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Which factor does NOT contribute to a healthy immune system?
Which factor does NOT contribute to a healthy immune system?
Antigenic drift and antigenic shift are types of immune evasion strategies employed by pathogens.
Antigenic drift and antigenic shift are types of immune evasion strategies employed by pathogens.
True (A)
What is the term for the state in which viruses are not replicating but can be reactivated?
What is the term for the state in which viruses are not replicating but can be reactivated?
latency
Immunodeficiency disorders make individuals more susceptible to __________.
Immunodeficiency disorders make individuals more susceptible to __________.
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Match the following immune system conditions with their definitions:
Match the following immune system conditions with their definitions:
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Which of the following is an example of an autoimmune disease?
Which of the following is an example of an autoimmune disease?
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Regular exercise can reduce the risk of infections.
Regular exercise can reduce the risk of infections.
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List one example of a primary immunodeficiency disorder.
List one example of a primary immunodeficiency disorder.
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Which of the following is a characteristic of allergies?
Which of the following is a characteristic of allergies?
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Primary immunodeficiencies can be caused by environmental factors.
Primary immunodeficiencies can be caused by environmental factors.
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What percentage of individuals living with a primary immunodeficiency are estimated to be undiagnosed?
What percentage of individuals living with a primary immunodeficiency are estimated to be undiagnosed?
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The most common B-cell disorder is __________.
The most common B-cell disorder is __________.
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Which of the following is a common T-cell disorder?
Which of the following is a common T-cell disorder?
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Match the type of immunodeficiency with its classification:
Match the type of immunodeficiency with its classification:
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Secondary immunodeficiencies are characterized by inherited genetic mutations.
Secondary immunodeficiencies are characterized by inherited genetic mutations.
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How are primary immunodeficiencies classified?
How are primary immunodeficiencies classified?
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What is the main antibody involved in the destruction of cells during Type II hypersensitivity reactions?
What is the main antibody involved in the destruction of cells during Type II hypersensitivity reactions?
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Exogenous antigens are derived from the body's own substances or cells.
Exogenous antigens are derived from the body's own substances or cells.
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What type of immune cells are NK cells classified as?
What type of immune cells are NK cells classified as?
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Type III hypersensitivity reactions may result from the accumulation of ____________ complexes.
Type III hypersensitivity reactions may result from the accumulation of ____________ complexes.
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Match the following mechanisms with their descriptions:
Match the following mechanisms with their descriptions:
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Which of the following is an example of a Type III hypersensitivity reaction?
Which of the following is an example of a Type III hypersensitivity reaction?
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In Type II hypersensitivity, antibodies bind to intrinsic antigens found in the body.
In Type II hypersensitivity, antibodies bind to intrinsic antigens found in the body.
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What triggers an Arthus reaction in sensitized individuals?
What triggers an Arthus reaction in sensitized individuals?
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What is the primary immunodeficiency characterized by a failure to produce T-cell dependent antibody responses?
What is the primary immunodeficiency characterized by a failure to produce T-cell dependent antibody responses?
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DiGeorge's syndrome is caused by an absence of the thymus and parathyroid glands.
DiGeorge's syndrome is caused by an absence of the thymus and parathyroid glands.
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What is the most common cause of X-linked SCID?
What is the most common cause of X-linked SCID?
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In Wiskott-Aldrich syndrome, affected males have ___________ and severe eczema.
In Wiskott-Aldrich syndrome, affected males have ___________ and severe eczema.
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Match the immunodeficiency syndrome with its primary characteristic:
Match the immunodeficiency syndrome with its primary characteristic:
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Which condition involves a defect in phagocytic cells and is characterized by skin infections?
Which condition involves a defect in phagocytic cells and is characterized by skin infections?
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Complement deficiencies account for more than 15% of primary immunodeficiencies.
Complement deficiencies account for more than 15% of primary immunodeficiencies.
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What is the optimal treatment for infants with Severe combined immunodeficiency (SCID)?
What is the optimal treatment for infants with Severe combined immunodeficiency (SCID)?
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Which type of hypersensitivity reaction is immediately mediated by IgE antibodies?
Which type of hypersensitivity reaction is immediately mediated by IgE antibodies?
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C1 inhibitor deficiency is classified as an autosomal recessive disorder.
C1 inhibitor deficiency is classified as an autosomal recessive disorder.
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What serious consequence can result from impaired clearance of antigen-antibody complexes?
What serious consequence can result from impaired clearance of antigen-antibody complexes?
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A deficiency in a complement regulatory protein causes __________.
A deficiency in a complement regulatory protein causes __________.
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Which of the following is NOT a secondary immunodeficiency cause?
Which of the following is NOT a secondary immunodeficiency cause?
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Mast cell activation can cause symptoms ranging from urticaria to anaphylaxis.
Mast cell activation can cause symptoms ranging from urticaria to anaphylaxis.
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What are the additional components involved specifically in the alternate pathway of the complement system?
What are the additional components involved specifically in the alternate pathway of the complement system?
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Match the following hypersensitivity types with their characteristics:
Match the following hypersensitivity types with their characteristics:
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The most extreme case of immune suppression is acquried immune deficiency syndrome (AIDS) caused by __________.
The most extreme case of immune suppression is acquried immune deficiency syndrome (AIDS) caused by __________.
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Which syndrome is characterized by aggressive Kaposi’s sarcoma or B-cell lymphoma?
Which syndrome is characterized by aggressive Kaposi’s sarcoma or B-cell lymphoma?
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Study Notes
Immune System in Health and Disease
- The immune system defends against infections, removes damaged cells, and maintains overall well-being
- Key factors for a healthy immune system include balanced nutrition (rich in vitamins, minerals, and antioxidants), adequate sleep (to recharge and repair), regular exercise (boosts system and reduces infections), and stress management (chronic stress weakens the immune system)
Lecture 23 Contents
- Evasion of the immune system
- Immunodeficiencies
- Hypersensitivities
Evasion of the Immune Defenses
- Pathogens escape immunity via antigenic variation
- Three main forms of antigenic variation:
- Many pathogens exist in various antigenic types
- Antigenic drift/shift: minor antigenic changes/sudden emergence of new pathogen subtypes through genetic reassortment, leading to substantial antigenic differences.
- Programmed gene rearrangements
Streptococcus pneumoniae
- Streptococcus pneumoniae differ in the structure of their polysaccharide capsules
- Numerous types of S. pneumoniae exist, differing in capsular polysaccharides
- Initial infection with one type of S. pneumoniae results in a response that clears the infection, but subsequent infection with a different type is unaffected by the initial response.
Persistence and Reactivation of Infection
- Some viruses enter a latency stage, where they aren't actively replicating.
- Latent infections (e.g., herpesviruses like cold sores and shingles) can reactivate.
Immune System in Disease
- Immunodeficiency Disorders: Weakened immune system, increased susceptibility to infections (e.g., HIV/AIDS, primary immunodeficiencies).
- Autoimmune Diseases: Immune system mistakenly attacks the body's own tissues and cells (e.g., rheumatoid, arthritis, lupus, and type 1 diabetes).
- Allergies: Overactive immune response to harmless substances (e.g. sneezing, itching, inflammation).
- Cancer: Some cancers evade immune system surveillance, allowing uncontrolled growth and spread.
Immunodeficiency Diseases
- Primary immunodeficiencies: Caused by inherited mutations in genes controlling immune responses, highly variable clinical features, overwhelming infections in young children.
- Secondary immunodeficiencies: Acquired as a consequence of other diseases or environmental factors (e.g., starvation, medical intervention).
Humoral Immunity Deficiencies
- B-cell defects causing antibody deficiencies account for a significant portion of primary immunodeficiencies
- Serum antibody titers decrease, increasing susceptibility to bacterial infections
- Selective IgA deficiency is the most common B-cell disorder.
Cellular Immunity Deficiencies
- T-cell defects account for a smaller percentage of primary immunodeficiencies, predisposing individuals to infections by various pathogens.
- T-cell disorders also commonly cause immunoglobulins deficiencies due to their interdependent nature.
- DiGeorge syndrome, Zeta-associated protein 70 (ZAP-70) deficiency, X-linked lymphoproliferative syndrome, Chronic mucocutaneous candidiasis are among the most common T-cell disorders.
DiGeorge Syndrome
- Thymic epithelium fails to develop normally, resulting in the inability of T-cells to mature.
- Cell-mediated immunity and T-cell-dependent antibody production are affected.
- Normal serum immunoglobulin levels are often present but incomplete development of thymus and parathyroids, resulting in T-cell immunodeficiency.
Combined Humoral and Cellular Immunity Deficiencies
- B- and T-cell defects account for about 20% of primary immunodeficiencies
- Severe combined immunodeficiency (SCID) is the most important form
- In some combined immunodeficiency forms, immunoglobulin levels are normal or elevated but antibody formation is impaired due to inadequate T-cell function.
Severe Combined Immunodeficiency (SCID)
- Infants making neither T-cell dependent antibody responses nor cell-mediated immune responses
- X-linked SCID often more common, caused by mutations in the IL2RG gene (common gamma chain).
- Infants frequently exhibit prolonged diarrhea, pneumonia, and have a very low lymphocyte count in their blood
- Treatment is primarily bone-marrow transplant from a histocompatible donor (e.g., a normal sibling).
Wiscott-Aldrich Syndrome
- X-linked immunodeficiency disease
- Characterized by small/abnormal platelets (thrombocytopenia), severe eczema, and opportunistic infections
- Serum contains increased IgA and IgE with decreased IgM levels
- Defective T-cells' function worsening cell-mediated immunity.
Phagocytic Cell Defects
- Phagocytic cell defects involve dysfunction in monocytes, macrophages, granulocytes (like neutrophils and eosinophils) impairing their ability to kill pathogens, particularly those leading to staphylococcal or gram-negative infections.
- Chronic granulomatous disease, leukocyte adhesion deficiency types 1 & 2, cyclical neutropenia are some common (though still rare) phagocytic cell defects.
Complement Deficiencies
- Rare deficiencies in complement (≤2%) include hereditary or acquired deficiencies in components, leading to defective opsonization, phagocytosis, and pathogen clearance.
- Results in increased susceptibility to infections and autoimmune issues (e.g., SLE and glomerulonephritis).
- Deficiencies in complement regulatory proteins can cause hereditary angioedema.
Secondary Immunodeficiencies
- Very common in medical practice
- Malnutrition (e.g., measles) is a major factor, inducing immunosuppression
- Tumors (e.g., leukemia, lymphoma, metastasis from other cancers) can contribute by creating an environment that promotes opportunistic infection.
- Cytotoxic drugs used in cancer treatment often cause a side effect of secondary immunodeficiency.
Acquired Immunodeficiency Syndrome (AIDS)
- A severe immune suppression resulting from HIV infection
- HIV infection causes a gradual loss of immune competence.
- Characterized by an increased susceptibility to opportunistic infections . (Examples include pulmonary conditions like Pneumocystis pneumonia and tuberculosis, tumors, and gastrointestinal infections).
Hypersensitivity (Allergies)
- Type I: Immediate-type allergic reactions triggered by IgE antibodies. (e.g., allergies to food, pollen, house dust).
- Other Types: Involve IgG and other immune system components (e.g., serum sickness, allergic contact dermatitis, and celiac disease).
Type I Hypersensitivity Reactions
- IgE-mediated, causing mast cell degranulation.
- Binding of antigens to IgE receptors triggers mediator release.
- IgE secreted by plasma cells binds to FcεRI on mast cells.
- Activated mast cells provide signals to B cells, stimulating IgE production
Factors Contributing to IgE-Mediated Allergic Disease
- Genetic: Asthma susceptibility genes regulating immune response and TH2 cell differentiation
- Environmental: Changes in exposure to infectious diseases in early childhood. Exposure to other children, changes in diet, allergen exposure, atmospheric pollution, and tobacco smoke.
Effects of Mast Cell Activation
- Mast cell activation induces inflammatory responses by releasing mediators.
- Cytokines and chemokines are also released following activation.
- Symptoms vary (e.g., swollen eyes, rhinitis, conjunctivitis) to more severe cases.
Treatments for Allergic Disease
- In clinical use: Antihistamines, β-blockers, lipoxygenease inhibitors, Corticosteroids, desensitization therapy, Anti-IgE antibodies.
- Under investigation: Injection of specific antigen peptides, Administration of cytokines like IFN-γ, IL-10, IL-12, TGF-β and adjuvants like CpG oligonucleotides; inhibition of CD40L, IL-4, or IL-13. Blocking IgE receptors and their related cytokines
Allergen Introduction into Bloodstream Leading to Anaphylaxis
- Allergens in bloodstream cause anaphylaxis—a severe allergic reaction
- Can cause symptoms such as urticaria to potentially fatal anaphylactic shock.
- Characterized by increased permeability, loss of blood pressure, airways constriction, difficulty breathing, and potentially swelling of the epiglottis.
- Usually controlled with epinephrine.
Type II and Type III Hypersensitivity Reactions
- Hypersensitivity responses involving IgG antibodies.
- Type II involves antigens on cell surfaces (e.g., hemolytic anemia).
- Type III involves immune complex deposition in tissues (e.g., serum sickness).
Type II Hypersensitivity Reactions
- Target is fixed in tissues or on cell surfaces
- Mediated by IgG binding to specific cells/tissues
- Antigens: Can be exogenous (e.g., microbes, drugs) or intrinsic (e.g., self-antigens in autoimmune diseases).
- Effector cells: Macrophages, neutrophils, eosinophils, and NK cells.
- Mechanism: Complement activation and antibody-dependent cellular cytotoxicity (ADCC), opsonization and phagocytosis
Type III Hypersensitivity Reactions
- Characterized by accumulation of antigen-antibody complexes.
- Inflammatory response ensues
- Complexes deposited in tissues
- Activation of complement leads to recruitment of macrophages and neutrophils
Type IV Hypersensitivity Reactions (Delayed-Type Hypersensitivity)
- Mediated by antigen-specific effector T-cells (e.g., TH1).
- Antigen injected into tissues, processed by APC's.
- TH1 effector cell recognizes antigen and releases cytokines.
- Cytokines influence vascular endothelium, recruiting phagocytes and causing visible lesions
- Takes hours to days to develop
Mantoux Tuberculin Test
- Used for diagnosis of tuberculosis infection
- Intradermal injection of tuberculin triggers T-cell-mediated immune response
- Swelling size (erythema) measured over time.
Celiac Disease
- Chronic condition of the upper small intestine due to immune response against gluten
- Pathology: loss of intestinal villi and inflammation.
- Autoimmune features: Presence of autoantibodies (e.g., IgA against tissue transglutaminase)
Further Study
- Continue exploring Autoimmunity (a follow-up session based on the presentation) for more detailed information.
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Description
Test your knowledge on the immune system with this quiz. Explore concepts like immunodeficiency disorders, autoimmune diseases, and immune evasion strategies. Understand various factors that contribute to a healthy immune response and the consequences of primary and secondary immunodeficiencies.
