| what are the major types of hypersensitivity reactions? | 1- Immediate hypersensitivity, ( type I hypersensitivity)
2- Antibody-mediated ( type II hypersensitivity)
3- Immune complex diseases ( type III hypersensitivity)
4- T cell–mediated diseases (type IV hypersensitivity) |
| what's Immediate hypersensitivity, ( type I hypersensitivity)? | a type of pathologic reaction that is caused by the release of mediators from mast cells. This reaction most often depends on the production of immunoglobulin E (IgE) antibody against environmental antigens and the binding of IgE to mast cells in various tissues. (Most frequent of all hypersensitivity,known as allergy or atopy ) |
| what's Antibody-mediated ( type II hypersensitivity)? | Antibodies that are directed against cell or tissue antigens can damage these cells or tissues or can impair their function. (Antibody-mediated (IgM or IgG) against cell surface or extracellular matrix proteins) |
| what's Immune complex diseases ( type III hypersensitivity)? | Antibodies against soluble antigens in the blood may form complexes with the antigens, and the immune complexes may deposit in blood vessels in various tissues, causing inflammation and tissue injury. (Immune complex-mediated (IgM or IgG) against soluble antigens) |
| what's T cell–mediated diseases (type IV hypersensitivity)? | These are diseases that result from the reactions of T lymphocytes specific for self antigens or microbes in tissues. (T cell-mediated, involving pro-inflammatory cytokines and secondary effectors). |
| what are the two types of antigens that cause hypersensitivity? | 1- responses to foreign antigens (microbes and noninfectious environmental antigens) may cause tissue injury, especially if the reactions are repetitive or poorly controlled.
2-the immune responses may be directed against self (autologous) antigens, as a result of the failure of self-tolerance.Responses against self antigens are termed autoimmunity, and disorders caused by such responses are called autoimmune diseases |
| what are the cell types involved in Immediate hypersensitivity ? | B cells, Tfh cell, IgE recreating plasma cells, Mast cells, |
| what are the sequences of events that occur in type 1 Immediate Hypersensitivity? | 1. In response to certain antigens (allergens), a Th2 and Tfh response is activated. Allergens include pollen, food, insect venom, animal dander, penicillin, causing hay fever, food allergies, bronchial asthma and anaphylaxis.
2. Th2 and Tfh secrete IL-4 and IL-13 that induce switching to IgE production by B cells. IgE bind to mast cells via Fc receptor. (Individual becomes sensitized).
3. On second exposure to allergens, Fc-bound IgE binds to antigens and becomes cross-linked.
4a. Crosslinking of surface IgE causes mast cell degranulation with release of vasoactive amines (histamine) causing immediate hypersensitivity:
increase in vascular permeability
smooth muscle contraction
4b. Other products released from mast cells include cytokines like IL-4 and TNF- that attract eosinophils and neutrophils causing more severe inflammatory response and tissue injury, called the late-phase reaction. |
| What is the late-phase reaction, and how is it caused? | it's when a severe inflammatory response and tissue injury that occurs.
A) Kinetics of the immediate and late-phase reactions. The immediate vascular and smooth muscle reaction to allergen develops within minutes after challenge (allergen exposure in a previously sensitized individual), and the late-phase reaction develops 2 to 24 hours later.
B) Morphology of the immediate reaction is characterized by vasodilation, congestion, and edema.
C) The late-phase reaction is characterized by an inflammatory infiltrate rich in eosinophils, neutrophils, and T cells. This inflammatory component is called the late-phase reaction, and it is mainly responsible for the tissue injury that results from repeated bouts of immediate hypersensitivity. |
| Type II hypersensitivity: what's the Mechanisms of Antibody-Mediated Tissue Injury? | Antibodies against tissue antigens (cells or extracellular matrix) induce inflammation by attracting and activating leukocytes. IgG antibodies bind to neutrophil and macrophage Fc receptors and activate these leukocytes, resulting in inflammation.
IgG, as well as IgM antibodies, activate the complement system by the classical pathway, resulting in the production of complement by-products that recruit leukocytes and induce inflammation.
When leukocytes are activated at sites of antibody deposition, these cells release reactive oxygen species and lysosomal enzymes that damage the adjacent tissues. |
| Type II hypersensitivity: Mechanisms of Antibody-Mediated Tissue Injury? | If antibodies bind to circulating cells, such as erythrocytes, neutrophils, and platelets, the cells are opsonized and may be ingested and destroyed by host phagocytes. |
| What are some examples of diseases caused by antibodies specific for cell surface or tissue matrix antigens? | Type II hypersensitivity: antibody-mediated diseases:
-autoimmune hemolytic anemia (red cell destruction),-autoimmune thrombocytopenia (destruction of platelets), -Graves disease (hyperthyroidism, targeting TSH). |
| how are the clinical manifestations different from most diseases caused by antibodies specific for cell surface or tissue matrix proteins? | Type III hypersensitivity:Diseases Caused By Antigen-Antibody Complexes:
-systemic lupus erythematosus, polyarteritis nodosa, serum sickness.
Complexes containing positively charged antigens are particularly pathogenic because they bind avidly to negatively charged components of the basement membranes of blood vessels and kidney glomeruli. |
| How do immune complexes cause disease? | Type III hypersensitivity:
Immune complexes usually deposit in blood vessels, especially vessels through which plasma is filtered at high pressure (e.g., in renal glomeruli and joint synovium). Therefore, in contrast to diseases caused by tissue antigen-specific antibodies, immune complex diseases tend to be systemic and often manifest as widespread vasculitis involving sites that are particularly susceptible to immune complex deposition, such as kidneys and joints. |
| How do antibodies cause disease without tissue injury? | Some antibodies may cause disease without directly inducing tissue injury.
In some cases of myasthenia gravis, antibodies against the acetylcholine receptor inhibit neuromuscular transmission, causing paralysis.
Other antibodies may directly activate receptors, mimicking their physiologic ligands.
For example, Graves disease, in which antibodies against the receptor for thyroid-stimulating hormone activate thyroid cells even in the absence of the hormone. |
| Diseases Caused by T Lymphocytes? | 1-cytokine-mediated inflammation.
2-T-cell-mediated killing of host cell. |
| what happens in cytokine-mediated inflammation? | Inflammation may be triggered by cytokines produced mainly by CD4+ T cells in which tissue injury is caused by activated macrophages and inflammatory cells.
Excessive polyclonal T cell activation by certain microbial toxins produced by some bacteria and viruses can lead to production of large amounts of inflammatory cytokines, causing a syndrome similar to septic shock. These toxins are called superantigens because they stimulate large numbers of T cells. |
| what happens in T-cell-mediated killing of host cell? | Direct killing of target cells is mediated by CD8+ cytotoxic T lymphocytes (CTLs) |
| What are some examples of diseases caused by T cells? | T cell–mediated autoimmune diseases are usually limited to a few organs and usually are not systemic.
Examples of T cell–mediated hypersensitivity reactions against environmental antigens include contact sensitivity to chemicals like therapeutic drugs and substances found in plants ( poison ivy)). Tissue injury also may accompany T cell responses to microbes. For example, in tuberculosis, a T cell–mediated immune response develops against protein antigens of Mycobacterium tuberculosis, and the response becomes chronic because the infection is difficult to eradicate. The resultant granulomatous inflammation causes injury to normal tissues at the site of infection. |
| the role of superantigens in type IV hypersensitivity? | they are Toxins that stimulate large numbers of T cells. Superantigens bind to invariant parts of T cell receptors on many different clones of T cells, regardless of antigen specificity, thereby activating these cells. |
