Download Types II and III: Antibody-Mediated and Antigen

Types II and III Immediate Hypersensitivity:
Antibody-Mediated
and Antigen-Antibody Complex-Mediated
Immediate Hypersensitivity
Folder Title: AgAbHypeNoTP
Updated: December 06, 2016
Four Types of Hypersensitive (Allergic) Responses
Type II Immediate Hypersensitivity:
Antibody-Mediated Cytotoxic Attack
on Host Cells
Complement-Mediated or ADCC* - Mediated
*ADCC = Antibody-dependent Cell-mediated Cytotoxicity
Examples Shown:
ABO Blood Group in Red Blood Cell Transfusions
Rh Factor in Erythroblastosis Fetalis
Auto-antibody to Acetyl Choline Receptors in Myasthenia Gravis
If Red Cell Surface Antigens are not correctly matched in
Red-Blood Cell Transfusion…..
A, B, or AB Blood into O Recipient
A Blood into B or O Recipient
B Blood into A or O Recipient
(Type O blood is tolerated by A, B, AB, or O Recipients)
If there are RBC blood group incompatibilities between donor
and recipient:
Can get antibody attack on A or B antigens on RBC
Complement Lysis of Red Cells with bound antibody
Or
ADCC (Cell Mediated Cytotoxicity) on Red Cells
Baby with
Hemolytic Disease
of the New-Born
(HDNB)
Should be anti-ACR
(Receptor)
Auto-antibody
to Acetyl
Choline
Receptor:
Blockage of
Acetyl-Choline
Signalling in
Myasthenia
Gravis
From Roitt,
4th Ed.
Fig. 23.16
Complement-dependent attack on Ig-Fc labelled
acetyl choline receptors and progressive damage to
muscle cell end-plate and loss of acetyl-choline
receptors.
Myasthenia Gravis
Definition
Myasthenia gravis (MG) is an autoimmune disorder. The signal from the nerves to the
muscles is blocked. As a result, the muscle cannot move and become increasingly weaker.
Symptoms may grow more severe over time. This is a potentially serious condition. MG
requires care from your doctor. If you suspect you have this condition, contact your doctor
immediately.
Causes
The root cause of MG is unknown. It occurs when the body’s immune system attacks
receptors in muscle. Normally, these receptors respond to the chemical acetylcholine
(ACh). This chemical allows nerve signals to prompt the muscles to move. When the
immune system prevents these receptors from working well, the muscles cannot respond to
nerve signals.
The thymus is thought to play a role in some cases of MG. The thymus is an organ behind
the breastbone. Immune proteins called antibodies are produced there. It is these antibodies
that may target the ACh receptors. It is still not clear why the thymus begins to produce
these. helper T-cells that activate an auto-reactive B-cell antibody response to acetylcholine receptors.
"Frustrated
Phagocytosis" as a
Damage
Mechanism
in Types II and III
Hypersensitivity
From Roitt,
4th Ed.,
Fig. 23.4
Please put away all desktop stuff and all electronic
devices except your NXT Transmitter.
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Type III Immediate Hypersensitivity:
Antigen-Antibody Complex Mediated
Attack on Host Tissues
Localized: Arthritis, Nephritis
Systemic: Serum Sickness
Complement-Mediated:
• Complement Activation - General Response to AgAb
Deposition
• Complement Deficiency Failure to Clear Autoimmune AgAb Complexes
e.g. Systemic Lupus Erythrematosis (SLE)
Features of AgAb-Complex Disposition Contributing to
Type III Immediate Hypersensitivity:
Normal Removal of AgAb Complexes
• By macrophages (Ab binds to Fc receptor)
• By RBC binding of C3b Opsin to CR1 (C3b-receptor);
• Transport to Spleen for removal.
Site of Accumulation of AgAb Complexes
• At local sites (e.g. joints, kidneys, lungs)
• Systemically - "Serum Sickness"
Persistence of Triggering Antigen
Role of Complement
• Keeps AgAb from precipitating in tissues
• Marks AgAb for Removal by Reticuloendothelial
System
• Complement Deficiency leads to AgAb Accumulation
Antigen-generation and Persistence in Type III
Immediate Hypersensitivity
Persistent Infection
•
•
•
•
•
•
•
Leprosy
Malaria
Viral hepatitis
Dengue hemorrhagic fever
Staphylococcal Endocarditis
Streptococcal glomerulonephritis
Mononucleosis
Autoimmunity
• Rheumatoid arthritis
• Systemic Lupus Erythrematosis (Also autoreactive T-Cells)
Persistent Exogenous Acquisition (Inhalation of Ag)
• Extrinsic Allergic Alveolitis (e.g. Fungal antigens)
Systemic Lupus Erythematosus Patient (Systemic autoimmune Disease).
Mediated by auto-reactive T-cell clones. Attacks DNA and blood cells and other.
Shut down T-cell response with anti-CD4 Monoclonal attacking activated T-cells.
See Figure 16 -07, p. 530, Kuby 7th Edition
A.D.A.M. Medical Encyclopedia.
Systemic lupus erythematosus
Disseminated lupus erythematosus; SLE; Lupus; Lupus erythematosus;
Discoid lupus
Last reviewed: February 14, 2011.
Systemic lupus erythematosus (SLE) is a long-term autoimmune disorder that
may affect the skin, joints, kidneys, brain, and other organs.
Causes, incidence, and risk factors
Systemic lupus erythematosus (SLE) is an autoimmune disease, which means
the body's immune system mistakenly attacks healthy tissue. This leads to
long-term (chronic) inflammation.
The underlying cause of autoimmune diseases is not fully known.
SLE is much more common in women than men. It may occur at any age, but
appears most often in people between the ages of 10 and 50. African
Americans and Asians are affected more often than people from other races.
SLE may also be caused by certain drugs. For information on this cause, see
Drug-induced lupus erythematosus
Stop here: Thursday Dec. 3, 2015
Initial: Antigen-Antibody Complex
Activation of Complement
1. Complement break-down product
activation of Type 1 mast cell
degranulation with histamine release.
Extravasation of neutrophils.
2. Neutrophil activation by
complement break-down products.
Tissue damage by constant
inflammation
Autoantibodies to basement membrane
proteins. Kidney failure
Features of Rheumatoid Arthritis
Auto-IgM-antibody attack (“Rheumatoid Factor” ) on the Fc region of IgG
antibodies.
Chronic antigen-antibody deposition in joint.
Activation of complement and induction of Type III hypersensitivity with
chronic inflammation of joints.
Effects also on cardiovascular, respiratory, and hematological systems.
Elevated occurrence in women ages 40 to 60.
Please put away all desktop stuff and all electronic
devices except your NXT Transmitter.
Response
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A.D.A.M. Medical Encyclopedia.
Goodpasture syndrome
Anti-glomerular basement membrane antibody disease; Rapidly progressive glomerulonephritis
with pulmonary hemorrhage; Pulmonary renal syndrome; Glomerulonephritis - pulmonary
hemorrhage. Last reviewed: August 13, 2009.
Goodpasture syndrome is a rare disease that can involve rapidly progressive kidney failure
along with lung disease.
However, some forms of the disease involve just the lung or kidney, not both.
Causes, incidence, and risk factors
Goodpasture syndrome is an autoimmune disorder, a condition that occurs when the immune
system mistakenly attacks and destroys healthy body tissue. Persons with this syndrome
develop substances that attack a protein called collagen in the tiny air sacs in the lungs and the
filtering units (glomureli) of the kidney.
These substances are called anti-glomerular basement membrane antibodies. Glomerular
basement membrane is a part of the kidneys that helps filter waste and extra fluid from the
blood. Anti-glomerular basement membrane are antibodies against this membrane. They can
lead to kidney damage.
Sometimes the disorder is triggered by a viral respiratory infection or by breathing in
hydrocarbon solvents. In such cases, the immune system may attack organs or tissues because it
mistakes them for these viruses or foreign chemicals.
The immune system's faulty response causes bleeding in the air sacs and inflammation in the
kidney's filtering units.
Men are eight times more likely to be affected than women. The disease most commonly occurs
in early adulthood.