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Immunology > Hypersensitivity > Flashcards

Hypersensitivity Flashcards

1
Q

Hypersenstivity

A

Exaggerated immune responses that cause inflammation and tissue damage

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2
Q

The 4 types of hypersensitivity reactions are classified by thier ____

A

Effector mechanisms

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3
Q

Type 1 Overview

A

IgE mediated hypersensitivity to harmless antigens (soluble)

  • mas cell activation
  • allergic rhinitis, asthma, systemic anaphylaxis
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4
Q

Type 2 Overview

A

Antibody mediated destruction of cells

  • IgG
  • self antigen
  • FcR+ cells, phagocytosis by NK cells
  • autoimmune diseases
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5
Q

Type 3 Overview

A

Immune complex mediated

  • IgG
  • soluble antigen
  • FcR+ cells, complement
  • serum sickness, arthus reaction
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6
Q

Type 4 Overview

A

T cell mediated

  • Th1 cells –> soluble antigen, macrophage activation, DTH
  • CTL –> cell- associated antigen, cytotoxicity, contact dermatitis
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7
Q

Type 1 mechanism

A

Allergic response to harmless environmental antigen

  • sensitization
  • germinal center formation in 2nd week of primary response
  • isotype switching to IgE
  • memory B cells and long lived plasma cells
  • mast cells express high-affinity Fc receptor for IgE and bind free IgE from blood
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8
Q

Sensitization

A

Initial exposure generates a primary immune response

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9
Q

Allergy

A

State of hypersensitivity to a non-harmful antigen

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10
Q

Type 1 what happens with a second exposure to the original allergen?

A

Early phase: immediate
- effector function of IgE-mediated activation of mast cells = degranulation and release of histamine and TNF-alpha, leading to an inflammatory response at the site of allergy exposure

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11
Q

Allergen specific IgE

A

Mast cells express Fc-receptors for IgE

- found in connective tissues surrounding blood vessels and in the mucosa of the gut and airways

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12
Q

Mast cell degranulation effect on tissues

A

GIT: increased fluid secretion, increased peristalsis = expulsion of GIT contents
Airways: decreased diameter, increased mucus secretion = expulsion of airway contents
Blood vessels: increased blood flow, increased permeability = edema, inflammation, increased lymph flow and carriage of antigen to lymph nodes

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13
Q

Late phase (6-8 hours)

A

Mast cell synthesis

  • prostaglandins and leukotrienes = vasodilation and vascular permeabiltiy
  • cytokines and chemokines = leukocyte recruitments
  • eosinophils: respond to mast cell derived cytokines, release damaging proteases
  • basophils: IgE mediated activation or respond to mast cell derived cytokines= histamine release
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14
Q

What is the goal of the late phase response?

A

Recruit leukocytes with anti-parasite effector functions (eosinophils and basophils)
- could result in narrowing of airway or sustained edema

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15
Q

Type 1 systemic response

A

Allergen enters blood stream

- IgE mediated activation of mast cells (CT mast cells associated with blood vessels throughout the body

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16
Q

Anaphylaxis

A

Immediate type 1 hypersensitive reaction causing circulatory shock and suffocation due to bronchiole constriction

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17
Q

Histamine release by mast cells

A
  • vasodilation and vascular permeability = decrease in blood pressure
  • bronchial smooth muscle contraction
  • intestinal smooth muscle contraction
18
Q

Examples of allergens

A
  • drugs
  • insect venom
  • foods
19
Q

Heart/vascular system systemic response

A
  • increased capillary permeabilty and entry of fluid into tissues
  • swelling of tissues including tongue
  • loss of blood pressure
  • reduced oxygen to tissues
  • irregular heartbeat
  • anaphylactic shock
  • loss of consciousness
20
Q

Respiratory tract systemic response

A
  • contraction of smooth muscle and constriction of throat and airways
  • difficulty in swallowing
  • difficulty in breathing, wheezing
21
Q

GIT systemic response

A
  • contraction of smooth muscle
  • stomach cramps
  • vomiting
  • fluid outflow into gut
  • diarrhea
22
Q

Type 2 drug-induced hemolytic anemia

A
  • sensitization
  • some drugs can bind to self proteins and induce a primary immune response in allergic individuals
  • ex: antibiotics (penicillin)
23
Q

Type 2 mechanism

A
  • drug binds to self proteins to generate a new epitope (could include proteins expressed on surface of RBCs)
  • activation of a primary response to a new epitope
  • germinal center formation results in high affinity IgG
24
Q

Type 2 second exposure

A
  • antibiotics bind to self proteins expressed on RBCs
  • drug induced IgG binds to the surface of RBCs
  • drug induced hemolytic anemia: RBCs are opsonized by IgG and activated complement (C3b) = removal of opsonized RBCs by macrophages in the spleen
25
Q

Is there a type 1 hypersensitivity to penicillin in some people?

A

Yes

26
Q

Is type 3 hypersensitivity due to an allergy?

A

No, its immune complex mediated

27
Q

Type 3 local response

A

Arthus reaction: immune complexes form in tissue, cause localized inflammation
- ex: booster vaccine sometimes results in swelling and/or pain at injection site due to residual antibodies from previous vaccine forming immune complexes with vaccine antigen

28
Q

Immune complexes activate what pathway of complement?

A

Classical
- complement activation is proinflammatory
- mast cells degranulate in response to C5a and signals through the Fc recptor for IgG
- activation of Fc-gamma-R3 on mast cell induces degranulation
= local inflammation, increased fluid and protein release, phagocytosis, and blood vessel occlusion (within 2 hrs)

29
Q

Type 3 systemic response

A

Serum sickness: immune complexes form in the bloodstream in capillaries of various tissues and induce inflammation

30
Q

Type 3 systemic example

A

Snake bite treatment

  • antiserum from horses immunized with snake venom occurs with injection of a large amount of poorly catabolized foreign antigen (horse IgG)
  • excess of antigen will cause formation of small immune complexes which are depositied in blood vessel walls, leading to activation of complement in vessel wall and inflammation
  • later in immune response, large complexes are rapidly cleared form bloodstream by macrophages in liver and spleen
31
Q

Early in type 3 response there is little _____ and excess of _____

A

Antibody; antigen
= small immune complex formation
- do NOT fix complement and are not cleared

32
Q

Late in type 3 response there is large amount of ____ and little ____

A

Antibody; antigen

= medium-sized immune complexes that fix complement and are cleared from circulation

33
Q

Type 4 (delayed-type)

A
  • sensitization phase: primary immune response

- elicitation phase: mediated by memory T cells

34
Q

Is type 4 in response to an allergy?

A

NO

35
Q

Type 4 mechanism

A
  • antigen is introduced into sub q tissue and processed by local APCs
  • Th1 effector cell recognizes antigen and releases cytokines which act on vascular endothelium
  • recruitment of T cells, phagocytes, fluid, and protein to site of antigen injection causes visible lesion
36
Q

Type 4 example

A

Turberculin skin test

  • requires previous infection with Mycobacterium tuberculosis or vaccination with the attenuated M. bovis vaccine
  • mediated by memory Th1 T cells
  • Others: anthraxin test or candidin test
37
Q

Is type 4 contact hypersensitivity in response to an allergen?

A

Yes!

- T cell mediated, allergic response to chemically modified self proteins

38
Q

Contact hypersensitivity example

A

Poison ivy
- chemical from leaf can form covalent bonds and modify extracellular skin proteins (presented by MHC2) or enter cell and modify intracellular proteins (MHC1)

39
Q

Allergic contact dermatitis

A
  • activation of memory Th1 cells = proinflammatory cytokines

- activation of memory CTL = cellular cytotoxicity and IFN-gamma

40
Q

Contact hypersensitivity mechanism

A
  • contact sensitizing agent penetrates skin and binds to self proteins, which are taken up by Langerhans cells –> Langerhan cells present self peptides haptenated with contact sensitizing agent to Th1, which secrete IFN-gamma –> activated keratinocytes secrete cytokines (IL-1, TNF-alpha) and chemokines (CXCL8, CXCL11, CXCL9) –> product of keratinocytes and Th1 cells activate macrophages to secrete mediators of inflammation
41
Q

2 types of contact dermatits

A
  • allergic: immunological form, allergic response to antigen
  • irritant: non-immunological, response to chemicals that irritate or traumatize skin (no sensitizaiton, occurs immediately, chemicals activate keratinocytes to produce pro-inflammatory cyo/chemokines)

Immunology (28 decks)

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