Hypersensitivity Flashcards Preview

Skin > Hypersensitivity > Flashcards

Flashcards in Hypersensitivity Deck (52):
1

Type I hypersensitivity immune reactant

IgE

2

Hypersensitivity

An excessive immune response against foreign, often innocuous, antigens - which may result in tissue damage or death

3

Sensitization

The initial exposure to an antigen that primes the immune system to elicit a reaction to a subsequent exposure to that antigen

4

Allergen

Antigen that elicits immediate hypersensitivity

5

Allergy

A reaction caused by an allergen

6

Atopy

Familial predisposition (genetic) reaction to allergen

7

Cells involved in type I hypersensitivity

Mast cells, basophils, and eosinophils

8

Histamine

An amine derivative of histidine that is involved in vasodilation and increase capillary permeability

9

Where is histamine released from?

Exosomes; means immediate result (no transcription/translation)

10

What do mast cells and basophils release to mediate type I hypersensitivity reaction?

-Histamines
-Lipid mediators: Leukotrines and prostaglandins
-Cytokines

11

Leukotrienes function

Smooth muscle contraction, increase capillary permeability, and mucus secretion

12

Prostaglandins function

Vasodilation and increase capillary permeability, PMN recruitment

13

Cytokines involved in type I hypersensitivity with mast cells/basophils and their functions

TNF-alpha: proinflammatory cytokine
IL-4, IL-5, IL-13: Th2 response

14

Sensitization response

1.) Prior to the hypersensitivity reaction, the individuals must have been exposed to the allergen
2.) Prototypical immune response for adaptive immunology takes place
3.) Production of plasma cells that secrete allergen-recognizing IgE
4.) IgE associates with the Fc receptor (FcεRI) on mast cells and primes, or sensitizes it for quick activation

15

2 phases of immediate reaction

Effector or elicitation phase and late-phase reaction

16

Effector/elicitation phase in immediate reaction

1.) Exposure to the antigen again is immediately recognized by the IgE-bound antibody on mast cells (crosslinking of the FcεRI receptors activate mast cells)
2.) Activation of mast cells result in degranulation and release of mediators (the vasoactive amines and lipid mediators result in the immediate reaction)

17

Late-phase reaction in immediate reaction

-Cytokines result in this a few hours after exposure
-Few hours post exposure
-Accumulation of PMNs, eosinophils, basophils, T helper cells, and their mediators
-May occur without prominent immediate reaction

18

Immediate reaction in immediate hypersensitivity

-Seconds to minute exposure
-Histamine and lipid mediators increase vascular permeability
-Wheal-and-flare response

19

Wheal

Redness and local swelling due to initial vessel dilation

20

Flare

Subsequent dilation promotes red rim

21

Chronic allergic inflammation

repeated exposure that results in persistent inflammation – may alter tissue (asthma, eczema, hay fever)

22

Immediate hypersensitivity anaphylaxis

Systemic activation of mast cells (such as from a bee sting) can lead to severe anaphylaxis

23

Anaphylaxis leads to...

Widespread vascular permeability and fluid leaving blood, may cause BP to drop

24

Clinical features of anaphylaxis

Resp: nasal obstruction, increased mucus, dyspnea, wheezing
CV: hypotension, shock
Skin: urticaria, angioedema, pruritus, erythema
GI: pain, nausea, diarrhea
Hematological: thrombocytopenia, DIC

25

How does epinephrine counteract the disease state during anaphylaxis?

Vascular smooth muscle contraction, increased cardiac output, and inhibit mast cell degranulation

26

Hygiene hypothesis

-Allergy is on the rise in developed countries
-Treg cells and IL-10 production capacity are low
-skew towards Th2 response
-IgE, IL-4, IL-5, IL-13

27

Function of chemokines in type I hypersensitivity

Recruit PMNs, monocytes, and macrophages

28

Late-phase reaction in immediate hypersensitivity

-Few hours post exposure
-Accumulation of PMNs, eosinophils, basophils, T helper cells, and their mediators
-May occur without prominent immediate reaction

29

Immediate hypersensitivity clinical responses

-Food/drug allergies (hives, anaphylaxis, flushing, angioedema)
-Atopic dermatitis (eczema)
-Atopic urticaria (hives)
-Atopic rhinoconjunctivitis (allergic rhinitis, hay fever)
-Asthma

30

Genetics of atopy (reaction to allergen)

MHCII, TCR-alpha, IL-4, FcεRI, and Th1/2 balance

31

IL-10 function

-Elevated in helminth infested individuals
-Blocks mast cell degranulation

32

Type I hypersensitivity diagnostics

-Application (skin prick or intradermal injection) of allergen in skin to visualize wheal and flare
-Blood test to detect specific IgE (results take days)

33

Type I desensitization

To gradually decrease IgE-dominant response towards IgG or Treg response (IL-10)

34

Type II hypersensitivity

-Antibody mediated disease caused by anti-tissue antibody
-Main antibody – IgG, IgM
-Antibody targets tissues or extracellular matrix
-2 - 24 hours

35

Effector mechanisms of type II hypersensitivity

1.) Opsonization and phagocytosis
2.) Complement and Fc receptor-mediated inflammation
3.) Abnormal physiologic response w/o injury

36

HDNB

Rh- mothers may carry an Rh+ fetus; fetal erythrocytes enter mother's circulation during childbirth and anti-Rh antibodies produced in the mother; subsequent pregnancies in which the fetus is Rh+ may result in fetal erythrocyte destruction due to IgG crossing placenta (RhIG administration w/i 72 hours after first Rh+ birth)

37

Type II hypersensitivity reactions

Blood transfusions
Autoimmune hemolytic anemias
Autoimmune thrombocytopenic purpura
Goodpasture syndrome
Pemphigus vulgaris
Penicillin sensitivity (non allergic)
Acute rheumatic fever

38

Grave's

receptor of thyroid gland targeted by TSI (triggers production of TSH); symptoms: irregular heartbeat, bulging eyes, anxiety, heat sensitivity, weight loss, goiter

39

Myasthenia gravis

-Autoantibody targets acetylcholine receptors
-Blocks acetylcholine binding, resulting in defective neuromuscular transmission
-Symptoms: muscle weakness, localized paralysis, strabismus (eye misalignment), ptosis (drooping eyelids), difficulty swallowing

40

Type III hypersensitivity

-Antibody mediated disease caused by immune complexes
-Main antibody – IgG, IgM
-Antibody targets soluble antigen
-Hours, days, weeks

41

Effector mechanisms of type III hypersensitivity

-Immune complex formation (normally cleared by classical complement and phagocytes)
-Certain immune complexes may get deposited on tissue
-Phagocytes (PMNs) recognize antibody via Fc receptors and complement via CRs (receptors activate cells to secrete inflammatory mediators>>tissue inflammation and injury)

42

Most common sites of immune complex deposition

Small arteries (vasculitis)
Renal glomeruli (nephritis)
Joint synovium (arthritis)

43

Serum sickness

-Individuals w/ no prior exposure
-Antitoxin administration from horse serum
-Controls toxin but mounts response against horse antibodies
-Symptoms: fever, weakness, rash, edema (7-21 days later)

44

Arthus reaction

-Localized form of type III hypersensitivity that causes vasculitis
-Subcutaneous antigen is delivered to a previously immunized individual to that antigen
-Antibody-antigen complexes form in the area of injection
-Symptoms: inflammation, pain, and necrosis in severe cases

45

Type III hypersensitivity reactions

Systemic lupus erythematosus
Polyarteritis nodosa
Granulomatosis with polyangiitis (Wegener’s disease)
Farmer’s lung

46

Type IV hypersensitivity

-Type IV hypersensitivity is also delayed type hypersensitivity (DTH)
-Cell-mediated reaction
Th1
Th2
CTL (CD8+)
-2 days to weeks post exposure

47

Effector mechanisms of type IV

-Antigen processed by APC,
-Th1 activated (IFN-gamma, macrophage activation and inflammatory mediators released)>>tissue damage
-Th2 cells are activated
IL-5 – Eosinophil activation and inflammatory mediators released>>tissue damage
-Th17 cell are activated
IL-17 – PMN recruitment and activation>>tissue damage
-CTL activation – direct cytotoxicity of recognized MHCI-antigen

48

Basis of tuberculin/PPD/Mantoux test

-Individuals who have had Mycobacterium tuberculosis infection have produced memory CD4+ T cells to mycobacterial antigens
-Exposure to PPD (tuberculin purified protein derivative) will activate these memory CD4+ T cells, release proinflammatory cytokines, and recruit macrophage, resulting in an indurated skin lesion 48-72 hours later

49

Allergic contact dermatitis

-skin inflammation including pruritic papules and vesicles on an erythematous base
-Upon first contact with an allergen, sensitization may take 10 - 14 days (Langerhans cells (DCs))
-Subsequent contact = hours to days (T cell mediated)
-most common chemicals that cause ACD are:
-Nickel Preservatives, dyes, and fragrances
-Chemicals in rubber gloves
-Many are haptens

50

Poison Ivy

-ACD reaction
-component of plant penetrates skin and associated with proteins in keratinocytes
-Primary exposure: memory T cells
-Secondary exposure: Th1, macrophage, and CTL cells target skin

51

Chronic DTH reactions

-Cell types involved derived from macrophages
-Epithelioid cells
-Multinucleated giant cells
-Tissue damage due to size and location of granuloma
-Granulomas often form in diseases with persistent antigen
-Tuberculosis
-Leprosy
-Leishmaniasis

52

Type IV hypersensitivity reactions

Hashimoto thyroiditis
Rheumatoid arthritis
Type I Diabetes
Celiac disease
Crohn disease
Multiple Sclerosis