Disorders of the Immune System
Four Major Categories of Immune
Mechanisms
• Humoral or antibody-mediated immunity
• (B lymphocytes)
• Cell-mediated immunity
• (T lymphocytes)
• Complement system
• Phagocytosis
• (neutrophils and macrophages)
Types of immune defenses
– Innate, or nonspecific immunity: the natural
resistance with which a person is born
– Adaptive, or specific immunity: the second line
of defense, responding less rapidly than innate
immunity but more effectively
Innate Immunity
• Components
– Epithelial barriers
– Phagocytic cells
• Neutrophils and macrophages
– Natural killer cells
– Plasma proteins
– Opsonins, cytokines, and acute-phase proteins
• Induction of inflammatory response
• Red, Heat, Edema, Pain, Pus
Adaptive Immunity
• Able to recognize and react to a large number of
microbes and non-microbial substances
• Ability to distinguish among different, even closely
related, microbes and molecules and to “remember”
the pathogen by quickly producing a heightened
immune response on subsequent encounters
• Lymphocytes and their products
• Antigenic identification
Types of Adaptive Immune
Responses
• Humoral immunity
– Mediated by molecules in the blood
– B Cells secrete antibodies
– The principal defense against extracellular microbes
and toxins
• Cell-mediated immunity, or cellular immunity
– Mediated by specific T lymphocytes
– Defends against intracellular microbes such as viruses
Histocompatibility Complex
• Major histocompatibility complex (MHC)
– Set of molecules displayed on cell surfaces
• Lymphocyte recognition
• Antigen presentation
– Control the immune response through
recognition of self and nonself
Properties of MHC Molecules
• HLA antigens
– Class I: HLA-A, HLA-B, HLA-C
– Class II: HLA-DR, HLA-DP, HLA-DQ
• Distribution
– Class I: virtually all nucleated cells
– Class II: restricted to immune cells, antigenpresenting cells, B cells, and macrophages
Properties of MHC Molecules (cont.)
• Functions
– Class I: present processed antigen to cytotoxic
CD8+ T cells
– Class II: present processed antigenic fragments to
CD4+ T cells; necessary for effective interaction
among immune cells
Antigen Presentation
• Macrophages and dendritic cells process and
present antigen peptides to CD4+ helper T cells
• Capture antigens and then enable their
recognition by T cells
• Initiation of adaptive immunity
Immunodeficiency
States
Immunodeficiency Disorders
• Abnormality in the immune system that
renders a person susceptible to diseases
Classifications of
Immunodeficiency States
Primary (congenital or inherited)
Secondary (acquired later in life)
Malnutrition
Infection (e.g., AIDS)
Neoplastic disease (e.g., lymphoma)
Immunosuppressive therapy
(e.g., corticosteroids or transplant
rejection medications)
Results of Alterations of the Immune System
• Immunodeficiency states
• Allergic or hypersensitivity reactions
• Transplantation rejection
• Autoimmune disorders
Deficiencies of Antibody (B Cell)
Immunity
• B-cell function and immunoglobulin or antibody
production are involved.
• Defects in humoral immunity increase the risk of
recurrent pyogenic (bacterial infections that make
pus) infections.
• Humoral immunity usually is not as important in
defending against intracellular bacteria (mycobacteria),
fungi, and protozoa.
• Viruses usually handled normally, except for the
enteroviruses that cause gastrointestinal infections
Deficiencies of Antibody (B Cell)
Immunity
• Genetic disorders of the B lymphocytes
• Approximately 70% of primary immunodeficiencies
• Immunoglobulin production depends on
– The differentiation of stem cells to mature B
lymphocytes
– The generation of immunoglobulin-producing
plasma cells
• Can interrupt the production of one or all of the
immunoglobulins
Deficiencies of Antibody (B Cell)
Immunity
X-Linked Agammaglobulinemia
•
•
•
•
Recessive trait that affects only boys
No immunoglobulins
Susceptible to many diseases
Gene necessary for pre-B-cell expansion is
missing
• Become symptomatic around 6-9 months of
age
Symptoms include
Frequent episodes of
• Chronic Diarrhea
• Conjuctivits
• Chronic Otitis Media
• Pneumonia
• Bronchitis
• Upper Respiratory Tract Infections
Deficiencies of Antibody (B Cell)
Immunity
Selective Immunoglobulin A Deficiency
• Most common type
– Affects 1 in 400 persons
• Moderate reduction of IgA levels
– Found in mucous, tears, saliva
• In both men and women
Deficiencies of Antibody (B Cell)
Immunity
Selective Immunoglobulin A Deficiency
• Less harmful than many other
immunodeficiency diseases
• 2/3rd have no symptoms
• Symptoms include frequent episodes
of: Bronchitis, chronic diarrhea, conjuctivis,
otitis media, pneumonia, upper respiratory
tract infections
• No treatment
Deficiencies of Cell-Mediated (T-cell)
Immunodeficiency
DiGeorge Syndrome
• 22q11.2 deletion syndrome
• Partial or complete failure to develop the
thymus and parathyroid glands
• Many different problems can occur from this
due to lack of T-cell production
• Outward appearance changed
– Low-set ears, hypoplastic mandible
bowing upward lip
22q11.2 deletion syndrome
Signs and symptoms may include some combination of the
following:
•
•
•
•
•
•
•
Bluish skin due to poor circulation of oxygen-rich blood (cyanosis)
Weakness or tiring easily
Failure to thrive
Failure to gain weight
Poor muscle tone
Shortness of breath
Delayed development, such as delays in rolling over, sitting up or other infant
milestones
• Delayed speech developmentLearning delays or difficulties
• A gap in the roof of the mouth (cleft palate) or other problems with the
palate
• Certain facial features, such as low-set ears, wide-set eyes or a narrow groove
in the upper lip
22q11.2 deletion syndrome
Combined T-Cell and B-Cell
Immunodeficiencies
• Severe combined immunodeficiency
(SCID)
– X-linked SCID
• Absence of all T and B-cell function (maybe NK cells
as well)
• Disease resembles AIDS in infants
– Bubble boy disease
David Vetter
-Lived in a Bubble up
to the age of 12yrs.
-Was given a bone
marrow transplant
from his sister
-She had EpsteinBarr virus dormant
in her bone marrow
-He contracted
Burkitt’s Lymphoma
and died in two
weeks
Wiskott-Aldrich Syndrome
• Rare X-linked disorder
• Both B and T cell immunity is impaired
• Complete failure to produce antibodies to an entire class
of antigens, namely polysaccharides
– Recurrent infections
– Hemorrhages secondary to thrombocytopenia
– Eczema
– Petechiae
– Infections (otitis media)
Wiskott-Aldrich Syndrome
• Clinical Features
– Infections from opportunistic organisms
• Pneumocystitis carnii and Candida albicans
– Some die from disseminated herpes simplex and
varicella
• Bone transplants seem to be very effective in this
syndrome
Complement System
• The following are the basic
functions of the
complement:
• Opsonization - enhancing
phagocytosis of antigens
• Chemotaxis - attracting
macrophages and neutrophils
• Lysis - rupturing membranes
of foreign cells
• Clumping of antigen-bearing
agents
Disorders of the Complement
System
• Primary
– Mostly transmitted as autosomal-recessive traits and
can involve one or more complement components
• Secondary
– Can occur in persons with functionally normal
complement
– Caused by
• Diabetes mellitus
• Leukemia
• Immunosuppressive drugs
Hereditary
angioedema
Inhibition of C1
protein in the
complement system
Autosomal Dominant
http://www.youtube.c
om/watch?v=ualR2rCZ
-J8
The Phagocytic System
• Definition: Composed primarily of polymorphonuclear
leukocytes and mononuclear phagocytes
• Action of these cells
–
–
–
–
Migrate to the site of infection
Aggregate around the affected tissue
Envelope invading microorganisms
Generate microbicidal substances to kill the ingested
pathogens
http://www.youtube.com/watch?
v=KxTYyNEbVU4&feature=related
Dysfunction of the Phagocytic
System
• A defect in phagocytic functions or a reduction in the
absolute number of available cells disrupt the system
• Susceptible to:
– Candida species
– Filamentous (thread-like) fungi
• Chronic granulomatous disease (CGD)
– Symptoms are:
• Impetigo
• Recurrent Pneumonia
• Skin and rectal abscesses
Impetigo
http://www.youtube.com/watch?v=mUcE1Y_bOQE&featu
re=related
Stem Cell Transplantation
• Many primary immunodeficiency disorders traced to
deficient stem cells can be cured with allogeneic
stem cell transplantation from an unaffected donor.
– SCID, Wiskott-Aldrich syndrome, and chronic
granulomatous disease
• Stem cells can repopulate the bone marrow and
re-establish hematopoiesis.
– Taken from bone marrow, blood or umbilical cord
of donor
• To be effective, the bone marrow cells of the host are
destroyed by myeloablative doses of chemotherapy.
Introduction
• Normal immune reactions do their job
without hurting the host.
• Sometimes, immune reactions can be
excessive, resulting in disease.
• People who mount normal immune
responses are sensitized to that antigen.
• People who have excessive responses are
hypersensitive.
What happens in these reactions?
• The immune response is triggered and
maintained inappropriately.
• Hard to eliminate stimulus!
• Hard to stop response once it starts!
• …so hypersensitivity diseases are often
chronic, debilitating, hard to treat.
Hypersensitivity Reactions Outline
• Introduction
• Type I Hypersensitivity
Type I Hypersensitivity Disorder
• Also known as Immediate Hypersensitivity
• First Exposure
– Antigen is presented to B and T cells
– IgE antibodies are produced and bind to Mast
Cells
– Mast cells are primed for the second exposure
– Upon second exposure mast cells degranulate
– End result: vessels dilate, smooth muscle
contracts, inflammation persists
What do mast cells release upon Second
Exposure?
• Granule contents
• Histamine
• Some chemotactic factors
• Membrane phospholipid metabolites
• Prostaglandin D2
• Leukotrienes
• Cytokines
• TNF
• Interleukins
• IL-13
Mast cells: Normal (left) and degranulated (right)
What do these substances do?
• Act on blood vessels, smooth muscle, and
WBCs.
• Immediate response (minutes)
• vasodilation, vascular leakage, smooth muscle
spasm
• granule contents, prostaglandin, leukotrienes
• Late phase reaction (hours)
• inflammation, tissue destruction
• cytokines
What happens to the patient?
• Local reactions
• Skin: itching, hives
• GI: diarrhea
• Lung: bronchoconstriction
• Anaphylaxis
– Wide spread edema due to Histamine
» Vascular leakage
• Itching, hives, erythema
• Constriction of bronchioles, wheezing
• Laryngeal edema, hoarseness, obstruction
• Shock
• DEATH
Hypersensitivity Disorders
• Type I
– Allergies
– Asthma
– Hay Fever
Hypersensitivity Reactions Outline
• Introduction
• Type I Hypersensitivity
• Type II Hypersensitivity
Type II
• Cytotoxic Hypersensitivity
• Action
– An antibody attaches directly to an antigen in
the target tissue, usually a cell membrane
– Mediated by IgG or IgM antibodies
Type II Hypersensitivity
• ANTIBODIES
• “Antibody-mediated” hypersensitivity
• Antibodies bind to antigens on cell surface
• Macrophages eat up cells, complement gets
activated, inflammation comes in
• End result: cells die, inflammation harms
tissue
Which diseases involve type II hypersensitivity?
Disease
Antigen
Symptoms
Autoimmune
hemolytic anemia
RBC antigens, drugs
Hemolysis
Pemphigus vulgaris
Goodpasture
syndrome
Myasthenia gravis
Graves disease
Proteins between
epithelial cells
Proteins in
glomeruli and
alveoli
Acetylcholine
receptor
TSH receptor
Bullae
Nephritis, lung
hemorrhage
Muscle weakness
Hyperthyroidism
Sequence of Events
• Antibodies bind to cell-surface
antigens
• One of three things happens:
• Opsonization and phagocytosis
• Inflammation
• Cellular dysfunction
Opsonization and Phagocytosis
Inflammation
Cellular Dysfunction
Graves disease
Myasthenia gravis
Type II
• Two Types of cytotoxic reactions occur
– Direct
• The target cell is coated by antibodies and
macrophage destroy it.
• Complement can be used to destroy the
cell
• Lysis is mediated by complement by
opsonization
• An example is autoimmune
hemolytic anemia
Type II
• Indirect
– IgG antibodies bind to target-cell
membrane receptors and block receptor
function
• An example is myasthenia gravis
Type II – Cytotoxic Hypersentivity
• Other Examples
– Graves’ Disease
– Erythroblastosis Fetalis
– Idiopathic Thrombocytopenic Purpura
Mechanisms of Autoimmune
Disease
• Heredity and gender specific
• Failure of self-tolerance
– Disorders in MHC–antigen
complex/receptor interactions
– Molecular mimicry
– Super-antigens
Heredity
• Certain HLA types seem to inherit certain
autoimmune diseases
– 90% of patients with ankylosing spondilitis
have HLA-B27 antigen
• Only 7% without the disease have the
antigen
• May be a “trigger event” that precipitates the
altered immune state
– Like stress
Mechanisms Postulated to Explain
Immunologic Tolerance
• Self-tolerance: Differentiate self from
non-self
–HLA antigens encoded by MHC genes
are used as markers
Failure of Self-Tolerance
• Breakdown in T-cell Anergy
– Anergy is the unresponsiveness of the
immune system to an antigen
• Infections , tissue necrosis or inflammation
may cause breakdown in Anergy
Failure of Self Tolerance
• Molecular Mimicry
– Many autoimmune diseases are associated
with infections
• Microbes share an immunologic epitope
(part of an antigen molecule to which an
antibody attaches itself) with the host
• One HLA may bind self-mimicry molecules
for presentation to T cells and another’s
HLA type may not
Failure of Self Tolerance
• Superantigens
– A family of related substances that can shortcircuit the normal sequence of events in an
immune response
• Interact with T-cell receptors
• Binds to MHC class II molecules leading to
activation of T cells
– Found in food poisoning, toxic shock
syndrome, Streptococcal and Staphylococcal
infections
Criteria for Determining an
Autoimmune Disorder
1.Evidence of an autoimmune reaction
2.Determination that the immunologic findings
are not secondary to another condition
3.Lack of other identified causes for the
disorder
Rheumatoid Arthritis
• Autoimmune disease affecting the synovium
that lines joints
• May begin with low-grade fever, malaise and
early morning joint pain and stiffness
• Detection of rheumatoid factor in blood test
• HLA-B27
Rheumatoid Arthritis
Ankylosing Spondylitis
• A severe vertebral
arthritis
– Associated with
inflammatory bowel
disease and psoriasis
– Causes the vertebrae
to fuse together
• May not even be
able to lift your
head
– Effects men more
often than women
Scleroderma – Systemic Sclerosis
• Connective tissue autoimmune disease
– Excessive collagen deposition in the skin and
internal organs
• ScL-70 antibodies
– Includes
• Blood vessels
• Kidneys
• Lungs
• Heart
• Gastrointestinal tract
Other Autoimmune Diseases
• Raynaud Phenomenon
– Resulting from spasm of small blood vessels that cause coldness,
blanching, numbness and pain in finger and toes
– Can also occur in internal organs
• Polyarteritis Nodosa
– Generalized blood vessel inflammation (systemic vasculitis)
• 1/3 caused by hepatitis B infection
• Associated with inflammation in the vascular wall owing to
deposition of immune complexes (type 3 hypersensitivity)
• Inflammatory Myopathies
– Autoimmune skeletal muscle injury
– Occurs alone of in conjunction with other autoimmune diseases such
as SLE or RA
• Muscle weakness, fatigues, lymphocytic inflammation
Hypersensitivity Reactions Outline
• Introduction
• Type I Hypersensitivity
• Type II Hypersensitivity
• Type III Hypersensitivity
Type III – Immune Complex
Hypersensitivity
• Immune Complexes – Normal Response
– Aggregations of antigen and their
corresponding antibodies
– Large complexes are formed in a person who
has an infection
– Carried in the bloodstream
• Quickly removed by the liver and spleen
• Infection is neutralized or else --• End result: bad inflammation, necrotizing
vasculitis
Which diseases involve type III
hypersensitivity?
Disease
Systemic lupus
erythematosus
Post-streptococcal
glomerulonephritis
Antigen
Symptoms
Nuclear antigens
Nephritis, skin
lesions, arthritis…
Streptococcal
antigen
Nephritis
Polyarteritis nodosa Hepatitis B antigen
Systemic vasculitis
Serum sickness
Foreign proteins
Arthritis, vasculitis,
nephritis
Arthus reaction
Foreign proteins
Cutaneous vasculitis
Two Kinds of Type III Hypersensitivity Reactions
• Systemic immune complex disease
• Complexes formed in circulation
• Deposited in several organs
• Example: serum sickness
• Local immune complex disease
• Complexes formed at site of antigen
injection
• Precipitated at injection site
• Example: Arthus reaction
Serum sickness
• In olden days: used horse serum for
immunization
• Inject foreign protein (antigen)
• Antibodies are made; they form complexes
with antigens
• Complexes lodge in kidney, joints, small
vessels
• Inflammation causes fever, joint pain,
proteinuria
Serum sickness
– Symptoms: rash, uticaria, exensive edema,
and fever
– Treatment: corticosteroids and remove
allergen
Serum sickness
Type III – Immune Complex
Mediated Hypersensitivity
Localized immune
complex reactions
• Arthus reaction
– Localized tissue
necrosis by immune
complexes
– Caused by injecting an
antigen into the skin
• Usually from a drug
Systemic Lupus Erythematosus
• Chronic, multi-systemic, inflammatory
disease
• Involves almost any organ
– Characteristically the kidneys, joints,
serous membranes and skin
SLE
• Auto-antibodies are formed against self-antigens
– Plasma proteins
• Complement, clotting factors
– Cell surface antigens
• Lymphocytes, platelets, RBCs
– Intracellular cytoplasmic components
• Microfilaments and microtubules, lysosomes,
ribosomes, RNA
– Nuclear DNA
SLE
• May be a Type III Hypersensitivity disorder
• Involves
– Skin
– Joints
– Kidneys
– Heart
– Serous membranes
• May be drug induced
• Rashes: Butterfly-shaped rash over the cheeks — referred to as malar
rash red rash with raised round or oval patches — known as discoid
rashrash on skin exposed to the sun
• Mouth sores: sores in the mouth or nose lasting from a few days to
more than a month
• Arthritis: tenderness and swelling lasting for a few weeks in two or
more joints
• Lung or heart inflammation: swelling of the tissue lining the lungs
(referred to as pleurisy or pleuritis) or the heart (pericarditis), which
can cause chest pain when breathing deeply
• Kidney problem: blood or protein in the urine, or tests that suggest
poor kidney function
• Neurologic problem: seizures, strokes or psychosis (a mental health
problem)
• Abnormal blood tests:low blood cell counts: anemia, low white blood
cells or low platelets
• Positive ANA : antinuclear antibodies
Discoid Rash from SLE
How do the complexes cause inflammation?
• Immune complexes activate complement, which:
• attracts and activates neutrophils and monocytes
• makes vessels leaky
• Neutrophils and monocytes release bad stuff (PG,
tissue-dissolving enzymes, etc.)
• Immune complexes also activate clotting, causing
microthrombi
• Outcomes: vasculitis, glomerulonephritis, arthritis,
other -itises
Type III Immune Complex Allergic
Disorders
• Mediated by the formation of insoluble antigen–
antibody complexes that activate complement
– Activation of complement by the immune
complex generates chemotactic and vasoactive
mediators that cause tissue damage by
• Alterations in blood flow
• Increased vascular permeability
• Destructive action of inflammatory cells
Type III Immune Complex Allergic
Disorders (cont.)
• Immune complexes formed in the circulation
produce damage when in contact with the vessel
lining or when deposited in tissues
– Elicit an inflammatory response by activating
complement
– This leads to chemotactic recruitment of
neutrophils and other inflammatory cells.
• Responsible for the vasculitis seen in certain
autoimmune diseases like SLE
Immune-complex-mediated vasculitis
What complement fractions are important to know?
• C3b: promotes phagocytosis of complexes (and bugs!)
• C3a, C5a (anaphylatoxins): increases permeability
• C5a: chemotactic for neutrophils, monocytes
• C5-9: membrane damage or cytolysis
Question
Is the following statement true or false?
• The difference between alloimmune reactions
and autoimmune reactions lies in the
hypersensitivity reaction.
A. True
B. False
Answer
• False: Alloimmunity refers to reaction to
tissue from a donor, whereas autoimmune
reactions occur against the host tissue.
Hypersensitivity Reactions Outline
• Introduction
• Type I Hypersensitivity
• Type II Hypersensitivity
• Type III Hypersensitivity
• Type IV Hypersensitivity
TYPE IV Delayed Hypersensitivity
• TYPE IV is very different from the other types of
hypersensitivities
1. It is a T-lymphocyte reaction (the others are
B-lymphocyte reactions)
2. It does not depend on the development of
antibodies
3. The clinical appearance of the reaction is
delayed a few days after antigen contact
4. The reaction is a slower process and is known
as delayed hypersensitivity
TYPE IV Delayed Type Hypersensitivity
• Antigen are captured by macrophages for
presentation to T-Lymphocytes.
• T-lymphocytes react only to the antigen
presented by macrophages that are sensitized to
become cytotoxic T cells and memory T cells
• Cytotoxic T cells attach antigen and cause either
– Inflammation or
– Direct cell death (cytotoxic reaction)
Type IV Delayed Type Hypersensitivity
• Helper T cells orchestrate the attack
against
• Intracellular bacterium in tuberculosis
and leprosy
• Persistent immune complex in contact
dermatitis
• Or against foreign tissue in
transplantation
Type IV – DTH
• Type IV reactions are characterized by
accumulations of macrophage around the antigen
to form a nodule of lymphocytes and macrophage
– The large cells surrounding a central area of tissue
necrosis = Granulomas
• Seen in TB Bacillus
• Also seen in the Mantoux (TB) test
• Cytotoxicity is the mode of type IV hypersensitivity Tcell reaction that is important in tissue transplant
rejection
• The most common Type IV reaction is contact dematitis
Type IV – DTH
• Principle mechanism of damage in:
– Contact dermatitis
– Tuberculosis
– Transplant rejection
Contact Dermatitis
Delayed-Type Hypersensitivity (DTH)
Perivascular cuffing by CD4+ cells
Delayed-Type Hypersensitivity
• Good example of DTH: positive Mantoux
test
• Patient previously exposed to TB
• Inject (inactive) TB antigen into skin
• See reddening, induration. Peaks in 1-3
days
Delayed-Type Hypersensitivity
• Prolonged DTH can lead to granulomatous
inflammation
• Perivascular CD4+ T cells replaced by
macrophages
• Macrophages are activated, look “epithelioid”
• Macrophages sometimes fuse into “giant cells”
• Granuloma = collection of epithelioid
macrophages
Summary
Type I
• Allergy
• TH2 cells, IgE on mast cells, nasty mediators
Type II
• Antibodies
• Opsonization, complement activation, or cell dysfunction
Type III
• Immune complexes
• Lodge, cause inflammation, tissue injury
Type IV
• CD4+ or CD8+ T cells
• DTH or T-cell-mediated cytotoxicity
Granuloma
DTH sounds a lot like cell-mediated immunity!
• The same mechanisms underlie both.
• Cell-mediated immunity is the major defense we
have against intracellular bugs (like TB and fungi).
• Cell-mediated immunity (good) can coexist with
DTH (bad)!
• Patients with AIDS:
• Lack CD4+ cells
• So have poor cell-mediated immune response!
• Macrophages sit there unactivated; can’t kill
bugs.
T-Cell Mediated Cytotoxcity
• CD8+ T cells recognize antigens on the surface of
cells
• T cells differentiate into cytotoxic T lymphocytes
(CTLs) which kill antigen-bearing cells
• CTLs normally kill viruses and tumor cells
• In T-cell mediated cytotoxicity, CTLs kill other
things:
• Transplanted organ cells
• Pancreatic islet cells (Type I diabetes)
T-Cell-Mediated Cytotoxicity
Routes of Exposure to Latex
• Cutaneous
• Mucous membrane
– Most severe
reactions result
from contact with
the mouth, vagina,
urethra, or rectum
• Inhalation
• Internal tissue
• Intravascular routes
• Reaction types
– Type I vs. type IV
Delayed-Type Hypersensitivity
Disorder
• Cytokines are secreted causing an
inflammatory response
– Ie. Tuberculin skin test
• Can be involved in transplant rejection and
autoimmune disorders
Categories of Transplanted Tissue
• Allogeneic
– The donor and recipient are related or
unrelated but share similar HLA types.
• Syngeneic
– The donor and recipient are identical
twins.
• Autologous
– The donor and recipient are the same
person.
Basic Patterns of Transplant Rejection
• Hyperacute reaction
– Occurs almost immediately after transplantation
– Produced by existing recipient antibodies to graft
antigens initiating a type III
• Acute rejection
– Occurs within first few months after
transplantation with signs of organ failure; may
occur months or years after immunosuppression
has been terminated
– T lymphocytes respond to antigens in the graft
tissue.
Basic Patterns of Transplant
Rejection (cont.)
• Chronic host-versus-graft rejection
– Immunocompetent cells are transplanted into
immunologically compromised recipients (TH)
– Close MHC matching and selective T-cell
depletion of donor are often effective in
preventing this major problem
Basic Requirements for Graftversus-Host Disease
1. The transplant must have a functional
cellular immune component.
2. The recipient tissue must bear antigens
foreign to the donor tissue.
3. The recipient immunity must be
compromised to the point that it cannot
destroy the transplanted cells.
Question
Is the following statement true or false?
• Immunodeficiency disorders arise only later in life
and are associated with viral infections.
A. True
B. False
Answer
• False: Many immunodeficiency disorders
are congenital.
Question
Is the following statement true or false?
• The function of MHC molecules is to mark
foreign proteins, rendering them antigenic.
A. True
B. False
Answer
• False: The MHC molecules are used by the
immune cells to differentiate host tissue from
foreign tissue. They are found on all host
tissues.
Question
• Which of the following hypersensitivity reactions
can be treated with the administration of
epinephrine?
a.
b.
c.
d.
Type I
Type II
Type III
Type IV
Answer
a. Type I: Type I reactions are anaphylactic; thus
airway constriction is a major concern.
Epinephrine stimulates airway relaxation.
b. Type II
c. Type III
d. Type IV
Hypersensitivity Disorders
• Definition
– Excessive or inappropriate activation of the
immune system
• Types
– Type I, Ig-E–mediated disorders
– Type II, antibody-mediated disorders
– Type III, complement-mediated immune disorders
– Type IV, T-cell–mediated disorders
THE END
Type I
• Primary or initial-phase response
– Vasodilation
– Vascular leakage
– Smooth muscle contraction
• Secondary or late-phase response
– More intense infiltration of tissues with
eosinophils and other acute and chronic
inflammatory cells
– Tissue destruction in the form of epithelial cell
damage
Type I
• Two types of cells used:
– Type 2 helper T-cell
– Mast cells or Basophils
• Type 2 helper T-cell
– CD4+
• Responds to microbes
– Tβ2
• Respnds to allergens or helminths
(intestinal parasites)
Type I
• Mast Cell
– Allergen-specific IgE-antibodies attach to receptors
on the surface of mast cells and basophils
– The sensitizing allergen binds to the cell-associated
IgE
• Triggers a series of events that ultimately lead to
degranulation and the Primary Early Response
– The Secondary or late Response occurs 2 to 8 hours
• Lasts for several days
Types of IgE-Mediated Allergic
Reactions
• Atopic disorders
– Hereditary predisposition and production of a
local reaction to IgE antibodies produced in
response to common environmental agents
• Urticaria (hives), allergic rhinitis (hay fever),
atopic dermatitis, food allergies, some forms of
asthma
• Non-atopic disorders
– Lack the genetic component and organ specificity
of the atopic disorders
Type II (Antibody Mediated)
Hypersensitivity Reactions
• Examples
– Mismatched blood transfusion reactions
– Hemolytic disease of the newborn
– Certain drug reactions
Type IV (Cell Mediated) Delayed Type
Hypersensitivity
• Cell-mediated immune response
• Mediated by sensitized T lymphocytes
– The principal mechanism of response to a
variety of microorganisms including intracellular pathogens and extracellular agents
– Can lead to cell death and tissue injury in
response to chemical antigens or self-antigens
• Basic types
– Direct cell-mediated cytoxicity
• Hepatitis
– Delayed-type hypersensitivity
• Allergic contact dermatitis
• Hypersensitivity pneumonitis
Type III – Immune Complex
Hypersensitivity
• Abnormal Response
– Too much antigen (dust in the lungs)
– Too many antibodies (autoimmune disease)
• Small Antigen-antibody complexes are
formed in the circulation and deposited
mainly in the tissues
–microthrombi
• These complexes induce a localized
inflammatory response by activating the
complement system