How To Understand And Understand The Biological Basis Of Hypersensitivity

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Roger Gray
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1 Types of Hypersensitivity Type of Reaction Type I (anaphylactic) Type II (cytotoxic) Type III (immune complex) Type IV (delayed cellmediated) Time After Exposure for Clinical Symptoms <30 min 5 12 hours 3 8 hours 1 day

complex) Type IV (delayed cellmediated) Time After

2 Figure 19.1a The mechanism of anaphylaxis. Mast cell or basophil Granule IgE Antigen Histamine and other mediators IgE antibodies, produced in response to an antigen, coat mast cells and basophils. When an antigen bridges the gap between two adjacent antibody molecules of the same specificity, the cell undergoes degranulation and releases histamine and other mediators.

produced in response to an antigen, coat mast cells and basophils.

3 A degranulated mast cell that has reacted with an antigen and released granules of histamine and other reactive mediators Figure 19.1b The mechanism of anaphylaxis. Mast cells

4 Figure 19.2 Localized anaphylaxis. A micrograph of pollen grains A micrograph of a house mite on fabric

5 Figure 19.3 A skin test to identify allergens.

6 Table 17.1

7 Table 19.2 The ABO Blood Group System Insert Table 19.2 See blood maps by Anstee 2010

8 Figure 19.4 Hemolytic disease of the newborn. Placenta Rh + father. Rh mother carrying her first Rh + fetus. Rh antigens from the developing fetus can enter the mother's blood during delivery. In response to the fetal Rh antigens, the mother will produce anti-rh antibodies. If the woman becomes pregnant with another Rh + fetus, her anti-rh antibodies will cross the placenta and damage fetal red blood cells.

Rh antigens from the developing fetus can enter the mother's blood during delivery.

9 Figure 19.5 Drug-induced thrombocytopenic purpura. Platelet Drug (hapten) Drug binds to platelet, forming hapten platelet complex. Complex induces formation of antibodies against hapten. Hapten platelet complex Anti-hapten antibody Action of antibodies and complement causes platelet destruction. Complement

complex. Complex induces formation of antibodies against hapten.

10 Figure 19.6 Immune complex mediated hypersensitivity. Basement membrane of blood vessel Ag Immune complexes are deposited in wall of blood vessel. Neutrophils Endothelial cell Presence of immune complexes activates complement and attracts inflammatory cells such as neutrophils. Enzymes released from neutrophils cause damage to endothelial cells of basement membrane.

Neutrophils Endothelial cell Presence of immune complexes activates complement and attracts

11 Figure 19.7 The development of an allergy (allergic contact dermatitis) to catechols from the poison ivy plant. Pentadecacatechol molecules Skin protein Poison ivy Dermatitis on arm Pentadecacatechol molecules combined with skin proteins 7 10 days 1 2 days T cells: Sensitization step (No dermatitis) T memory cells: Immune response Many active T cells: Disease Dermatitis PRIMARY CONTACT SECONDARY CONTACT

Pentadecacatechol molecules Skin protein Poison ivy Dermatitis on arm Pentadecacatechol molecules

12 Figure 19.8 Allergic contact dermatitis. Insert Fig 19.8

13 What Is the Delayed Rash? Clinical Focus: A Delayed Rash, unnumbered figure, page 537.

14 Figure 19.9 Tissue typing, a serological method. Lymphocyte being tested HLA Anti-HLA antibodies attach to HLAs on lymphocyte. Complement and trypan blue dye are added. Cell damaged by complement takes up dye.

15 Diseases Related to Specific HLAs Disease Multiple sclerosis Rheumatic fever Addison s disease Graves disease Hodgkin s disease Increased Risk of Occurrence with Specific HLA 5 times 4 5 times 4 10 times times times

disease Hodgkin s disease Increased Risk of Occurrence

16 Figure Derivation of embryonic stem cells. (1 day) Embryo, usually a fertilized egg discarded from attempt at in vitro fertilization. Embryoblast (inner cell mass of embryonic cells) Outer cell mass (1 5 days) Blastocyst stage; the embryo divides repeatedly and forms a hollow ball of cells about the size of the period at the end of a sentence. Stem cell lines Blood and lymphatic cells Pancreatic islet cells Nerve cells Embryonic stem cells from embryoblast are grown on feeder cells in culture medium. Stem cell lines and groups of stem cells form colonies in culture medium. Different conditions, as well as growth factors added to culture medium, direct stem cells to become stem cell lines for various tissues of the body (e.g., blood and lymphatic cells, pancreatic islet cells, nerve cells).

a sentence. Stem cell lines Blood and lymphatic cells Pancreatic islet cells Nerve cells Embryonic stem cells from embryoblast are grown on feeder cells in culture medium.

17 Figure The interaction between a cytotoxic T lymphocyte (CTL) and a cancer cell. Cancer cell Remains of cancer cell CTL CTL The small CTL has already made a perforation in the cancer cell. The cancer cell has disintegrated.

19 Questions and Answers Provenge Description fda.gov What is PROVENGE and how does it work? PROVENGE (sipuleucel-t) is an autologous cellular immunotherapy designed to stimulate a patient s own immune system against cancer. PROVENGE is manufactured in several steps. First the patient s blood is run through a machine in a process known as leukapheresis. During the process, some of the patient s immune cells are collected. These immune cells are then exposed to a protein intended to stimulate and direct them against prostate cancer. Following this exposure, the activated immune cells are then returned to the patient to treat the prostate cancer. PROVENGE is administered intravenously in a three-dose schedule at approximately two week intervals. Each dose is preceded by the leukapheresis procedure approximately three days prior to the scheduled treatment, and is administered only to the patient from whom the cells were obtained. What are the ingredients in PROVENGE? The active components of PROVENGE are autologous antigen presenting cells (APCs) and the protein called PAP-GM-CSF. APCs are activated during a defined culture period with a recombinant human protein, PAP-GM- CSF, consisting of prostatic acid phosphatase (PAP), an antigen expressed in prostate cancer tissue, linked to granulocyte-macrophage colony-stimulating factor (GM-CSF), an immune cell activator. The cellular composition of PROVENGE will vary, depending on the cells obtained from the individual patient during leukapheresis. In addition to the APCs, the product also contains T cells, B cells, natural killer (NK) cells, and other cells. Each dose of PROVENGE is suspended in 250 ml of Lactated Ringer s Injection, USP in a sealed, patientspecific infusion bag. PROVENGE contains no preservatives or adjuvants.

First the patient s blood is run through a machine in a process known as leukapheresis. During the process, some of the patient s immune cells are collected.

20 Immunodeficiencies Disease AIDS Selective IgA immunodeficiency Common variable hypogammaglobulinemia Reticular dysgenesis Severe combined immunodeficiency Thymic aplasia (DiGeorge syndrome) Wiskott-Aldrich syndrome X-linked infantile (Bruton s) agammaglobulinemia Cells Affected T H (CD4 + ) cells B, T cells B, T cells (decreased immunoglobulins) B, T, and stem cells B, T, and stem cells T cells (defective thymus) B, T cells B cells (decreased immunoglobulins)

infantile (Bruton s) agammaglobulinemia Cells Affected T H (CD4 + ) cells B, T cells B, T cells (decreased

21 Figure A nude (hairless) mouse infected with Mycobacterium leprae in the hind foot. Site of M. leprae bacteria

ANIMALS FORM & FUNCTION BODY DEFENSES NONSPECIFIC DEFENSES PHYSICAL BARRIERS PHAGOCYTES. Animals Form & Function Activity #4 page 1

ANIMALS FORM & FUNCTION BODY DEFENSES NONSPECIFIC DEFENSES PHYSICAL BARRIERS PHAGOCYTES. Animals Form & Function Activity #4 page 1 AP BIOLOGY ANIMALS FORM & FUNCTION ACTIVITY #4 NAME DATE HOUR BODY DEFENSES NONSPECIFIC DEFENSES PHYSICAL BARRIERS PHAGOCYTES Animals Form & Function Activity #4 page 1 INFLAMMATORY RESPONSE ANTIMICROBIAL