Pathology Of Immune System (MODULE 8A & 8B) Flashcards
The immune system is composed of:
• Leukocytes and Immune cells • Adaptable and Innate Immune system • Lymphatic System
And proteins
Innate immunity overview:
- Non-Specific Response
• The innate immune system provides a general defense against pathogens, meaning it does not recognize specific pathogens but rather responds to several indicators of infection - Immediate Response
• It responds to pathogens within minutes to hours of exposure and is the body’s first line of
defense - No Memory
• Innate responses do not adapt to repeated infections; the response is the same each time a pathogen invades - Components
• Physical Barriers: Skin and mucous membranes • Chemical Barriers: Stomach acid, enzymes in tears and skin oils • Cellular Defenses: Phagocytic • Inflammatory Response: Release of cytokines that recruit immune cells to sites of infection
Advantages = provides immediate protection; protects against all pathogens
Disadvantages = lacks specificity; no immunological memory
Compare and contrast innate vs adaptable immune systems
Key Differences
Speed and Timing
• Innate immune system acts immediately
• Adaptive system takes longer to respond but develops memory for a faster response on subsequent exposures
Specificity
• Innate immunity is non-specific
• Adaptive immunity is highly specific to a pathogen’s antigens
Memory
• Innate immunity lacks memory
• Adaptive immunity develops immunological memory, leading to an enhanced and faster response to repeated
exposures to the same pathogen’s antigens
• Both systems are interconnected • The innate system capture and process pathogens presenting their antigens to cells of the adaptive
immune system to initiate a specific immune response
Adaptable immunity overview:
Key Differences
Speed and Timing
• Innate immune system acts immediately
• Adaptive system takes longer to respond but develops memory for a faster response on subsequent exposures
Specificity
• Innate immunity is non-specific
• Adaptive immunity is highly specific to a pathogen’s antigens
Memory
• Innate immunity lacks memory
• Adaptive immunity develops immunological memory, leading to an enhanced and faster response to repeated
exposures to the same pathogen’s antigens
• Both systems are interconnected • The innate system capture and process pathogens presenting their antigens to cells of the adaptive
immune system to initiate a specific immune response
What are the innate immune cells?
• Neutrophils
• Most abundant type of WBC in humans and are a critical component of the innate
immune system • Primarily responsible for responding to infections, especially bacterial and fungal
• Eosinophils
• Involved in combating parasitic infections and mediating allergic inflammatory
responses
• Basophils
• Least common WBC Macrophages and Neutrophils • Monocytes
are classified as phagocytic cells.
• Differentiate into Macrophages
• Numerous roles within the immune system
What are the adaptable immune cells?
T-Lymphocytes (T-Cells)
• WBC responsible for mediating cellular immunity through the direct killing
of infected host cells • Created in the bone marrow and mature in the thymus • Can differentiate into various subsets such as cytotoxic T cells, helper T cells,
and regulatory T cells
B-Lymphocytes (B-Cells)
• Create humoral immunity by producing and secreting antibodies that target
specific antigens • Created and mature in the bone marrow and differentiate into plasma cells • Plasma cells produce antibodies and memory B cells that provide long-term
immunity to a specific antigen
Types of T-lymphocytes overview:
• Helper T Cells (CD4+ T Cells)
• Assist other cells in the immune system by releasing cytokines, which can amplify
the immune response • Helper T cells are further categorized based on the cytokines they produce:
• T Helper 1 Cells (TH1), T Helper 2 Cells (TH2), T Helper 17 Cells (TH17)
• Cytotoxic T Cells (CD8+ T Cells)
• Cells are responsible for directly killing infected cells, primarily those infected with
viruses or transformed by cancer • Recognize antigens presented by MHC class I molecules on the surface of infected
cells
• Memory T Cells
• After an initial response to a specific antigen, some T cells become memory cells
• Persist long-term in the body and enable a faster response upon re-exposure to the same antigen
Types of B-lymphocytes overview:
• B-Lymphocytes, when activated, differentiation into: • Plasma Cells
• Create and secrete large amounts of antibodies specific to the antigen they
are exposed to • Antibodies play a key role in the immune response by neutralizing
pathogens or marking them for destruction by other immune cells
• Memory B Cells
• Do not secrete antibodies but persist in the body for years or even decades
• Provide a rapid and robust response upon re-exposure to the same antigen
• Forms the basis of immunological memory.
Antigen — Antibody: overview. What are the 5 classifications of antibodies?
IgG
• Most abundant (~80%)
• Humoral immunity
IgA
• Body secretions (saliva, tears, mucous membranes)
IgM
• First antibody produced with detection of foreign antigens
IgE
• Associated with allergies
IgD
• Found on the surface of B cells
Three Classifications to Immune System Disorders
• 1. Hypersensitivity
• 2. Autoimmune
• 3. Immunodeficiency
Normally the immune system should react and protect the organism. With immune system disease…
This protection is lost or directs immunity
reactions against itself or overreacts
• Causes damage to the host
Hypersensitivity reactions is what?
Can be initiated by?
Df - It is an excessive or harmful reaction to an antigen that normally does
not illicit an immunologic response
Exogenous Antigens
• Microbes, chemicals, food, pollen, dust, drugs
• May range from itchy nose, runny eyes to extreme fatal situations- anaphylaxis
• Commonly referred to as allergies
Endogenous Antigens
• Our own cell antigens
• Lead to autoimmune diseases
21
What are the four types of hypersensitivity reactions?
- Immediate (type I) hypersensitivity
• Commonly referred to as allergies - Antibody-mediated (type II) hypersensitivity
- Immune complex-mediated (type III) hypersensitivity
- Cell-mediated (type IV) hypersensitivity
THINK: ACID
T1 (IgE mediated) - Anaphylaxis/Allergies/Antibody mediated
T2 - Cytotoxic - IgG-mediated cytotoxic/Complement *has 4 outcomes; first 3 are cytotoxic)
T3 - Immune complex mediated (associated diseases are glomerulonephritis,(kidney) rheumatoid arthritis (joint), lupus erythematosus), vasculitis (small BV)
T4 - Delayed - Diseases such as Diabetes T; Dermatitis, *not antibody mediated
Autoimmune disorders work how?
• Disorders and diseases that are due to a failure of the body’s
immune system for self-tolerance
• Immune system is unable to distinguish self-antigens from foreign
antigens
• Immune system produces autoantibodies that attack the body’s
own antigens
Immunodeficiency disease is defined as?
Has what two categories?
Df- The immune system is deficient or not functioning at full capability
- Leaves the body vulnerable for the development of diseases and
disorders
Two Categories of Immunodeficiency Diseases
• 1. Primary (congenital) immunodeficiencies
(EX: Born w it)
• 2. Secondary (acquired) immunodeficiencies
(EX: chemo/aids)
Hypersensitivity reactions are when the body’s immune system
causes a deficient response to identified antigens.
• A) True • B) False
B
Immunodeficient disorders can be due to a genetic abnormality or
due to a viral infection.
• A) True
• B) False
A
Type I hypersensitivity are also known as?
• Immediate (Type I) Hypersensitivity
• IgE hypersensitivity reactions
• Allergies
Can become life-threatening = anaphylaxis (anaphylactic shock)
T or F
Type I hypersensitivity reactions are very fast
T
Very fast immunologic reaction
How is type I hypersensitivity triggered?
Triggered by the binding of an antigen to IgE antibody on the surface of
mast cells
What are the pathogensesis key players in type I hypersensitivity?
-Allergen
• Substance that causes an immune response
• Causes sensitization of the mast cells
-IgE Antibodies
• Antibodies created in response to specific allergen (antigen)
-Mast Cells
• Immune cells that release chemical mediators that cause the physiological changes
What are the two steps of type I hypersensitivity? What do they entail?
• 1. First Exposure
• Sensitization
- Dander is phagocytized by an APC
• Carries the antigen (called an allergen) to a lymph node
• APC presents allergen (antigen) to a Naïve T Helper Cell
• Naïve T helper cell is built to recognize a specific antigen, but has not
been exposed to it yet
- Naïve T helper cell differentiates to a Type 2 T Helper Cell (TH2)
• Becomes Primed
• Primed TH2 releases Interleukin 4 (IL-4) that causes B cells to make IgE
antibodies
— Specific to the cat dander
— Instead of IgM antibodies
• These IgE antibodies have a HIGH affinity for receptors on mast cells
— Bind to mast cells
• IgE antibodies bound to mast cells- are now sensitized
—Specifically for cat dander
• 2. Re-Exposure
Go back to your friend’s place with that annoying cat lol
• Re-exposure to the cat dander
• Dander antigens bind to IgE antibodies on the mast cells
• Sensitized mast cells
• Mast cells go crazy and release their chemical mediators
Three types of mediators released from mast cells:
• Vasoactive amines
• Lipid mediators (arachidonic acid)
• Cytokines
Ty pe I Hypersensitivity: Chemical Mediators
- Vasoactive Amines
• HISTAMINE is the main vasoactive amine
• Causes: Vasodilation, Increased vascular permeability, Smooth muscle contraction, Increased secretion of mucus
- Lipid Mediators
• Prostaglandins and leukotrienes from the arachidonic acid pathway • Causes:
• Bronchospasm (smooth muscle contraction) • Increased mucus secretion • Increase vascular permeability - Cytokines
- Tumor necrosis factor (TNF) and cytokines. Causes; increased mucus secretion, promote leukocyte recruitment
What are the two phases of type I hypersensitivity? What entailed these?
- Immediate response
- Late-phase response
• Immediate Response
—Vasodilation, increased vascular permeability, smooth muscle contraction
—5-30 minutes after exposure; subsides in about 60 minutes
• Late-Phase Response
—Roughly 2-24 hours afterwards
—Characterized by inflammation and tissue damage
• Recruitment of leukocytes can amplify and sustain inflammatory processes
• Eosinophils, Basophils
What are common treatments for type I hypersensitivity symptoms?
• Antihistamines
—Block the effects of histamine
• Corticosteroids
—Decrease inflammatory
What does life threatening type I hypersensitivity reaction entail?
What is the treatment ?
• Massive and intense systemic type 1 hypersensitivity reaction • Causes immediate and severe reactions
• Mast cell mediator release and an increased intensity of reactions
Individuals go into Anaphylactic Shock
—Airways spasm and fill with mucus
—Hives, itchiness, swelling of skin
—Abdominal pain, diarrhea, vomiting
Treatment
• Epinephrine pen
All of the options must occur for type 1 hypersensitivity reactions,
except?
• A) APCs must present antigen to T helper cells
• B) IgM antigens must bind to mast cells
• C) A person must have prior exposure to the antigen
• D) Mast cells must release histamine
B
All the options are true regarding type 1 hypersensitivity
reactions, except?
• A) Urticaria is a possible outcome
• B) Corticosteroids are a treatment option
• C) A complication of anaphylaxis is high blood pressure
• D) The majority of symptoms are a result of a massive secretion of histamine
C
Type II hypersensitivity can be called what? What does it entail?
AKA: Antibody-Mediated (Type II) Hypersensitivity • AKA: Cytotoxic Hypersensitivity
— Due to the mediated destruction of cells
• IgG antibodies directed against target antigens on the surface of cells or
other tissue components or exogenous molecules
—Basically- our own antibodies bind to our own cells’ antigens eliciting various reactions that cause disease, damage, and destruction
IgG antibodies bind to healthy cells’ antigens or extrinsic antigens = this is the key with type II hypersensitivity reactions. Antibodies bind directly to a healthy cell which then causes complications.
• Intrinsic antigen
—Cell normally makes these antigens This is the key with Type II
• Extrinsic (exogenous) antigen
Hypersensitivity reactions. Antibodies bind directly to a
—A drug antigen
healthy cell which then causes
Antibody-Antigen Complexes Cause ?
• 1. Activation of the complement system
• 2. Interference with normal cellular
functions
There are 4 mechanisms that are associated with Type II Hypersensitivity
Reactions
— Three of these mechanisms are cytotoxic (cell death)— One of these mechanisms is non-cytotoxic (only cell dysfunction). What are these?
• 1. Opsonization and phagocytosis (cytotoxic)
• 2. Complement system activation (cytotoxic)
• 3. Antibody Dependent Cell Mediated Cytotoxicity (cytotoxic)
• 4. Antibody Mediated Cellular Dysfunction (non-cytotoxic)
Type II (antibody-mediated) hypersensitivity reactions are associated with several diseases:
• Autoimmune hemolytic anemia
• Myasthenia gravis
• Graves disease
• Pernicious anemia
• Vasculitis
• Acute rheumatic fever
• Goodpasture syndrome: Rapidly progressive glomerulonephritis (kidney) with pulmonary hemorrhage; Anti-glomerular basement membrane
antibody disease; Glomerulonephritis - pulmonary hemorrhage
What option is TRUE regarding type II hypersensitivity reactions?
• A) It only involves self antigens
• B) It can lead to opsonization
• C) All the outcomes lead to cytotoxic processes
• D) All the options are true
B
All of the options are true regarding type II hypersensitivity reactions reactions, except?
• A) Cell lysis is a possible outcome
• B) Overactivation of a cellular receptor is a possible outcome
• C) All outcomes lead to cellular death
• D) Can lead to the formation of MAC
C
Type III hypersensitivity can be referred to as? What does it entail?
Overview:
• AKA: Immune Complex–Mediated Diseases
• Antigen-antibody complexes (called immune complexes) that are
formed in the circulation may deposit in blood vessels
—Leading to complement system activation and acute inflammation
—Causes tissue damage
• Only involves antibodies bound to soluble antigens
—Not attached to a cell
• Type II Hypersensitivity: Antibodies target antigens bound on cell
surfaces in the blood
T or F
Type III hypersensitivity involves antigen-antibody complexes that are formed in the circulation may deposit in blood vessels
T
T or F
Antigens that form immune complexes may only be endogenous
F
• Antigens that form these immune complexes may be:
Exogenous
—Foreign protein that is injected or produced by an infectious microbe •
Endogenous
— Individual produces antibodies against self antigens (autoimmunity)
Three Steps/Phases to Type III Hypersensitivity Reactions
**look at written notes
• 1. Formation of antigen
• Antibody complexes in circulation; Introduction of a protein antigen triggers an immune response that results in the formation of antibodies; Antibodies are secreted into the blood and react with the antigen still present in the blood • Antibody-Antigen complexes form (immune complexes)
• 2. Deposition of these immune complexes in tissues
• Blood vessels primarily
Circulating antigen-antibody complexes are deposited
in various tissues • Site where these immune complexes are deposited:
• Organs where blood is filtered at high pressure to form
other fluids
• Urine and synovial fluid for example
• Like the glomeruli and joints
• 3. Inflammatory reaction in various sites
• Complement system
Immune complexes deposited in tissues initiate
acute inflammatory reactions via complement system
• Tissue damage is similar no matter where
complexes are deposited
• Depending on the location, the name is different:
• Vasculitis if it occurs in blood vessels
• Glomerulonephritis if it occurs in renal glomeruli
• Arthritis if it occurs in the joints
**Look at slides 67-70 and understand Type III hypersensitivity steps/ written notes
• 1. Formation of antigen
• Antibody complexes in circulation; Introduction of a protein antigen triggers an immune response that results in the formation of antibodies; Antibodies are secreted into the blood and react with the antigen still present in the blood • Antibody-Antigen complexes form (immune complexes)
• 2. Deposition of these immune complexes in tissues
• Blood vessels primarily
Circulating antigen-antibody complexes are deposited
in various tissues • Site where these immune complexes are deposited:
• Organs where blood is filtered at high pressure to form
other fluids
• Urine and synovial fluid for example
• Like the glomeruli and joints
• 3. Inflammatory reaction in various sites
• Complement system
Immune complexes deposited in tissues initiate
acute inflammatory reactions via complement system
• Tissue damage is similar no matter where
complexes are deposited
• Depending on the location, the name is different:
• Vasculitis if it occurs in blood vessels
• Glomerulonephritis if it occurs in renal glomeruli
• Arthritis if it occurs in the joints
Common Immune Complex-Mediated (Type III) Hypersensitivity Diseases
• Systemic lupus erythematosus
• Reactive arthritis
• Arthus reaction
• Nephritis (glomerulonephritis)
• Vasculitis
What is true of type III hypersensitivity reactions?
• A) Involves antibodies binding to both cellular and soluble antigens
• B) When the antibody-antigen complexes are deposited, they activate the complement system
• C) A common location for the antibody-antigen complexes to be deposited is the heart
• D) None of the options are true
B
All of the following options are common locations for the antibody-antigen
complexes to be deposited associated with type III hypersensitivity reactions, except?
• A) Kidney
• B) Liver
• C) Joint
• D) Small blood vessels
B
The difference between type II and type III hypersensitivity reactions is that type III only binds to soluble antigens and type II only binds to cellular antigens?
• A) True • B) False
A
Type IV hypersensitivity can be referred to as what? Involves what?
• AKA: T cell-mediated (type IV) hypersensitivity • AKA: Delayed Type Hypersensitivity • It is NOT antibody mediated but CELLULAR mediated reactions • Involves the actions of two different types of T lymphocytes
• Remember where lymphocytes were also associated?
• Each type has its own outcomes and physiological changes
What processes are involved with Ty pe IV Hypersensitivity Tissue Injury and Disease ?
• 1. Cytokine-Mediated Inflammation
• Cytokines are produced mainly by CD4+ T cells
• 2. Direct Cell Cytotoxicity
• Mediated by CD8+ T cells
CD 4+ Cells
• AKA: Helper T Cells • Release cytokines
CD8+ Cells
• AKA: Killer T Cells and Cytotoxic T Cells • Kill specific targets (assassins)
***look at slides 83-84 that discuss the type IV hypersensitivity process of CD4 and 8+
What option is TRUE regarding cytokine–mediated inflammation reaction?
• A) Antibodies activate CD4+ cells
• B) There is recruitment of macrophages
• C) Cells are directly destroyed
• D) There is recruitment of neutrophils
B
All of the options are true regarding type IV hypersensitivity reactions, except?
• A) Activation of cytotoxic T cells leads to cellular death via perforins
• B) Macrophages release pro-inflammatory chemical mediators with cytokine-mediated
inflammation
• C) Both versions utilize antibodies to destroy foreign antigens in the body
• D) The reason there can be delayed type hypersensitivity is due to the time it takes for
leukocytes to be recruited and activated
C
No antibodies with type IV
Three Classifications to Immune System Disorders
• 1. Hypersensitivity
• 2. Autoimmune
• 3. Immunodeficiency
What are some common autoimmune diseases?
Normally, immune system should react and protect the organism
• With immune system diseases- this protection is lost or directs immunity reactions against
itself or overreacts
• Causes damage to the host
Common Autoimmune Diseases
• Multiple sclerosis, Myasthenia gravis, Pernicious anemia, Reactive arthritis, Rheumatoid
arthritis, Sjögren syndrome, Systemic lupus erythematosus, Type I diabetes, Systemic Sclerosis
Autoimmune disease can be directed against?
Directed toward?
Can be directed against one particular organ or cell type
• Results in localized tissue damage
‘Can also be directed toward multisystem organ systems
• Characterized by lesions in many organs
• Primarily affect the connective tissues and blood vessels of involved organs
Mechanisms of Self-Tolerance Can Be Broadly Classified Into Two Groups
- Central Tolerance
• Immature self-reactive T and B lymphocyte clones that recognize self antigens
during their maturation are killed • Referred to as: Negative Selection or Clonal deletion - Peripheral Tolerance
• Some lymphocytes (B and T) with autoantigens reactions sometimes escape into
the blood • Several mechanisms in the peripheral tissues that kill autoreactive B and T cells
It is believed that the breakdown of self-tolerance and
development of autoimmunity is a result of a combination of?
• 1. Inherited Susceptibility Genes
• Influence lymphocyte tolerance
• 2. Environmental Factors
• Infections or tissue injury that alter the display of self antigens
• Activate APCs and lymphocytes in the tissues
What is negative selection or clonal deletion?
Both occur with Central tolerance
Immature self-reactive T and B lymphocyte clones that recognize self antigens during their maturation are killed
- negative selection or clinical deletion is a protective mechanism in the immune system to ensure that I cells do not attach the body;s own tissues, thus preventing autoimmune diseases
Negative selection occurs with peripheral tolerance?
• A) True
• B) False
B
Occurs with central tolerance
A viral infection could be a variable that leads to the development of an autoimmune disorder?
• A) True
• B) False
A
What is system if lupus erythematous (SLE)?
Autoimmune disease involving multiple organs
• Characterized by a vast array of autoantibodies, particularly
antinuclear antibodies (ANAs)
• Injury is caused mainly by deposition of immune complexes and
binding of antibodies to various cells and tissues- like blood vessels
It is an unpredictable, remitting and relapsing disease of acute or insidious
onset that may involve virtually any organ in the body
• Primarily affects the skin, kidneys, serosal membranes, joints, and heart
• Makes Dx difficult can it influence so many organs/tissues
• Hallmark of SLE is the production of autoantibodies
• Especially anti-nuclear antibodies (ANAs)
• To a host of other autoantibodies- blood cells, organelles, plasma membrane
What is anti-nuclear antibodies (ANA)?
ANAs Can Be Grouped Into Four Categories
(1) Antibodies to DNA
(2) Antibodies to histones
(3) Antibodies to nonhistone proteins bound to RNA
(4) Antibodies to nuclear antigen
Antinuclear antibodies (ANAs) are antibodies that target the components inside the nucleus of cells. The presence of ANAs in the blood can indicate autoimmune diseases, particularly conditions like lupus, rheumatoid arthritis, and scleroderma.
What are the risk factors, epidemiology, diagnosis, and pathogenesis, clinical manifestations associated with lupus?
Risk Factors
• Genetic Factors • Environmental Factors
• UV radiation, smoking, sex hormones • Immunological Ab
Epidemiology
• 9/10 diagnosed cases are women
• B/w ages of 15-45 years of age • Systemic lupus is about 70% of the lupus diagnoses • Lupus 2-3x times more prevalent in women of color
• African American women affects roughly 1 in 245 • 1/3 suffer from multiple autoimmune conditions • Estimated about 1.5 million individuals are diagnosed with lupus
Diagnosis
• Diagnosis is challenging due to variability of symptoms and overlapping of
other autoimmune disorders
Pathogenesis
• Autoantibodies are formed
*Most damage is formed by hypersensitivity type III reactions
• Depending on the tissue/organ these antigen-antibody complexes are
deposited – tissue/organ destruction will vary
Clinical Manifestations (top 3 most common)
—Kidneys (common)
• Renal failure is the most common cause of death with lupus
• Glomerulonephritis
—Skin (common)
• Involvement within majority of patients
• Erythematous- butterfly pattern
—Blood vessels (common)
• Acute necrotizing vasculitis
—CNS (common)
• Focal neurological deficits
• Due to ischemia
What are the common clinical manifestations of lupus disease?
Clinical Manifestations (top 3 most common)
—Kidneys (common)
• Renal failure is the most common cause of death with lupus
• Glomerulonephritis
—Skin (common)
• Involvement within majority of patients
• Erythematous- butterfly pattern
—Blood vessels (common)
• Acute necrotizing vasculitis
—CNS (common)
• Focal neurological deficits
• Due to ischemia
**look at SLE slides on clinical manifestations and treatment on slide 109
SLE is characteristically associated with the production of antibodies
against DNA and DNA associated proteins.
• A) True • B) False
T
(1) Antibodies to DNA
(2) Antibodies to histones
(3) Antibodies to nonhistone proteins bound to RNA (4) Antibodies to nuclear antigen
All of the following are common clinical manifestations of SLE, except?
• A) Glomerulonephritis
• B) Pericarditis
• C) Retinopathy
• D) Erythematous
C
Corticosteroids are a common treatment because of their ability to
activate CD4+ cells.
• A) True
• B) False
B
What is Sjögren’s syndrome?
Immune cells attack and destroy the lacrimal and salivary glands
• Produce tears and saliva
Symptoms:
• Dry eyes: Keratoconjunctivitis sicca
• Dry mouth: Xerostomia
Caused by destruction of the lacrimal and salivary glands
• Primarily CD4+ Helper T cells and B lymphocytes
**Look at slides on 116-120 on sjogren’s and sclerosis epidemiology, treatment, prognosis, etc. Write notes on this?
Overview of system sclerosis. AKA scleroderma
Group of rare diseases that affect the skin and connective tissues
• Causes EXCESSIVE FIBROSIS in tissues leading to hardening and
tightening of the skin
• Skin is the primary area affected
—GI tract, lungs, kidneys, heart, skeletal muscle can be affected
—Other organs lead to morbidity and mortality
• Virtually all patients have ANAs that react with a variety of nuclear antigens
Epidemiology
• Affects women 3x more than men
• Around 50-60 years of age • Diffuse Scleroderma
• Widespread skin involvement and early viscera involvement • Limited Scleroderma
• Mild skin involvement-fingers and face
• Involvement of viscera is later and slower to progress
• Also called CREST syndrome
Autoimmune Diseases: Steroid Treatments
Corticosteroid Treatment (Steroids) are POWERFUL anti-inflammatory
medications • Medications that closely resemble hormone cortisol • Adrenal Gland
• Adrenal Cortex
• Glucocorticoids: Cortisol
• Mineralocorticoids: Aldosterone
• Androgens: DHEA, testosterone • Adrenal Medulla
• Catecholamines: Epinephrine, Norepinephrine
**Corticosteroid Treatment (Steroids)- Cortisol Hormone
• Powerful anti-inflammatory • Suppresses immune system • Increases blood sugar levels (gluconeogenesis) • Function with lipid, protein, carbohydrate metabolism • Decreases bone formation • Increases blood pressure • Affects sleep-wake cycle
All of the options are associated with Sjogren’s Syndrome, except?
• A) Xerostomia (dry mouth)
• B) Commonly occurs in individuals older than 50
• C) Keratoconjunctivitis sicca (dry eyes)
• D) Mainly affects men
D
All of the options are associated with systemic sclerosis, except?
• A) GI tract dysfunction
• B) Excessive fibrosis being deposited into tissues
• C) Damage to the salivary glands
• D) Skin is the most common location that is affected
C
Define immunodeficiency and immunocompromised.
ID - Simple means the immune system is impacted by a change in its
function that leads to an inability to function properly and is
suspectable to disease and infection
When this happens we refer to the patient as immunocompromised
What are the two classifications of immunodeficiency?
• 1. Primary (congenital) immunodeficiencies: Genetic defects that affect the innate or adaptive immunity
• Commonly detected in infancy
• Between 6 months and 2 years of age
• A family of rare genetically distinct syndromes
**All have impaired development of mature T lymphocytes and/or B lymphocytes
• All have defects in both humoral and cell-mediated immunity
— O-Linked SCID:
• Accounts for 50% to 60% of cases of SCID • X-linked so is will it be more common in females or males? Failure of T-cell and B-cell maturation
• 2. Secondary (acquired) immunodeficiencies
AKA: Acquired Immunodeficiencies
• Much more common than primary immunodeficiencies!!!
*Seen In Individuals With
• Cancer
• Diabetes and other metabolic diseases
• Malnutrition
• Chronic infection
• Individuals receiving chemotherapy or radiation therapy for cancer,
• Individuals taking immunosuppressive drugs to prevent graft rejection or to
treat autoimmune diseases
Secondary Immunodeficiency Can Be Caused
- Defective Lymphocyte Maturation
• When the bone marrow is damaged by radiation or chemotherapy or
involved by tumors, such as leukemias - Inadequate Ig Synthesis
• As in malnutrition - Leukocyte Depletion and Dysfunction
• From drugs or severe infections
Severe combined immunodeficiency (SCID) is associated with:
• A) Viral infection that depletes the function of the immune system
• B) A genetic condition that impairs the development of T and B lymphocytes
• C) Genetic condition that only affects humoral immunity
• D) None of the options are associated with SCID
B
All of the following options are mechanisms that can lead to
secondary immunodeficiency, except?
• A) Malnutrition
• B) Chemotherapy
• C) Taking a specific drug
• D) Genetic abnormality
D
***Rare Immun disorders are popular board specific topics
Slides 138-end
Overview of DiGeorge syndrome.
AKA: 22q11.2 Deletion Syndrome • DiGeorge syndrome is a congenital defect in thymic development
resulting in deficient T-cell maturation • Leads to an immunodeficiency • Caused when a small part of chromosome 22 is missing • T cells are absent in the lymph nodes, spleen, and peripheral blood • Infants diagnosed with this are extremely vulnerable to viral,
fungal, and protozoal infections
Leads to other complications:
• Heart defects
•Hypoparathyroidism
• Cleft palate and other facial features
• Autoimmune disorders
Overview: Goodpasture syndrome
• AKA: Goodpasture disease; Rapidly progressive glomerulonephritis
with pulmonary hemorrhage; Anti-glomerular basement membrane
antibody disease; Glomerulonephritis - pulmonary hemorrhage • Autoimmune disease that affects the lungs and kidneys
**TYPE II HYPERSENSITIVITY REACTION • Characterized By • 1. Pulmonary alveolar hemorrhage • 2. Glomerulonephritis • Most often occurs in people ages 20 to 30 or older than age 60
Overview: aruthus reactions
• Hypersensitivity reaction that occurs several hours to days following the
intradermal injection of a vaccine into an animal and is marked by the
formation of antigen-antibody complexes accompanied by localized
inflammation, pain, redness, and sometimes tissue destruction
• Merriam Webster Dictionary
• The Arthus reaction is a rare adverse reaction that usually occurs after
vaccination with large and more severe local reactions, belonging to type III hypersensitivity reaction. This reaction is characterized by pain, swelling, induration (Tissue that becomes firm) and edema, even accompanied by severe necrosis or ulceration at the injection sites
•
Overview: amyloidosis
• Condition associated with a number of disorders in which
extracellular deposits of fibrillar proteins are responsible for tissue
damage and functional compromise
• Basically- amyloid fibrils (abnormal proteins) build up in the ECM
within your organs/tissues and interfere with their normal function
• AL (primary) amyloidosis is associated with excessive production of abnormal proteins associated with antibodies
Normally…
• Intracellular misfolded proteins are degraded in proteasomes
• Extracellular protein aggregates are taken up and degraded by macrophages • In amyloidosis, these quality control mechanisms fail and fibrillar proteins
(amyloid fibrils) accumulate outside of cells
• Interfere with function
• Many different types and forms of this condition • The pattern of organ involvement in different forms of amyloidosis is variable,
but commonly:
• Kidney • Spleen • Liver • Heart • Integument
This condition is characterized by the absence of T cells within the body?
• A) Goodpasture Syndrome
• B) Amyloidosis
• C) DiGeorge Syndrome
• D) Arthus Reaction
C
This condition is a hypersensitivity reaction associated with complications from injection of
antigens into the body?
• A) Goodpasture Syndrome
• B) Amyloidosis
• C) DiGeorge Syndrome
• D) Arthus Reaction
D
This condition is characterized by alveolar hemorrhaging and glomerulonephritis?
• A) Goodpasture Syndrome
• B) Amyloidosis
• C) DiGeorge Syndrome
• D) Arthus Reaction
A
All of the options are true, except?
A. DiGeorge syndrome is associated with a type IV hypersensitivity reaction.
B. Arthus reaction occurs after a vaccination.
C. Amyloidosis is associated with extracellular deposits of fibrillar proteins.
D. Goodpasture syndrome is associated with a type II hypersensitivity reaction.
A
What option is accurate regarding hypersensitivity reactions?
A. Only type II hypersensitivity reactions involve the complement system.
B. Type III hypersensitivity reactions involves the formation of immune complexes that ultimately activate the complement system.
C. Type I hypersensitivity involves IgE binding to neutrophils.
D. Anaphylaxis is due to an intense type II hypersensitivity reaction.
B
Type III hypersensitivity reactions involve immune complexes forming in the blood and being deposited into cells of tissues and causing damage.
False.
True
F
Antigen-antibody complexes are deposited in tissues, causing activation of complement, which attracts neutrophils to the site
What is TRUE regarding HIV/AIDS?
A. HIV inserts RNA directly into the cell’s genome.
B. The acute phase is asymptomatic.
C. HIV can only infect cells that have the CD4 receptor.
D. Candidas infections are common in the acute phase.
C
Which type of hypersensitivity reaction could have antibodies bind to receptors on the individual’s cells, ultimately blocking that receptor’s function?
A. Type I Hypersensitivity Reaction.
B. Type III Hypersensitivity Reaction.
C. Type II Hypersensitivity Reaction.
D. Type IV Hypersensitivity Reaction.
C
This condition is a result of deficient levels of T-lymphocytes?
A. Goodpasture syndrome.
B. Sjogren’s syndrome.
C. DiGeorge syndrome.
D. Systemic sclerosis.
C
The most common affected area for this disease is the fingers.
A Systemic Lupus Erythematous.
B. Scleroderma.
C. SCID.
D. Sjogren’s syndrome.
B
What option is TRUE regarding systemic lupus erythematous?
A. Erythematous exhibits as an abnormal heart rate..
B. Impacts caucasian women at a higher rate.
C.Glomerulonephritis is a common complication.
D. It is associated with a type IV hypersensitivity reaction.
C
Which type of disorder/disease is associated with xerostomia?
A. Type III Hypersensitivity Reaction.
B. Sjögren’s Syndrome.
C. Scleroderma.
D. Systemic Lupus Erythematous.
B
All of the options are possible causes of secondary immunodeficiency, except?
A. Genetic issues with the bone marrow.
B. Radiation exposure to bone marrow.
C. Chemotherapy treatment.
D. Prescription medications.
A
T or F
Autoimmune utilises hypersensitivity
T
Terminology
• -ology = study of
• -oma = suffix meaning tumors and abnormal growth
• -plasia = formation of cells • Neo- = new
• Carcin/o = cancer; cancerous
• Aden/o = gland
• Onc/o = tumor
• Sarc/o = connective tissue
• Lymph/o = lymph
Carcinogenesis means
Initiation/formation of cancer
Neoplasia is what?
Formation of new, abnormal growth that is not under physiological control
• Often referred to as a tumor
Benign.
Malignant.
B- Tumor, or growth that is not cancerous and does not spread to other parts of the body nor does it invade nearby
tissue
M - Tumor, or growth that is cancerous and spreads to other parts of the body and invades nearby tissues
Metastasis
The development of secondary malignant growths at a distance from a primary site of cancer
In situ
Cancer in which abnormal cells have not spread beyond where they first formed
Good b/c its stayed and not spread (though it looks like malignant)
Oncology/Oncologist
Study and treatment of cancer; one who specializes in the study and treatment of cancer
Carcinoma
Malignant cancer that originates from epithelial tissue and cells that line glands
Lymphoma
Malignant cancer that originates in the lymph tissue or blood cells
Sarcoma
Malignant cancer that originates in connective tissue
Remission
- Partial remission means tests demonstrate tumor has shrunk (1/2 size) and isn’t growing
• Complete remission means diagnostic tests do not demonstrate any cancer cells within your body
Differentiation
When cell changes from one type to another
• Typically, go from immature (unspecialized) cells to mature cells (specialized) with individual characteristics that have
specific form and function
Anaplasia
Loss of the mature or specialized features of a cell or tissue, as in malignant tumors
Tumor Suppressor Genes
Group of genes that slow down cell division, repair DNA, and initiate apoptosis
p53 and Rb
Proto-Oncogenes
Group of genes that produce proteins that regulate cell growth and division, differentiation
RAS —> always turned on and uncontrolled
Oncogenes
Mutated or over expressed proto-oncogenes
This term refers to malignant cancer that originates from epithelial tissue or cells that line glands?
• A. Sarcoma
• B. Metastasis
• C. Lymphoma
• D. Carcinoma
D
A tumor can be malignant or benign.
• A. True
• B. False
A
Cancer is always classified as malignant tumors.
• A. True
• B. False
A
Malignant cancer in the bone would be labeled as a sarcoma.
• A. True
• B. False
A
What are two major categories for carcinomas?
This glands, and tissue
Adenocarcinomas (form from glands: Brest, prostate, ovary, colon, pancreas)
Squamous cell carcinoma (form epithelial tissue)
Sequence of AA determines the ____ of the protein.
The shape of the protein determines _______.
Why is this important in understanding neoplasm?
Shape
Function
The change in DNA can affect the mRNA sequence which then results in change in the AA and different shape of protein that is dysfucntional (loses function)
DNA abnormalities- lead to abnormal protein production these include?
• Mutations caused by exogenous and endogenous stimuli
• Epigenetic changes- nongenetic influences on gene expression
Common Signs/Symptoms of Malignant Tumors!!!!
MUST KNOW!
• Weight loss without lifestyle changes
• Pain that doesn’t resolve with OTC (over the counter medication)
• Pain at night (less O2 at night; Cells are still running quickly)
• Fatigue
• Changes in other physiological processes (GI, bowel movements, urination)
— Depend on organ/area involved
Cancer is a problem of genetics and can be caused by?
DNA mutations = Mutations can lead to altered or abnormal expression of specific
genes that regulate fundamental cellular processes (cell cycle and cell growth)
Epigenetic changes = Turn a gene on or block it; Involves changes in gene activity that don’t alter the DNA sequence but can turn genes on or off leading to abnormal cell growth and development of tumors.
Normal cell function does not require an outside signal or factor to initiate cell growth
and replication.
• A. True
• B. False
F
Normal cell function does require an outside signal or factor to initiate cell growth and predication, along with internal factors as well.
All of the following are common major signs/symptoms of malignant tumors, except?
• A. Fatigue
• B. Pain at night
• C. Weight loss
• D. Pain that is relieved with pain medications
D
Cancer that originates from breast gland tissue would be classified as:
• A. Squamous cell carcinoma
• B. Lymphoma
• C. Sarcoma
• D. Adenocarcinoma
D
What are the two major categories for carcinomas?
- Adenocarcinomas
• Form from glands (breast, prostate, ovary, colon, pancreas) - Squamous Cell Carcinoma
• Form epithelial tissue
What are lymphomas?
• Refer to cancers that originate from lymph tissue or blood cells
- Lymphoma Cancers (lymph tissue)
• Hodgkin Lymphoma
• Non-Hodgkin Lymphoma - Leukemia Cancers (blood cells)
• Acute myeloid (or myelogenous) leukemia (AML)
• Chronic myeloid (or myelogenous) leukemia (CML)
• Acute lymphocytic (or lymphoblastic) leukemia (ALL)
• Chronic lymphocytic leukemia (CLL)
What are sarcomas?
— Refer to cancers that originate from connective tissue
• Osteosarcoma (bone)
• Chondrosarcoma (cartilage)
• Synovial cell sarcoma (joint)
• Liposarcoma (fat)
• Angiosarcoma (blood vessel)
• Rhabdomyosarcoma (skeletal muscle)
T or F
Neoplasm is uncontrolled proliferation of cells
T
Define cancer and difference between benign and malignant
Cancer
• A classification of malignant tumors that are caused by an uncontrolled
division of abnormal cells in a part of the body that have the potential to invade or spread to other areas of the body
Vital differences between benign and malignant
• Benign (not cancer)
• Malignant (cancer)
There are four fundamental characteristics how benign and malignant
tumors are distinguished from one another: What are they?
• 1. Differentiation and anaplasia
• 2. Rate of growth
• 3. Local invasion
• 4. Metastasis
What is parenchyma?
What is Stroma?
Parenchyma - Functional tissue of an organ as distinguished from the connective and supporting
tissue
Stroma - Supportive tissue of an organ consisting of connective tissues and blood vessels
** look at written notes of benign tumors, malignant tumors, and ceoplasm characteristics (differentiation and anaplasia)
Anaplastic cells display what characteristics?
- Pleomorphism
• Variation in size and shape - Nuclei are extremely hyperchromatic (dark-staining), large, variable and
bizarre in size and shape - Fail to develop recognizable patterns of orientation to one another
*The more rapidly growing and the more anaplastic a tumor, the
less likely it is to have specialized functional activity
Dysplasia and Anaplasia
D- Alteration in size, shape, and organization of adult cells
A - Loss of differentiation of cells and of their orientation to one another
• An extremely advance form of dysplasia
*** Look at Rate of growth; local invasion; and metastasis on written notes
T or F
Benign tumors do not under metastasis
T
T or F
Malignant cells normally do not invade or infiltrate surrounding normal tissues
F
Locally invasive, infiltrating surrounding tissue; sometimes may be misleadingly cohesive and expansile
Leiomyoma is _____
Leiomyosarcoma is ______
Benign
Malignant
Both benign and malignant tumors can be deadly due to their ability to
metastasize.
• A. True • B. False
F
All of the options are true regarding tumors, except?
• A. Benign tumor cells commonly resemble normal cells in form and function
• B. Malignant tumors are encapsulated
• C. Both benign and malignant tumor cells are a result of DNA dysfunction
• D. Malignant tumors have the capability to metastasize
B
What is TRUE of malignant tumors?
• A. They are non-encapsulated
• B. Generally, their rate of growth is very fast and aggressive
• C. Can lead to development of hemorrhaging in the location of the tumor site
• D. All the options are true
D
Define epidemiology
The study (scientific, systematic, and data-driven) of the distribution (frequency, pattern)
and determinants (causes, risk factors) of health-related states and events (not just diseases) in specified populations (neighborhood, school, city, state, country, global).
• Contributes to the knowledge about the origin of cancer
How does the environmental variable of reproductive history increase risk of cancer?
Lifelong cumulative exposure to estrogen stimulation, particularly if unopposed by
progesterone, increases the risk of cancers of the breast and endometrium, tissues that are responsive to these hormones
What are carcinogens?
Any substance capable of causing cancer in living tissue
• Don’t freak out- but there are carcinogens all around you
Most cancers have environmental and genetic etiology
• Hereditary forms of cancer can be divided into three categories
based on their pattern of inheritance:
• 1. Autosomal Dominant Cancer
• Inheritance of a single mutant gene greatly increases the risk of developing a tumor
• 2. Autosomal Recessive Syndromes of Defective DNA Repair
• Predisposition to these tumors shows an autosomal recessive pattern of inheritance
• 3. Familial Cancers of Uncertain Inheritance
• Features that characterize familial cancers include early age at onset, tumors arising in
two or more close relatives of the index case, and sometimes multiple or bilateral tumors
Precancerous dentitions are referred to as what?
preneoplastic lesions or precancer
Condition or lesion that involves abnormal cells which have an
associated risk with developing cancer
(Ex: squamous metaplasia and dysplasia of the bronchial mucosa)
Death rates and cancer incidences of specific types of cancers can
vary from country to country.
• A. True • B. False
T
All of the statements are true regarding cancer, except?
• A. Carcinogens only pertain to environmental toxins
• B. Cancer incidence is normally higher within individuals 55+ years of age
• C. Cancers can be associated with obesity
• D. Preneoplastic lesions involve dysplastic tissue
A
T or F
If there is a DNA mutation non-lethal and or a epigenetic change to a regulatory gene, that is likely origin to lead to the development of cancer
T
What are the Four categories of regulatory genes that are extremely important in the development of cancer
• 1. Genes that promote cell growth ( Proto-Oncogenes)
• 2. Genes that inhibit growth ( Tumor Suppressor Genes)
• 3. Genes that regulate apoptosis
• 4. Genes that regulate DNA Repair
What are genes?
What do they code for?
What is the importance of the sequence of DNA?
What is the importance of a proteins shape?
Genes are a sequence of nucleic acids found on a strand of DNA.
They code for how to make a specific protien.
The sequence of nucleotides determines the sort of sequence of AA in the protien
The sequence of AA determines the proteins shape and that shape determines function
So, a change in DNA sequence process to change the shape of the protein and in this case the protein is dysfunctional or always in a state of being turned on or running.
How does the proto-oncogenes gene promote cell growth?
If we disrupt a protein in a tumor suppressor gene from a tumor suppressor gene?
It is always going to be stimulating that cell to go through cell growth from the background.
Tumor suppressor gene- We may los the ability to do the DNA repair or check to see if everything is good before proceeding.
Proto-Oncogenes: Growth Promoting
• Group of genes that produce proteins that regulate cell growth, division, differentiation
• Ras, HER2, Cyclin D • Mutations of proto-oncogenes are referred to as: ONCOGENES
Tumor Suppressor Genes: Growth Inhibiting
Group of genes that slow down cell division allow for DNA repair
• p53, Rb, p21, and BRCA1/BRCA2 (disruption in one of these genes can lead to that uncontrolled and unregulated cell growth)
• Mutated p53 genes have been identified in more than one-half of all human
tumor cells
Genetic Lesions
Damage to DNA can initiate tumor growth development
—Especially to the regulatory genes
• Causes changes in the protein synthesis
Epigenetics
Changes in the way genes are switched on and off without changing the actual DNA sequence (no mutations)
Two types: DNA Methylation and Histone Modifications
• These changes can affect a person’s risk of disease and may be passed from
parents to their children
The main role of tumor suppressor genes is to produce proteins that
regulate cell growth, division, and differentiation.
• A. True • B. False
F
All of the following options are true regarding carcinogenesis, except?
A. Epigenetics can influence regulatory gene expression
• B. Proto-oncogenes are mutated oncogenes that can lead to cancer
• C. G1 checkpoint determines if internal/external factors are present to allow for cell
replication
D. Normal cell cycle function is dependent upon proper kinase function
B
Tumor cells have the capability to evolve and become more aggressive.
• A. True
• B. False
T
What is epigenetic?
Altering the activity of DNA gene expression without changing the DNA sequence
What is Genotoxic?
Genotoxic
• Damage to the DNA changing the DNA sequence
What is a carcinogen?
Any cancer-producing substance; often a distinction is made between epigenetic
and genotoxic carcinogens
What causes changes to DNA? ()mutations in the DNA; Epigenetic changes)
Carcinogens
What are three classes of carcinogens?
Chemicals
Radiant energy
Microbial agent
Chemotherapeutic treatment is classified as a ________
Carcinogen
Microbial is associated with ___________
Viruses
What are the four types of oncogenic DNA viruses? Briefly describe each.
- Human Papillomavirus (HPV)
• Numerous strains of this virus- each having different effects on body
—Benign and Malignant tumors
— Some cause benign squamous papillomas (warts) tumors
— Others cause several cancers
— Squamous cell carcinoma of the cervix and anogenital region
— Sexual and physical contact is an ability to contract it - Epstein-Barr Virus (EBV)
• The first virus linked to a human tumor: Burkitt lymphoma
• Discovered with the cells of a surprisingly diverse list of cancers including various lymphomas (Hodgkin lymphoma), nasopharyngeal carcinoma, gastric carcinomas
*Causes infectious mononucleosis (mono)
• Spreads through direct contact from an infected person (bodily fluids) - Kaposi Sarcoma Herpesvirus (KSHV)
• Also known as human herpesvirus 8 (HHV8)
• Causes Kaposi sarcoma
• Cancer of the soft tissues of connective tissues
Associated with what condition? = immunodeficiency patients - Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV)
• Epidemiologic evidence linking chronic HBV and HCV infection with
hepatocellular carcinoma is strong
• Estimated that 70% to 85% of hepatocellular carcinomas worldwide are due to
infection with HBV or HCV
• Hepatitis B virus contraction occurs when blood, semen, or other body
fluid infected with the hepatitis B virus enters the body of someone who is
not infected
• Even a toothbrush- gross, don’t share your toothbrush • Hepatitis C virus contraction occurs with contact of infected blood
All of the following are classified as carcinogens, except?
• A. X-Ray exposure
• B. Chemotherapeutic treatments
• C. Human papillomavirus virus (HPV)
• D. Radiation therapy
• E. All of the options are a possible source of a carcinogen
E
This type of virus is associated with the development of liver cancer
development?
• A. Epstein-Barr Virus (EBV)
• B. Hepatitis viruses
• C. Kaposi sarcoma herpesvirus
• D. All of the above can lead to the development of liver cancer
B
T or F
Normal cells require stimulation by growth factors outside cell to start the stimulation of the proliferation process of the cell grpwth
T
Rb Protein Dysfunction
Abnormal Rb protein- always in activated state • ALWAYS ALLOWS CELL TO PROGRESS THROUGH
THE G1/S checkpoint
• Increase of cyclin-CDK complexes • Loss of CDKIs
• HPV binds to the hyperphosphorylated state of Rb • Preventing it it from inhibiting the E2F transcription
factors
TP53 Gene: Guardian of the Genome
Most commonly mutated gene in human cancers*** • Produces p53 protein
• Involved in regulation of cell cycle and apoptosis • The p53 protein prevents neoplastic transformation by three
interlocking mechanisms:
• Activation of temporary cell cycle arrest (termed quiescence)
• Induction of permanent cell cycle arrest (termed senescence)
• Triggering of programmed cell death (termed apoptosis)
• If Rb protein “senses” external signals, p53 can be viewed as a central
monitor of internal stress, directing the stressed cells toward one of
these three pathways
p53 Protein
• Activates DNA repair • Arrest growth by holding the cell cycle at the G1/S regulation point
on DNA damage recognition
• Gives cell time to repair itself • Initiate apoptosis
• Irreversible DNA damage • Initiate senescence
• Short telomeres, morphological changes
***look at written notes of hallmark characteristics of cancer
Angiogenesis is a pathway for metastasis.
• A. True
• B. False
A
The Warburg effect is when tumor cells utilize sugar to encourage
angiogenesis.
• A. True
• B. False
B
Process known as aerobic glycolysis or the Warburg effect (Cancer cells derive most of their energy from glycolysis Glucose is converted to lactate for energy followed by lactate fermentation, even when O2 is avaliable)
Tumor cells have antigens that our immune system recognize and build
an immune response against.
• A. True • B. False
A
What defines the normal function of RAS protein?
• A. It provides external stimulation of for cell proliferation
• B. Stimulates downstream signaling to stimulate the nucleus to proceed with cell proliferation
• C. It slows or even stops the cell cycle process to allow for DNA repair
• D. Receives internal cues to allow cell proliferation to continue
B
If p53 protein is mutated, how could it lead to cancer?
• A. It could allow the cell to progress through cell proliferation with DNA damage
• B. Allows cyclin dependent kinases to stay active and lead to cell proliferation
• C. Allows the cell to undergo cell proliferation without outside signals
• D. None of the options are accurate
A
What mutated protein is associated with the development of leukemias?
• A. RAS protein
• B. Rb protein
• C. p53 protein
• D. ABL
D
Three are three main categories for cancer diagnosis
• Laboratory Tests - Lab tests of your blood, urine, or other body fluids that measure these
substances can help doctors make a diagnosis
• Involve testing blood or tissue samples for tumor markers
• Tumor markers are substances that are produced by cancer cells or by other cells
of the body in response to cancer
• Prostate Specific Antigen (PSA) as an example
• Imaging Tests -
• CT Scan
• MRI
• Nuclear Scan
• Receive an injection of a small amount of radioactive material
• Bone Scan
• PET Scan (positron emission tomography)
• Makes detailed 3-D pictures of areas inside your body where glucose is taken up
• Cancer cells often take up more glucose than healthy cells
• Receive an injection of a tracer called radioactive glucose
• Ultrasound
• X-Rays
• Biopsy
-Pathologist looks at removed tissue under a microscope and runs
other tests to see if the tissue is cancer
• Describes the findings in a pathology report, which contains details about
your diagnosis
• May be obtained in several ways
• Needle
• Endoscopy
• Colonoscopy
• Bronchoscopy
• Surgery
Staging Of Cancer
• Based on the size of the primary lesion, its extent of spread to regional
lymph nodes, and the presence or absence of blood-borne metastases
• Uses a classification called the TNM system
• T for primary tumor, N for regional lymph node involvement, and M for metastases
Cancer is staged (Stage I – IV) and dependent upon:
• T = Tumor size/grade
• N = Node status
• M = Presence or absence of metastases
• G = Degree of differentiation
Staging I, II, III, IV
Grade: Microscopic/Histology - how anaplastic are they?
Grading and Staging of Cancer: Overview
Different cancers have different metastatic capabilities and
characteristics
• Important to have a system to grade and stage cancerous tumors
-Understand how serious your cancer is and your chances of survival
-Plan the best treatment for you -Identify clinical trials that may be treatment options for you
• Grading Cancer
—Based on the level of cellular differentiation
• Staging Cancer
— Extent of spread of cancer cells within the patient
—Has more clinical value than grading
New Formats of Treatment Include
• Immunotherapy
- Helps your immune system fight cancer
• Targeted Therapy
- Targets the changes in cancer cells that help them grow, divide, and spread
• Hormone Therapy
- Treatment that slows or stops the growth of breast and prostate cancers that use hormones to grow
• Stem Cell Therapy
- Procedures that restore blood-forming stem cells in cancer patients who have had theirs destroyed by very high doses of chemotherapy or radiation therapy
• Precision Medicine
- Helps doctors select treatments that are most likely to help patients based on a
genetic understanding of their disease
Benign and Malignant Tumors Can Have Serious Impacts
• 1. Location and impingement on adjacent structures
• 2. Functional activity such as hormone synthesis or the development of
paraneoplastic syndromes
• 3. Bleeding and infections when the tumor ulcerates through adjacent
surfaces
• 4. Symptoms that result from rupture or infarction
• 5. Cachexia or wasting
Cancer Cachexia
Progressive loss of body fat and lean body mass
• Accompanied by profound weakness, anorexia, and anemia
• Current evidence indicates that cachexia results from the action of
soluble factors such as cytokines produced by the tumor and the
host, rather than reduced food intake
Paraneoplastic Syndromes (NBCE loves this)
“Paraneoplastic syndromes are a group of rare disorders that are
triggered by an abnormal immune system response to a cancerous
tumor known as a “neoplasm.” Paraneoplastic syndromes are
thought to happen when cancer-fighting antibodies or white blood cells (known as T cells) mistakenly attack normal cells in the nervous
system.”
** Basically- Antibodies and cytotoxic T cells created for the tumor
attack the body’s own cells
Most Common Paraneoplastic Syndromes Are (NBCE loves this)
• Hypercalcemia
• Cushing syndrome
• Nonbacterial thrombotic endocarditis
Common Type of Cancers That Lead to Paraneoplastic Syndromes (NBCE loves this)
- Lung Cancers
• Breast cancers
• Lymphomas and leukemias
Imaging scans are used to identify tumor markers.
• A. True
• B. False
B
Biopsies can be obtained through several different mechanisms.
• A. True
• B. False
A
All of the options are true regarding staging of cancer, except?
• A. It is has more clinical importance compared to grading cancer
• B. Partially depends on the extend of spreading to regional lymph nodes
• C. Focuses strictly on level of cellular differentiation
• D. Partially depends on presence of metastasis
• E. Partially depends on the level of cellular differentiation
C
Chemotherapy treatment can lead to the development of cancer.
• A. True
• B. False
T
Benign and malignant tumors can cause damage in the area of growth.
• A. True
• B. False
T
All of the following are true regarding paraneoplastic syndromes, except?
• A. Caused by the body’s own immune system attacking its own cells
• B. Cushing’s syndrome is a common paraneoplastic syndrome
• C. Commonly associated with bone cancers
• D. Can lead to a whole array of symptoms including difficulty walking and other fine
motor control
C
Carcinogenesis involves an abnormal function of gene expression.
False.
True.
T
Epigenetic changes cause certain genes to be expressed more or less leading to the development of cancer.
False.
True
T
All of the options are true regarding malignant tumors, except?
A. Malignant tumors are not encapsulated.
B. Malignant tumors can metastasize.
C. Benign and malignant tumors cells commonly experience the same level of cellular differentiation.
D. The development of cancer can be influenced by your geographical location you live in
C
All of the following options are true regarding paraneoplastic syndromes, except?
A. Commonly associated with bone cancers.
B. Caused by the body?s own immune system attacking its own cells.
C. Can lead to a whole array of symptoms including difficulty walking and other fine motor control.
D. Cushings syndrome is a common syndrome.
A
An individual with TP53 gene mutation (p53 protein) could experience uncontrolled tumor growth due to:
A. All of the options could occur with a TP53 gene mutation.
B. Inactivation of DNA repair.
C. Inability of committing cells to cell cycle arrest (senescence).
D. Inability to induce apoptosis.
A
What statement is correct regarding carcinogens?
A. They can lead to either mutations or epigenetic changes in the DNA.
B. Carcinogens are derived from only exogenous (outside) sources.
C. Carcinogens affecting non-regulatory genes will lead to cancer.
D. Bacteria carcinogens are more common than viral carcinogens.
A
An individual with a Rb gene mutation could experience uncontrolled tumor growth due to:
A. By inhibiting DNA repair to occur.
B. By blocking the cell from undergoing apoptosis..
C. Providing the cell with a consistent signal to the nucleus to proceed with cell proliferation.
D. Loss of regulation of the G1/S checkpoint.
D
All of the options are true regarding tumors, except?
A. Both malignant and benign growths will have undergone a level of dysplasia.
B. Sarcomas are tumors that are derived from epithelial tissue.
C. Both malignant and benign growths are classified as tumors.
D. Only malignant tumors will invade local tissues in the area of growth
B
All of the options are associated with a possible clinical impact of tumor growth, except?
A. Disruption of hormonal production.
B. Spinal nerve impingement.
C. Abnormal reaction of immune system to attack its own cells.
D. Decreased blood vessel formation in the area of tumor growth
D
Malignant and benign tumors cause hemorrhaging in the area of tumor growth causing complications.
False.
True
F
Why are corticosteroids used so frequently with autoimmune diseases?
Corticosteroids work to reduce inflammation because they work to block phospholipase which leads to the ability to creat araco acid. But it will decrease the function of the immune system = in this case, the autoimmune disease is less severe.
