BIO:31 - Ch.19 part 1, in-class quiz #16

Hypersensitivity

• Hypersensitivity is an antigenic response beyond normal
• Hypersensitivity occurs when sensitized by a previous exposure to an antigen (allergen)
• The four types of hypersensitivity are anaphylactic, cytotoxic, immune complex, and delayed cell-mediated
• The hygiene hypothesis suggests limited exposure to pathogens may lower immune tolerance and the ability to cope with harmless antigens

Dysbiosis and IBD

• Dysbiosis is an imbalance that causes adverse effects in humans
• Antibiotic therapy can kill normal gut microbiota, causing Clostridium difficile to proliferate
• Dysbiosis is a possible cause of IBDs such as ulcerative colitis and Crohn's disease
• Fecal transplants involve taking gut microbiota from a healthy individual and transplanting it into the patient
• Whipworm eggs suppress T helper cell pathways, and can be used to treat Crohn's Disease

Types of Hypersensitivity

• Type 1 (Anaphylactic) reactions occur in fewer than 30 minutes
• IgE binds to mast cells or basophils, and causes degranulation of mast cells or basophils
• Results in the release of reactive substances like histamine
• Examples: anaphylactic shock from drug injections and insect venom, common allergic conditions, such as hay fever, asthma
• Type 2 (Cytotoxic) reactions occur in 5-12 hours
• Antigen causes formation of IgM and IgG antibodies that bind to target cells
• Destroys target cells with the action of complement
• Examples: transfusion reactions, Rh incompatibility
• Type 3 (Immune Complex) reactions occur in 3-8 hours
• Antibodies and antigens form complexes that cause damaging inflammation
• Examples: Arthus reactions, serum sickness
• Type 4 (Delayed Cell-Mediated or Delayed-Hypersensitivity) reactions occur within 24-48 hours
• Antigens activate T_C that kills target cells
• Examples: rejection of transplanted tissues, contact dermatitis such as poison ivy, certain chronic diseases such as tuberculosis

Type 1: Anaphylactic Reactions

• Occur minutes after a person sensitized to an antigen is re-exposed to that antigen
• Antigens combine with IgE antibodies
• IgE attaches to mast cells and basophils
• Mast cells and basophils undergo degranulation, releasing mediators
• 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 a sensitized individual is exposed to an antigen again
• Systemic anaphylaxis may result in circulatory collapse and death
• Epinephrine is used to treat systemic anaphylaxis
• Localized anaphylaxis is usually associated with ingested or inhaled antigens
• Symptoms of localized anaphylaxis depend on the route of entry
• Hives, hay fever, and asthma are symptoms of localized anaphylaxis
• Antigens are inoculated beneath the epidermis to test for a rapid inflammatory reaction (wheal)
• Desensitization increases dosages of antigen injected beneath the skin
• Desensitization produces IgG, which acts as blocking antibodies to intercept and neutralize antigens

Type 2: Cytotoxic Reactions

• Activation of complement occurs due to the combination of IgG or IgM antibodies with an antigenic cell
• This leads to cell lysis or damage by macrophages
• The ABO blood group system sees antibodies forming against certain carbohydrate antigens on RBCs
• A antigens, B antigens, or both can be found on RBCs
• Type O RBCs have no antigens
• Rh factor antigen (Rh+) is found on RBCs of 85% of the population
• Rh+ blood given to an Rh- recipient will stimulate anti-Rh antibodies in the recipient
• Hemolytic disease of the newborn (HDNB) can occur
• Rh- mother with an Rh+ fetus causes the mother to produce anti-Rh antibodies
• A second Rh+ fetus will receive anti-Rh antibodies, damaging fetal RBCs
• Drug-induced cytotoxic reactions can occur
• Thrombocytopenic purpura sees platelets combine with drugs, forming a complex that is antigenic
• Antibody and complement destroy platelets
• Agranulocytosis is a drug-induced immune destruction of granulocytes
• Hemolytic anemia is a drug-induced immune destruction of RBCs

Type 3: Immune Complex Reactions

• Antibodies form against soluble antigens in the serum
• Immune complexes lodge in the basement membranes beneath the cells
• This activates complement, causing inflammation
• Glomerulonephritis is inflammatory damage to the kidney glomeruli caused by immune complexes due to an infection

Type 4: Delayed Cell-Mediated Reactions

• Cell-mediated immune responses are caused by T cells
• This results in delayed hypersensitivity
• Antigens are phagocytized and presented to receptors on T cells, causing sensitization
• Reexposure to an antigen causes memory cells to release destructive cytokines
• Allergic contact dermatitis sees haptens combine with proteins in the skin, producing an immune response
• Allergic responses can occur to poison ivy, cosmetics, metals, and latex

Autoimmune Diseases

• The immune system responds to self-antigens, causing damage to the organs
• Autoimmunity is the loss of self-tolerance
• This is the ability to discriminate self from non-self
• It can be cytotoxic, immune complex, or cell-mediated
• Antibodies react with cell-surface antigens in cytotoxic autoimmune reactions
• In Graves' disease, abnormal antibodies in the thyroid produce excessive amounts of hormones
• In myasthenia gravis, antibodies coat acetylcholine receptors, and muscles fail to receive nerve signals
• Immune complexes of antibodies and complement deposit in tissues in immune complex autoimmune reactions
• In systemic lupus erythematosus, immune complexes form in the kidney glomeruli
• In rheumatoid arthritis, immune complexes form in the joints
• Cell-mediated autoimmune reactions are mediated by T cells that attack tissues
• Insulin-dependent diabetes mellitus sees T cell destruction of insulin-secreting cells
• Psoriasis and psoriatic arthritis are autoimmune disorders of the skin

Reactions Related to the Human Leukocyte Antigen (HLA) Complex

• Histocompatibility antigens are self-antigens on cell surfaces
• The major histocompatibility complex (MHC) refers to genes encoding histocompatibility antigens
• The human leukocyte antigen (HLA) complex are MHC genes in humans
• Certain HLAs are related to increased susceptibility to specific diseases
• HLA typing identifies and compares HLAs
• In transplant surgery, the donor and the recipient must be matched by tissue typing
• This uses standardized antisera or monoclonal antibodies specific for HLAs

HLA Related Diseases

• Multiple sclerosis poses a 5 times increased risk
• It is a progressive inflammatory disease affecting the nervous system
• Rheumatic fever poses a 4–5 times increased risk
• There is a cross-reaction with antibodies against streptococcal antigen
• Addison’s disease poses a 4–10 times increased risk
• It is a deficiency in production of hormones by the adrenal gland
• Graves’ disease poses a 10–12 times increased risk
• It is a disorder in which antibodies attached to certain receptors in the thyroid gland cause it to enlarge and produce excessive hormones
• Hodgkin’s disease poses a 1.4–1.8 times increased risk
• It includes cancer of lymph nodes

Reactions to Transplantation

• Transplants may be attacked by T cells, macrophages, and complement-fixing antibodies
• Transplants to a privileged site and privileged tissue do not cause an immune response
• Examples include cornea transplants and heart valve transplants

Stem Cells

• Stem cells are master cells capable of generating many different cell types
• Embryonic stem cells (ESCs) are harvested from blastocysts and are used to regenerate tissues and organs
• They are pluripotent, and can generate all types of cells
• Adult stem cells are stem cells in adult tissues that have differentiated
• They can become induced pluripotent stem cells by introducing genes