1. Types II and III Immediate Hypersensitivity:
Antibody-Mediated and Antigen-Antibody Complex-Mediated
Immediate Hypersensitivity
Folder: AgAbHype
This folder deals with two related types of allergic reactions called "Immediate Hypersensitivity Type II" and "Immediate Hypersensitivity Type III". Type II hypersensitivity involves antibody attack on host cells, sometimes with Complement activation, and involves IgM and IgG isotypes, unlike Type I which involves the IgE isotype.
Type III hypersensitivity reactions involve the deposition of antibody-antigen complexes and the triggering of inflammatory processes, including Complement activation and antibody-dependent cell-mediated attack (ADCC).
Folder Title: AgAbHypeNoTP
Updated: December 06, 2016

2. Four Types of Hypersensitive (Allergic) Responses
This repeats the four types of hypersensitivity including Type IV T-cell mediated hypersensitivity.

3. Complement-Mediated or ADCC* - Mediated
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

4. This and the next two slides repeat what we showed about responses to mismatched blood transfusions when we talked about antigens in the first part of the course.
This is a type of antibody-mediated attack on cell surface antigens in the recipient of the mismatched transfusion. As such it is a version of Type II allergy.

7. 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

8. This and the following three slides repeat the Rh-factor story relating to hemolytic disease of the new-born. Again we covered this under antigens. The maternal IgG antibodies in the mother attack the Rh+ fetus in the second Rh+ pregnancy if she has been sensitized during the first pregnancy. This is antibody-mediated attack on cells and as such is a version of type II hypersensitivity, although the attack is not on the mother who generates the IgG antibody, but on the developing fetus that has the Rh+ antigen target on her/his red cells.

9. Baby with
Hemolytic Disease
of the New-Born
(HDNB)

12. Should be anti-ACR
(Receptor)
Auto-antibody to Acetyl Choline Receptor: Blockage of Acetyl-Choline Signalling in Myasthenia Gravis
This and the following slide show autoimmune attack by antibodies to the acetyl choline receptor. Note that the slide should say anti-AChR antibody, not anti-Ach antibody. The antibody is to the receptor, not to the acetyl choline signal.
The anti-AChR antibody blocks the receptor preventing the receptor from receiving the acetyl choline signal. This shuts down normal neuro-motor responses.
From Roitt,
4th Ed.
Fig

13. Complement-dependent attack on Ig-Fc labelled acetyl choline receptors and progressive damage to muscle cell end-plate and loss of acetyl-choline receptors.

14. 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 acetyl- choline receptors.

15. "Frustrated Phagocytosis" as a Damage Mechanism in Types II and III Hypersensitivity
From Roitt,
4th Ed.,
Fig. 23.4
In the top panel the neutrophil is ingesting a bacterium and degranulating, releasing its contents to destroy the bacterium. The bacterium is marked with an antibody and the neutrophil attaches to the Fc region of the bound antibody. A C3 co-receptor on the neutrophil confirms the interaction with C3 (a complement break-down product) on the bacterium.
In the bottom panel an antibody has labeled cells in a tissue, but the neutrophil cannot “ingest” the tissue the way it did the bacterium. The neutrophil tries to “eat” (phagocytose) the tissue cell, but it can’t because the cell is attached to other tissue cells. The neutrophil degranulates in an effort to kill what it “thinks” is a pathogen, and the granule contents damage the tissue just the way the granule contents would damage a bacterium. Again there is a confirmatory interaction between a C3 receptor on the neutrophil and a C3-labeled tissue cell.

16. Please put away all desktop stuff and all electronic devices except your NXT Transmitter.

18. (Fill in the blank Question)
Rank
Responses 1 2 3 4 5 6

19. (Fill in the blank Question)
Rank
Responses 1 2 3 4 5 6

20. 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)

21. 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

22. 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)

23. 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 , p. 530, Kuby 7th Edition

24. Systemic lupus erythematosus
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

25. 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

26. Different routes of exposure to excess antigen can give immune complex disease in different tissues.

27. Autoantibodies to basement membrane proteins. Kidney failure
This is a repeat of Slide 18, but shows also that drug reactions, for example to penicillin or sulphonamides can trigger Type III allergy and the deposition of Antigen-Antibody complexes.
This slide also shows additional infectious disease syndromes such as meningitis, and trypanosomiasis (a worm disease), that can trigger Type III allergy.

28. 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.

29. Please put away all desktop stuff and all electronic devices except your NXT Transmitter.

30. Response Counter

31. 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.