ch. 14 - disorders in immunity

Hematopoiesis

Creation of cellular components of blood

• All blood cells arise from stem cells

Abnormal immune functions are involved in:

• Asthma • Diabetes • Rheumatoid arthritis • Graft rejection

Immunopathology:

study of disease states associated with the overreactivity or underreactivity of the immune response

Hypersensitivity (overreactivity):

tissues attacked by immune components that can’t distinguish one’s own tissues from foreign material

(allergy, autoimmunity)

Hyposensitivity (immunodeficiency):

Immune system is incompletely developed, suppressed, or destroyed

Hypersensitivity Type 1: immediate hypersensitivity

IgE-mediated; involves mast cells, basophils, and allergic mediators

“common” allergy and anaphylaxis, atopy

Hypersensitivity Type 2: antibody mediated

antibodies + complement act & cause cell lysis; includes some autoimmune diseases

IgG- and IgM-mediated cell damage

Hypersensitivity Type 3: immune complex

Antibody-mediated inflammation; circulating IgG complexes deposited in basement membranes of target organs; includes some autoimmune diseases

immune complex

Hypersensitivity Type 4: T-cell mediated

Delayed hypersensitivity and cytotoxic reactions in tissues; includes some autoimmune diseases

Type 1 ex.

Anaphylaxis, allergies such as hay fever, asthma

Type 2 ex.

Blood group incompatibility; pernicious anemia; myasthenia gravis

Type 3 ex.

Systemic lupus erythematosus; rheumatoid arthritis; serum sickness; rheumatic fever

Type 4 ex.

Infection reactions; contact dermatitis; graft rejection

Allergy:

exaggerated immune response; causes inflammation

Allergens:

antigens that induce allergy in sensitive individuals

Atopy:

chronic local allergy (i.e. hay fever or asthma)

Anaphylaxis:

systemic, sometimes fatal, reaction that involves airway obstruction and circulatory collapse

Type 1 affects

majority…mild

½ U.S. pop. - airborne allergies like dust, pollen, mold)

• asthma

• food allergies

• some last, some outgrown

Generalized susceptibility to allergens is inherited, not the allergy to a specific substance

i.e. parent with cat hair allergy may have child with pollen allergy

parents…25%

siblings/grandparents…50%

Genetic basis for atopy:

• Increased IgE production

• Increased reactivity of mast cells (granular leukocyte)

• Increased susceptibility of target tissue to allergic mediators

Hygiene Hypothesis

Immune systems need to be “trained” by interaction with microbes as we develop but current state is hygienic

• Children who grow up on farms have lower incidences of several types of allergies

• Delivery by cesarean section and maternal history of allergy elevates childhood risk of allergy by a factor of eight

Effect of Breast Feeding

• breast fed for the first 4 months have a lower risk of asthma and eczema

  • has Cytokines & growth factors - act on gut mucosa to induce tolerance to allergens

• 600 species bacteria fr. breast milk…dev. of tolerance to foreign antigens

Nature of Allergens

allergens have certain immunogenic characteristics

• Proteins are more allergenic than carbohydrates, fats, or nucleic acids

Portals of Entry

• Mucosa of the gut and respiratory tract

  • (Thin, moist surface, penetrable)

• Skin

  • (Dry, tough keratin= less permeable so thru tiny breaks, glands, and hair follicles)

Inhalants:

airborne environmental allergens such as pollen, house dust, dander, or fungal spores

Ingestants:

allergens that cause food allergies

Injectants:

allergies triggered by drugs, vaccines, or bee venom

Role of Mast Cells in Type I Allergy

• Located in all connective tissues

• After first allergen exposure (sensitization), mast cells bind IgE.

• In future exposures, allergen binds IgE, then mast cells degranulate (release cytokines)

degranulate

release cytokines

Cytokine types

• Histamine

• Bradykinin

• Serotonin

• Leukotriene

• Prostaglandins

IgE-Mast-Cell-Mediated Allergic Conditions

• Hay Fever (Allergic Rhinitis)

• Asthma

• Atopic Dermatitis/Eczema

• Food Allergy

• Drug Allergy

Anaphylaxis/anaphylactic shock

swift reaction to allergen

Cutaneous anaphylaxis:

wheal-and-flare inflammatory reaction to the local injection of allergen

Systemic anaphylaxis:

characterized by sudden respiratory and circulatory disruption that can be fatal within minutes due to airway blockage

Blood testing methods

• Radioallergosorbent test

• Tryptase test

• Differential blood cell count

• Leukocyte histamine-release test

Radioallergosorbent test:

measures levels of IgE to specific antigens

Tryptase test:

measures enzyme (tryptase) released by mast cells during allergic response

Leukocyte histamine-release test:

measures histamine released from basophils after allergen exposure

Skin testing:

in vivo method to detect precise atopic or anaphylactic sensitivities

• Skin is injected, scratched, or pricked with a small amount of pure allergen extract

Treatment and Prevention of Allergy

• drugs to block the action of lymphocytes, mast cells, or chemical mediators

• Avoid the allergen

• Desensitization

Desensitization:

• controlled exposure to the antigen to reset the allergic reaction

  • IgG produced in response to allergen & binds allergen on next exposure instead of IgE on mast cells

Type II Hypersensitivities: Reactions That Lyse Foreign Cells

• Transfusion reactions and organ donations

• Hemolytic disease of the newborn

• Some types of autoimmunities

Alloantigens:

Present in some, but not all members of the same species

• Donor cells may have different surface alloantigens that are that are recognized as foreign by host lymphocytes

Rh Factor and Its Clinical Importance

• Rh+ is dominant gene; Rh- is recessive

  • Antibodies only develop against Rh through exposure to fetus’s antigen or by transfusion

Hemolytic Disease of the Newborn and Rh Incompatibility

• mother is Rh- and the unborn child is Rh+:

• Fetal RBCs leak into motherʼs circulation

• Motherʼs immune system detects foreign Rh factors on fetal RBCs

  • firs born unaffected, next is hemolytic disease of newborn (HDN)…anemia & jaundice

RhoGAM antiserum:

• given with each pregnancy with Rh- mother and Rh+ fetus

  • Sequesters fetal RBCs that have escaped into maternal circulation

Type III Hypersensitivities: Immune Complex Reactions

Reaction of soluble antigen (not attached to cell surface) with antibody, and deposition in various tissues in the body

Immune complex reaction:

produces free-floating complexes that are deposited into tissues

Arthus reaction and serum sickness associated with…

…passive immunization (providing Ig from healthy patients to recipients)

Immune complex disease – complexes deposited into basement membranes of epithelial tissues:

Neutrophils release granules that digest tissues and cause destructive inflammation

Type IV Hypersensitivities: Cell-Mediated (Delayed) Reactions

• Results when T cells respond to antigens displayed on self tissues or transplanted foreign cells

• (delayed hypersensitivity)

delayed hypersensitivity:

Symptoms arise one to several days following the second contact with antigen

Infectious Allergy

ex:

• Tuberculin reaction: Acute skin inflammation at the tuberculin extract injection site

• Contact Dermatitis: Allergen (i.e. poison ivy/oak) penetrates the outer skin layers

T Cells and Their Role in Organ Transplantation

• tendency of lymphocytes to seek out and destroy foreign antigens

  • most dmg. from cytotoxic T-cell action (graft rejections)

Genetic and Biochemical Basis for Graft Rejection

• MHC classes I and II for immune response regulation

• similar in siblings & parents, less similar w/more distance

• diff. MHC molecules = rejection (seen as foreign)

Host Rejection of Graft

• Cytotoxic T cells of host recognize foreign class I MHC markers

• Cytotoxic T cells of host recognize foreign class I MHC markers

Graft Rejection of Host

Some grafted tissues (bone marrow) contain indigenous populations of lymphocytes

• Make it possible for graft to reject the host

Autograft:

transplant from one body site to another on same individual

Isograft:

tissue from an identical twin is used

Allograft:

between genetically different individuals of same species; most common graft

Xenograft:

tissue exchange between individuals of different species

Autoimmune diseases:

individuals develop hypersensitivity to themselves

• Autoantibodies, T cells, or both, mount an abnormal attack against self antigens

Systemic autoimmune disease:

involves several major organs

organ specific autoimmune disease:

involves only one organ or tissue

Possible Causes of Autoimmune Disease

• Genetics

• Molecular mimicry

• Infection

• Gut Microbiome

Systemic Autoimmunities ex.

• Systemic lupus erythematosus (SLE, or lupus):

  • Autoantibodies against organs, tissues, or intracellular materials

• Rheumatoid arthritis:

  • Progressive, debilitating damage to joints, sometimes to lungs, eyes, skin, and nervous system

Autoimmunities of the Endocrine Glands

• Graves’ disease:

  • autoantibodies to receptors on cells of the thyroid gland

• Type I diabetes:

  • Cytotoxic T cells attack and lyse insulin-producing cells

  • Reduced amount of insulin

Neuromuscular Autoimmunities

• Myasthenia gravis:

  • Progresses to complete loss of skeletal muscle function and death

• Multiple sclerosis:

  • Paralyzing neuromuscular disease associated with lesions on myelin sheath that surrounds neurons of central nervous system

Immunodeficiency Diseases: Hyposensitivities

• weakened immune responses

• Predominant consequences of immunodeficiencies are recurrent, infections w/ opportunistic microbes

  • Primary & secondary diseases

Primary diseases:

present at birth (congenital), usually stemming from genetic errors

Secondary diseases:

acquired after birth and caused by natural or artificial agents

Primary Immunodeficiency Diseases

• inherited abnormality

• lack either B or T cells, or both

• Lymphocytes may be

  • absent, or present at low levels

  • present, but not functioning normally

Secondary Immune Deficiences ex.

• Infections (AIDS) or cancers

• nutrition deficiencies

• stress

• pregnancy

• aging

• irradiation

• severe burns

• steroids

• removal of spleen