Immunology - Type IV Hypersensitivity Flashcards

1
Q

Reactions caused by…

A

T lymphocyte (sometimes known as T-cell-mediated hypersensitivity)

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2
Q

T cells

A

mature in the thymus, two types that cause damage to tissues in type IV hypersensitivity = CD8+ T cells aka killer T cells or cytotoxic T cells aka CD4+ T cells/helper T cells, both start off as naive cells because their T cell receptor (TCR) has not yet bound to their target antigen

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3
Q

CD8+ killer T cells

A

silent killers of the immune system that go after very specific targets, destroy cells directly, can target antigen when they’re presented on MHC class I molecules (present on all nucleated cells in the body so every cell is a potential victim for CD8+ T cells), MHC class I molecules present antigens from inside the cell (this process is particularly important for when cells become infected with viruses or mutated like with cancer (an effector cytotoxic T cell specific to that antigen would use its TCR to bind to the MHC class I molecule which would cause it to release its perforin and granzymes, perforin would perforate the target cell by forming pores, these pores would allow the granzymes to enter into the cell, once inside the granzymes would induce apoptosis)), diseases where this cytotoxic mechanism is involved include tissue destruction in type I diabetes mellitus (CD8+ T cells attack pancreas islet cells) and hashimoto thyroiditis (CD8+ T cells attack thyroid epithelial cells)

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4
Q

CD4+ T cells

A

locally release cytokines (small proteins that can stimulate or inhibit other cells) to coordinate immune cells around them

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5
Q

Summary

A

Leads to inflammation and tissue damage via T cells which can be via either CD4+ T helper cells (help coordinate the attack) or CD8+ killer or cytotoxic T cells (directly do the attacking)

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6
Q

Urushiol reaction (poison ivy) - mechanism

A
quickly makes its way through the epidermis to the dermis where it might combine with small proteins -> might get picked up by a langerhans cell aka dendritic (a type of antigen-presenting immune cell) -> nearest lymph node (the draining lymph node) where it presents the antigen on its surface using a MHC class II molecule -> if a TH cell recognizes the antigen it binds to the MHC class II molecule using its T cell receptor as well as CD4 which is a co-receptor ->
CD4+ or helper T cell will also express a CD28 protein which will bind to the B7 protein on the surface of the dendritic cell -> dendritic cell releases interleukin 12 (cytokine, or signaling molecule) that tells the naive CD4+ T cell to mature and differentiate into a type 1 helper T cell (TH1 cell) -> 
CD4+ T cell no longer consider naive (becomes an effector cell) and able to release the cytokine IL-2, which helps both it and other T cells in the area proliferate as well as interferon gamma which activates phagocytes like macrophages and creates more TH1 cells -> activated macrophages release proinflammatory cytokines like tumor necrosis factor + IL-1 + IL-6 which cause leakiness in the endothelial barriers and allows more immune cells into the area -> local swelling or edema + redness + warmth + systemic symptoms (ie fever), lysosomal enzymes + complement components + reactive oxygen species into the exposed area damage tissue
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7
Q

Urushiol reaction (poison ivy) - type of inflammation

A

contact dermatitis (inflammation of the skin), can also happen in some people in response to wearing nickel

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8
Q

tuberculin skin test

A

sometimes called a PPD, a protein from the bacteria Mycobacterium tuberculosis is injected into the skin, if person has been exposed to TB previously they’ll develop a type IV reaction where TB specific TH1 cells will migrate to the injection site and created an inflammatory response that results in the skin getting thick or hard (induration)

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9
Q

A type IV hypersensitivity is also referred to as a ________ hypersensitivity, since it usually takes about ______ hours to recruit ___ _____ to the site of exposure, so these skin reactions usually appear over that time window.

A

delayed-type, 48-72, TH1 cells

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10
Q

pathophysiology - CD4+

A

rheumatoid arthritis (TH1 cells cause inflammation in the joints), multiple sclerosis (TH1 cells damage myelin around nerve fibers), and inflammatory bowel disease (TH1 cells cause inflammation in the lining of the intestine)

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11
Q

In addition to TH1 cells, a naive T helper cell (CD4+ T cells) might differentiate into…

A

a TH17 cell, develop in response to dendritic cells secreting slightly different cytokines (IL-6 and TGF-beta), produce IL-17 (recruiting neutrophils)

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12
Q

_______ ____ test is an example of a type __ hypersensitivity reaction

A

Tuberculin skin, IV

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13
Q

The primary cellular recruitment in a type IV hypersensitivity reaction involves T-cells and ________

A

macrophages

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14
Q

The most common type IV hypersensitivity reaction is ______ ________ that occurs after touching poison ivy

A

contact dermatitis

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15
Q

Type IV hypersensitivity is characterized by _______ symptom onset

A

delayed

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16
Q

The results of tuberculin skin test are interpreted by measuring the area of ______

A

induration

17
Q

_______ __________ are the first line of treatment for contact dermatitis

A

topical corticosteroids

18
Q

Type IV delayed hypersensitivity reaction generally peaks __ hours after antigen exposure

A

48

19
Q

Type IV hypersensitivity reaction is primarily a ___-_____ response

A

cell-mediated

20
Q

The ______ phase of the type IV hypersensitivity reaction occurs after the second exposure to a particular antigen

A

effector

21
Q

Type IV hypersensitivity reaction induces the activation of sensitized _-____

A

T-cells

22
Q

In the sensitization phase of the type IV hypersensitivity reaction T helper cells proliferate and differentiate into T _ helper cells

A

1

23
Q

pathology and causes

A

delayed T cell-mediated (antibody-independent), 24-72 hour delayed nature due to stepwise sensitization- response progression (antigen presentation by antigen presenting cells (APCs) -> naive T-cells recognition -> T-cells + macrophages migration and response)

24
Q

Role of CD4+ (helper) T cells

A
  • antigen presenting cell (APC) displays antigen on MHC II receptor -> naive CD4+ T cell binds MHC II via T cell receptor (TCR) + CD4 coreceptor -> T cell expresses CD28 -> binds APC B7 -> cobinding stimulates APC cytokine secret
  • IL 12 produced -> TH1 cell maturation -> -> Th1 secrete IL-2 and IFN gamma -> proliferation of TH1 response + macrophage recruitment and activation
  • IL 6 and TGF-beta produced -> TH17 secrete IL-17 -> recruit neutrophils
25
Q

Role of macrophages

A
  • secrete TNF alpha + IL-1 + lL-6 -> promote inflammation and leaky endothelium -> edema + fever
  • secrete lysosomal enzymes + complement + reactive oxygen species (ROS) -> tissue damage
26
Q

Role of CD8+ (cytotoxic/effector/killer) T cells

A
  • altered host cell MHC I signal -> CD8+ T cell receptor -> activate CD8+ T cells
  • secrete perforins + granzymes -> create membrane pores -> induce apoptosis
27
Q

pathophysiology - CD8+

A

type I diabetes mellitus (islet cells), Hashimoto’s thyroiditis (epithelial cells), immune response

28
Q

common type IV hypersensitivity reactions

A

allergic contact dermatitis, mantoux test, diabetes mellitus type I, hashimoto’s thyroiditis, multiple sclerosis, coeliac disease, giant-cell arteritis, postorgasmic illness syndrome, reactive arthritis, GVHD (transfusion-associated graft vs host disease)

29
Q

types - contact hypersensitivity

A

molecules covalently alter major histocompatibility complex (MHC) I receptors to neo-self antigens (nickel, urushiol)

30
Q

types - chronic, delayed hypersensitivity

A

agents unusually resistant to elimination by immune system (TB, leprosy, silicosis, sarcoidosis)

31
Q

complications

A

granuloma formation in chronic delayed hypersensitivity reactions, due to hyperactive macrophages surrounding inflammatory reaction walls off offending agent (ie sarcoidosis, tuberculosis, silicosis)

32
Q

signs and symptoms

A
  • local inflammatory reaction -> erythema, warmth, edema, fever
  • sequelae of organ-specific cell destruction (islet cell destruction in pancreas -> insulin deficiency (lethargy, seizure, coma…)
  • chronic inflammation -> granuloma formation -> organ failure
33
Q

diagnosis

A
  • exposure history of molecule/agent at site of symptoms
  • contact hypersensitivity: patch test (adhesive-mounted patches with minuscule amounts of allergen imbued in tape) and evaluate in 48-96 hours for local skin reaction
  • tuberculosis: tuberculin skin test (TST)/purified protein derivative (PPD) test, intradermal injection of tuberculin protein -> pre-sensitized T cells react to antigen -> measure induration size at 48-72 hrs, positive test (induration size) inversely related to TB exposure risk of individual
34
Q

treatment

A

corticosteroids for inflammatory control (systemic for severe, generalized reactions, otherwise site-specific (topical for contact dermatitis, inhaled for hypersensitivity pneumonitis))