Block 9 Hypersensitivity MCQ's

Serum sickness, and Arthurs reaction are Type III

In type II hypersensitivity (or cytotoxic hypersensitivity) the antibodies produced by the immune response bind to antigens on the patient's own cell surfaces.

DTH is type 4, which involves Tcells, macrophages IFN-g and TNF-a

Type IV hypersensitivity is often called Delayed Type Hypersensitivity as the reaction takes two to three days to develop. Unlike the other types, it is not antibody mediated but rather is a type of cell-mediated response.

CD4+ helper T cells recognize antigen in a complex with either type 1 or 2 major histocompatibility complex. The antigen-presenting cells in this case are macrophages that secrete IL-12, which stimulates the proliferation of further CD4+ T cells. CD4+ T cells secrete IL-2 and interferon gamma, further inducing the release of other Type 1 cytokines, thus mediating the immune response. Activated CD8+ T cells destroy target cells on contact, whereas activated macrophages produce hydrolytic enzymes and, on presentation with certain intracellular pathogens, transform into multinucleated giant cells.

IN TYPE II HYPERSENSITIVITY-- (or cytotoxic hypersensitivity) the antibodies produced by the immune response bind to antigens on the patient's own cell surfaces. The antigens recognized in this way may either be intrinsic ("self" antigen, innately part of the patient's cells) or extrinsic (adsorbed onto the cells during exposure to some foreign antigen, possibly as part of infection with a pathogen). These cells are recognized by macrophages or dendritic cells, which act as antigen-presenting cells. This causes a B cell response, wherein antibodies are produced against the foreign antigen.
An example of type II hypersensitivity is the reaction to penicillin wherein the drug can bind to red blood cells, causing them to be recognized as different; B cell proliferation will take place and antibodies to the drug are produced. IgG and IgM antibodies bind to these antigens to form complexes that activate the classical pathway of complement activation to eliminate cells presenting foreign antigens (which are usually, but not in this case, pathogens). That is, mediators of acute inflammation are generated at the site and membrane attack complexes cause cell lysis and death. The reaction takes hours to a day.
Another form of type II hypersensitivity is called antibody-dependent cell-mediated cytotoxicity (ADCC). Here, cells exhibiting the foreign antigen are tagged with antibodies (IgG or IgM). These tagged cells are then recognised by natural killer (NK) cells and macrophages (recognised via IgG bound (via the Fc region) to the effector cell surface receptor, CD16 (FcγRIII)), which in turn kill these tagged cells.
TYPE III HYPERSENSITIVITY --occurs when antigens and antibodies (IgG or IgM) are present in roughly equal amounts, causing extensive cross-linking.
Presentation
Type III hypersensitivity occurs when there is little antibody and an excess of antigen, leading to small immune complexes being formed that do not fix complement and are not cleared from the circulation. It is characterized by solvent antigens that are not bound to cell surfaces (which is the case in type II hypersensitivity). When these antigens bind antibodies, immune complexes of different sizes form. Large complexes can be cleared by macrophages but, comparatively macrophages have difficulty in the disposal of small immune complexes. These immune complexes insert themselves into small blood vessels, joints, and glomeruli, causing symptoms. Unlike the free variant, a small immune complex bound to sites of deposition (like blood vessel walls) are far more capable of interacting with complement; these medium-sized complexes, formed in the slight excess of antigen, are viewed as being highly pathogenic.
Such depositions in tissues often induce an inflammatory response, and can cause damage wherever they precipitate. The cause of damage is as a result of the action of cleaved complement anaphylotoxins C3a and C5a, which, respectively, mediate the induction of granule release from mast cells (from which histamine can cause urticaria), and recruitment of inflammatory cells into the tissue (mainly those with lysosomal action, leading to tissue damage through frustrated phagocytosis by PMNs and macrophages)
The reaction can take hours, days, or even weeks to develop, depending on whether or not there is immunlogic memory of the precipitating antigen. Typically, clinical features emerge a week following initial antigen challenge, when the deposited immune complexes can precipitate an inflammatory response. Because of the nature of the antibody aggregation, tissues that are associated with blood filtration at considerable osmotic and hydrostatic gradient (e.g. sites of urinary and synovial fluid formation, kidney glomeruli and joint tissues respectively) bear the brunt of the damage. Hence, vasculitis, glomerulonephritis and arthritis are commonly-associated conditions as a result of type III hypersensitivity responses
As observed under methods of histopathology, acute necrotizing vasculitis within the affected tissues is observed concomitant to neutrophilic infiltration, along with notable eosinophilic deposition (FIBRINOID NECROSIS). Often, immunofluorescence microscopy can be used to visualize the immune complexes. Skin response to a hypersensitivity of this type is referred to as an ARTHUS REACTION, and is characterized by local erythema and some induration. Platelet aggregation, especially in microvasculature, can cause localized clot formation, leading to blotchy hemorrhages. This typifies the response to injection of foreign antigen sufficient to lead to the condition of SERUM SICKNESS

The lepromin skin test is intended to detect a Type IV hypersensitivity reaction. Type IV hypersensitivity is also known as delayed-type hypersensitivity (DTH) and is mediated by T cells and macrophages. In this test, inactivated Mycobacterium leprae organisms are injected, and if a person has a positive test, they will develop an area of induration with erythema after 48 hours. This reaction indicates a delayed immune response against the organism, which is characteristic of a Type IV hypersensitivity reaction.

Leukotrienes are the most likely cause of the severe asthma symptoms in this patient. Leukotrienes are inflammatory molecules released by immune cells in response to triggers like allergens. They cause bronchoconstriction, mucus production, and inflammation in the airways, leading to asthma symptoms. Antihistamines, on the other hand, primarily target histamine, which is involved in allergic reactions but not as strongly linked to asthma symptoms as leukotrienes. IL-2, serotonin, and bradykinin are not typically associated with asthma symptoms.

In anaphylactic (type I) hypersensitivity, the immune system overreacts to an allergen, leading to the release of histamine and other chemicals that cause an immediate allergic reaction. This type of hypersensitivity is mediated by IgE antibodies. On the other hand, immune complex (type III) hypersensitivity occurs when antigen-antibody complexes deposit in tissues, leading to inflammation and tissue damage. Complement, a group of proteins involved in the immune response, is involved in both types of hypersensitivity reactions. However, the statement that less antigen is typically needed to trigger an anaphylactic reaction than an immune complex reaction is the most accurate. Anaphylactic reactions can occur with minimal exposure to an allergen, while immune complex reactions typically require a higher antigen load.

The patient's symptoms of fever, rash, and proteinuria are suggestive of an immune-mediated reaction. IgG and complement are involved in type III hypersensitivity reactions, which can cause a maculopapular rash and glomerulonephritis with proteinuria. IgE and histamine are involved in type I hypersensitivity reactions, which typically present with urticaria and not proteinuria. IL-2 and cytotoxic T cells are involved in cell-mediated immune responses, which do not typically cause rash and proteinuria. Gamma interferon and macrophages are involved in type II hypersensitivity reactions, which are not associated with the symptoms described.

not type I b/c no IgE
not type II b/c the antigen is not membrane bound

Hypersensitivity to penicillin and hypersensitivity to poison oak are both initiated by haptens. Haptens are small molecules that can bind to larger molecules in the body, forming a complex that is recognized as foreign by the immune system. This triggers an immune response, leading to hypersensitivity reactions. In the case of penicillin, the hapten is the penicillin molecule itself, while in the case of poison oak, the hapten is a chemical called urushiol found in the plant. These haptens can bind to proteins in the body, forming haptens-protein complexes that activate the immune system and cause hypersensitivity reactions.

This reaction is considered a Type III Hypersensitivity reaction because it occurs 8 days after the administration of the drug, which is consistent with the time frame for a Type III reaction. In Type III reactions, immune complexes are formed between the drug and antibodies, which then deposit in tissues and activate complement. This can lead to the symptoms of chills, fever, and rash seen in the patient.

it is a type 3 rxn which usually involves IgM, but Henoch-Schonlein is an exception that involves IgA.