Hypersensitivity Disorders

Question 1

Hypersensitivity Disorders

Answer 1

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.”

Question 2

Causes of Hypersensitivity Disorders

Answer 2

Autoimmunity: reactions against self antigens
Reactions against microbes.
Reactions against nonmicrobial environmental antigens. (allergies)

Question 3

Hypersensitivity diseases are commonly classified according to

Answer 3

the type of immune response and the effector mechanism responsible for cell and tissue injury.
Types I-IV.

Question 4

immediate type 1 Hypersensitivity Disorder

Answer 4

= allergies
pathologic immune mechanisms: IgE antibody, TH2 cells

Mechanism of tissue injury/disease:
activation of mast cells and esinophils (and their mediators)

Question 5

antibody mediated type II Hypersensitivity Disorder

Answer 5

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

Question 6

• immune complex mediated type III Hypersensitivity Disorder

Answer 6

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

Question 7

• T cell mediated type IV Hypersensitivity Disorder

Answer 7

pathologic immune mechanisms:

1. CD4+ T cells (TH1 and TH17) and
2. CD8+ CTLs

Mechanism of tissue injury/disease:

1. cytokine mediated inflammation and macrophage activation
2. direct target killing of certain cells, cytokine mediated inflammation

Question 8

Antibody-mediated diseases are produced either by

Answer 8

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.

Question 9

three main mechanisms of how antibodies against tissue antigens cause disease
(antibody mediated type II Hypersensitivity Disorder)

Answer 9

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

Question 10

Antibodies that cause cell- or tissue-specific diseases are usually

Answer 10

autoantibodies produced as part of an autoimmune reaction, but sometimes the antibodies are specific for microbes

Question 11

acute rheumatic fever

Answer 11

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

Question 12

Goodpasture syndrom

Answer 12

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

Question 13

Serum sickness (acute)

Answer 13

-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)

Question 14

examples of T cell mediated diseases

Answer 14

Rheumatoid arthritis, multiple sclerosis, type 1 diabetes inflammatory bowl disease, psoriasis

Question 15

Delayed-Type Hypersensitivity (DTH)

Answer 15

• 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.

Question 16

Chronic DTH reactions can develop if

Answer 16

• 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.

Question 17

Therapeutic Approaches for Immunologic Diseases

Answer 17

Broadly Acting Antiinflammatory Agents
Anticytokine Therapies
Depletion of Cells and Antibodies
Other Biologic Agents
Intravenous IgG
Tolerance-Inducing Therapies

Question 18

systemic Lupus Erythematosus SLE (lupus)

Answer 18

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

Question 19

Treatments for SLE

Answer 19

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

Question 20

Rheumatoid arthritis (RA)

Answer 20

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

Question 21

Treatments:

Answer 21

blocking of cytokines to prevent T cell activation:
Antagonists of TNF
Anti-IL-6 receptor
IL-1 antagonist
JAK signalling inhibition