PHRM 542 Antibodies, Hypersensitivity, Drug Allergies, and Autoimmunity

What are the components of antibodies?

Light chain and heavy chain components

Mostly constant regions

'Ends' variable regions, then hypervariable regions

What are the 5 types of immunoglobulins (Ig)?

IgM, IgG, IgA, IgD, IgE

Describe IgM

First response

Largest (pentamer)

Describe IgG

Smallest, most common

Where is IgA usually found?

In areas open to the external environment (ex: eyes, ears, mouth, urinary tract, reproductive tract)

Where is IgD usually found?

Small amounts in the mesenchyme

Where is IgE usually found?

Lungs, skin, mucous membranes (overlaps where you find IgA)

What is an important function of IgE?

MAJOR part of allergic response and anaphylaxis

Define hypersensitivity

Too much immune system activation that causes an allergic response

Describe type I hypersensitivity

Immediate reaction

IgE-mediated degranulation

How does IgE mediate type I hypersensitivity reactions?

IgE binds basophils which get rid of all their content and degranulates when bound by IgE

The stuff in a basophil causes an immune reaction

What are symptoms of a type I hypersensitivity reaction?

Anaphylaxis, asthma, hives

Describe type II hypersensitivity

Ag:Ab complexes with IgM or IgG which "gunks up the system" because of the conglomerate masses of antibodies and antigens

Think blood transfusion reactions

Describe type III hypersensitivity

Ag:Ab complexes deposit in basement membranes and vessels which causes a localized immune reaction with increased vascular permeability

What are examples of type III hypersensitivity reactions?

Skin rash, glomerulonephritis, arthritis

Describe type IV hypersensitivity

Cell mediated

2-3 days post exposure

Describe a type I drug allergy

IgE-mediated and acute

Includes anaphylaxis, urticaria, angioedema

How does IgE mediate a type I drug allergy?

IgE fixed to mast cells and basophils, interaction releases potent mediators

Describe a type II drug allergy

Modification of host proteins, eliciting Ab response

IgG or IgM mediated, fixes to a host cell, leading to complement-associated lysis or Ab-dependent cytotoxicity

Antigen is the DRUG

Describe a type III drug allergy

Serum sickness involving immune complexes with IgG and multi system complement-dependent vasculitis = URTICARIA

Describe a type IV drug allergy

Cell-mediated allergy with contact dermatitis or skin induration from injection

How can prednisone help treat drug allergies?

Immunosuppressive = blocks proliferation of IgE producing clones and inhibits TH cells making IL-4

How can epinephrine help treat drug allergies?

Reduces release of mediators from mast cells and basophils

Induces bronchodilation, contracts vascular muscle

Opposes histamine

How can antihistamines help treat drug allergies?

Inhibit histamine induced bronchoconstriction and increased capillary permeability

How can other glucocorticoids help treat drug allergies?

Reduce tissue injury and edema

Facilitate catecholamines in epi-resistant cells

How can desensitization help treat drug allergies?

Small doses may bind IgE on mast cells, leading to gradual granule release

Once degranulated, safe enough to give therapeutic doses

What are important considerations of desensitization?

Hazardous, high risk of anaphylaxis

Define autoimmunity

Body sees self as foreign which activates self-reactive T and B cells

Cell mediated or humoral responses against self

How does autoimmunity happen?

Exposure of self-reactive T cells previously sequestered

Invading pathogens look like self (molecular mimicry)

Aberrant MHC II expression by non-immune self cells

What are examples cases in which we would want to suppress the immune system?

Transplantation to prevent rejection

Autoimmunity

When would we want to selectively modulate the immune system?

Immunodeficient disorders

Chronic infection diseases

Cancer related myelosuppression