Lecture 18: Immune Disorders

Hypersensitivities

  • Hypersensitivities: immune system overreacts to a something harmless

    • example: allergies

Type I Hypersensitivity

  • allergens: harmless antigen that trigger an inflammatory response

  • Type I Hypersensitivity: Triggered by allergens, mediated by IgE (Immunoglobulin E).

    • may be localized

      • example: an exaggerated reaction to pollen (hay fever) or peanuts

    • may be systematic

      • example: anaphylaxis effects on a systemic level, inflammation throughout the body, causing blood vessels to get leaky as once, and reducing blood pressure quickly

Mechanism of Type 1 Hypersensitivity

  • Initial exposure to an allergen causes the immune system to produce IgE antibodies.

    • IgE antibodies bind to mast cells, which contain histamine, but do not trigger histamine release yet.

      • at secondary exposure to antigen, histamine is released from mast cells

        • histamine = pro-inflammatory

        • results in exaggerated response

  1. Sensitization Phase:

    • Upon initial exposure, Antigen presenting cells (APCs) takes in allergen (harmless, foreign molecule) by mistake, thinking it is dangerous when it is actually harmless

      • APC presents antigen to CD4 T cell and sends an activation signal to CD4 T cell, turning it in to helper T cell

        • Helper T cells activate B cells.

          • B cells transform into plasma cells that produce IgE antibodies.

            • IgE is inserted on surface of mast cells (which sensitizes them to future exposures to the allergen)

  2. Subsequent Exposure:

    • Upon re-exposure to the allergen, allergen binds to the IgE on mast cells,

      • leading to histamine release

        • causes allergy symptoms

Type II Hypersensitivity (Cytotoxic Reactions)

  • Type II Hypersensitivity: cytotoxic hypersensitivity, where the immune system attack foreign cells that are harmless.

    • cytotoxic: attacks antigens present on cells

    • antibody mediated - involves IgG or IgM

      • IgG or IgM antibodies bind to antigens on foreign cells, promoting their lysis and inflammation.

Example of Type II Hypersensitivity: Blood Transfusions

  • during Blood transfusions, mismatched blood types cause the recipient's immune response to attack foreign red blood cells.

  • different blood types have red blood cells with different antigens:

    • If a mismatched blood type is transfused, the recipient’s immune system produces IgG or IgM antibodies against the foreign antigens.

      • example:

        1. donated type A blood with type A antigen enters bloodstream of type B recipient

        2. IgG or IgM antibodies in plasma of type B recipient binds to donated type A red blood cells

        3. IgG or IgM antibodies activate complement cascade (opsonization, inflammation, and lysis), promoting lysis of cells and inflammation

          • can lead:

            • to hemolysis (red blood cells get lysed) and release hemoglobin

            • antibodies clumped together can cause blockages in bloodstream

            • inflammation is triggered, shock can occur, reducing blood pressure

Blood Donation Rules

  • person with AB blood type can only donate to others with AB

    • if person with AB blood type attempts to donate to someone with A blood type, body will make antibodies against the B blood type because it perceives the B antigen as foreign

    • if person with AB blood type attempts to donate to someone with B blood type, body will make antibodies against the A blood type because it perceives the A antigen as foreign

    • AB blood type can accept blood from anyone because it contains both A and B antigens and therefore does not produce antibodies against either type.

      • AB blood type: universal recipient

  • person with A blood type can only donate to others with A OR AB blood type

  • person with B blood type can only donate to others with B OR AB blood type

  • person with O blood type can donate to ALL blood types

    • O blood type cannot accept from any other blood types other than its own because body will raise antibodies to both A and B blood types

      • O blood type: universal donor

Example of Type II Hypersensitivity: Hemolytic disease of Newborn
Rh Positive and Rh Negative Rules

  • Rh Factor: Describes the presence (+) or absence (-) of Rh antigens on red blood cells, in addition to blood type antigen

    • if A positive, means have A antigen and Rh molecule on red blood cells

    • if A negative, means have A antigen, but do NOT have Rh molecule on red blood cells

  • Rh positive individuals can donate to ONLY Rh positive

  • Rh negative individuals can donate to both Rh negative AND Rh positive

    • O negative blood type: True universal donor but also the most restricted

      • can donate to everyone

      • can only receive blood from others who are also O negative

Hemolytic disease of Newborn

  • If an Rh-negative mother carries an Rh-positive fetus, she can develop antibodies against the Rh factor, affecting future pregnancies.

  • Treatment: Rh immunoglobulin injections in Rh-negative mothers prevent the formation of anti-Rh antibodies during pregnancy

  • Example:

    • During first pregnancy with Rh+ fetus:

      • Rh+ red blood cells from fetus enter into mother’s bloodstream

        • anti-Rh antibodies are produced in mother, upon exposure to fetal antigens

    • During second pregnancy with Rh+ fetus:

      • anti-Rh antibodies remain in mother bloodstream and cross placenta

        • Mothers anti-Rh antibodies attack and destroy fetal Rh+ red blood cells

          • results in fetus becoming hemolytic

    • Treatment: During first pregnancy with Rh+ fetus and anti-Rh antibody treatment:

      • Mother is injected with Anti-Rh antibodies during pregnancy

        • Rh+ red blood cells from fetus enters mothers bloodstream

          • Anti-Rh antibodies bind and inactivate fetal Rh antigens before they stimulate immune response in fetus

Type 3 Hypersensitivity (Immune Complex-Mediated)

  • Type III Hypersensitivity: Characterized by the formation of immune complexes

    • antibody mediated - IgG antibody

    • immune complexes: more antibodies than antigens

      • Excessive IgG antibody concentrations can lead to cluster of antibodies accumulating around same antigen

        • forms immune complex that:

          • deposit in tissues and prevents phagocytosis

          • obstruct small blood vessels, leading to tissue damage.

          • activate complement response (opsonization, inflammation, and lysis)

            • Opsonization: complement proteins stick to pathogens and make them more recognizable to white blood cells to be engulfed. (phagocytosis)

            • Inflammation: complement proteins make factors to signal and alert for white blood cells by causing inflammation

            • Lysis: complement proteins form holes in microbial cells to make cells leak and burst

          • trigger inflammation

Type 3 Hypersensitivity: Glomerulonephritis

  • Glomerulonephritis: inflammation of glomerulus

    • can be caused by accumulation of immune complexes stuck in glomerulus

Type IV Hypersensitivity (Delayed-Type)

  • Type IV hypersensitivity: delayed response, T cells inappropriately attack self cells that are displaying harmless hapten on MHC I

    • mediated by T cells (rather than antibodies)

Mechanism of Type IV Hypersensitivity:

  • Sensitization:

    • Antigen Presenting Cell (APC) detects harmless hapten antigen and activate T cells

      • haptens: small molecules that combine with larger, self-molecules, creating an antigen

    • memory helper T cells saved

    • memory cytotoxic T cells saved

  • Subsequent Exposure:

    • Helper T cells and macrophages stimulate an inflammatory response when they come in contact with the same hapten again.

    • Cytotoxic T cells attack body cells presenting the harmless hapten, causing damage.

      • common in poison ivy, poison oak

Summary of Hypersensitivities

  • Type I Hypersensitivity: Allergies

    • IgE antibodies

  • Type II Hypersensitivity: Cytotoxic, kills foreign molecules

    • IgG or IgM antibodies

  • Type II Hypersensitivity: Immune complexes

    • IgG antibodies

  • Type II Hypersensitivity: Delayed

    • T cell-mediated

  • Remember by ACID:

    • allergies (type 1), cytotoxic (type 2) , immune complexes (type 3), delayed/T-cell mediated (type 4)

Hypersensitivity Treatments

  • Desensitization: Repeated injections of diluted allergens

    • cause IgG production

      • if enough IgG is present, it can help neutralize allergens before they bind IgE.

    • Block immune response:

      • Antihistamines: Block histamine release from mast cells or bind to histamine and prevent it from being detected from immune cells, preventing action

        • reduce inflammation

      • Corticosteroids: hormone body makes naturally when stressed that suppress the immune system

        • given to patients to suppress the immune response.

        • longer lasting

    • Counter anaphylaxis:

      • Epinephrine: Emergency treatment for anaphylaxis - counteracts inflammatory response, quickly restoring blood pressure and countering severe allergic reactions.

        • hormone body makes naturally when stressed that suppress the immune system

          • given to patients to suppress the immune response.

Autoimmune Disorders

  • Autoimmune Diseases: those in which body is attacked by its own specific adaptive immune response

    • immune response targets self-antigens, causing tissue damage without external pathogens.

    • Examples: Hyperthyroidism, rheumatoid arthritis, lupus, etc.

Immunodeficiency Disorders

  • Immunodeficiencies: inherited (primary) or acquired (secondary) disorders in which elements of host immune defenses are either absent or functionally defective

    • Types:

      • primary: inherited, born with it

      • secondary: acquired, get it you’re older

    • immune system UNDER reacts

      • reduced ability of the immune system to respond effectively to pathogens