1. Chapter 16 Disorders of the Immune Response
Essentials of Pathophysiology
Chapter 16 Disorders of the Immune Response

2. PRE LECTURE QUIZ (True/false)
Allergic rhinitis is a systemic, life-threatening hypersensitivity reaction characterized by widespread vasodilation that leads to severe hypotension, airway constriction that causes difficulty breathing, and vascular permeability that causes swelling and obstruction of the upper airway.
Virtually any food can produce an allergic reaction.
In host-versus-graft disease, the immune cells of the transplant recipient attack the donor cells of the transplanted organ
Severe combined immunodeficiency is a disorder that results from the loss of B-cell function, while all other immune function remains normal.
The HIV-infected person can transmit the virus only when symptoms are present and the antibody test is positive.

3. PRE LECTURE QUIZ
Autoimmune I
Opportunistic
Self
tuberculin
Type __________ hypersensitivity responses result from immune responses to exogenous and endogenous antigens that produce inflammation and cause tissue damage.
The _______________ test, a test in which purified protein derivative is injected under the skin, is an example of delayed-type hypersensitivity.
Rheumatoid arthritis, insulin-dependent diabetes mellitus, ulcerative colitis, and myasthenia gravis are all examples of probable ___________________ disease.
The HIV-infected person is at risk for many ___________ infections, potentially affecting the respiratory tract, the gastrointestinal tract, and the nervous system.
_____________ tolerance refers to the inability to mount an immune response against a person’s own antigens.

4. Hypersensitivity
Excessive or inappropriate activation of the immune response
The body is damaged by the immune response, rather than by the antigen (often called allergen)
Discussion:
How many different allergies do the members of this class have?
What are their common signs and symptoms?
Can the general process of inflammation explain these signs and symptoms?

5. Type I Hypersensitivity
Commonly called “allergic reactions”
Systemic or anaphylactic reactions
Local or atopic reactions (genetic)
Rhinitis (hay fever)
Food allergies
Bronchial asthma
Hives
Atopic dermatitis (inherited)

6. Mechanism of Type I Hypersensitivity
Mast cell
Mechanism of Type I Hypersensitivity
Allergen
Allergen
attaches
to IgE
IgE attaches to mast cell
Sensitized Mast cell
Mast cell degranulates

7. Type I Allergies Are Mediated by IgE
What cells must be involved in this process:
On the first exposure to the allergen?
On repeated exposure?
When the allergen binds to IgE?
What inflammatory mediators are involved? How?

8. Question
True or False. When mast cells degranulate, histamine is released.

9. Answer
True Rationale: Histamine is one of the first chemical mediators released during the inflammatory response as a result of mast cell degranulation. Mast-cell stabilizers (used to treat asthma) prevent the histamine from being released; antihistamines (used to treat allergies) compete with histamine for receptor sites, lessening the inflammatory response.

10. Anaphylaxis
Systemic response to the inflammatory mediators released in type I hypersensitivity
Histamine, acetylcholine, kinins, leukotrienes, and prostaglandins all cause vasodilation
What will happen when arterioles vasodilate throughout the body?
Acetylcholine, kinins, leukotrienes, and prostaglandins all can cause bronchoconstriction
What will happen when the bronchioles constrict?

11. Scenario
A woman had an anaphylactic reaction and you are trying to explain the mechanism to her husband; he says he can see what you mean, but it does not make sense because what his wife experienced was different.
She said her heart was pounding and she was terrified.
Her eyes were dilated.
She was shaking.
Question:
How could anaphylaxis cause these signs and symptoms?

12. Type II Hypersensitivity
Cytotoxic
IgG or IgM attack antigens on cell surfaces
Usually involves antigens on red or white blood cells
Transfusion reactions
Rh disease
Drug reactions

13. Mechanism of Type II Hypersensitivity
Example incompatable blood transfusion
Immunoglobulins
Immunoglobulins attach to antigens
Antigens introduced
Complement activated
Directly
causes cell lysis
Cell lysis
WBCs attracted to eat cell

14. Scenario
A woman is Rh negative and her husband is Rh positive.
She is pregnant with their first child and the doctor has prescribed RhoGAM, but the woman is confused about this.
She says she does not want to take any drugs while she is pregnant—and besides, the doctor told her that her first child was not at much risk for Rh disease.
Question:
Why can’t she wait to take RhoGAM until she gets pregnant again and really needs it?

15. RHOgam a solution of IgG anti-Rh+ antibodies
bind to, and lead to the destruction of, Rh+ red blood cells that have passed from the fetal circulation to the maternal circulation.
prevents sensitization in a Rh negative mother to Rh+ antigens,
Sensitization can cause hemolytic disease in the current or in subsequent pregnancies.

16. Question
Why is type O blood considered the universal donor?
It has both A and B antigens on the RBC.
It has neither A nor B antigens on the RBC.
It has no antibodies in the plasma.
It has A and B antibodies in the plasma.

17. Answer
It has neither A nor B antigens on the RBC.
Rationale: Antigens are the components that elicit an immune response (type II hypersensitivity reaction). Type O blood has no antigens on the RBC, so anyone can receive it because there is nothing to stimulate production of antibodies against it. The fact that type O blood has both A and B antibodies has nothing to do with creating the antigen- antibody response.

18. Type III Hypersensitivity
Free-floating antigen + antibody 
circulating immune complex in the circulatory system
Autoimmune vasculitis
Glomerulonephritis
Serum sickness
Arthus reaction

19. Mechanism of Type III Hypersensitivity
Immune complexes deposit on walls of blood vessels and activate complement
Blood vessels are damaged
Immunoglobulins
Antigens
Immune complexes

20. Question
True or False. Administration of certain antibiotics may result in type III hypersensitivity reaction.

21. Answer
True Rationale: A side effect associated with antibiotic administration (especially penicillin) is serum sickness, which may cause a type III hypersensitivity reaction.

22. Type IV Hypersensitivity (Cellular immunity)
Cell-mediated: sensitized T cells attack antigen
Direct cell-mediated cytotoxicity
Viral reactions
Delayed-type hypersensitivity
Tuberculin test
Allergic contact dermatitis
Hypersensitivity pneumonitis

23. Mechanisms of Type IV Hypersensitivity
TH1 cell
Antigen
Sensitized TH1 cell
Delayed-type hypersensitivity: TH1 cell secretes inflammatory mediators
Activated Cytotoxic T cell
Direct cell-mediated cytotoxicity: Cytotoxic T cells kill tissue cells

24. Mechanisms of Type IV Hypersensitivity
An antigen enters the system
The antigen is taken up, processed, and presented on the surface of APC and local cells
APC cells present epitope to T4 helper cells
T4 cells stimulate T8 cytotoxic cells to destroy local cells that have taken up the antigen.
T4 cells release cytokines that initiated an inflamatory response
Example: TB tine test T4

25. Autoimmune Diseases Immune system attacks self-antigens
Normally, self-reactive immune cells are killed in the lymphoid organs or suppressed by regulatory T cells
In autoimmunity, this self-tolerance breaks down
Immune system destroys body tissues
Antitissue antibodies appear in blood (e.g., antithyroid antibodies)

26. Transplant Rejection Host-versus-graft disease (HVGD) Hyperacute
Circulating antibodies react with graft
Acute
Exposure to transplant causes activation of immune system, especially T cells
Chronic
Blood vessels in transplant gradually damaged

27. Graft-versus-host Disease
Transplanted immune cells attack host
A recent study suggested that men who get bone marrow transplants from women might be more prone to GVHD than men who get bone marrow transplants from other men
It also suggested that the more children a woman has had, the more likely her bone marrow will cause GVHD
Discussion:
Why might this be the case?

28. Question
True or False. Patients who suffer from autoimmune disease have hypoactive immune systems.

29. Answer
False Rationale: In autoimmune diseases, the immune system is hyperactive—it attacks self-antigens and destroys its own body tissues.

30. Immunodeficiency Primary B-cell deficiencies Ig deficiencies
T-cell deficiencies
Combined immunodeficiencies
Acquired
AIDS

31. Human Immunodeficiency Virus
Transmitted by body fluids
Sexual contact
Breast milk
Blood-to-blood contact
Contaminated needles
Transfusions
During pregnancy or birth

32. Which of your body cells have CD4 proteins and CD4 receptors?
What does reverse transcriptase do?
HIV Infects a Cell
Binds to CD4 protein receptor
Bind
Uncoat
Integrate

33. The Infected Cell Produces New HIV
Polyprotein broken into subunits by protease
HIV may lie dormant in the genome for many years before it is activated to produce viral proteins
Viral proteins are produced in a long string called a polyprotein
Transcription
Protein subunits are assembled into new virus particles
Exit

34. Question
One AIDS drug is a fusion inhibitor (Fuzeon)—the drug prevents fusion of HIV to the CD4 receptor. In the previous slides’ illustrations, which step in the infection process is targeted by a fusion inhibitor? 1 3 6 8

35. Answer
1 Rationale: In the illustration, step #1 marks the point of attachment between HIV and the CD4 receptor site on the T lymphocyte.

36. Course of HIV Infection
Primary infection phase
Signs of systemic infection
Seroconversion: immune system responds and antibodies against HIV appear (1–6 months)
Latent period
Virus is replicating, TH cell count gradually falls
May last 10–11 years or longer
Overt AIDS
TH cell count <200 cells/mL or AIDS-defining illness

37. AIDS-associated Illnesses
Opportunistic infections
Respiratory
Gastrointestinal
Nervous system
AIDS dementia complex
Malignancies
Wasting syndrome

38. Scenario A man was diagnosed as HIV-positive.
He says this is nonsense because the test does not measure whether he is sick or not
In fact, it means “his immune system is working”
Question:
Is he right?

39. Author: Please add title.