1. Foundations in Microbiology Sixth Edition
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.

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

5. 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

6. 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.

7. 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.

8. 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.

10. 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.

11. Insert figure 16.3
Cellular reactions

12. 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

14. 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

15. 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

16. 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

17. Diagnosis of Allergy
Important to determine if a person is experiencing allergy or infection
Skin testing

18. Treatment and Prevention
General methods include:
Avoiding allergen
Use drugs that block the action of the lymphocytes, mast cells, chemical mediators – antihistamines.
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

21. 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

22. 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.

24. 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.

27. 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+ fetus; usually requires subsequent exposure to the antigen to be hemolytic
Prevention requires the use of passive immunization with antibodies against the Rh antigen; prevents sensitization of mother.

28. Development and control of Rh
Insert figure 16.12
Development and control of Rh

29. 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

31. 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

33. 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

34. Classes of Grafts
Classified according to the degree of MHC similarity between donor and host:
autograft – recipient also serves as donor
isograft – tissue from identical twin is grafted
allograft – genetically different individuals but of the same species (humans)
xenograft – 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.

36. 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

39. 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

40. 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

42. 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

43. The Immune System and Cancer
Overgrowth of abnormal tissue arises due to malfunction of immune surveillance.
Tumors may be benign (nonspreading) self-contained; or malignant 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.