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Immunology Lecture 7
Clinical Immunology I- Allergy, Autoimmunity, Immunodeficiency & Vaccination
29
Immunology
Graduate
11/20/2012

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Term
Type I Hypersensitivity
Definition
reactions result from the binding of antigen to antigen-specific IgE antibody bound to the Fc(epsilon)RI on mast cells
Term
Type II Hypersensitivity
Definition
reactions are mediated by IgG or IgM Abs developed to the epitopes, which are surface components of self cells modified by covalently bound to them small foreign particles
Term
Type III Hypersensitivity
Definition
reactions are due to small soluble complexes made of soluble antigens and antibodies
Term
Type IV Hypersensitivity
Definition
reactions are due to small soluble complexes made of soluble antigens and Abs
Term
Role of antibodies in Type I Hypersensitivity
Definition
IgE antibodies were produced during earlier encounter with antigen. The IgE antibodies remain bound to the Fc Receptors attached to mast cells, eosinophils and basophils. This complex makes these cells antigen specific. When the antigen comes back into the body, the IgE antibodies attached to mast cells (via FcEpsilon) cross-link and cause the mast cell to degranulate and release histamine into the environment. Histamine results in contraction of muscles, increased vessels’ permeability and secretion of mucus. This causes expulsion of GI tract or airways and inflammation to blood vessels.
Term
Role of antibodies in Type II Hypersensitivity
Definition
caused by antibodies specific for altered components of the human cells. Usually a drug modifies an epitope on a human cell, which causes it to be recognized as foreign. The now foreign cell is acted upon by IgG, which binds and promotes complement fixation. Complement fixation can lead to membrane attach complex or phagocytosis.
Term
Role of antibodies in Type III Hypersensitivity
Definition
smaller immune complexes (IgG) from regular immune responses are not efficiently fixed via complement. They circulate in the blood and eventually stick to blood vessel walls. After enough of them have accumulated, they become large enough to fix complement and interact with immune cells (i.e. Mast cells and FcGamma receptor). This interaction leads to histamine release and recruitment of platelets and inflammatory cells to the blood vessel. Clots cause the blood vessel to burst.
Term
Role of T cells in Type IV Hypersensitivity
Definition
First the foreign peptides-derived antigen is presented by macrophages & dendritic cells to that Antigen-specific memory T cells (which exited from blood into tissue). As a result a TH-1 response is generated locally & induced further inflammatory reactions, mediated by TH-1 panel of cytokines
Term
Mast cells
Definition
degranulate when the IgE linked to their FcEpsilon receptor cross-links with an antigen. Degranulation of histamine causes 1) increased fluid secretion and increased peristalsis in the GI tract which causes vomiting and diarrhea, 2) decreased diameter and increased mucus secretion in the airways which leads to coughing and 3) increased blood flow and increased permeability in the blood vessels which leads to edema, inflammation and increased lymph flow and carriage of antigen to lymph nodes. Also secrete leukotrienes. They are residents of the connective tissue
Term
Basophils
Definition
Express receptors for IgE, IgG, complement & histamine. They have granules that contain: heparin & peroxidase, prostaglandins & leukotrienes (factors of anaphylaxis), platelet activating factor, IL-4 (cytokine that stimulates the proliferation of activated B-cells) and IL-5 (the growth factor for eosinophils). Function of these factors results in (i) increased permeability of the blood vessels leading to accumulation of the phagocytic cells in the center of inflammation, (ii) preventing spread of microorganisms, (iii) regulation of other cells involvement & (iv) allergic reactions.
Term
Eosinophils
Definition
mostly are residing in the connective tissues underlying epithelia of the respiratory, gastrointestinal & urogenital tracts. Once activated they release of the pre-formed highly toxic molecules (for direct killing of microorganisms & parasites) and inflammatory mediators. This is followed by synthesis & secretion of prostaglandins & leukotrienes.
Term
Immediate reaction
Definition
a ‘wheal and flare’ pattern on the skin occurs as a result of IgE-mediated degranulation of mast cells, which can last up to 30 minutes.
Term
late phase IgE-mediated reaction
Definition
occurs 6-8 hours later as a more wide spread swelling. This is due to the leukotrienes, chemokines & cytokines synthesized by mast cells after IgE-mediated activation
Term
Allergens
Definition
stimulate an IgE-mediated immune response. They are usually small, soluble proteins that are present in dried-up particles derived from plants or animals. Once inhaled and rehydrated the present their antigenic proteins to T cells by antigen-presenting cells in a way that TH2 response is induced. This leads to IgE production and its binding to mast cells, basophils & eosinophils.
Term
biological nature of anaphylaxis
Definition
• Occurs when allergens enter the blood stream and mast cells degranulate which causes vascular permeability and muscular constriction of smooth muscle.
Term
clinical manifestations of anaphylaxis
Definition
Swelling of the airways and epiglottis causes choking
Term
Hemolytic anemia due to Type II Hpersensitivity
Definition
related to reactions caused by antibodies from a drug that causes a change in the epitope of the red blood cells, which then causes the immune system to attack and lyse the red blood cells (hemolysis).
Term
Hemolytic anemia due to Type II Autoimmune reactions
Definition
antibodies are produced against cell surface proteins of the red blood cells. IgG and IgM bind to RBC surface and activate complement. Complement system causes phagocytosis in spleen or membrane attack formation, which leads to lysis
Term
Type III Hypersensitivity pathogenesis
Definition
due to build up of small IgG complexes on the blood vessels walls which eventually cause complement fixation and attack of own blood vessels by the immune system.
Term
Type III Hypersensitivity disorders
Definition
Serum Sickness. Depending on where the immune complexes accumulate there can be inflammation in that area. Subcutaneous accumulation causes perivascular inflammation. Inhalation causes farmer’s lung or inflammation due to accumulation on the alveolar/capillary interface.
Term
Type III autoimmunity pathogenesis
Definition
due to soluble immune complex accumulation
Term
Type III autoimmunity disorders
Definition
include lupus, in which auto IgG antibodies cause release and accumulation of soluble immune complexes on the kidneys, blood vessels and joints. Butterfly face rash is characteristic of lupus
Term
Poison ivy
Definition
The TH1 cells specific to these damaged skin cells’ antigens produce cytokines activating macrophages, which present these antigens to the CD8+ TC cells. The Tc cells kill the skin cells
Term
Celiac’s disease
Definition
inflammation in the mucosa of the small intestine is caused by CD4 T cells responding to peptides derived from gluten that are deaminated by tissue transglutaminase & presented by HLA-DQ8 or HLA-DQ2 molecules
Term
disorders caused by Type IV Hypersensitivity
Definition
Poison Ivy and Celiac's Disease
Term
agonist
Definition
Antibodies act as agonist when they stimulate a receptor on binding it
Term
agonist antibodies cause
Definition
Grave’s disease, hypoglycemia
Term
antagonist
Definition
Antibodies act as antagonist when they block function of a receptor on binding it
Term
antagonist antibodies cause
Definition
Myasthenia gravis, insulin-resistant diabetes
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