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CHAPTER 16 DISORDERS OF THE IMMUNE RESPONSE Essentials of Pathophysiology.

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Presentation on theme: "CHAPTER 16 DISORDERS OF THE IMMUNE RESPONSE Essentials of Pathophysiology."— Presentation transcript:

1 CHAPTER 16 DISORDERS OF THE IMMUNE RESPONSE Essentials of Pathophysiology

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. F T T F F

3 PRE LECTURE QUIZ  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. Autoimmune I Opportunistic Self tuberculin

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 Mast cell degranulates Sensitized Mast cell Allergen attaches to IgE IgE attaches to mast cell Allergen

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 º What will happen when arterioles vasodilate throughout the body?  Acetylcholine, kinins, leukotrienes, and prostaglandins all can cause bronchoconstriction º 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 Immunoglobulins Complement activated WBCs attracted to eat cell Cell lysis Directly causes cell lysis Immunoglobulins attach to antigens Antigens introduced Example incompatable blood transfusion

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 R HO GAM  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? a. It has both A and B antigens on the RBC. b. It has neither A nor B antigens on the RBC. c. It has no antibodies in the plasma. d. It has A and B antibodies in the plasma.

17 ANSWER b. 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 Immunoglobulins Antigens Immune complexes Immune complexes deposit on walls of blood vessels and activate complement Blood vessels are damaged

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 T H 1 cell Sensitized T H 1 cell Activated Cytotoxic T cell Antigen Direct cell-mediated cytotoxicity: Cytotoxic T cells kill tissue cells Delayed-type hypersensitivity: T H 1 cell secretes inflammatory mediators

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 T 4 helper cells T 4 cells stimulate T 8 cytotoxic cells to destroy local cells that have taken up the antigen. T 4 cells release cytokines that initiated an inflamatory response Example: TB tine test T4T4

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 º Contaminated needles º Transfusions º During pregnancy or birth

32 HIV INFECTS A CELL Binds to CD4 protein receptor Which of your body cells have CD4 proteins and CD4 receptors? What does reverse transcriptase do? 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 Protein subunits are assembled into new virus particles Transcription 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? a. 1 b. 3 c. 6 d. 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, T H cell count gradually falls  May last 10–11 years or longer  Overt AIDS  T H cell count <200 cells/  L 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?


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