Micro Chapter 14 (Exam 4)

immunoglobulins

Ig

antibody structure

four protein chains form a Y-shape
variable regions: at the ends of the arms; bind epitopes
constant region: the stem, which is identical for a particular Ig class

5 classes of Ig

IgG, IgM, IgA, IgD, IgE

Ig monomers

IgG, IgD, IgE

IgM

pentamer
first response to an infection; short-lived
especially effective against microorganisms and agglutinating antigens

IgA

dimer
prevent microbial attachment to mucous membranes

hematopoiesis

creation of cellular components of blood

where are blood cells created?

stem cells

SEE SLIDE 2!!

abnormal immune functions are involved in:

asthma
diabetes
rheumatoid arthritis
graft rejection

immunopathology

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

hypersensitivity

overreactivity
allergy and autoimmunity
the tissues are innocent bystanders attacked by immune components that can't distinguish one's own tissues from foreign material

hyposensitivity

immunodeficiency
immune system is incompletely developed, suppressed, or destroyed

4 types of hypersensitivity

Type I: "common" allergy and anaphylaxis
Type II: IgG- and IgM-mediated cell damage
Type III: immune complex
Type IV: T-cell response

B-cell-IgG type hypersensitivities

Types I-III

T-cell type hypersensitivity

Type IV

humoral immunity

antibodies or immunoglobulins (Ig)

IgG

monomer (Y-shaped)
80% of serum antibodies
in the blood, lymph, and intestine
PASSES THROUGH BLOOD VESSELS AND INTO TISSUES

allergy

exaggerated immune response that is manifested by inflammation

allergens

antigens that induce allergy in sensitive individuals

atopy

chronic local allergies such as hay fever or asthma (seasonal allergies)

anaphylaxis

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

Who is affected by Type I hypersensitivities?

nearly half the population of the U.S. is affected by airborne allergens (dust, pollen, mold)

Type I allergy severity

majority are relatively mild
asthma and some food allergies may require hospitalization and can cause death
some allergies last for a lifetime, some are "outgrown," and others develop later in life

What aspects of allergens are inherited?

generalized susceptibility
not the allergy to a specific substance (parent with cat hair allergy may have child with pollen allergy)

prospect of a child developing an atopic allergy

25% if parents are afflicted
50% if siblings or grandparents are also afflicted

genetic basis for atopy

increased IgE production
increased reactivity of mast cells (granular leukocyte) increased susceptibility of target tissue to allergic mediators (cytokines)

Type I hypersensitivity: hygiene hypothesis

cleaner, disinfected house = more susceptibility to allergies
children who grow up on farms = lower instances of several types of allergies
delivery by cesarean section and maternal history of allergy elevates childhood risk of allergy by a factor of eight

Type I hypersensitivity: effect of breast-feeding

newborns breast fed exclusively for the first 4 months = lower risk of asthma & eczema
cytokines & growth factors in human milk act on the baby's gut mucosa to induce tolerance to allergens

Human Microbiome Project

600 species of bacteria can be transferred to infants through breastmilk
important role in the development of tolerance to foreign antigens

Which organic molecule is more allergenic then the rest?

proteins (more allergenic than carbohydrates, fats, or nucleic acids)

allergen portals of entry

mucosa of the gut and respiratory tract (thin, moist surface that is normally penetrable)
skin (access occurs through 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

contactants

allergies that enter through the skin

Where are mast cells located?

all connective tissues
high numbers in lungs, skin, G.I. tract, and genitourinary tract

sensitizing dose

first exposure of an effective amount of allergens
mast cells bind IgE

degranulation

happens in future exposures after the first exposure of an allergen
allergen binds IgE & cytokines are released

Allergens cause symptoms of an allergic reaction.

a. true
b. false

b
symptoms are caused by affects of allergens on host immune molecules on target organs

histamine

most profuse & fast-acting allergic mediator
CONSTRICTS smooth muscle in the small bronchi and intestine, causing labored breathing and increased intestinal motility
RELAXES vascular smooth muscle and dilates blood vessels, resulting in skin reactions and itching
stimulates eosinophils to release inflammatory cytokines, escalating symptoms

bradykinin

(breathing)
prolonged smooth muscle contraction of the bronchioles
dilation of peripheral blood vessels, increased capillary permeability, increased mucus secretion

serotonin

effects complement those of histamine and bradykinin

leukotriene

(common in anaphylaxis)
"slow-reacting substance of anaphylaxis"
induces gradual contraction of smooth muscle
prolonged bronchospasm, vascular permeability, and mucus secretion of the asthmatic individual

prostaglandins

regulate smooth muscle contraction; stimulate uterine contractions during delivery
vasodilation, increased vascular permeability, increased sensitivity to pain, bronchoconstriction
nonsteroidal anti-inflammatory drugs (NSAIDs) prevent the actions of prostaglandins

SEE SLIDE 18!!

IgE-mast-cell-mediated allergic conditions

hay fever (allergic rhinitis)
asthma
atopic dermatitis/eczema
food allergy
drug allergy

hay fever (allergic rhinitis)

(seasonal allergy)
seasonal reaction to inhaled plant pollen or mold, or a chronic, year-round reaction to airborne allergens are inhalants
targets: respiratory membranes

hay fever symptoms

nasal congestion; sneezing; coughing; profuse mucus secretion; itchy, red, and teary eyes; mild bronchoconstriction

asthma

respiratory disease characterized by episodes of impaired breathing due to severe bronchoconstriction
airways of asthmatics are extremely sensitive to minute amounts of inhalants, ingestants, or other stimuli, such as infectious agents

asthma symptoms

range from bouts of difficult breathing to fatal suffocation
rales: clicking, bubbling, or rattling sounds in the lungs

atopic dermatitis/eczema

intensely itchy inflammatory condition of the skin
sensitization occurs through ingestion, inhalation, and skin contact with allergens

dermatitis/eczema in infants

characterized by reddened, encrusted skin lesions on the face, scalp, neck, and inner surfaces of limbs and trunk

dermatitis/eczema in adults

dry, scaly, thickened skin condition

food allergy: most common allergens

peanuts, fish, cows milk, eggs, shellfish, and soy beans

food allergy: mode of entry

intestinal

food allergy: symptoms

vomiting, diarrhea, and abdominal pain
other manifestations include hives, rhinitis, asthma, and occasionally anaphylaxis

Drug allergy

one of the most common side effects of treatment, affecting 5 to 10% of hospitalized patients
reactions range from mild rash to fatal anaphylaxis
compounds implicated:
- antibiotics: penicillin
- synthetic antimicrobials: sulfa drugs
- aspirin
- opiates
- contrast dye used in x-rays

anaphylaxis/anaphylactic shock

swift and severe reaction to allergens
bee stings and injection of antibiotics or serum are most commonly implicated
result of the sudden, massive release of chemicals into the tissues and blood, which act rapidly on target organs

cutaneous anaphylaxis

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

systemic anaphylaxis

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

in vitro

outside body/in test tube

in vivo

in body

in vitro method to diagnose allergy

blood testing

blood testing

radioallergosorbent test
tryptase test
differential blood cell count
leukocyte histamine-release test

radioallergosorbent test

measures levels of IgE to specific antigens

tryptase test

measures tryptase, an enzyme released by mast cells during allergic response

leukocyte histamine-release test

measures histamine released from basophils when exposed to specific allergen

in vivo method to diagnose allergy

skin testing

skin testing

detects precise atopic or anaphylactic sensitivities
skin is injected, scratched, or pricked with a small amount of pure allergen extract
a wheal and flare result 20 minutes after antigenic change is indicative of histamine release
the diameter of the wheel is measured and rated on a scale from 0 (no reaction) to 4 (greater than 15 mm)

treatment and prevention of allergy

1) blocking the processes of allergy
2) avoiding the allergen
3) desensitization

blocking the processes of allergy

TAKE DRUGS TO BLOCK THE ACTION OF LYMPHOCYTES, MAST CELLS, OR CHEMICAL MEDIATORS
steroids: shut down IgE production
antibodies: keep IgE from mast cells
cromolyn: prevents degranulation
antihistamines, etc: counteract affect of cytokines on target cells

desensitization

controlled exposure to the antigen through ingestion, sublingual absorption, or injection to reset the allergic reaction
produces IgG in response to allergen
in subsequent exposures, IgG binds allergen before it can bind to IgE on mast cells, stopping degranulation
SEE SLIDE 29!!

Type II hypersensitivities

reactions that lyse foreign cells
syndrome where host IgG and IgM antibodies target foreign cell surface antigens which results in complement-assisted destruction (lysis) of the targeted cells

examples of Type II hypersensitivities

transfusion reactions and organ donations
hemolytic disease of the newborn
some types of autoimmunities

alloantigens

an antigen present only in some individuals (as of a particular blood type)
donor cells may have different surface alloantigens that are recognized/destroyed by host lymphocytes

Rh factor

monkey antigen (Rh for rhesus) present in ~85% of humans
Rh+ is dominant gene; Rh- is recessive

clinical importance of the Rh factor

antibodies only develop against Rh through exposure to fetus's antigen or by transfusion

placental sensitization

mother is Rh- and the unborn child is Rh+
fetal RBCs leak into mother's circulation during childbirth when placenta detaches
mother launches immune response against foreign Rh factors on fetal RBCs

Which child does placental sensitization effect?

does not usually affect the first child because the process occurs so late in pregnancy
after first child, mother has developed anti-Rh antibodies, which elicit a memory response & attack RBCs of the second Rh positive fetus

hemolytic disease of the newborn (HDN)

caused by placental sensitization
characterized by severe anemia and jaundice
potentially fatal

RhoGAM antiserum

must be given with each pregnancy with Rh- mother & Rh+ fetus
sequesters fetal RBCs that have escaped into maternal circulation & prevents sensitization

Type III hypersensitivities

immune complex reactions

immune complex reactions

reaction of soluble antigen (not attached to cell surface) with antibody
produces free-floating complexes that are deposited into tissues

arthus reaction & serum sickness

associated with passive immunization (providing Ig from healthy patients to recipients)
characterized by inflammation, presents as red patches on skin

mechanisms of immune complex disease

antibodies produced in response to antigens -> antigen-antibody complexes recruit neutrophils -> neutrophils release granules -> digest tissues & cause destructive inflammation

Type IV hypersensitivities

cell-mediated (delayed) reactions (T cell)

delayed hypersensitivity

results when T cells respond to antigens displayed on self tissues or transplanted foreign cells
symptoms arise one-several days following the second contact with antigen

infectious allergy

tuberculin reaction

tuberculin reaction

acute skin inflammation at the tuberculin extract injection site
mainstay diagnostic tool for TB infections
TH1 cells release cytokines that recruit macrophages, neutrophils, and eosinophils to the site, causing a red bump

contact dermatitis

allergen (i.e. poison ivy/oak) penetrates the outer skin layers
processed by skin dendritic cells and presented to T cells
subsequent exposures attract lymphocytes and macrophages
cells release enzymes and cytokines that damage epidermis

T cells & organ transplantation

lymphocytes seek out and destroy foreign antigens

MHC classes I and II

extremely important for regulating the immune response
people can exhibit variability in the pattern of these markers (similarity in related siblings and parents), but the pattern is identical in cells of the same person

What causes graft rejection?

cytotoxic T-cell action
varying MHC molecules signal to T cells that graft is a foreign substance

host rejection of graft

cytotoxic T cells of host recognize foreign class I MHC markers on grafted cells
helper and cytotoxic T cells bind grafted tissue and begin rejection process (within 2 weeks)
antibodies formed against the graft contribute to damage
result is destruction of vascular supply & death of graft

graft rejection of host

occurs in grafted tissues that contain indigenous populations of lymphocytes (bone marrow)

graft versus host disease

graft attacks host tissue bearing foreign MHC markers
effects are systemic and toxic
papular, peeling skin rash is the most common symptom; other organs are also affected
occurs within 100 to 300 days of the graft

autograft

transplant from one body site to another on same individual (think potential route of your surgery- tendon in wrist to replace tendon in finger)

isograft

tissue from an identical twin is used (best match, same MHC)

allograft

between genetically different individuals of the same species (most common graft)