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Microbiology - Hypersensitivity
pgs 177 - 189
35
Microbiology
Professional
09/30/2010

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Term
hypersensitivity definition

ATOPIC
Definition
= to allergy = exaggerated immune responses/reactivity

1. it exceeds healthy limits of intensity and/or
2. it is directed at tissues that are sensitive to the products of such responsiveness/reactivity

highly allergic patients termed (blank)
Term
allergen

allergic
Definition
harmless antigen

stimulates (blank) responses in atopic individual

particularly used in reference to antigens responsible for IgE associated allergy
Term
sensitization vs. elicitation

sensitization

elicitization
Definition
hypersensitivity diseases require initial (blank) to then be (blanked) against

(blank) phase may be completed before antigen is cleared from the body - (blank) can then happen during initial allergen exposure, but usually happens after second exposure to allergen
Term
immune response vs. immune reaction

immune response
Definition
sensitization can be required to involve an (blank) (blank) in hypersensitivity diseases

these initial (blank) (blank)s could produce potentially harmful soluble or cellular factors

(blank) (blank)s happen when these responses CAUSE damage to host tissues - it is the effect of above

time frame between immune response and immune reaction (pathology) may vary
Term
list types of hypersensitivity
Definition
Type I - immediate hypersensitivity (IgE antibody)

Type II -cytotoxic antibody (target cell-specific IgG)

Type III - immune complex disease (IgG binds antigen big time and causes insoluble antibody-antigen complexes to form)

Type IV - Delayed-type (effector T cells/macs attack antigen-coated host cells)
Term
Type I (Immediate) Hypersensitivity
Definition
sensitization - TRANSMUCOSAL exposure, IgE antibody production; IgE bound to Fc-epsilon-R on mast cells/basophils elicitation (minutes) - second allergen exposure; allergen binds IgE "fixed" to mast cell; crosslinking and degranulation; release of pharmacologically active factors
Term
Type I hypersensitivity - sensitization
Definition
[image]
Term
type I hypersensitivity - elicitation
Definition
[image]
Term
allergic rhinitis
Definition
minor localized irritations

happens in nasopharynx and upper airway in type I hypersensitivity
Term
allergic asthma
Definition
serious localized allergic reaction

happens in submucosa of lower airways in type I hypersensitivity
Term
anaphylactic shock
Definition
life-threatening SYSTEMIC circulatory collapse
Term
degranulation
Definition
mast cells, when stimulated in type I hypersensitivity (remember, IgE hooked on to mast cells via Fc-epsilonRI and bind antigen)

in this process, granules that are let out of mast cells and basophils contain anyanplyotoxins that increase vascular permeability, increased blood flow, decreased blood pressure, increased mucous secretions and smooth m contraction

bridging of IgE molecules and mast cell causes influx of calcium into mast cell that results in DECREASED CYLCIC AMP

this causes destabilization of membrane

influx of calcium also results in MEMBRANE LIPID TURNOVER yielding via ARACHIDONIC ACID, LUEKOTRIENES and PROSTAGLANDINS
Term
examples of products released by degranulation
Definition
histamine (^ vas perm and local blood flow)

leukotrienes and prostaglandins (sm m. contraction and ^ vas perm)

chemokines (attract leukocytes)

enzymes (break down tissue matrix proteins)

cytokines (promote inflammatory activities, amp of TH2 responses, ^ growth of eosinophils)
Term
wheal-and-flare reactions

urticaria (hives)
Urticaria (hives)
Definition
skin reaction in type I HS

follows local intracutaneous exposure to allergen (such as insect bite)

skin tests for antigen-specific IgE hypersensitivity mimic and measure this type of localized reaction

in a related condition called (blank) - allergin is ingested, but then migrates to the skin
Term
treatments of type I HS (4)
Definition
Avoidance

Desensitization - small to large doses changes IgE-dominated responses to IgG that doesn't bind well to mast cells

inhibition of mediator release - designed to either inhibit calcium or raise levels of cAMP

inhibition of mediator effects - administer epinephrine (reverse effect of anaphylotoxins), inhalation of bronchodialators and antihistamines (H receptor antagonists)..... inflammation can be treated with corticosteroids
Term
common symptoms of type I HS
Definition
allergic rhinitis

allergic asthma (S.O.B.)

venom reactions

food allergies

drug allergies

urticaria (hives)

anaphylactic shock
Term
describe sensitization of type II hypersensitivity
Definition
antibodies made that are specific to EXTRINSIC (foreign) ANTIGENS or reactive with INTRINSIC ANTIGENS (produced by target tissue itself
Term
describe elicitation of type II HS
Definition
time of onset varies

symptoms caused by binding of antigen-reactive antibody (IgG usually) specifically to ANTIGEN-COATED HOST CELLS; followed by direct lysis due to complement activation and further aggravated by release of active by-products of complement cascade (anaphylatoxins C3a, C5a)

FcR-bearing and CR-bearing leukocytes are also recruited to the area
Term
what distinguishes type II (cytotoxic antibody) from type III (immune complex) in the biopsy?
Definition
type II will demonstrate SMOOTH layer of antibody/complement coating host tissue
Term
two examples of type II (cytotoxic antibody) HS
Definition
Hemolytic Disease of the Newborn (HDN) - mom is Rh(neg) and fetus is Rh(pos); mom is sensitized after first Rh(pos) birth; next pregnancy, she elicits type II HS to Rh(pos) antigens in fetus (IgG antibodies can cross into placenta); causes SEVERE ANEMIA in fetus; RhoGam can be used to avoid these complications

Goodpasture's Syndrome - antibodies produced that attack BASEMENT MEMBRANES of renal glomeruli and (in some cases) pulmonary alveoli; binding occurs specifically to alpha-3 chain of type IV collagen of BM
Term
goodpasture's syndrome... tell me about it
Definition
type II (cytotoxic antibody) HS

antibodies produced that attack BASEMENT MEMBRANES of renal glomeruli and (in some cases) pulmonary alveoli;

binding occurs specifically to alpha-3 chain of type IV collagen of BM
Term
hemolytic disease of the newborn
Definition
mom is Rh(neg) and fetus is Rh(pos);

mom is sensitized after first Rh(pos) birth; next pregnancy, she elicits type II HS to Rh(pos) antigens in fetus (IgG antibodies can cross into placenta);

causes SEVERE ANEMIA in fetus;

RhoGam can be used to avoid these complications
Term
describe sensitization in type III HS (immune complex disease)
Definition
initial antigen exposure = activation of antigen-specific B cells

specific IgG antibodies reactive with antigen; antigen is soluble and freely circulating
Term
describe elicitation in type III HS (immune complex disease)
Definition
no need for additional antigen exposures! this response is direct

many molecules of antibody bind to many molecules of antigen forming multiple crosslinks to each other - eventually form LARGE INSOLUBLE ANTIBODY-ANTIGEN COMPLEXES

normally, phagocytes eat up these immune complexes, but this reaction builds up so fast that they can't keep up

deposition of the complexes can occur in/on filtering organs such as kidneys or areas rich in capillary beds (lungs)
Term
what are symptoms of type III (immune complex disease) HS
Definition
** symptoms caused by non-specific deposition of immune complexes

serum sickness
farmers lung syndrome
rheumatoid arthritis
systemic lupus erythematosus
Term
arthus reaction
Definition
test of type III hypersensitivity

inject antigen into skin; if it attracts circulating IgG (forms immune complexes) then this patient has type III HS to that antigen
Term
serum sickness
Definition
happens when large quantities of foreign antigen are given to a patient to treat infects or intoxications (snake bite)
Term
describe sensitization process of type IV hypersensitivity (delayed-type)
Definition
activate CD4+ TH1/TH17cells (not TH2s)

10-14 days

antigen covalently attaches to host tissue membranes - effector activities then directed against host tissues

CD8+ cells can also be activated if antigen is lipid soluble and crosses PM of host cells
Term
describe elicitation process of type IV hypersensitivity (delayed-type)
Definition
type 4 HS (DTH) is exaggerated form of cell-mediated immunity

symptoms caused by T cell derived cytokines (chemokines, IFN-gama, TNF-alpha, TNF-beta, IL-3/GM-CSF)

nonspecific T cells

significant EDEMA and INDURATION (hardness)
Term
what are the 3 different variants of DTH (delayed type hypersensitivity)
Definition
contact hypersensitivity - langerhans' cell is APC to T cells in EPIDERMIS; 24-48 hrs; POISON IVY

tuberculin hypersensitivty - intradermal reaction; macrophages present antigen to T cells; TB tests with purified protein derivative (PPD) of tubercule bacilli

granulomatous hypersensitivity - 21-28 days; antigens within macrophage difficult to degrade; GRANULOMA FORMATION; make multi-nucleated giant cells (from T cell cuff around a core of macs); EPITHELIOD CELLS also present inside these cuffs; size/mass of granulomas keep growing
Term
contact hypersensitivity
Definition
langerhans' cell is APC to T cells in EPIDERMIS;

24-48 hrs;

POISON IVY
Term
tuberculin hypersensitivity
Definition
intradermal reaction;

macrophages present antigen to T cells;

TB tests with purified protein derivative (PPD) of tubercule bacilli
Term
granulomatous hypersensitivity
Definition
21-28 days;

antigens within macrophage difficult to degrade;

GRANULOMA FORMATION - make multi-nucleated giant cells (from T cell cuff around a core of macs);

EPITHELIOD CELLS also present inside these cuffs;

size/mass of granulomas keep growing
Term
type II HS

goodpasture's syndrome

alpha-3 chain

type IV collagen of basement membrane

triggers complement cascade

type II HS called CYTOTOXIC ANTIBODY hypersensitivity
Definition
this is an example of type (blank) HS

(blank) (blank) - antibodies produced that attack BASEMENT MEMBRANES of renal glomeruli and (in some cases) pulmonary alveoli

antibody binding triggers (blank) cascade, resulting in cell death = reason why type (blank) HS is called (blank) (blank) hypersensitivity

binding occurs specifically to (blank) chain of type (blank) collagen of (blank)
Term
type II HS

goodpasture's syndrome

alpha-3 chain

type IV collagen of basement membrane

triggers complement cascade

type II HS called CYTOTOXIC ANTIBODY hypersensitivity
Definition
this is an example of type (blank) HS

(blank) (blank) - antibodies produced that attack BASEMENT MEMBRANES of renal glomeruli and (in some cases) pulmonary alveoli

antibody binding triggers (blank) cascade, resulting in cell death = reason why type (blank) HS is called (blank) (blank) hypersensitivity

binding occurs specifically to (blank) chain of type (blank) collagen of (blank)
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