Hypersensitivity I, II - Grayson Flashcards

1
Q

Allergic individuals exhibit the condition termed ___ and are termed ___. These individuals exhibit higher than normal levels of circulating ___ and ___—important effectors of the allergic response. ___ is linked to several genetic loci including region encoding several cytokine genes and HLA class ___ alleles.

A

Allergic individuals exhibit the condition termed atopy and are termed atopic. These individuals exhibit higher than normal levels of circulating IgE and eosinophils—important effectors of the allergic response. Atopy is linked to several genetic loci including regions encoding several cytokine genes and HLA class II alleles. Atopic: is a syndrome characterized by a tendency to be “hyperallergic”

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2
Q

___ in immune system genes can determine whether you are atopic or not.

A

Polymorphisms

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3
Q

___ allergen doses favor what response?

A

Low allergen doses favor Th2 response.

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4
Q

Low doses of antigens favor ___ response. The antigens are almost always very small and typically soluble. Allergens are always ___ because they are recognized by __ cells.

A

Low doses of antigens favor Th2 response. The antigens are almost always very small and typically soluble. Allergens are always peptides because they are recognized by Th2 cells.

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5
Q

Features of inhaled allergens that may promote the priming of Th2 cells that drive IgE response.

Protein - only proteins induce the ___ response

Allergens are often ____

A low dose of allergen favors ___ (cytokine) producing CD_ T__ cells

Allergen can diffuse out of particle into mucus because they are ___

A

Features of inhaled allergens that may promote the priming of Th2 cells that drive IgE response.

Protein - only proteins induce the T cell response

Allergens are often proteases

A low dose of allergen favors IL-4 (cytokine) producing CD4 Th2 cells

Allergen can diffuse out of particle into mucus because they are small

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6
Q

Cross linking antigen to IgE bound to mast cell induces what?

A

Mast cell activation and granule response

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7
Q

Granule release from mast cells in the GI tract will cause what?

A

Increased fluid secretion, increased peristalsis –> vomiting and diarrhea

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8
Q

Mast cell activation and granule release in the airways cause:

A

decreased diameter, increased mucus secretion –> congestion and blockage of airways (wheezing, coughing, phlegm)

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9
Q

Mast-cell activation and granule release in blood vessels cause:

A

increased blood flor, increased permeability –> increased fluid in tissues causing increased flow of lymph to lymph nodes, increased cells and protein in tissue, and an increased effector response in tissues

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10
Q

Mediators released by mast cells:

Enzymes are ____ and ___. They work by ___ the tissue matrix

Toxic mediators are __ and ___. These are toxic to ___, increase ___ permeability, and cause __ ___ contraction.

Cytokines are ___, ___, which stimulate Th2 response, and ___, __ and ___ which promote eosinophilic production and activation

Chemokines are ___ (MIP 1 alpha) which attract ___,__ and ___.

Lipid mediators are ___, which cause SM contraction, increased vascular permeability and stimulation of mucus secretion. ____ attracts leukocytes, amplified production of lipid mediators and activates __, __ and __.

A

Mediators released by mast cells:

Enzymes are tryptase and chymase. They work by remodeling the tissue matrix

Toxic mediators are heparin and histamine. These are toxic to parasites, increase vascular permeability, and cause smoth muscle contraction.

Cytokines are IL 4, IL-13, which stimulate Th2 response, and IL-3, IL-5, and GM-CSF which promote eosinophilic production and activation

Chemokines are CCL3 (MIP 1 alpha) which attract monocytes, neutrophils and macrophages.

Lipid mediators are leukotrienes, which cause SM contraction, increased vascular permeability and stimulation of mucus secretion. Platelet activating factor attracts leukocytes, amplified production of lipid mediators and activates neutriphils, eosinophils and platelets.

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11
Q

Type I HSR are usually done in two phases:Immediate and Late

Immediate and Late

Immediate Phase: in response to allergen binding and crosslinking of the IgE receptor, mast cells are rapidly triggered to release preformed granule-associated contents:

P____

L____

P___

H___

TNFa

Then, immediate phase initiates the production of:

Cytokines (IL-4, IL-5, IL-13, TNFa)

Chemokines

Leukotrienes

Results in the recruitment and activation of Th2 cells, eosinophils, basophils and neutrophils.

Late Phase occurs 8-12 hours later

A

Immediate and Late

Immediate Phase: in response to allergen binding and crosslinking of the IgE receptor, mast cells are rapidly triggered to release preformed granule-associated contents:

Prostaglandins

Leukotrienes

Platelet activating factor (PAF)

Histamine

TNFa

Then, immediate phase initiates the production of:

Cytokines (IL-4, IL-5, IL-13, TNFa)

Chemokines

Leukotrienes

Results in the recruitment and activation of Th2 cells, eosinophils, basophils and neutrophils.

Late Phase occurs 8-12 hours later

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12
Q

Which two cytokines are produced after allergy exposure?

A

IL4, and IL-13.

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13
Q

What are some possible reasons for why there is increased allergic airway disease?

A
  • Antibiotic use early in life
  • Altered gastrointestinal microbiota
  • Dietary changes
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14
Q

____ are the mediators of peripheral immunologic tolerance

The normal microbiota may promote activation of _____ in the GI tract and thus prevent unwanted responses against many harmless antigens

How?

Most likely by releasing ___ signals that dampen inflammation and promote ___ activation

A

Regulatory T cells are the mediators of peripheral immunologic tolerance

The normal microbiota may promote activation of regulatory T cells in the GI tract and thus prevent unwanted responses against many harmless antigens

How?

Most likely by releasing chemical signals that dampen inflammation and promote regulatory T cell activation

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15
Q

Fox3p is expressed at high levels only in ____ cells.

A

CD4+CD25+T cells.

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16
Q

What is IPEX?

A

Immunodysregulation, polyendrocrinopathy, and enteropathy, X-linked (IPEX)

  • Mutation present in fox3p gene resulting in the absence of Fox3p, a transcription factor
  • Patients exhibit a broad range of autoimmune pathologies
  • Fox3p is expressed at high levels ONLY in CD4+CD25+ T cells (a phenotype of the Treg cells)
  • CD4+CD25+Fox3p+ cells exhibit regulatory activity in suppress self-reactivity and responses in the absence of TLR signaling by direct contact, by creating immunosuppression cytokines, and can also cause death in self-reactive cells.
17
Q

What is the phenotype of a Treg cell?

What happens if someone has IPEX?

A

CD4+CD25+FOX3P

Immunodysregulation, polyendrocrinopathy, and enteropathy, X-linked (IPEX)

  • Patients exhibit a broad range of autoimmune pathologies
  • Mutation present in fox3p gene resulting in the absence of Fox3p, a transcription factor
  • Fox3p is expressed at high levels only in CD4+CD25+ T cells
  • CD4+CD25+Fox3p+ cells exhibit regulatory activity in preventing self-reactivity and responses in the absence of TLR signaling
18
Q

In immunodysregulation, polyendrocrinopathy, and enteropathy, X-linked (IPEX)

  • Patients exhibit a broad range of ____ pathologies
  • Mutation present in ___ gene resulting in the absence of ____, a transcription factor
  • ____ is expressed at high levels only in ___ T cells
  • ____ cells exhibit regulatory activity in preventing self-reactivity and responses in the absence of ___ signaling
A

In immunodysregulation, polyendrocrinopathy, and enteropathy, X-linked (IPEX)

  • Patients exhibit a broad range of autoimmune pathologies
  • Mutation present in fox3p gene resulting in the absence of Fox3p, a transcription factor
  • Fox3p is expressed at high levels only in CD4+CD25+ T cells
  • CD4+CD25+Fox3p+ cells exhibit regulatory activity in preventing self-reactivity and responses in the absence of TLR signaling
19
Q

Treg gets turned down when you get positive __ signaling. This makes sense, because if you have positive ___ signaling, it probably means you have an infection.

A

Treg gets turned down when you get positive TLR signaling. This makes sense, because if you have positive TLR signaling, it probably means you have an infection.

20
Q
  • CD4+CD25+ Treg cells arise in the ____
  • They are activated by ____ cells in the absence of ___ signaling
  • Suppressive function occurs via release of ___ and ___
A
  • CD4+CD25+ Treg cells arise in the thymus
  • They are activated by dendritic cells in the absence of TLR signaling
  • Suppressive function occurs via release of TGF-beta and IL-10
21
Q

Treg cells can be stimulated by DC’s in the absence of TLR signaling. Once stimulated, they release __ and __. Normally, you want Treg function. It is only when you get TLR signaling that you want to turn ___ Tregs. Why?

A

Treg cells can be stimulated by DC’s in the absence of TLR signaling. Once stimulated, they release TGF-beta and IL-10. Normally, you want Treg function. It is only when you get TLR signaling that you want to turn off Tregs, so that you can turn the rest of the immune system up.

22
Q

In a person with ____ microbiota, the microbiota activates the ____ cells, and ___ them. In ___ microbiota, __ cells are NOT activated, and the cells are uninihibited.

A

In a person with normal microbiota, the microbiota activates the Treg cells, and inhibits Th2 cells. In abnormal microbiota, Treg cells are NOT activated, and Th2 cells are uninihibited.

23
Q

Breast-feeding results in the transfer of:

____ - Introduces the soluble antigens via the oral route –> often results in antigen-specific tolerance

____ - promotes the generation of Tregs

Outcome: ____ tolerance and the absence of a subsequent allergic response

A

Breast-feeding results in the transfer of:

Allergen - Introduces the soluble antigens via the oral route –> often results in antigen-specific tolerance

TGF-beta - promotes the generation of Tregs

Outcome: Antigen-specific tolerance and the absence of a subsequent allergic response

24
Q

The following two examples are examples of a ___ HSR.

  1. Drug-induced (penicillin) hemolytic anemia and thromobocytopenia
  2. Hemolytic anemia of the newborn

How does this drug induced hemolytic anemia occur?

How does hemolytic anemia of a newboth occur?

A

The following two examples are examples of a Type II HSR.

  1. Drug-induced (penicillin) hemolytic anemia and thromobocytopenia
  2. Hemolytic anemia of the newborn

How does drug induced hemolytic anemia occur?

  1. Drug (e.g., penicillin) binds to red blood cells or a platelet.
  2. IgG antibodies recognized this penicillin bound to the platelet or RBC (it won’t recognize the penicillin or RBC separately..only together).
  3. Classical complement pathway is activated, resulting in red blood cell (hemolytic anemia) or platelet (thrombocytopenia) destruction via lysis or phagocytosis.

How does hemolytic anemia is newborns occur?

  1. Maternal RBC are Rh-negative, whereas fetal RBC are Rh-positive
  2. During first delivery, fetal RBC enter maternal circulation resulting in sensitization and maternal production of anti-Rh antibodies
  3. In a subsequent pregnancy, anti-Rh antibodies (IgG) cross the placenta resulting in fetal damage or death
25
Q

Hemolytic anemia of the newborn, and drug-induced anemic hemolytica are a type __ HSR.

A

II

26
Q

Your patient’s RBC”s are Rh-, while her fetal RBC’s are Rh+. What are you most worried about and how will you deal with this problem?

A

Since the mom is Rh-, she has anti-Rh+ antibodies. If her fetus is Rh+, then the mothers IgG’s against Rh+ RBC’s will cross the plancenta and cause damage or death to the fetus’ RBCs.

Prevention:

Give large amount of anti-Rh IgG to mother at time of delivery of the first child.

Why?

Presence of antibodies suppresses anti-Rh antibody response and thus the generation of memory B cells specific for Rh antigen

27
Q

Type __ HSR:

  1. Antigen and antibody (IgG) interact in solution and cause inflammation and tissue/organ damage.
  2. If complexes are retained locally, then the damage is also local, e.g., Arthus reaction or Farmer’s lung.
  3. If immune complexes can circulate, then systemic, multi-organ effects occur, e.g., glomerulonephritis.
  4. Renal glomeruli and synovia are the most common sites of deposition because these are sites of ultrafiltration of plasma under high hydrostatic pressure.
A

Type III

  1. Antigen and antibody (IgG) interact in solution and cause inflammation and tissue/organ damage.
  2. If complexes are retained locally, then the damage is also local, e.g., Arthus reaction or Farmer’s lung.
  3. If immune complexes can circulate, then systemic, multi-organ effects occur, e.g., glomerulonephritis.
  4. Renal glomeruli and synovia are the most common sites of deposition because these are sites of ultrafiltration of plasma under high hydrostatic pressure.
28
Q

In a ___ HSR,

Renal glomeruli and synovia are the most common sites inflammation because of ___ deposition, and because these are sites of ____ of plasma under high hydrostatic pressure.

A

In a Type III HSR,

Renal glomeruli and synovia are the most common sites inflammation because of antibody-antigen deposition, and because these are sites of ultrafiltration of plasma under high hydrostatic pressure.

29
Q

Arthur’s reaction or farmers lung, is an example of a ___ HSR.

A

Type III HSR

30
Q

Type IV HSR:

Also termed a ____ Response.

Occurs between ____ hours after exposure to antigen ____ cell-dependent

Classic example: ???

A

Type IV HSR:

Also termed a Delayed Hypersensitivity Response.

Occurs between 24-72 hours after exposure to antigen Th cell-dependent

Classic example: TB skin test

31
Q

Which one, Th1 or Th2, is involved in Type IV HSR?

A

Th1

32
Q

What type of HSR is this?

  1. Contact sensitizing agent penetrates the skin and binds to self proteins, which are taken up by Langerhans’ cells – an immature dendritic cell.
  2. Mature Langerhans’ cells (mature DC’s) present self peptides haptenated with the contact sensitizing agent to Th1 cells.
  3. Activated Th1 cells secrete gamma interferon and chemokines which attract macrophages.
  4. Th1 cells activate macrophages to secrete mediators of inflammation such as cytokines (IL-1, TNFa), nitric oxide, lipid mediators (prostaglandins and leukotrienes), oxygen radicals.

This is how poison ivy works.

A

Type IV

33
Q

Poison ivy contact dermatitis is a type ___ HSR and invovles what type of T cells?

A

CTL (Cytolytic T lymphocytes)

Poison ivy contact dermatitis:

Pentadecacatechol interacts with intracellular proteins to create altered self.

CTLs target cells expressing these altered proteins.