Type I hypersensitivity, also known as allergy or immediate hypersensitivity, involves an exaggerated immune response to normally harmless allergens. The response involves IgE antibodies, mast cells, and basophils. Upon re-exposure, mast cells and basophils degranulate, releasing chemical mediators that cause symptoms. Type II hypersensitivity involves antibody-mediated cytotoxic reactions against foreign cells. Type III hypersensitivity involves immune complex-mediated hypersensitivity and can cause local or systemic inflammatory responses. Immunodeficiency diseases occur when components of the immune system are absent, including primary and secondary deficiencies. Cancer arises due to malfunctions in immune surveillance that allow abnormal cells to proliferate unchecked.

1. Foundations in Microbiology
Chapter
17
PowerPoint to accompany
Fifth Edition
Talaro
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Disorders in Immunity
Chapter 17

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Immunopathology
• Allergy, hypersensitivity – an exaggerated,
misdirected expression of immune responses
• Involves the same types of immune reactions as
those at work in protective immunities.
• Autoimmunity – abnormal responses to self Ag
• Immunodeficiency – deficiency or loss of
immunity
• Cancer – results from a lack of surveillance

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Type I Hypersensitivity
• Atopy – any chronic local allergy such as
hay fever or asthma
• Anaphylaxis – a systemic, often explosive
reaction that involves airway obstruction
and circulatory collapse

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Mechanism of Type I
• sensitizing dose – on first contact with allergen,
specific B cells form IgE which attaches to mast
cells and basophils
• provocative dose - subsequent exposure with the
same allergen binds to the IgE-mast cell complex
• degranulation releases mediators with
physiological effects such as vasodilation and
bronchoconstriction
• symptoms are rash, itching, redness, increased
mucous discharge, pain, swelling, and difficulty
breathing

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Role of Mast Cells & Basophils
• Mast cells are located in the connective tissue
of virtually all organs; high conc. in lungs,
skin, GI and genital tract
• Basophils circulate in blood, migrate into
tissues
• each cell can bind 10,000-40,000 IgE
• cytoplasmic granules contain physiologically
active cytokines, histamine, etc
• cells degranulate when stimulated by allergen

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Chemical mediators

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Systemic Anaphylaxis
• Sudden respiratory and circulatory
disruption that can be fatal in a few minutes
• Allergen and route are variable
• Bee stings, antibiotics or serum injection

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Strategies for circumventing allergic
attacks

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Blocking Ab

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Type II Hypersensitivity
• Reactions that lyse foreign cells
• Involve antibodies, complement, leading to
lysis of foreign cells
• Transfusion reactions
– ABO blood groups
– Rh factor – hemolytic disease of the newborn

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Type III Hypersensitivity
• A large quantity of soluble foreign Ag
stimulates Ab that produce small, soluble
Ag-Ab complexes
• Immune complexes become trapped in
tissues & incite a damaging inflammatory
response
– Arthus reaction – local reaction to series of
injected Ag to same body site
– Serum sickness – systemic disease resulting
from repeated injections of foreign proteins

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Autoimmunity
• In certain type I & II hypersensitivities, the immune
system has lost tolerance to self molecules and
forms autoantibodies and sensitized T cells against
them.
• More common in females
• Disruption of function can be systemic or organic
specific
– Systemic lupus erythematosus
– Rheumatoid arthritis
– Endocrine autoimmunities
– Myasthenia gravis
– Multiple sclerosis

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Type IV Hypersensitivity
• Cell-mediated
• A delayed response to Ag involving activation of
and damage by T cells
• Delayed allergic response – skin response to
allergens – tuberculin skin test, contact dermititis
from plants, metals, cosmetics
• Graft rejection – reaction of cytotoxic T cells
directed against foreign cells of a grafted tissue;
involves recognition of foreign HLA

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Immunodeficiency diseases
• Components of the immune response system are absent.
Deficiencies involve B and T cells, phagocytes, and
complement
– Primary immunodeficiency – genetically based
congenital lack of B-cell and/or T cell activity
– B cell defect – agammaglobulinemia – patient lacks
antibodies
– T cell defect – thymus is missing or abnormal
– Severe combined immunodeficiency - both limbs of
lymphocyte system are missing or defective; no
adaptive immune response
– Secondary (acquired) immune deficiency – due to
damage after birth (infections, drugs, radiation) AIDS

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Cancer
• Overgrowth of abnormal tissue arises due to
malfunction of immune surveillance
• Tumors may be benign (nonspreading) or
malignant (a cancer) that spreads from tissue of
origin to other sites
• Malignant tumors may be
– carcinomas originate from epithelial tissue
– sarcomas originate from embryonic connective tissue
• Cancers occur in nearly every cell type

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Characteristics of cancerous growths
• Disorganized behavior and independence
from surrounding normal tissues
• Permanent loss of cell differentiation
• Expression of special markers on their
surface

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Interrelationship between genes and
cancer
1. Cancer cell often have damaged chromosomes
2. A specific alteration in a gene can lead to cancer
3. Predisposition for some cancers is inherited
4. Rates of cancer are highest in individuals who
cannot repair damaged DNA
5. Mutagenic agents cause cancer
6. Cells contain genes that can be transformed to
cancer-causing oncogenes
7. Tumor-supressor genes exist in the normal
genome

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Mechanism of Cancer
• Some type of gene alteration turns a normal
gene (proto-oncogene) that regulates the
onset of mitosis into an oncogene
• The oncogene overrides normal mitotic
controls and cause the cell to divide
continuously
• Tumor suppressor genes may be missing or
inactivated

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Role of viruses in cancer
• Some viruses carry oncogenes whose
products cause transformation of host cells
into cancer cells
• Viral genome may be inserted into
regulatory sites
• Human papillomavirus cervical cancer
• Epstein-Barr virus – Burkitt’s lymphoma

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Function of immune system in
cancer
• Cells with cancer-causing potential arise
constantly in the body but the immune system
normally discovers and destroys them
• Cell-mediated immunity, TC, NK & macrophages,
antibodies
• Immune system fails in cancer
– may not be immunogenic enough
– may retain self-markers and not be targeted
• Maybe a slight or transient failure allows cancer to
develop