Unit 2 Pathophysiology - Chapter 9 Alterations in Immunity and Inflammation

Question 1

autoimmunity

Answer 1

immune response misdirected against host’s own tissues

Question 2

alloimmunity

Answer 2

directed responses against beneficial foreign tissues, such as transfusions or transplants

Question 3

allergy

Answer 3

exaggerated response against environmental antigen

Question 4

Hypersensitivity reaction times

Answer 4

immediate (develop within mins to few hrs) or delayed (developing within several hours or days)

Question 5

Anaphylaxis

Answer 5

most rapid immediate hypersensitivity rxn, it occurs within minutes of reexposure to the antigen and l/t cardiovascular shock

blood pressure drops suddenly and the airways narrow, blocking breathing. Signs and symptoms include a rapid, weak pulse; a skin rash; and nausea and vomiting.

Question 6

Allergens

Answer 6

antigens causing allergic responses

Question 7

Type I (IgE-mediated) hypersensitivity reaction – simple version

Answer 7

immediate hypersensitivity; mediated by antigen specific IgE and products of tissue mast cells

IgE (attached to immune cells in blood) - antibodies produced d/t allergen => IgE antibody bind to Fc receptors on mast cells and then those bounded IgE antibodies are cross-linked by antigens that bind to the Fab portions of IgE

• causes mast cell degranulation and release of histamine and others

Question 8

Histamine receptors

Answer 8

H1 receptor
* contracts bronchial smoooth muscles => constriction
* increases vascular permeability => edema + vasodilation
* increase blood flow to affect area

Histamine w/ h2 receptor
* increased gastric acid secretion
* decrease of histamine relased from mast cells + basophils (immune cells or WBC with granules that release during allergic rxn or asthma)

Question 9

Histamines and eosinophils?

Answer 9

Histamine enhances chemotaxis of eosinophils (parasitic infections, allergy, or cancer) into sites of type 1 allergic reactions

Question 10

Atopic individuals

Answer 10

produce more Ige and more Fc receptors for IgE on their mast cells

Question 11

Type II (tissue-specific) hypersensitivity reaction

Answer 11

Specific cell or tissue being targeted by an immune response; tissue-specific antigens (e.g platelets have groups of antigens that are found on no other cells of the body OR environmental antigens bind to specific plasma membranes of specific cells (erythrocytes and platelets)

mediated by IgG (blood and tissue) or IgM (mostly in blood) antibodies

5 possible mechanisms:
* complement-mediated lysis => 1st antibody IgG or IgM => complement cascade => membrane attak complex (c5-9) created to damage and lyse cell (e.g autoimmune hemolytic anemia or alloimmune rxn to ABO-mismatched transfused blood cells)
* opsonization and phagocytosis (IgG and C3b of complement system bind to receptors of macrophage => l/t phagocytosis of target cell)
* neutrophil-mediated tissue damage (antibody and complement may attract neutrophils => 1st endothelial cells with deposited antigens on its surface may bind to antibody => l/t complement cascade producing c3a and c5a [chemotactic for neutrophils] and deposition of complement component c3b => neutrophils bind to tissues w/ Fc receptor (contribute to the protective functions of the immune system, by binding to antibodies that are attached to infected cells or invading pathogens) or for c3b to attempt to phagocytose the tissue => neutrophil granules and toxic o2 products will damage cell, but cannot complete phagocytosis d/t large tissue
* antibody-dependent cell-mediated cytotoxicity => NK natural killer cells [not antigen specific], instead antibody on target cell recognized by Fc receptors on NK cells => l/t released substances to destroy cell
* modulation of cellular function => cause cell to malfunction rather than destroy cell => antibody reacts to target cell receptors by preventing interactions with normal ligands and replacing ligand and simulating receptor or destroying receptor (e.g Graves disease - autoantibody binds, instead of TSH, to receptors for TSH l/t increased thyorixine b/c anti-TSH receptor antibody is not controlled by pituitary (if increased thyroxine detected then TSH decreases and in this case it is but the antibody continues to be present)

Question 12

Type III (immune complex-mediated)

Answer 12

caused by formation of immune complexes deposited in target tissues => activate complement cascade => generate chemotatic fragments that attract neutrophils into inflammatory sites => releasing lysosomal enzymes that result in tissue damage

Question 13

What can intermediate-sized complexes do?

Answer 13

severe pathologic consequences

Question 14

Immune complex disease can be a systemic reaction or localized?

Answer 14

Yes
* serum sickness (systemic) - characterized by skin rash, joint stiffness, joint pain, facial and extremity swelling, and fever. Sometimes vomiting or respiratory distress happen. It may be mistaken for anaphylaxis.
* arthrus reaction (localized) - a dermal inflammatory reaction due to local IC (circulating immune complexes) formation after repeated subcutaneous or intradermal injections of foreign antigens.

Question 15

Type IV (cell mediated) hypersentivity reactions

Answer 15

Cell mediated

delayed hypersensitivity; caused by either cytotoxic T lymphocytes (Tc cells) or lymphokine-producing Th1 cells (substance produced by lymphocytes, such as interferon, that acts upon other cells of the immune system)

examples: graft rejection and allergic reactions resulting from contact w/ substances such as poison ivy and metals (versus type 1 where it is more generalized due to a particular food while type IV is localized in terms of lesion presentation)

Question 16

Typical allergens

Answer 16

pollen, mold, fungi, certain foods (milk, eggs, fish, peanuts), animals, certain drugs, cigarette smoke and house dust

Question 17

Clinical manifestations of allergic reactions

Answer 17

confined to areas of initial intake or contact w/ allergen

Question 18

Clinical symptoms of type I allergies

Answer 18

Tissues with most mast cells and sensitive to effects of hsitamine: GI tract, skin, and respiratory tract

• Eyes, nose, and respiratory tract: conjunctivitis (lining eyelids inflammation), rhinitis, and asthma (constriction of bronchi) d/t vasodilation, mucus secretions, edema, and swelling of respiratory mucosa (including accessory sinuses, nasopharynx, upper/lower resp tracts)
• Skin: urticaria or hives => localized release of histamine and increased vascular permeability, resulting in limited areas of edema /// wheals (white fluid-filled blisters) surrounded by flares (areas of redness) + itching. These wheals and flaring can be caused by cold temp, emotional stress, medications, systemic diseases, hyperthyroidism
• GI: active immunogen (usually product of food breakdown); vomiting, diarrhea, abdominal pain, can be severe enough to result in malbsorption or protein-losing enteropathy (ongoing irritation and swelling of intestine) //// most commonly milk, chocolate, egg, soy, wheat, tree nuts, peanuts, shellfish, fish

Question 19

Bee sting allergy

Answer 19

Bee venoms has enzymes and proteins as allergens; 1% of children have anaphylatic reaction to it; edema at sting site, generalized hives, itching, and swelling in distal regions of sting, flushing, sweating, dizziness, and headache

severe sx
* stomach cramps/vomiting
* tightness in throat, wheezing
* low blood pressure, shock
* death

Autonomic nervous system mediators (epinephrine)
* bind to receptors on smooth muscle and reverse histamine => muscle relaxation

Question 20

Poison Ivy

Answer 20

contact dermatitis; antigen is a plant catechol, urushiol, reacts w/ skin proteins => cell-mediated immune response

Question 21

Autoimmune disease tolerance

Answer 21

Central tolerance => develops during embryonic period (eliminates self-reactive lymphocytes during initial development in bone marrow or thymus
Peripheral tolerance is maintained in secondary lymphoid organs by regulatory T lymphocytes or anatigen-presenting dendritic cells (eliminates lymphocytes that escape central mechanisms)

Question 22

Autoimmune disease can be caused by?

Answer 22

previous antigen
neoantigen (result from genetic or epigenetic modifications, or posttranslational modification response to lifestyle)

infectious disease

emergence of lymphocyte cloning (can interact with self-antigens thats why process of apoptosis needed)

consequence of ineffective peripheral tolerance (antigen-presenting dendritic cells and t-regulatory lymphoytes (Treg cells normally suppress immune responses against self => secondary lymphoid organ control is not regulated as well => l/t lupus erthematosus (large array of autoantibodies)

Question 23

Alloimmunity specific conditions

Answer 23

• transient neonatal disease, or maternal immune system becomes sensitized against antigens expressed by the fetus
• transplant rejection
• transfusion reactions

when individual immune system react against antigens on tissues of other members of same species

Question 24

Examples of maternal immunologic hypersensitivity diseases

Answer 24

• graves disease: autoimmune disease in which maternal antibody against receptor for TSH causes neonatal hyperthyrodism
• mysathenia gravis: autoimmune disease => maternal antibody bind w/ receptors for neural transmitters on muscle cells (acteylcholine receptors) => neonatal muscle weakness
• immune thrombocytopenic purpura - autoimmune + alloimmune variants in maternal antiplatelet antibody destroy platelets in fetus and neonate
• alloimmune neutropenia - maternal antibody => destroys neutrophils in neonate
• systemic lupus erythematosus - autoimmune diseasein which maternal autoantibodies induce anomales (cogenital heart defects) in the fetus or cause pregnancy loss
• Rh and ABO alloimmunization: disease in which maternal antibody against erythrocyte antigens induces anemia in child

Question 25

Systemic lupus erythematosus (SLE)

Answer 25

* chronic, multisystem, inflammatory disease * production of large variety of autoantibodies

Question 26

Hyperacute graft rejection

Answer 26

immediate, rare, acute rejection; cell mediated and occurs days to months after transplantation * chronic rejection is caused by inflammatory damange to endothelial cells as a result of weak cell-mediated reaction

Question 27

Red blood cell antigens

Answer 27

Target of autoimmune or alloimmune reactions; ABO and Rh systems

Question 28

Immune deficiencies are either?

Answer 28

Congenital (primary) or acquired (secondary) Primary caused by genetic defects that disrupt lymphocyte development Secondary - secondary to disease or other physiologic alterations

Question 29

Common infection in individuals w/ defects of cell-mediated immune response

Answer 29

fungal and viral

Question 30

Infection common in individuals with defects of humoral immune response or complement response

Answer 30

primarily bacterial; humoral creates antigen-specific antibodies while cell-mediated does not

Question 31

Bruton agammaglobulinemia

Answer 31

Immunodeficiency disorder, severe hypogammaglobulinemia, deficiency of all AB classes => inc susceptibility to infection Aka bruton's disease Familial and sporadic mutation in BTK gene --- x linked recessive genetic condition (manifests with males, females are carriers) B lymphocyte precursors do not mature into b lymphocyte + plasma cells // precursors b pre cell stage stop differentiation leaving no b cell and all ig's in circulation l/t high risk of infections T cell intact, viral fungal and protozoa

Question 32

selective IgA deficiency

Answer 32

an immune system condition in which you lack or don't have enough immunoglobulin A (IgA), a protein that fights infection (antibody) Although individuals with Selective IgA Deficiency do not produce IgA, they do produce all the other kinds of immunoglobulin. This is why many people with IgA deficiency appear healthy or only have mild illness such as gastrointestinal infections.

Question 33

DiGeorge syndrome

Answer 33

congenital thymic aplasia or hypoplasia; complete or partial lack of the thymus (result in depressed T-cell immunity) and the parathyroid glands (result in hypocalcemia) and the presence of cardiac anomalies

Question 34

SCID (Severe combined immunodeficiency)

Answer 34

**total lack of T-cell function and a severe (either partial or total) lack of B-cell fx; a result from mutations in critical enzymes, such as ADA deficiency and PNP deficiency** **Adenosine deaminase deficiency (ADA) - an autosomal recessive disorder that causes the immunodeficiency // Purine nucleoside phosphorylase (PNP) deficiency is a disorder of the immune system (primary immunodeficiency) characterized by recurrent infections, neurologic symptoms, and autoimmune disorders. PNP deficiency causes a shortage of white blood cells, called T-cells, that help fight infection)** Cytokine receptors ===> X-linked SCID (most common 44% of SCID): defect in IL-2 receptor gamma (y)-chain [IL-2Ry]. This protein is component of several receptors for cytokines; a similar (but autosomal) deficiency occurs with mutation in JAK3 deficiency, an enzyme important in associating with IL2RY; however the receptors do not work properly and do not react to cytokines. IL-7 receptor deficiency (necessary for T-cell maturation within thymus while still having normal levels of B-cells and NK cells Antigen receptors => RAG-1/RAG-2 deficiencies: autosomal recessive and result in arrested lymphocyte development from blocked recombination of variable regions of B-cell and T-cell receptors, NK cells are not affected CD45 deficiency, CD3 deficiency, and ZAP-70 deficiency: T-cell defect in ecah can range from mild to severe w/ normal B-lymphocystes and NK cells; antibody production may be depressed

Question 35

bare lymphocyte syndrome

Answer 35

group of immune deficiences where lymphocytes and macrophages cannot produce major histocompatibility complex (MHC) class I or class II molecules. Without them, antigen presentation and intercellular copperation cannot work effectively.

Question 36

Wiskott-Aldrich syndrome

Answer 36

x-linked recessive d/o; sporadic mutations in WAS protein, involved in intracellular signaling and regulation of cell's actin cytoskeleton (contractile filaments of cells)

Question 37

ataxia-telangiectasia

Answer 37

autosomal recessive d/o; variety of sporadic mutations in the ATM gene, which encodes a protein important in repairing of double-stranded breaks in DNA * infants have unsteady gait or ataxia => wheelchair use * Telangiestasia (dilation of capillaries) => eyes, skin, ears, neck and extremities; IgA deficient, B/T cells affects and unrepaired DNA breaks observed in regions encoding T-cell and B-cell receptors

Question 38

Complement cascade can be defective?

Answer 38

Most severe is c3 deficiency => recurrent bacterial infections; Neisseria spp. common d/t defects in attack complex

Question 39

Phagocyte function defect

Answer 39

Insufficient number, defects in chemotaxis, phagocytosis, or killing => l/t septicemia and disseminated pyogenic lesions (raised, red, and moist, and the skin around them may be inflamed)

Question 40

Autoinflammatory disorders

Answer 40

high levels of inflammation secondary to mutations in inflammasome activation or defects in cellular receptors of cytokines designed to decrease inflammation

Question 41

Acquired immunodeficiencies

Answer 41

Superimposed conditions d/t aging, malnutrition, infections, malignancies, trauma, environmental factors, treatments

Question 42

Deficient antibody production tx

Answer 42

replacement of missing immunoglobulins with commerical gamma-globulin preparations

Question 43

Lymphocyte deficiencies

Answer 43

treated w/ replacement of host lymphocytes with transplants of bone marrow, fetal liver, or fetal thymus from a donor