WEEK 3: HYPERSENSITIVITY AND AUTOSENSITIVITY Flashcards
What is hypersensitivity?
Excessive or inappropriate immune response reaction.
Can lead to tissue damage.
Outline the symptoms of hypersensitivity.
Trivial itchy skin rushes
Catastrophic or life threatening laryngeal edema
Sudden cardiovascular collapse
Describe the causes of hypersensitivity.
1.Autoimmunity:
- Failure to recognize own body constituent parts leading to immune response against own cells and tissues.
2.Reactions against microbes.
*Reactions excessive or the microbes are unusually persistent. T cell response against the persistent microbes may give rise to severe inflammation such as tissue injury in TB.
3.Reactions against environment antigens:
*Abnormal response to common generally harmless environmental substances.
Outline other terms used to refer to type I hypersensitivity.
*Anaphylaxis
*Allergic reaction
*Immediate hypersensitivity
Describe what happens in Type I hypersensitivity.
1.Allergens (or antigens) are presented to T-cells by Antigen-presenting cells (APCs) during the sensitization phase of Type I hypersensitivity.
2.T-cells then signal for stimulation of B-cells to produce IgE antibodies, which bind to the Fc receptors on mast cells and basophils.
3.Subsequently, the free antigen induces the crosslinking of these mast cell and basophil bound IgE antibodies.
4.This results in the degranulation of the cells and the release of histamine, proteolytic enzymes, and other mediators (i.e., prostaglandin, cytokines, leukotrienes, platelet-activating factors, macrophage inflammatory proteins, tryptase, etc.).
What are allergens?
An allergen is a type of antigen that produces an abnormally vigorous immune response in which the immune system fights off a perceived threat that would otherwise be harmless to the body.
These are antigens that elicit immediate hypersensitivity reactions.
Describe reactions due to type 1 hypersensitivity.
There is increased:
*Vascular permeability
*Peripheral vasodilation
*Smooth muscle contraction
*Mucous secretions
*Bronchospasm
*Abdominal cramping
*Rhinitis
*Hypovolemia or hypoxia.
-Pulmonary edema or general edema can also occur due to fluid shifting into interstitial space.
-Individuals can experience pruritis and local response of asthma or a systemic response of anaphylaxis.
Describe treatments for Type I hypersensitivity.
*Epinephrine:
-Epinephrine has alpha-1, beta-1, and beta-2 adrenergic agonist effects.
- As such, it can increase vasoconstriction and peripheral vascular resistance and decrease airway or mucosal edema.
-The beta effects lead to increased inotropy, chronotropy, vasodilation, and decreased release of inflammatory mediators from both mast cells and basophils.
*Bronchodilators:
-Beta-agonists, such as albuterol, are given as either metered-dose inhaler (MDI), dry-powder inhaler (DPI), or nebulized solution and are usually administered when the patient is not responsive to epinephrine for treating bronchospasm.
*Antihistamines:
-i.e., diphenhydramine (H1 antagonist), famotidine or ranitidine (H2 antagonists)
-Antihistamines are considered second-line adjunctive therapy and can provide relief of symptoms such as hives or pruritis.
3 of the types if hypersensitivity are antibody- mediated immunity. Only one of them is cell-mediated immunity.
Which one is that?
Type IV hypersensitivity
What are the other names for Type II hypersensitivity?
Is also known as cytotoxic reactions.
Describe what happens in Type II hypersensitivity reactions.
State the etiology of Type II hypersensitivity.
*Type II hypersensitivity reaction refers to an antibody-mediated immune reaction in which antibodies (IgG or IgM) are directed against cellular or extracellular matrix antigens.
*Result in cellular destruction, functional loss, or damage to tissues. Damage can occur through multiple mechanisms.
*It leads to the complement system activation and cell damage or lysis.
- Develops in response to cell surface modifications or matrix-associated antigens generating antigenic epitopes that are regarded as foreign by the immune system.
*The most common causes include medications like penicillin, thiazides, cephalosporins, and methyldopa.
*The drug molecule either binds to the surface of cells resulting in a neoantigen or alters the epitopes of the existing self-antigen on the cell surface.
*This directs the immune system to recognize modified antigens as foreign, with the breakdown of the immune tolerance and the production of antibodies directed to self-antigens.
Outline 4 ways in which the complement activation in Type II hypersensitivity executes immune response.
1.C3a and C5a will act as Inflammatory mediators.
2.C3b carry out opsonization hence enhance phagocytosis
3.C5b activates a MAC which admits fluid in the target cell causing it to lysis
4.NK cells activation.
NOTE: The complement system in this case is activated by The classical pathway due to the IgG which are produced when the in response to the drug, e.g Penicilin.
What is the other name for Type III hypersensitivity response?
Immune complex reactions.
Describe Type III hypersensitivity response.
1: Immune complex formation: Endogenous or exogenous antigen exposure triggers an antibody formation. In both cases, the antigens bind to antibodies, forming circulating immune complexes, later migrating out of plasma and depositing in host tissues.
2: Immune complex deposition: The pathogenicity of immune complexes is partly dependent on the antigen-antibody ratio.
-When the antibody is in excess, the complexes are insoluble, do not circulate, and are phagocytosed by macrophages in the lymph nodes and spleen.
-However, when the antigen is in excess, the aggregates are smaller. They freely filter out of circulation in organs where the blood is transformed into fluids such as urine and synovial fluid. Therefore, immune complexes affect glomeruli and joints.
3: Inflammatory reaction:
-After the deposition of the immune complexes, the final step is activating the classical pathway, leading to the release of C3a and C5a, which then recruit macrophages and neutrophils and causes inflammatory damage to tissues.
- Depending on the site, symptoms of vasculitis (blood vessels), arthritis (joints), or glomerulonephritis (glomeruli) develop
What is the difference between exogenous and endogenous antigens?
Exogenous antigens are foreign proteins such as infectious microbes or pharmaceutical products.
Endogenous antigens are self-antigens against which autoantibodies are generated (autoimmunity).
