Microbiology Chapter 17.1

who was responsible for the initial anaphylaxis?

Charles Richet and Paul Portier

What can happened if there is a mismatch of either Rh antigen or ABO antigen?

Transfusion reactions, hemolytic Disease of the newborn

Anaphylaxis is name given to allergic reactions caused by IgE-mediated release of mast cell granules.

True

Type I, II, III & IV are associated with immunoglobulin or system & which cells if any?

Type 1 hypersensitivity is associated with IgE antibodies which binds to Fc protion on mast cells (peripheral) or basophils(circulatory). Binding triggers release of inflammatory mediators. IgE accumulates, attaches to mast cells in the tissues and basophils in the systemic circulation. (immediate) When you get a first immune response you get synthesized and the first is IgM (pentamenic) and hold together by a J- chan. Class switch is IgM to IgE (two forms 1.) now has the ability to bind to mast cells and basophils. When does the antigen go into your blood?---penicillin. Antigen have to cross link between mast cells. In Type 2 hypersensitivity (Cytotoxic) antibodies react with molecules on blood cell surface such as the A and B antigens. This triggers the destruction of cells; By two methods a. Activation of complement system by the Classical pathway, that will lead to lysis of cells via membrane attack complexes (MACs) b. Antibody-dependent cellular cytotoxicity (ADCC), leads natural killer (NK) cells to bind to Fc regions of antibodies and deliver chemicals (perforin/fragmentin and proteases) to destroy cell which opsonized. Involves two antibodies IgG and IgM. Red blood cells result in transfusion reaction and hemolytic disease in fetus. Rh incompatibility blood has to be given by positive or negative and deals with gender. RH+ does not go with RH- person because result in a transfusion reaction. In pregnant women Type 3 hypersensitivity occur from the formation of immune complexes: That results from IgG or IgM antibodies binding to soluble antigens c. Usually removed from the circulatory system by phagocytic cells if they are large through binding of phagocytes to the Fc regions of the antibodies. d. If there is an excess of antigen than antibodies, smaller immune complexes will form. This remains in the circulation or at the sites of immune complex formation in the tissues e. Circulating immune complexes can lodge in blood vessel walls in the skin, joints, kidneys (filtration will be compromised, nephron filter blood and if you can't get urine out you get fluid retention) & other tissues with small blood vessels. f. This can trigger a blood-clotting cascade as well as activate the complement system, which will recruit phagocytes. (coronary artery supplies blood to the heart) - Phagocytes then release pro-inflammatory cytokines, as well as enzymes and toxic molecules Involves IgM and IgE Type 4 hypersensitivity are due to antigen-specific T-cell responses • Can occur almost anywhere in body. Induration starts at 6 to 24 hours; then peak 2 to 3 days following antigen exposure, unlike Antibodies where Hypersensitivity occur within minutes following exposure to an antigen • Contact dermatitis is type 4 an unusual it caused by effector t cells and antigen is on the skin. Effector cytotoxic t cell will produce interferon gamma, protease, and fragmenting. The cell becomes inflamed.

In type II hypersensitivity reaction what triggers what reaction?

Type II hypersensitivity reactions, or cytotoxic reactions, are caused by antibodies that can destroy normal cells by complement lysis or by antibody-dependent cellular cytotoxicity (ADCC)

How long does it take for type IV hypersensitivity reactions to peak?

2-3 days

Anti-A and anti-B antibodies are natural antibodies and are present at birth.

FALSE, generally appear six months after birth

Anti-Rh antibodies may not cross the placenta.

False

First exposure to an allergen results in violent hypersensitivity reaction.

False

In type I hypersensitivity to produce an allergic reaction the antigen need to bind to? Pg. 402

Fc Region of IgE must bind to Mast cells or Basophil cells and when they capture an antigen, or allergen the cell is triggered to release inflammatory mediators.

The characteristics of generalized anaphylaxis is?

Anaphylaxis can occur when antigen enters the blood stream and spreads throughout the body. When this antigen binds to IgE on circulating basophils, the cells release their inflammatory mediators systemically, causing extensive blood vessel dilation that results in fluid loss from the blood. This causes a severe drop in blood pressure that may lead to heart failure and insufficient blood flow to the brain and other vital organs- a condition called anaphylactic shock. (Antigen must enter the circulatory system because the effect is systemic)

What are Anti-A & Anti-B and when do they occur and in which blood groups?

Anti-A and anti-B are called natural antibodies because they occur without obvious pre-exposure. Appear EXAM QUESTION within six months after birth and are mostly of the class IgM. Anti-A & Anti-B are in blood type O. Blood type A have Anti-B, Type B have Anti-A, and AB has neither.

Which is the most common primary immunodeficiency disease?

Antibody Deficiency (Selective IgA deficiency) Pg. 414

What precautionary steps need to be taken to avoid transplant rejection?

Antigen incompatibilities are minimized by using (clerical check) MHC tissue typing and ABO blood typing to match donor and recipient tissues. Indefinite use of immunosuppressive drugs. (group is ABO and type is RH) pg. 411

Which two cells are involved in transplant rejection?

Cytotoxic T cells and Natural Killer

What APC cell does what in Contact Hypersensitivities (Contact dermatitis)?

Dendritic cells take up and process these hapten: protien complexes and present the resulting hapten:peptides to T cells in nearby lymph nodes. T cells that become activated form memory cells, sensitizing the individual to the substance. (Hapten is a molecule by itself is not able to produce antibodies.) picture on 410

What can happened if the thymus gland fails to develop?

Di George's syndrome, lymphocyte deficiency results when the thymus does not develop in the embryo, so T cells do not differentiate or they are absent in circulation. (pg.415)

Mast Cells so what to produce what during what type of hypersensitivity reaction?

During Type 1 hypersensitivity reactions mast cells release histamine (degranulation) and other Inflammatory mediators in process called degranulation, this occurs within seconds of an event called cross linking in which at least two cell-bound IgE molecules react with specific antigen and come together.

How are cytotoxic T cells and Helper T cells involve in Type IV Hypersensitivity reactions?

Hapten:peptide bind to the Naive helper T cell and Naive cytotoxic T cell to proliferate and differentiate. then it attaches to the macrophages to release inflammatory mediators . (T helper cell , Cytotoxic T cells react to

Urticaria is characterized by?

Hives (urticarial) is an allergic skin condition characterized by the formation of a wheal and flare. PG. 403

What is recombinant human monoclonal antibody (rhuMab) & hyposensitization?

Hypo-sensitization-a procedure that causes the immune system to mount an IgG response rather that IgE. Over a period of many months, the person is injected with the allergen in extremely diluted, but gradually increasing concentrations. RhuMab-uses a genetically engineered form of an IgG molecule that binds specifically to the Fc portion of the IgE molecules, thereby blocking the sited that would otherwise attach to mast cells and basophils.

IgE binds to which two cells that is located where & in what hypersensitivity type?

IgE binds to the Fc portion on mast cells or basophils in Type 1 Hypersensitivity.

Which antibodies are involved in immune complex formation?

IgG & IgM

What are immune complexes and in what type of hypersensitivity are they involved?

Immune complex is a combination of antibody and soluble antigen capable of triggering the classical pathway of complement system activation. And it is involved in Type III Hypersensitivity by formation of immune complexes consisting pf IgG or IgM antibodies binding to soluble antigen. (when you have an excess of antigen to antibodies which forms a mesh like structure and inloged in veins, etc.

What are immune complexes and which pathological conditions result from them?

Immune complexes are often deposited in small blood vessels in organs, where they cause inflammatory disease-for example, glomerulonephritis in the kidney or arthritis in the joints. a. Type III hypersensitivities are caused by the formation of immune complexes consisting of IgG or IgM antibodies bond to soluble antigen. b. Usually removed from circulatory system by phagocytic cells if they are large through binding of phagocytes to the Fc regions of the antibodies. c. If there is an excess of antigen than antibodies smaller complexes form, this remains in the circulation oral sites of immune complex formation in tissues. d. The circulating immune complexes can lodge into blood vessel ways in the skin, joints, kidneys, and other tissues. e. Can trigger blood clotting cascade as well activate complement system - recruiting phagocytes - then will release proinflamatory cytokines, enzymes and toxic molecules. f. May arise during - viral, bacterial, protozoan infections; also from inhaled dust particles, bacteria injected medications. g. Immune complexes trigger - DIC h. Disseminated Intravascular Coagulation- is a condition in which clots form in small blood vessels; leading to failure of vital organs i. Arthus reaction- Localized immune complex reaction occurs following injection of antigen into a previously immunized individual who already has high level of circulatory antibody (when tetanus-diphtheria booster is given too often) Serum sickness- System immune complex disease, caused by passive immunization. When antibody-containing serum from horse or other animal is injected to humans to prevent/treat disease, may mount an immune response to antigens from foreign serum.

Cyclosporin A and tacrolimus function as what?

Immunosuppressive drugs (prevent from you rejecting the transplant ogan)

Advantage of using an individual's stem cell instead of pancreatic cells as allografts to treat Type 1 diabetes?

It has your own MHC molecules

What is localized allergic reaction & systemic anaphylaxis?

Localized anaphylaxis (type I) reactions include hives (urticarial), hay fever allergic rhinitis, and asthma (must enter through the skin, and in the lungs, bee sting and penicillin) Generalized anaphylaxis, or systemic is rare but serious reaction that can lead to shock and death (antigen enters the blood)

Grafts rejection involves which tissue antigens?

MHC I or II molecule

What is RhoGAM?

Medication for newborn to prevent hemolytic disease. RhoGam contains anti-Rh antibodies given to pregnant mothers during the first trisemester of pregnancy to prevent a second pregnancy of Rh + baby to prevent class switch from IgM to IgG. • RhoGAM contains anti-RH antibodies, bind to any RH+ Erythrocytes that have entered mother's circulation. • Prevents stimulation of primary immune response with development of memory cells. • RH - negative women who are carrying an RN - + fetus are injected with ant - RH antibodies during pregnancy and again after delivery. • Anti - RH antibody is not effective if RH - negative mother is already sensitized and has formed memory cells.

Insulin-dependent diabetes mellitus is what type of autoimmune disease that involves what?

Organ-specific autoimmune disease caused when Cytotoxic T cells destroy a group of pancreatic cells called B cells produce insulin.(isolates of Langerhans which is Alpha produce glucagon or Beta) This results in cells of the body no longer able to properly take up glucose resulting in increased blood levels of glucose, causing water to be drawn from cells. Results in increased thirst and urination.

What are privileged sites; identify those in our body?

Privileged site are autoimmune responses may occur after injury in which seld antigens are released from privileged (isolated) or damaged organs and stimulate production of antibodies to them (autoantibodies). (because you don't do tissue typing here)The ones in our body are the uterus, eyes and testes. Pg. 421

Identify two Secondary Immunodeficiencies.

Secondary (acquired) - occur as a result of infection or other stresses on the system (malnutrition) Result from malignancies, advanced age (arthritis), pregnancy, certain infections (especially viral) immunosuppressive drugs, or malnutrition Pg.415. a. Measles - replicate in lymphoid cells and destroys them b. Syphilis, leprosy, and malaria - destroys T-cell population and macrophage function. c. HIV - Destroys Helper T-Cells (CD4 cells), results in AIDS. d. Multiple myeloma - is a malignancy arising from a single plasma cell that proliferate out of control, produces large quantities of immunoglobulin (antibodies) at expense of others needed to fight infection. e. Lymphoid Disorders including macroglobulinemia (overproduction of IgM) and other forms of leukemia.

Describe the process involved in hemolytic disease of the newborn.

The Rhesus blood group antigens are usually responsible for this potentially fatal disease. Injected anti-Rh antibody helps prevent Rh sensitization of Rh-negative mothers.The fetus of an Rh-negative (Rh-) mother may inherit paternal genes for Rh antigens and have Rh-positive (Rh+) blood. During delivery of a first Rh+ baby, enough Rh+ red cells can enter the Rh- mother to induce an anti-Rh response. The mother makes a primary response to Rh antigens and develops memory cells for anti-Rh antibodies. During subsequent pregnancies with an Rh+ fetus, the very few fetal red cells that cross the placenta can cause a vigorous secondary reponse. The igG anti-Rh antibodies cross the placenta and destroy the baby's red blood cells.

Auto-Immune disease result from what?

The body recognizes parts of itself as being foreign and from failure to remove self recognizing cells.(pg. 414)

Redness and induration found after a tuberculin skin test is positive due to?

The reaction results mainly from Effector helper T cells recognizing antigens and releases pro-inflammatory cytokines. Activate macrophages (Interleukin III, five and then become giant cells which invites dendritic cells and then the formation of granulomas) PPD Purified protein derivative and another name Mantol Test

How are blood cells destroyed in Type II Hypersensitivity?

a. Antibodies react with molecules on blood cells surface as the A and B antigens b. Antibodies react with molecules on the surface of a cell and trigger its destruction by the complement system or by antibody - dependent cellular cytotoxicity (ADCC). c. Recall that antibodies bound to an antigen trigger the classical pathway of complement activation and one out come of activation cellysis due to MACs assembly in membrane. d. In ADCC, the Fc regions of antibodies bound to a cell mark the cell for destruction. NK cells bind to Fc regions and deliver chemicals destroying the marked cell. e. Type III hypersensitivity are called cytotoxic hypersensitivities. i. When individual receives a transfusion of RBCs with different antigens from his or her own a transfusion reaction occurs. When natural antibodies bind to those cells, resulting in agglutination (clumping) - they are killed rapidly by MACs or NK cells. f. Donor and recipients are matched for ABO systems as well as for RH system. i. People with RH antigen are RH positive those without are RH negative. ii. If RH - positive blood is given in error, an RH negative recipient will then develop antibodies to the RH - positive blood cells if person is exposed to (RH positive blood again his/her immune system will destroy transfused cells.

What is Arthus reaction, Serum Sickness & to which hypersensitivity type so they belong?

a. Arthus reaction-Hypersensitivity reaction caused by immune complexes and neutrophils (injecting anti serum locally. EX. Vaccine on the contrary is a localized immune complex reaction that occurs following injection of antigen into a previously immunized individual who already has a high level of circulating antibody E.g., when tetanus-diphtheria booster is given too often. b. Serum Sickness-is an immune complex disease caused by passive immunization when an antibody-containing serum from a horse or other animal is injected into humans to prevent or treat a disease such as diphtheria or tetanus. on the other hand is a systemic immune complex disease caused by passive immunization (antibodies provided for protection; e.g., serum from horse). When an antibody-containing serum from a horse or other animal is injected into humans to prevent or treat a disease, the recipient may mount an immune response within 7-10 days to antigens in the foreign serum. c. Both parth of Type III hypersensitivities

How are cytotoxic T cells (TcCells) similar to NK cells?

a. Both destroy host cells through release of cytokines (perforin/fragementation / interferon gamma/ protease) initiating apoptosis.

define

a. Hypersensitivity: exaggerated immune response that injures tissue.; typically categorized as one of four types b. autoimmunity: inappropriate immune response that target body tissue. (SELF) c. cell-mediated immunity: immunity due to a T cell response. d. autograft: tissue transplanted from elsewhere on the recipients body. e. zenograft: grafts donated form an identical sibling. f. urticaria: another name for hives. allergic skin condition characterized by the formation of wheal and flare. g. desensitization: allergy treatment that induces IgG production by gradual exposure to small amounts of allergen; IgG competes with IgE. h. anaphylaxis: destructive immune response. ex. the small second dose of toxin from sea anemone tested on dogs at least three weeks later resulting in the dogs dying within minutes. An acute allergic reaction to an antigen (e.g., a bee sting) to which the body has become hypersensitive. i. anti-A & anti-B antibodies:are called natural antibodies because they occur without obvious pre-exposure. They are mostly of the class IgM, and therefore do not cross the placenta. People have blood type A, B, AB, O, depending on which specific carbohydrate antigens are present on their red blood cells; they have antibodies to the antigens not present on their own red blood cells. j. natural antibodies: is an antibody present in the circulation of an animal or a subject that had not been previously exposed to the corresponding antigen. k. Immune complexes: consist of IgG or IgM antibodies bound to soluble antigen. If there is slightly more antigen than antibody, smaller complexes form. These are not quickly destroyed but remain in circulation or at their sites of formation in tissue. l. Farmer's lung: Formation of immune complexes (continued...) Result in the production of: rashes, joint pains, other symptoms seen in diseases like: farmer's lung, lupus, bacterial endocarditis, early rubella infection, malaria and glomerulonephritis m. Serum sickness: is a systemic immune complex disease caused by passive immunization (antibodies provided as a source of protection). n. Arthus reaction: is a localized immune complex reaction. If antigen is injected into a previously immunized person who already has high levels lf circulating specific antibody, immune complexes can form at the site of injection where antigen levels are high. o. Allographs: Most human transplants involve allografts in which the tissue of the donor and recipient are not genetically identical. p. Immunologically Privileged sites: uterus, eyes, and testes q. Primary immunodeficiencies: are rare. They may affect B cells, T cells, natural killer cells, phagoxytes, or complement components. Many of the gene defects that cause primary immunological disorders are known and work is underway to correct them. r. SCID: stands for Severe combined immunodeficienct is an example of a primary immunodeficiency and involves a defect in bone marrow stem cells s. AIDS: stands for Acquired immunodeficiency syndrome is an example of a secondary immunodeficiency and is caused by infection with HIV and involves destruction of the T cells by viral infection. t. Agammaglobulinemia: few or no antibodies produced u. Chediak Higashi disease: Lysosomes in the phagocyte lack certain enzymes and cannot destroy phagocytized bacteria. People with this condition suffer from recurring pyogenic (pus-forming) bacterial infection. v. Secondary immunodeficiency disease: or acquired, immunodeficiency disease may result from malignancies, advanced age, pregnancy, certain infections (especially viral infections), immunosuppressive drugs, or malnutrition. w. Myasthenia gravis: the name means "grave muscle weakness" and reflects the fact that this systemic disease is caused by a disruption in nerve transmission to muscles. It is a form of autoimmune disease. x. Beta cells ( B cells): Produce insulin a protein that allows various cell types in the body to take up glucose from the blood stream.

What effector cells are involved in Tuberculosis and virally infected cells?

a. Type IV hypersensitive reaction - delayed type cell mediated reaction results mainly from T effector helper T- Cell - recognizing antigens and releases proinflamatory cytokines. The inflammatory response that characterizes a positive skin test also occurs in response to the infecting organisms, often resulting in formation of tubercles in lungs. b. Effector cytotoxic T cells - destroy infected host cells through the release of cytokines (perforin/ fragmentin protease) preventing the spread of infection, this damages tissue; in chronic infections, this damages to infected tissue function (damaged sensory nerves in Hansen's Disease) c. Contact Hypersensitivity or (contact dermatitis) caused by effector T cells responding to small molecules that penetrate intact skin - results in irritating rash, sometimes blisters. Ex. Nickel of metal, jewelry cosmetics latex, etc.

Disease forms that result from immune complex formation are?

•Disseminated intravascular coagulation (DIC) is a condition in which clots form in small blood vessels; leading to failure of vital organs •Arthus reaction is a localized immune complex reaction that occurs following injection of antigen into a previously immunized individual who already has a high level of circulating antibody E.g., when tetanus-diphtheria booster is given too often. •Serum sickness on the other hand is a systemic immune complex disease caused by passive immunization (antibodies provided for protection; e.g., serum from horse). When an antibody-containing serum from a horse or other animal is injected into humans to prevent or treat a disease, the recipient may mount an immune response within 7-10 days to antigens in the foreign serum. (on PowerPoints)