disorders of the immune system. four major categories of immune mechanisms humoral or...
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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, antigen-
presenting 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 syndromeSigns 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 Epstein-Barr 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 systemAutosomal Dominant
http://www.youtube.com/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&feature=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.
• 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.
Introduction
• 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.
What happens in these reactions?
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
• Granule contents• Histamine • Some chemotactic factors
• Membrane phospholipid metabolites• Prostaglandin D2
• Leukotrienes
• Cytokines• TNF• Interleukins• IL-13
What do mast cells release upon Second Exposure?
Mast cells: Normal (left) and degranulated (right)
• 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 do these substances do?
• 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
What happens to the patient?
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
• 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
Type II Hypersensitivity
Disease Antigen Symptoms
Autoimmune hemolytic anemia RBC antigens, drugs Hemolysis
Pemphigus vulgaris Proteins between epithelial cells Bullae
Goodpasture syndrome
Proteins in glomeruli and
alveoliNephritis, lung
hemorrhage
Myasthenia gravis Acetylcholine receptor Muscle weakness
Graves disease TSH receptor Hyperthyroidism
Which diseases involve type II hypersensitivity?
• Antibodies bind to cell-surface antigens
• One of three things happens:• Opsonization and phagocytosis• Inflammation• Cellular dysfunction
Sequence of Events
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 short-
circuit 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 reaction2.Determination that the immunologic findings
are not secondary to another condition3.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
Disease Antigen Symptoms
Systemic lupus erythematosus Nuclear antigens Nephritis, skin
lesions, arthritis…Post-streptococcal glomerulonephritis
Streptococcal antigen Nephritis
Polyarteritis nodosa Hepatitis B antigen Systemic vasculitis
Serum sickness Foreign proteins Arthritis, vasculitis, nephritis
Arthus reaction Foreign proteins Cutaneous vasculitis
Which diseases involve type III hypersensitivity?
• 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
Two Kinds of Type III Hypersensitivity Reactions
• 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
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
• 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
How do the complexes cause inflammation?
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
• C3b: promotes phagocytosis of complexes (and bugs!)
• C3a, C5a (anaphylatoxins): increases permeability
• C5a: chemotactic for neutrophils, monocytes
• C5-9: membrane damage or cytolysis
What complement fractions are important to know?
Question
Is the following statement true or false?• The difference between alloimmune reactions
and autoimmune reactions lies in the hypersensitivity reaction.
A. TrueB. False
• False: Alloimmunity refers to reaction to tissue from a donor, whereas autoimmune reactions occur against the host tissue.
Answer
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 hypersensitivities1. It is a T-lymphocyte reaction (the others are
B-lymphocyte reactions)2. It does not depend on the development of
antibodies3. The clinical appearance of the reaction is
delayed a few days after antigen contact4. 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 T-cell 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
• 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
Delayed-Type Hypersensitivity
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
Summary
Granuloma
• 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.
DTH sounds a lot like cell-mediated immunity!
• 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 Cytotoxcity
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 Graft-versus-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. TrueB. 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. TrueB. 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. Type Ib. Type IIc. Type IIId. Type IV
Answer
a. Type I: Type I reactions are anaphylactic; thus airway constriction is a major concern. Epinephrine stimulates airway relaxation.
b. Type IIc. Type IIId. 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 intra- cellular 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