Lecture PowerPoint to accompany

Foundations in Microbiology

Sixth Edition Talaro Chapter 16 Disorders in Immunity Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Immunopathology

• Allergy, hypersensitivity – an exaggerated, misdirected expression of immune responses to an

allergen

(antigen) • Involves the same types of immune reactions as those at work in protective immunities • •

Autoimmunity

– abnormal responses to self Ag

Immunodeficiency

immunity – deficiency or loss of • Cancer – results from a lack of surveillance 2

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Type I Hypersensitivity

• • Two levels of severity:

Atopy

– any chronic local allergy such as hay fever or asthma

Anaphylaxis

– a systemic, often explosive reaction that involves airway obstruction and circulatory collapse 5

Contact With Allergens

• Generalized predisposition to allergies is familial – not to a specific allergy • Allergy can be affected by age, infection, and geographic area.

• Atopic allergies may be lifelong or may be “outgrown”; may also develop later in life.

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Nature of Allergens and Their Portals of Entry

• Allergens have immunogenic characteristics.

• Typically enter through epithelial portals – respiratory, gastrointestinal, skin • Organ of allergic expression may or may not be the same as the portal of entropy.

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Mechanism of Type I Allergy

• Develop in stages:

Sensitizing dose

– on first contact with allergen, specific B cells form IgE which attache to mast cells and basophils; generally no signs or symptoms •

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 and Basophils

• Mast cells are located in the connective tissue of virtually all organs; high concentration in lungs, skin, GI and genital tract.

• Basophils circulate in blood and 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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Insert figure 16.3

Cellular reactions 11

Chemical Mediators and Allergic Symptoms

• Act alone or in combination; account for scope of allergic symptoms – histamine, serotonin, leukotriene, platelet-activating factor, prostaglandins, bradykinin • General targets include: skin, upper respiratory tract, GI tract, and conjunctiva.

– responses: rashes, itching, redness, rhinitis, sneezing, diarrhea, shedding tears • Systemic targets: smooth muscles, mucous glands, and nervous tissue – responses: vascular dilation and constriction resulting in change in blood pressure and respiration 12

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• Histamine – most profuse and fastest acting; stimulator of smooth muscle, glands, and eosinophils – response to chemical depends on the muscle location: constricts smooth muscles of small bronchi, intestines; relaxes vascular smooth muscles 14

Specific Diseases

• Atopic disease – hay fever, rhinitis; seasonal, inhaled plant pollen or mold – asthma – severe bronchoconstriction; inhaled allergen – eczema – dermatitis; ingestion, inhalation, skin contact • Food allergy – intestinal portal can affect skin and respiratory tract – vomiting, diarrhea, abdominal pain; possibly severe – eczema, hives, rhinitis, asthma, occasionally anaphylaxis • Drug allergy – common side effect of treatment; any tissue can be affected; reaction from mild atopy to fatal anaphylaxis 15

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 16

Diagnosis of Allergy

• Important to determine if a person is experiencing allergy or infection • Skin testing 17

Treatment and Prevention

General methods include: 1. Avoiding allergen 2. Use drugs that block the action of the lymphocytes, mast cells, chemical mediators – antihistamines.

3. Desensitization therapy – injected allergens may stimulate the formation of high-levels of allergen-specific IgG that act to block IgE; mast cells don’t degranulate 18

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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 21

Human ABO Antigens and Blood Types

• 4 distinct ABO blood groups • Genetically determined RBC glycoproteins; inherited as 2 alleles of A, B, or O • 4 blood types: A, B, AB, or O – named for dominant antigen(s) – type O persons lack both A and B antigens – Tissues other than RBCs also carry A and B antigens.

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Antibodies Against A and B Antigens

• Serum contains pre-formed antibodies that react with blood of another antigenic type-agglutination; potential transfusion complication • Type A contains Abs that react against B antigens.

• Type B contains Abs that react against A antigens.

• Type O contains Abs that react against A and B antigens.

• Type AB contains no Abs that react against A or B antigens.

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Rh Factor and Hemolytic Disease of the Newborn

• • RBC antigen – type results from combination of 2 alleles • Inheriting one dominant gene results in the production of the Rh antigen; no pre-formed antibodies exist; must have exposure.

Hemolytic Disease of the Newborn

(HDN) – an Rh mother forms antibodies to her Rh requires subsequent exposure to the antigen to be hemolytic sensitization of mother.

+ fetus; usually • Prevention requires the use of passive immunization with antibodies against the Rh antigen; prevents 27

Insert figure 16.12

Development and control of Rh 28

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 and 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 29

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Type IV Hypersensitivity

• T cell-mediated • 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 31

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T Cells and Organ Transplantation

• Graft/transplantation rejection – host may reject graft; graft may reject host • MHC markers of donor tissue (graft) are different; T cells of the recipient recognize foreignness. • Release interleukin-2 which amplifies helper and cytotoxic T cells which bind to donor tissue and release lymphokines that begin the rejection 33

Classes of Grafts

Classified according to the degree of MHC similarity between donor and host:

autograft isograft

– tissue from identical twin is grafted

allograft

– genetically different individuals but of the same species (humans)

xenograft

– recipient also serves as donor – individuals of different species • Rejection can be minimized by tissue matching HLA antigens, immunosuppressive drugs, and use of tissue that does not provoke a type IV response.

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Autoimmunity

• In certain type II & III hypersensitivities, the immune system has lost tolerance to

autoantigens

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 36

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Immunodeficiency Diseases

• Components of the immune response system are absent. Deficiencies involve B and T cells, phagocytes, and complement.

• 2 general categories: –

primary immunodeficiency

– congenital; usually genetic errors –

secondary diseases

– acquired after birth; caused by natural or artificial agents 39

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Primary immunodeficiency

- 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 (SCID)

- both limbs of lymphocyte system are missing or defective; no adaptive immune response 40

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Secondary diseases -

due to damage after birth – caused by: infection, organic disease, chemotherapy, or radiation – AIDS most common – T helper cells are targeted; numerous opportunistic infections and cancers 42

The Immune System and Cancer

• Overgrowth of abnormal tissue arises due to malfunction of immune surveillance.

• Tumors may be

benign

contained; or

malignant

(nonspreading) self that spreads from tissue of origin to other sites.

• Cancers occur in nearly every cell type.

• Appear to have genetic alteration that transforms a normal cell • Possible causes include: errors in mitosis, genetic damage, activation of oncogenes, or retroviruses.

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