Mim: Hypersensitivity Reactions

Front 1

what are hypersensitivity reactions?

Back 1

normal immune reactions that produce undesired results

Front 2

Type 1 Immune Reactions: Characteristics

Back 2

Antibody Mediated- IgE

soluble antigen

mechanism: mast-cell activation

Front 3

name the type of allergy reaction the results from the allergen entering the body thru different routes

Back 3

Systemic Anaphylaxis- blood

Acute Urticarial- skin

Seasonal Rhino Conjunctivitis- eyes and nose

Asthma- lungs

Food Allergy- GI tract

Front 4

which hypersensitivity reactions are antibody mediated? which are cell mediated?

Back 4

I, II, III are antibody mediated

IV is cell mediated (involves T cells in the immune response; does not involve antibodies)

Front 5

what makes types II and III different?

Back 5

where they occur

Type II occurs on cell surfaces

Type III occurs freely in fluid phase

Front 6

how do we develop sensitivity to a particular antigen?

Back 6

allergen must pass the barrier epithelium and be endocytosed by a DC, resulting in feeble activation

the feebly activated DC, along with help from TGF-beta polarizes a naive T-cell into a Th2 helper T cell

this Th2 cell then drives a class switch in the B-cell to a IgE producing plasma cell

the IgE antibodies attach to Fc receptors on the mast cells of the mucosa, preparing the body to mount an allergic response whenever it encounters that particular antigen

the allergic response involves the allergen cross-linking IgE antibodies on mast cells, causing them to degranulate and release their pharmacologically active mediators

Front 7

TH2 polarization and sensitization

Back 7

in NORMAL individuals, DC activation from an immunogen induces Treg production

in people with allergic predispositions, however, TH2 is produced, giving rise to IgE

Front 8

what facilitates TH2 polarization?

Back 8

-intrinsic properties of the antigen (small, soluble, and stable)
-low antigen dose
-route of presentation: skin and mucosa
-cytokines: IL-4, 5, 9, 13

Front 9

what signals facilitate class switching to IgE in B lymphocytes?

Back 9

IL-4 and IL-13 (TH2 cells, mast cells, basophils)

CD40 (B-cell) - CD40L (T-cell) ligation

Front 10

effects of mast-cell activation

Back 10

different effects in different tissues
-can actually amplify IgE production by interacting with plasma cells by releasing IL-4 and through CD40-CD40L interactions

the 2 main targets of the pharmacologically active mediators released by granulocytes are smooth muscle and blood vessels, allowing for typical immune response (edema, mucous secretion, etc.)

Front 11

IL-4, IL-13

Back 11

stimulate and amplify Th2-cell response

Front 12

TNF-alpha

Back 12

cytokine that promotes inflammation, stimulates cytokine production by many cell types, activates endothelium

Front 13

role of eosinophils

Back 13

type I reactions

similar role as mast cells

release granule antimicrobials that have hydrolytic effects and cause significant tissue damage

*secrete TH2-type cytokines (inducing further TH2 polarization, in addition to TH1 T-cell Toxic chemicals (IDO)
-inhibits TH1 polarization

Front 14

IgE-Mediated Allergic Reactions Rapid and Chronic Responses

Back 14

immediate onset- appears as a wheel and flair appearance on the skin, which are the effects of edema and inflammation

late onset- comes a few hours later; greater swelling of the area from increased cellular infiltrates (prostaglandins, leukotrienes, chemokines, and cytokines)
-more dangerous, especially in the lungs, because it can lead to fibroids and decreased lung capacity

Front 15

chronic response in Type I

Back 15

migration of TH2 cells and eosinophils to the site of inflammation from the increased permeability of the vascular tissue and the chemokines released by the mast celts

soluble Ag contacts IgE, facilitates cross-linking, releases, pro-inflammatory mediators from within mast cell, up regulates fluid secretion, and increases smooth muscle cell contraction

Front 16

type II hypersensitivity

Back 16

cell surface IgG mediated

occurs when antigens bind to IgG antibodies on cell surfaces in the body, usually red blood cells and platelets, and trigger cellular damage in one of the following manners
1. complement-mediated cell lysis
2. phagocytosis and clearance
3. Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC)- Arming of NK cells

Front 17

3 examples of Type II hypersensitivity reactions

Back 17

1. blood transfusion mismatch

2. erythroblastosis fatalis

3. drug-induced hemolytic anemia

Front 18

Erythroblastosis Fatalis

Back 18

If an Rh- mother were to become pregnant with a Rh+ baby, theres a possibility that RBCs with the Rh antigen will travel into the maternal circulation during delivery.
-if this happened, the mom would produce memory and plasma B cells with IgG antibodies specific for the Rh+ RBC's

In subsequent pregnancies with Rh+ babies, the mom's memory cells would recognize fetal Rh+ RBC's and IgG antibodies would cross the placenta to selectively attack the fetal RBCs, causing erythroblastosis fatal is

Front 19

how do we prevent erythroblastosis fatalis?

Back 19

treat the mom with Rhogam, which is a passive therapy of IgG for thesis antigen during delivery
-these IgG antibodies bind and clear the Rh+ RBCs before the maternal immune system can recognize them and mount an immune response

Front 20

how can we determine if the mother is producing IgG antibodies against fetal Rh+ RBCs?

Back 20

Coombs Test

Direct: Is there Ab bound to the fetal red blood cells?
-look for fetal RBC with maternal Ab bound
-add 2nd anti-human antibody, which is an antibody to human IgG
-agglutination/clumping occurs if moms Ab's are present

Indirect: Does mom have Ab's in her body that recognize Rh?
-incubate her blood serum with Rh+ RBC
-if she has Rh antibody, they will bind RBC
-use Coombs reagent again to facilitate cross-linking and agglutination

Front 21

drug induced hemolytic anemia

Back 21

type II hypersensitivity reaction

hapten drugs, like penicillin, like to bind to large carrier proteins, particularly RBCs and platelets

some individuals make IgG antibodies against these drugs, and since the metabolite is bound to a cell, the cell is damaged as a side effect

Front 22

type III hypersensitivity

Back 22

fluid-phase IgG mediated

also called the immune complex disease bc it forms immune complexes of soluble IgG antibodies bound to antigens

type III hypersensitivity occurs when the antigen's are in excess because they form small immune complexes (small antibody:antigen complexes)

Front 23

Type III hypersensitivity and Immune Complexes

Back 23

Type III hypersensitivity occurs when antigen's are in excess because they form small immune complexes
-these complexes are too small to precipitate so they get stuck in capillaries and cause damage

small immune complexes tend to lodge where there are large amounts of blood flow
-i.e., choroid plexus, glomerulus of the kidney, lung
this provokes an immune response and damages the tissue

the most efficient type of immune complex is when antibodies and antigens are in equivalency

Front 24

serum sickness

Back 24

"generalized" type III reaction

when a bunch of foreign serum is injected into the body , IgG antibodies against the antigen begin the be made

since antigen is in excess, it forms small immune complexes, which get trapped in the capillary beds

the immune system response by phagocytosis and complement mediated destruction, which causes fever, vasculitis, arthritis, and nephritis
-theses are all transient tho and disappear as the body is able to clear out the antigen

Front 25

arthus reaction

Back 25

"localized" type III reaction

occurs when an individual is immunized and has high levels of antibodies against the vaccine

at the site of vaccination, an IgG:Antigen immune complex forms, which then binds to the Fc receptor on mast cells
-this induces mast cell degranulation, which amounts an immune response

examples:
-bee stings
-farmers' lung from moldy sugar cane
-bird fancier's lung from bird sh!t

Front 26

Type IV Hypersensitivity Reactions

Back 26

Cell Mediated
-the only type of hypersensitivity that doesn't involve antibodies; uses T-cells instead

Takes MUCH longer bc DCs have to pick up the Ag, travel to the lymph node, present a peptide to a naive T cell, the T cell undergoes clonal expansion, and T-cell leaves the node to travel back to the site of infection

~24-38 hours after infection starts

Front 27

Tuberculosis skin test

Back 27

uses the Type IV hypersensitivity

involves injecting purified protein derivative (PPD) into the skin to see whether the body has already produced T cells to combat tuberculosis from a previous infection

if the T-cells are present, it will facilitate an immune reaction

Front 28

contact-sensitizing agents

Back 28

small, highly-reactive molecule that can easily penetrate skin

use T-cells

poison Ivy