Download Disorders in Immunity

CH 19 - DISORDERS IN
IMMUNITY
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Stephanie Lanoue
HYPERSENSITIVITY
Learning Objectives
19-1 Define hypersensitivity.
19-2 Describe the mechanism of anaphylaxis.
19-3 Compare and contrast systemic and localized
anaphylaxis.
19-6
19-7
19-8
Describe the mechanism of cytotoxic reactions and
how drugs can induce them.
Describe the basis of the ABO and Rh blood group
systems.
Explain the relationships among blood groups.
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BIG PICTURE: HUMAN MICROBIOME AND
INTESTINAL DISEASE
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IMMUNITY RESPONSE
Immunity process is a powerful system of _______
 Seek out, recognize, and ______ foreign materials
to prevent disease
 BUT, On the other side, overreactivity or
underreactivity of immune system can be
challenging

1.
2.
3.
Overreactivity, hypersensitivity
Immunodeficiency, hyposensitivity
Autoimmune
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HYPERSENSITIVITY
Antigenic response beyond ________
 Occurs when sensitized by _______ exposure to an
antigen (allergen)

Question – Are you hypersensitive to anything?
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TABLE 19.1 TYPES OF HYPERSENSITIVITY
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HYPERSENSITIVITY, TYPE I

Occurs -____________ after a person sensitized to
an antigen is reexposed to that antigen
Histamine: increases the permeability of blood capillaries
 Resulting in
1.
Edema, ____________
2.
Erythema, redness
3.
Increased mucous secretion, running nose
4.
Smooth muscle cells contraction, breathing difficulty

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HYPERSENSITIVITY, TYPE I, CONT.

Systemic anaphylaxis (anaphylactic shock)
Results when an individual sensitized to an antigen
is exposed to it _________
 May result in circulatory collapse and _______
 Treated with epinephrine


Localized anaphylaxis
Usually associated with ingested or inhaled antigens
 Symptoms depend on the route of entry
 Hives, hay fever, and asthma

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HYPERSENSITIVITY, TYPE II

Activation of complement by the combination of
____________ with an antigenic cell
Causes cell lysis or _________ by macrophages
 Antigen located on cell or tissue
 Cellular damage


ABO blood group system

Antibodies form against certain carbohydrate
antigens on RBCs
A antigens, B antigens, or both
 Type O RBCs have no antigens

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HYPERSENSITIVITY, TYPE II, CONT.

Rh blood group system
Rh factor antigen (Rh+) found on RBCs of ___% of
the population
 Rh+ blood given to an Rh– recipient will __________
anti-Rh antibodies in the recipient
 Hemolytic disease of the ________ (HDNB)

Rh– mother with an Rh+ fetus causes the mother to produce
anti-Rh antibodies
 Second Rh+ fetus will receive anti-Rh antibodies, damaging
fetal RBCs

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Figure 19.4 Hemolytic disease of the newborn.
Placenta
Rh+ father.
Rh– mother carrying
her first Rh+ fetus. Rh
antigens from the
developing fetus can
enter the mother's
blood during delivery.
In response to the fetal
Rh antigens, the mother
will produce anti-Rh
antibodies.
If the woman becomes
pregnant with another
Rh+ fetus, her anti-Rh
antibodies will cross the
placenta and damage
fetal red blood cells.
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HYPERSENSITIVITY, TYPE III
Type III, Immune complex reaction
 Antibodies form against soluble antigens in the
__________
 Form immune complexes that lodge in the
basement membranes beneath the cells


Activate complement, causing inflammation
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Figure 19.6 Immune complex-mediated hypersensitivity.
Immune
complexes
Immune complexes are
deposited in wall of
blood vessel.
Ag
Presence of immune
complexes activates
complement and attracts
inflammatory cells such as
neutrophils.
Endothelial
cell
Basement
membrane of
blood vessel
Neutrophils
Enzyme
Enzymes released from
neutrophils cause
damage to endothelial
cells of basement
membrane.
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HYPERSENSITIVITY, TYPE IV
Type IV, __________ hypersensitivity
 Mediated by __ cells (not antibody, hormonal
immune response)
 Appears after a ______ or more
 Time required for participating T cells and
macrophage to immigrate and accumulate near the
antigen


Ex. Transparent rejection, allergic contact dermatitis
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HYPERSENSITIVITY, TYPE IV

Allergic contact dermatitis

_________ combine with proteins in the skin,
producing an immune response

Allergic response to _______ _____, cosmetics, metals,
and latex
Google now! What is a Hapten?
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AUTOIMMUNE DISEASES
Immune system responds to _____ antigens,
causing damage to the organs
 Autoimmunity is ______ of self-tolerance



Ability to discriminate self from nonself
Cytotoxic, immune complex, or cell-mediated
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AUTOIMMUNE DISEASE
Response to self antigens and cause damage to
one’s own _________
 __% of population
 __% in women ???

Antibody producing B cells are more abundant in
female mice
 Activate via Toll like receptor , on X chromosome

When there is a loss of self tolerance, can not
distinguish themselves
1. T cells target host cells
2. Production of antibody

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CYTOTOXIC AUTOIMMUNE REACTIONS

Antibodies react with _____-surface antigens

_________ disease


Abnormal antibodies in the thyroid produce excessive
amounts of hormones
Myasthenia gravis

Antibodies coat acetylcholine receptors; muscles fail to
receive nerve signals
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IMMUNE COMPLEX AUTOIMMUNE
REACTIONS

Immune complexes of antibodies and complement
deposit in tissues

Systemic _______ erythematosus


Immune complexes form in the kidney glomeruli
Rheumatoid __________

Immune complexes form in the joints
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CELL-MEDIATED AUTOIMMUNE
REACTIONS

Mediated by __ cells that attack tissues

Insulin-dependent _________ mellitus


T cell destruction of insulin-secreting cells
Psoriasis and psoriatic arthritis

Autoimmune disorders of the skin
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HYPOSENSITIVITY

Immunodeficiencies
__________ of a sufficient immune response

Two categories:


___________ disease


_________ at birth, genetic disorder
 B cell development and expression
 T cell development and expression
 Abnormal development of thymus
Secondary disease
After birth, cause by natural and artificial agents and develop
during an individual's life
 Infections
 Radiation
 Chemotherapy
Ex. AIDS

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ACQUIRED IMMUNODEFICIENCY
SYNDROME (AIDS)

19___: the discovery of a virus causing the loss of
immune function (HIV)

Selectively infects T helper cells
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AIDS
Arisen by the mutation of virus from some area
of ________
 HIV virus, Genus Lentivirus, Retrovirus

two identical strands of RNA
 reverse transcription
 an envelope of phospholipid


Glycoprotein spikes (gp120)
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Figure 19.13 HIV structure and attachment to receptors on target T cell (2 of 3).
Glycoprotein spike:
gp120
gp41
transmembrane
glycoprotein
Envelope
Reverse
transcriptase
enzyme
Envelope
RNA
Core with
protein coat
Capsid
Structure of HIV and infection
of a CD4+ T cell. The gp120 glycoprotein spike on the membrane
attaches to a receptor on the CD4+
cell. The gp41 transmembrane
glycoprotein probably facilitates
fusion by attaching to a fusion
receptor on the CD4+ cell.
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THE INFECTIVENESS AND PATHOGENICITY
OF HIV
Inside the cell, viral _____ is transcribed into
DNA using reverse transcriptase
 DNA is ________ into the host's chromosomal
DNA

Active infection: new viruses bud from the host cell
 Latent infection: DNA is hidden in the chromosome
as a provirus



Some become memory T cells that serve as the reservoir for
HIV
Virus undergoes rapid antigenic changes and a
high rate of mutation
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Figure 19.14 Latent and active HIV infection in CD4+ T cells.
Chromosomal DNA
HIV
CD4 receptor
Provirus
CCR5 or CXCR4
receptor
Provirus
Viral
proteins
gp120
CD4+ T cell
gp41
Latent infection. Viral DNA is integrated into
cellular DNA as a provirus that can later be
activated to produce infective viruses.
Virus beginning
to bud from T cell
mRNA
Viral envelope
proteins
Viral RNA
gp120
gp41
Active infection. The provirus is activated, allowing it to control the
synthesis of new viruses. Final assembly takes place at the cell membrane,
taking up the viral envelope proteins as the virus buds from the cell.
Progeny HIV
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Figure 19.15 Latent and active HIV infection in macrophages and dendritic cells.
Chromosomal DNA
Provirus
HIV
Vacuole
HIV
Provirus
Macrophage
Latently infected macrophage. HIV can
persist either as a provirus or as a complete
virion in vacuoles.
mRNA
Viral RNA
Vacuole fuses with
plasma membrane
and releases virus.
Activated macrophage. New viruses are produced
from provirus. Completed virions are either released
or persist in the macrophage within vacuoles.
HIV being released
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THE STAGES OF HIV INFECTION
Phase 1: ____________ or lymphadenopathy
 Phase 2: T cells ________ steadily; only a few
infected cells release the virus; few serious
disease symptoms (persistent infections, fever,
and oral leukoplakia)
 Phase 3: AIDS develops; the T cell count is below
norm of 200 cells/μl

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HIV TRANSMISSION
Direct contact with infected body _______
 HIV survives (____ days) in the cells within fluids or
(__ hrs) outside of cells

Blood 1000 to 100,000 viruses per mm
 Semen 10 to 50 viruses per mm
 Saliva 1 viruses per mm ? Kissing ?

Routes of transmission:
 __________ transmitted infections (men to women
)
 Breast milk
 Organ transplants

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DISTRIBUTION OF HIV
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PREVENTING AND TREATING AIDS
Use of condoms and discouraging ______
promiscuity
 Use of ________ needles
 Availability of medications

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CHALLENGES OF DEVELOPING HIV
VACCINES

No model of natural immunity to _________
Lack of inexpensive research ________
Basic mechanisms of recognizing retrovirus by body is
__________
Quickly integrate into the DNA of host cell and become
_____________ to the immune system
High mutation rates, required _________ vaccine
_____________ strains

An ideal vaccine would :





Induce immunity before reservoirs of latent virus are established
 Antibodies
 T cells
 Be affordable

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