Hypersensitivity Disorders Flashcards
Hypersensitivity Disorders
Disorders caused by immune responses are calledhypersensitivity diseases
-“these responses are sometimes inadequately controlled, inappropriately targeted to host tissues, or triggered by commensal microorganisms or environmental antigens that are usually harmless.”
Causes of Hypersensitivity Disorders
Autoimmunity: reactions against self antigens
Reactions against microbes.
Reactions against nonmicrobial environmental antigens. (allergies)
Hypersensitivity diseases are commonly classified according to
the type of immune response and the effector mechanism responsible for cell and tissue injury.
Types I-IV.
immediate type 1 Hypersensitivity Disorder
= allergies
pathologic immune mechanisms: IgE antibody, TH2 cells
Mechanism of tissue injury/disease:
activation of mast cells and esinophils (and their mediators)
antibody mediated type II Hypersensitivity Disorder
pathologic immune mechanisms:
IgM or IgG antibodies against certain cell surfaces
Mechanism of tissue injury/disease:
opsonization/phagocytosis of cells, recruitment/activation of leukocytes, abnormalities in cellular functions
- immune complex mediated type III Hypersensitivity Disorder
pathologic immune mechanisms:
circulating immune complexes made up of antigens and antibodies IgM and IgG
Mechanism of tissue injury/disease:
complement- and Fc receptor- mediated recruitment and activation of leukocytes
- T cell mediated type IV Hypersensitivity Disorder
pathologic immune mechanisms:
- CD4+ T cells (TH1 and TH17) and
- CD8+ CTLs
Mechanism of tissue injury/disease:
- cytokine mediated inflammation and macrophage activation
- direct target killing of certain cells, cytokine mediated inflammation
Antibody-mediated diseases are produced either by
either by antibodies that bind to antigens on particular cells or in extracellular tissues or by antigen-antibody complexes that form in the circulation and are deposited in vessel walls.
three main mechanisms of how antibodies against tissue antigens cause disease
(antibody mediated type II Hypersensitivity Disorder)
Opsonization and phagocytosis:
antibodies opsonize cells and may activate complement, generating complement products that also opsonize cells, leading to phagocytosis of the cells through phagocyte Fc receptors or C3b receptors.
Inflammation:
antibodies recruit leukocytes by binding to Fc receptors or by activating complement and thereby releasing byproducts that are chemotactic for leukocytes
Abnormal cellular functions:
antibodies specific for cell surface receptors for hormones or NTs may stimulate the activity of the receptors even in the absence of the hormone, or may inhibit binding of the NT to its receptor
Antibodies that cause cell- or tissue-specific diseases are usually
autoantibodies produced as part of an autoimmune reaction, but sometimes the antibodies are specific for microbes
acute rheumatic fever
antibodies produced against streptococcal bacteria cross react with antigens in the heart, deposit antibodies in this organ and cause inflammation(Macrophage activation) and tissue damage
-can lead to myocarditis and arthritis
Goodpasture syndrom
the target antigen is noncollagenous NC1 protein of basement membrane in glomeruli and lung.
mechanism of disease includes complement- and Fc receptor-mediated inflammation which leads to nephritis (Antibodies in this region cause destruction of the glomerulus) and lung hemorrhage
Serum sickness (acute)
-Immune Complex–Mediated Diseases
the result of people who gets injection/treatments of antibodies from another person/species
-immune complexes start to form and accumulate in small capillaries/arteries,renal glomeruli and synovia of joints and causes them to eventually bleed out (esp. in heart and lungs) it leads to vasculitis, nephritis and arthritis (usually short lived unless antigen injected again)
examples of T cell mediated diseases
Rheumatoid arthritis, multiple sclerosis, type 1 diabetes inflammatory bowl disease, psoriasis
Delayed-Type Hypersensitivity (DTH)
- an injurious cytokine-mediated inflammatory reaction resulting from the activation of T cells, particularly CD4+T cells.
- Basis for “TB test”
- Loss of DTH (anergy) is an indication of disfunctions in T cell response (loss of immune responsiveness
- Accumulation of immune cells in certain spot indicating delayed type hypersensitivity reaction.
Chronic DTH reactions can develop if
- a Th1 response to an infection activates macrophages but fails to eliminate phagocytosed microbes.
- If a DTH reaction occurs but is not cleared and continues to exist = chronic reaction (tuberculosis- formation of granulosomes due to prolonged generation of TH1 cells, activation of macrophages and recruitment of leukocytes)
- Can impede blood flow in lung and breathing/exchange of O2.
Therapeutic Approaches for Immunologic Diseases
Broadly Acting Antiinflammatory Agents Anticytokine Therapies Depletion of Cells and Antibodies Other Biologic Agents Intravenous IgG Tolerance-Inducing Therapies
systemic Lupus Erythematosus SLE (lupus)
Chronic, remitting and relapsing multisystem autoimmune disease
Predominantly women (1:700 women in US)
Female to male 10:1
->Rashes, arthritis and glomerulonephritis (mainly)
->many different Autoantibodiesfound in SLE patients, most commonly are antinuclear (anti-DNA) also anti-histones, etc.
-Immune-complexes formed from these autoantibodies and their specific ligands are deposited in small arteries and capillaries and are the cause for glomerulonephritis, arthritis and vasculitis
-Combination of susceptibility genes and external triggers (UV radiation) results in accumulation of antinuclear antibodies that accumulate in small arteries/capillaries and may recruit specific immune cells that result in production of even more anti-nuclear IgG antibodies
-Red blood cells/protein do not enter the urine in normal conditions but if you have an inflammation of glomerulus and destruction of glomerulocytes, results in loss of proteins and red blood cells through the urine
Treatments for SLE
Anti- BAFF:
small molecule/antibody that blocks B cell growth factor BAFF
Depletion of B cells:
Anti-CD20
Depletion of long-lived plasma cells that produce IGG antibodies
Rheumatoid arthritis (RA)
Inflammatory diseaseinvolving small and large joints of extremities (fingers, toes, etc.)
-characterized by Inflammation of the synovium (synovitis)
-Leads to destruction of joint cartilage and bone
-Numerous cytokines in synovial fluid
Rheumatoid factors: = autoantibodies
patients often have circulating antibodies (IgM and IgG) that react with the Fc portions of their own IgG molecules
-70% of patients have antibodies specific for cyclic citrullinated peptides(CPP) called anti-CCP
-Combination of susceptibility genes and external factors(infection, smoking). If you have B and T cell responses to self antigens then you will have accumulation of these complexes which is inappropriate and leads to destruction of cartilage and bone
Treatments:
blocking of cytokines to prevent T cell activation: Antagonists of TNF Anti-IL-6 receptor IL-1 antagonist JAK signalling inhibition
