Disorders of the Immune System

Chapter 19

hygiene hypothesis

suggests that limiting exposure to pathogens may lower immune tolerance and the ability to cope with harmless antigens

allergies and asthma

• observation that there are fewer allergies and asthma in tribal populations and children growing up on farms compared to the number of incidence in children in urban settings

• possibly due to wider range of microbial exposures in farm settings

inflammatory bowel diseases

possible link to lack of normal microbiota metabolic products leading to chronic inflammatory state

hypersensitivity

• antigenic response that results in undesirable effects

  • occurs when sensitized by previous exposure to an antigen (allergen)

• four types of sensitivity

  • types I-IV

  • immunopathology: study of hypersensitivity reactions

type 1 hypersensitivity

• ANAPHYLACTIC

• less than 30 min before clinical signs

• IgE binds to mast cells or basophils

  • allergen binding to IgE antibodies causes degranulation of mast cell or basophil → causes release of reactive substances

    • histamine: causes vasodilation, increases permeability of blood capillaries, and induces contraction of smooth muscles in bronchi

    • leukotrienes

    • prostaglandins

• ex: anaphylactic shock, common allergic conditions (hay fever, asthma, food allergies)

localized anaphylaxis

• usually associated with limited body regions

• immediate, temporary, less severe

• food allergy with mild symptoms, inhaled antigens, contact antigens

  • pollen, fungal spores, dust mites, animal dander, seafood

• symptoms depend on the route of entry

  • hay fever: upper respiratory symptoms

  • asthma: affects lower respiratory tract

    • bronchial constriction, mucus build-up

    • treatment: bronchodilators, leukotriene blockers

systemic anaphylaxis (anaphylactic shock)

• involves cardiovascular and respiratory systems causing

  • vasodilation → hypotension (shock)

  • bronchoconstriction leading to breathing difficulties

  • increased capillary permeability → airway swelling

• may produce more dramatic responses or death

  • injected antigens, drug allergies such as penicillin

  • peanut allergy

  • bee stings (venom)

• nursing focus: watch for airway swelling, give epinephrine in emergincies

allergy testing

• suspected antigens are inoculated beneath epidermis to test for rapid inflammatory reaction

  • wheal and flare

desensitization

• injections of a series of small doses of the antigen beneath the skin

  • produces IgG, which act as blocking antibodies to intercept and neutralize antigens before they can react with cell-bound IgE

type 2 hypersensitivity

• CYTOTOXIC

• minutes to hours before clinical signs

• antigen causes formation of IgM and IgG antibodies that bind to target cell (antigenic cell)

• when combined with action of complement → destroys target cell (cell lysis)

• ex: transfusion reactions, Rh incompatibility

  • nursing focus: monitor blood type compatibility

• ABO blood group system

• Rh blood group system

blood group A

• A antigen

• Anti-B antibodies

• can receive A and O blood

blood group B

• B antigen

• Anti-A antibodies

• can receive B and O

blood group AB

• A and B antigen

• neither anti-A nor anti-B antibodies

• can receive A, B, AB, O

blood group O

• neither A or B antigen

• both anti-A and anti-B antibodies

• can receive O

Rh blood group system

• Rh factor antigen (Rh+) is found on RBCs of 85% of the population

• Rh+ blood given to an Rh- recipient will stimulate the production of anti-Rh antibodies in the recipient

• hemolytic disease of the newborns

  • Rh- mother with an Rh+ fetus may produce anti-Rh antibodies if sensitized during pregnancy or birth

    • first pregnancy with Rh+ baby is not affected → mother hasn’t developed antibodies yet

  • subsequent Rh+ fetuses will receive anti-Rh antibodies (produced by maternal memory B cells) from the mother which will damage fetal RBCs

  • prevention: RhoGAM shots to mother at 28 weeks and shortly after delivery

type 3 hypersensitivity

• IMMUNE COMPLEX

• 3-8 hours before clinical signs

• antibodies and soluble antigens form immune complexes that cause damaging inflammation

  • immune complexes lodge in the basement membranes beneath the endothelial cells of blood vessels → activate complement → causes inflammation

• ex: systemic lupus erythematosus (SLE), arthus reactions, serum sickness, rheumatoid arthritis

• nursing focus: assess for joint pain, rash, kidney issues

type 4 hypersensitivity

• DELAYED CELL-MEDIATED or DELAYED HYPERSENSITIVITY

• 24-72 hours before clinical signs (delayed)

• cell-mediated immune responses caused by CD4+ T helper cells

  • delayed hypersensitivity

  • not antibody-mediated

• on first exposure: antigens are phagocytized and presented to receptors on T_h cells → causing sensitization

  • no obvious region on this exposure

• re-exposure to antigen causes T_h memory cells to become activated and release cytokines

  • recruit additional immune cells (macrophages and T cells) to the site

  • reaction takes a day or more to develop after reexposure to antigen

  • leading to inflammation and tissue damage

delated cell-mediated hypersensitivity reactions on the skin

skin test for TB

allergic contact dermatitis

• haptens combine with proteins in the skin, provoking an immune response

• allergic response to poison ivy, cosmetics, metal, and latex

immune system and cancer

• cancer cells arise frequently and are removed by immune surveillance

• cancer cells have tumor-associated antigens that mark them as nonself

• CTLs, NK cells, and activated macrophages destroy cancer cells

• limitations

  • in some cases, cancer cells may lack or have reduced expression of antigenic epitopes that the immune system can effectively target

  • tumor cells reproduce too rapidly

  • tumor becomes invisible to the immune system

  • in leukemia, lymphocytes that would normally facilitate the immune response become abnormal

immunotherapy for cancer

• chimeric antigen receptor (CAR) T-cell therapy (CAR T-cell therapy)

• cytokine therapy

• vaccines used for prophylaxis, e.g.:

  • cervical, anal, and throat cancer (HPV)

  • liver cancer (hepatitis B)

• monoclonal antibodies (Mabs)

  • Herceptin® for breast cancer

  • immunotoxin combines a Mab with a toxic agent

    • targets and kills a tumor without damage to healthy cells