Chapter 19: Disorders associated with the immune system

allergies and asthma

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

• Possibly due to wider range of microbial exposures in farm setting; also led to lower asthma rates

inflammatory bowel disease

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

hypersensitivity

an immune response that causes damage to the body rather than protection

• antigenic response that results in undesirable effects (ex. allergies)

• occurs in individuals who have been sensitized by previous exposure to an antigen (allergen)

antigenic response

body’s immune reaction to an antigen

allergen

antigen that causes an allergic or hypersensitivity reaction; when sensitized individual is exposed to antigen again body’s immune system reacts to it in damaging manner

sensitized

have memory cells

immunopathology

Study of hypersensitivity reactions

four types of hypersensitivity

anaphylactic, cytotoxic, immune complex, delayed cell-mediated

hygiene hypothesis

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

type I anaphylactic

• Occurs minutes after a person sensitized to an antigen is reexposed to that antigen or allergen

• Antigens combine with IgE antibodies that are attached to mast cells and basophils

• Mast cells and basophils undergo degranulation, which releases mediators

  • Histamine: increases the permeability of blood capillaries

  • Leukotrienes: cause prolonged contraction of smooth muscles

  • Prostaglandins: affect smooth muscle and increasemucus secretion

degranulation

the cells release stored inflammatory chemicals called mediators

first stage of anaphylactic

1. First exposure = sensitization

The first time a person encounters an allergen (such as pollen, peanuts, or bee venom):

• the immune system produces IgE antibodies

• IgE attaches to:

  • mast cells

  • basophils

At this stage, the person is sensitized but may not yet have symptoms

second stage

When the person encounters the same allergen again:

• the antigen binds to IgE antibodies on mast cells/basophils

• this triggers degranulation : The cells release stored inflammatory chemicals called mediators.

This occurs within minutes, which is why it is called immediate hypersensitivity.

histamine

increases the permeability of blood capillaries

Leukotrienes

cause prolonged contraction of smooth muscles

Prostaglandins

affect smooth muscle and increase mucus secretion

Systemic anaphylaxis

(anaphylactic shock)

• Results when an individual sensitized to an antigen is exposed to it again

• Involves cardiovascular and respiratory systems causing shock and breathing difficulties or death

• Allergic mediators cause dilation of peripheral blood vessels resulting in plummeting blood pressure (shock)

• Injected antigens or bee stings may produce more dramatic responses

• Treated with epinephrine which constricts blood vessels and increases blood pressure

Localized anaphylaxis

• Usually associated with limited body regions

• Immediate, temporary, less severe

• Ingested antigens, inhaled antigens, contact antigens

  • Pollen, fungal spores, dust mites, animal dander, nuts, 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

Preventing Anaphylactic Reactions

1. allergy testing

2. desensitization

allergy testing

• Antigens are inoculated beneath the epidermis to test for a rapid inflammatory reaction (wheal)

desensitization

• Increasing dosages of antigen injected beneath the skin

• Produces I g G, which act as blocking antibodies to intercept and neutralize antigens

Type II (Cytotoxic) Reactions

• Activation of complement by the combination of IgG or IgM antibodies with an antigenic cell

Causes cell lysis or damage by macrophages

transfsion reactions

transfusion reactions

most familiar cytotoxic hypersensitivity reaction where RBCs are destroyed as a result of reacting with circulating antibodies

• reactions involve (ABO and Rh antigens; blood group systems)

ABO blood group system

the classification of human blood into 4 principal types (A, B, AB, O)

• Antibodies form against certain carbohydrate antigens on R B Cs

  • A antigens, B antigens, or both

  • Type O red blood cells: lack both A and B antigens

  • person’s ABO type depends on the presence or absence of carbohydrate antigens located on the cell membranes of RBC

    • involves 3 carbs. antigens on surface of cells (A, B, H): type O only has H antigen

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 newborn (H D N B)

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

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

  • Prevention: Rho G A M® shots to mother at 28 weeks and shortly after delivery

Type III (Immune Complex) Reactions

• Antibodies form against and react with soluble antigens in the serum

• Form immune complexes that lodge in the basement membranes beneath the cells (usually IgG)

  • Activate complement, causing inflammation

  • Immune complexes form only when there is a certain ratio of antigen and antibody

Type IV (Delayed Cell-Mediated) Reactions

• Cell-mediated immune responses caused by T cells

  • Delayed hypersensitivity

• On first exposure, antigens are phagocytized and presented to receptors on T cells, causing sensitization

  • No obvious reaction on this exposure

• Re-exposure to antigen causes memory cells to release destructive cytokines

• Reaction takes a day or more to develop after antigen exposure

  • The delay represents the time for participating T cells and macrophages to migrate and accumulate

Delayed cell-mediated hypersensitivity reactions on the skin

Skin test for tuberculosis

Allergic contact dermatitis

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

• Allergic response to poison ivy, cosmetics, metals, and latex

immune surveillance

Cancer cells arise frequently and are removed; concept where cancer cells arise in body and that they’re eliminated by immune system

RhoGAM shots

anti-Rh antibodies, combine with any fetal Rh+ RBCs that have entered the mother’s circulating reducing risk of sensitization to the Rh antigen

cancer cells

cell becomes cancerous when it under goes transformation and begins to proliferate without control

cancer

represents a failure of the body’s defenses including immune system

immune system and cancer

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

• CTLs, activated macrophages, and N K cells can destroy cancer cells

• Limitations

  • No antigenic epitope for the immune system to target

  • Tumor cells reproduce too rapidly

  • Tumor becomes invisible to the immune system

immunotherapy

• Endotoxins from bacteria (Coley’s toxins) stimulate that interferes with the blood supply of cancers

• Vaccines used for prophylaxis

  • Cervical, anal, and throat cancer (H P V), liver cancer(hepatitis B)

• Monoclonal antibodies

  • Herceptin for breast cancer

• Immunotoxin combines a Mab with a toxic agent

  • Targets and kills a tumor without damage to healthycells

immunotoxin

combines a MAB with a toxic agent

• Targets and kills a tumor without damage to healthy cells