mech. same as Arthus: C’and neutrophils
diseases characterized by circulating complexes
glomerulonephritis
lupus (SLE), rheumatoid arthritis.
Can be fatal due to the systemic nature!!!!

48. Type IV hypersensitivity -
Delayed-type hypersensitivity

49. Type IV hypersensitivity -
Delayed-type hypersensitivity

50. Type IV (Cell-Mediated) Reactions
Involve reactions by T
Dmemory cells.
First contact sensitizes person.
Subsequent contacts elicit a reaction.
Reactions are delayedby one or more days
(delayed type hypersensitivity).
Delay is due to migration of macrophages and T cells
to site of foreign antigens.
Reactions are frequently displayed on the skin:
itching, redness, swelling, pain.
Tuberculosis skin test
Metals
Latex in gloves (3% of health care workers affected)
Anaphylactic shock may occur.

52. Figure 10-35

53. DTH
sensitizationphase = activation of T
Hcells
activated T
H→ T
DTH(subset of T
H1 that activates
macs) → memory & effector cells

54. DTH
effector phase:activated T
DTHsecrete CK, esp.
IFN-γ
IFN-γactivates macs
activated macs secrete IL-1, IL-6, TNF-α
chronic inflammation, granulomas(lump of T
Hand
macs)

55. DTH
detect DTH with skin test
TB skin test: inject PPD → 48 hr → lump
patch test for poison ivy / oak sensitivity
lepromin Ag for leprosy
DTH is an important cell-mediated Immune
Response (CMIR) defense against intracellular
pathogens
PPD –purified protein derivatives.

56. SUMMARY

57. (hives)
Allergies
4 types of hypersensitivity reactions

58. Delayed-type hypersensitivity
Immune
complex
disease

59. End of Part II
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