Chapter 17: Immunologic Disorders

What are secondary immunodeficiencies caused by?

1. Infection (e.g. AIDS); 2. bone cancer (multiple myeloma); 3. age; 4. immunosuppressive drugs; 5. malnutrition; 6. radiation.

LO 1: Compare and contrast the immunologic reactions involved in types 1 through 4 hypersensitivities.

ALREADY DONE IN PREVIOUS SLIDES.

MA 1: Describe the process of desensitization that reduces the IgE response to an allergen.

Activated regulatory T cells may also play a role through the release of cytokines that suppress the IgE response.

Terms related to hypersensitivities

Allergen: an antigen that is typically harmless, non-disease causing substance from the environment but which triggers an immune reaction. Sensitization: readiness for a severe secondary immune response. Systemic anaphylaxis: the antigen spreads in the blood and blinds IgE on basophils which then release inflammatory mediators (esp. histamine) which dilate vessels causing loss of fluids into tissues and swelling. The blood pressure drops very low. The heart may fail. The brain and other organs become oxygen-starved due to low blood pressure. Constriction of bronchi and swelling in the throat can suffocate. Death is often rapid.

MB pg. 446

Approximately half of the people with latex allergies are allergic to bananas as well.

What is the result of Type 2 hypersensitive reactions?

Blood incompatibility reaction; RBCs clump and die; kidney damage; hemolytic disease of newborns. ABO blood types: Ab agglutinates RBCs and blocks blood flow in vessels; reduced blood flow reduces oxygen supply to tissues and reduces ATP for cellular transport; MAC of CS kills RBCs as in IIR. Ab tags RBCs alerting NK cells to kill RBCs as in AIR. Rh factor: IgG marks RBCs for destrcution by phagocytes (AIR).

MC 10: In which one of the following combinations of hypersensitivity reactions are B cells involved: a. Type 1, but not types 2, 3, 4 hypersensitivity. b. Type 4, but not types 1, 2, 3 hypersensitivity. c. Types 1, 2, and 3 but not 4 hypersensitivity. d. Types 2, 3, and 4, but not type 1 hypersensitivity. e. B cells are involved in all types of hypersensitivity.

C

MC 5: Delayed-type hypersensitivity reactions in the skin: a. Are characterized by a wheal and flare reaction. b. Peak at 4 to 6 hours after exposure to the antigen. c. Require complement activation. d. Show induration because of the influx of sensitized T cells and macrophages. e. Depend of activities of the Fc portion of antibodies.

D

KT: autoimmune disease

Damaging reaction of the immune system against "self" antigens.

SA 8: Explain why a patient who received a successful lung transplant might subsequently die from pneumonia.

Due to being immunocompromised from the surgery, this would lead for the infection to attack when the immune system isn't as strong.

What are the three types of immunologic disorders?

Hypersensitivity, immunodeficiency, and autoimmunity.

Figure 14.11

Lysis of foreign cells C5b combines with complement proteins C6, C7, C8, and C9 to form membrane attack complexes that insert into cell membranes. (Type 2 hypersensitivity?)

FO pg. 453 Know ONE major point

Parasitic worm infestations appear to protect people from allergies and autoimmune diseases.

Features of Type 2 hypersensitive reactions.

Slow-hours or day; cellular Ag--RBCs; B cells produce IgG and IgM; RBCs clump; complement is activated; MAC and NK cells attack RBCs; no skin reaction.

Features of Type 3 hypersensitive reactions?

Slow-hours to days; overreaction makes phagocytes fail to remove Ab-Ag complexes which then block vessels, and the complexes accumulate in joints and damage organs.

AIDS

The AIDS virus parasitizes TH cells and reduces humoral immunity, phagocytosis and cytokine production. The infected person is subject to a variety of other infections due to reduced overall immune response.

MA 8: How can a person with multiple myeloma be immunodeficient?

They are immunodeficient due the fact that their body is going through constant stress and malignancy on the immune system, which causes a secondary immunodeficiency.

Table 17.3 Know by name any ONE autoimmune disease, the organ affected, and the major mechanism of the tissue damage.

Type 1 diabetes mellitus (organ: pancrease; major mechanism of tissue damage: T-cell destruction of pancreatic beta cells).

Final Point

"The immune response is indeed a double-edged sword, with a delicate balance between protective immunity and harmful hypersensitivity."

MC 3: Repeated injections of very small amounts of an antigen are an effective therapy for combating allergies because: a. IgG production is stimulated, which outcompetes IgE for the antigen. b. IgG binds to mast cells before IgE can do so. c. Repeated exposure will cause production of IgE to decrease. d. Antigen binds to mast cells and prevents their degranulation. e. Repeated exposure to antigen prevents the production of histamine.

A

KT: immunodeficiency

A condition in which the immune system provides an inadequate response, leaving an individual vulnerable to infection.

KT: allergy

A damaging immune response to a usually harmless environmental antigen (allergen).

KT: desensitization

Allergy treatment that induces IgG production by gradual exposure to small amounts of allergen; IgG competes with IgE.

SA 5: What causes hemolytic disease of the newborn?

An Rh- women carrying an Rh+ baby is likely to develop antibodies to the Rh antigen when she is exposed to the baby's blood. This happens when the placenta ruptures during childbirth. She may also be exposed during pregnancy or after induced or spontaneous abortion. Antibodies produced by the woman will not affect her red blood cells because her cells lack the Rh antigen. They will not affect her first baby because IgM, which is produced upon first exposure, cannot cross the placenta. If the woman carries a second Rh+ baby, however, her anti-Rh IgG antibodies can cross the placenta and damager her developing fetus.

MC 7: All of the following are true of autoimmune disease EXCEPT: a. Some seem to have a genetic component. b. Induction of tolerance may alleviate symptoms. c. Damage to organs occurs due to long-term exaggerated production of IgE. d. Disease may result from reaction to viral antigens that are similar to autoantigens. e. Some are organ-specific and some are widespread in the body.

C

MC 8: All of the following approaches are used to treat autoimmune disease EXCEPT: a. Immunosuppressant drugs b. Induction of tolerance c. Antibiotics d. Anti-inflammatory medications e. Replacement therapy, as with insulin in diabetes

C

KT: tolerance

Decreased reactivity of the immune system to a specific antigen.

Figure 17.3

Desensitization against plant allergens for hay fever sufferers.

Table 17.4 Know ONE ID disease. other than AIDS, and the system involved.

DiGeorge Syndrome (T cells (deficiency)).

KT: delayed-type hypersensitivity

Exaggerated immune response of antigen-specific T cells.

KT: hypersensitivity

Exaggerated immune response that damages tissue.

Figure 17.1 Know in a general way

Exposure to allergens.

What are primary immunodeficiencies?

Genetic errors can lead to any of the following: 1. Ab, esp. IgA, won't work or is not produced (agammaglobulinemia) due to amino acid sequence errors in the Ab. 2. Errors involving steps in phagocytosis. 3. The complement system proteins are defective. 4. Failure to produce functional T cells or B cells.

Figure 17.2

Hives (wheal and flare).

What are results of Type 1 hypersensitive reactions?

Hives (wheal and flare); itching; runny nose, watery eyes; hay fever; asthma; initial exposure sensitizes; more severe on subsequent exposure. Worst case: systemic anaphylaxis!

SA 9: Why does an IgA deficiency predispose a person to diarrheal diseases?

If someone has selective IgA deficiency, they don't have the necessary amount of IgA in the respiratory, gastrointestinal, or genitourinary tracts where they normally protect again colonization of invasions of pathogens.

SA 3: What are the major differences between an IgE-mediated skin reaction, such as hives, and a delayed-type hypersensitivity reaction, such as a positive tuberculin skin test?

IgE-mediated is immediate (up to 30 minutes and involves basophils and mast cells. The reaction on the skin are wheals and flares. This is caused by things such as hay fever, hives, asthma, or anaphylactic shock. Delayed-type is longer and peaks at aaround 48-72 hours. It does not include an antibody (where as IgE-mediated involves IgE) and involves dendritic cells. The skin reaction is induration and inflammation. This is caused by tuberculin skin tests, contact dermatitis, and tissue transplant rejection.

Autoimmunity

In autoiummune diseases, the immune system fails to distinguish between foreign and self cells due to inherited genetic flaws or due to mutations. Examples: Type 1 diabetes mellitus - TC cells kill insulin-producing cells in the pancreas. Rheumatoid arthritis - Ag-Ab complexes attack collagen of the joints. Ab against self cells is called autoantibody.

SA 1: Why are antihistamines useful for treating many IgE-mediated allergic reactions, but are not totally effective in treating asthma?

Injections of omalizumab are effective in treating most asthma cases, but the medication is expensive and can cause anaphylactic shock on rare occasions.

MA 5: What are the negative side effects of taking immunosuppressive drugs?

It obviously suppresses your immune system, so even though it is helping with your current autoimmune disease, it can make you more susceptible to other diseases because your immune system isn't in tip top shape.

What is an hypersensitivity immunologic disorders? Definition

It's an overreaction by the immune system.

Features of Type 4 hypersensitive reactions

Peaks at 2-3 days; no Ab involved; involves cytotoxic T cells; cell-mediated response to foreign tissue.

What is the cause of Type 3 hypersensitive reactions?

Penicillin; some microbial infections; bacteria-laden dust; antitoxins.

Table 17.5 Know by name any ONE opportunistic infection AIDS patients commonly get.

Pneumocystis pneumonia (causative agent: pneumocystis jiroveci).

What are causes of Type 1 hypersensitive reactions?

Pollen, venoms (bee stings; insect, spider, and snake bites); food and antibiotic allergies; molds; pet dander.

LO 5: Contrast the two main categories of immunodeficiency disorders.

Primary immunodeficiencies are generally rare. They may affect B cells, T cells, natural killer cells, phagocytes, or complement components. Usually people are born with primary immunodeficiencies. Secondary immunodeficiencies (or acquired) may result from malignancies, advanced age, pregnancy, certain infections (esp. viral infections), immunosuppressive drugs, radiation, or malnutrition.

Features of Type 1 hypersensitive reactions:

Rapid-often 30 minutes or less; in the presence of the Ag, B cells produce IgE which bind to mast cells which then produce excess histamine, etc.; blood vessels leak; smooth muscles contract; usually causes a skin reaction.

SA 2: List two physical responses of systemic anaphylaxis that can lead to rapid death.

Suffocation can occur when the bronchial tubes constrict.; When there is a severe drop in blood pressure that may lead to heart failure and insufficient blood flow to the brain and other vital organs (anaphylactic shock).

True or False? Any kind of immunodeficiency makes a person more susceptible to many infections?

TRUE

What is the cause of Type 4 hypersensitive reactions?

Tissue/organ transplants; poison ivy; poison oak; stinging nettle; latex; nickle jewelry; some leather products; contents in some cosmetics.

What is the cause of Type 2 hypersensitive reactions?

Transfusions of wrong blood type involving either ABO or Rh factors.

What is the result of Type 4 hypersensitive reactions?

Transplant rejection; contact dermatitis (itching, rash, blisters); inflammation; induration; organ/tissue damage from continuing cell death due to apoptosis.

What are the four types of hypersensitive reactions?

Type 1 - "Immediate"; IgE-mediated Type 2 - Cytotoxic Type 3 - "Immune"; complex-mediated Type 4 - "Delayed"; type; cell-mediated

LO 4: Give 2 examples of autoimmune diseases and the mechanism of tissue injury in each.

Type 1 diabetes mellitus (organ: pancreas; major mechanism of tissue damage: T-cell destruction of pancreatic beta cells); Graves disease (thyroid; autoantibodies bind thyroid-stimulating hormone receptors, overstimulating the thyroid).

LO 2: Describe 2 examples of each type of hypersensitivity.

Type 1: Inhaled substances (pollen, pet dander, mold) and ingested substances (peanuts, milk, seafood). Type 2: transfusion reactions and hemolytic disease of the newborn. Type 3: serum sickness (artificial passive immunization) and the Arthus reaction (localized immune complex reaction--if an antigen is injected into a previously immunized person who already has high levels of circulating specific antibody, immune complexes can form at the site of injection where antigen levels are high). Type 4: Tuberculin skin test and contact hypersensitivities.

LO 6: Explain how immunodeficiency can lead to multiple and unusual infections.

When people are immunodeficient, their immune system cannot create a response when bacteria and viruses come in contact with them. For usual "bugs" that our body will fight off, their's will not. This causes them to get multiple and unusual infections.

What is an autoimmunity immunologic disorders? Definition

When the immune system attacks the host's own cells.

What is an immunodeficiency immunologic disorders? Definition

When there is a weak or no immune system.