General Principles Week 7 Flashcards
Topic 1: Basic Components of the Immune System
TLO 1.1: List the main characteristics of the innate and adaptive immune systems
- Innate Immunity:
o Speed of Response: Immediate (minutes to hours) upon infection.
o Specificity: Recognizes broad pathogen-associated molecular patterns (PAMPs); not highly specific to a single epitope.
o Memory: No immunologic memory; repeated exposures to the same pathogen do not generally enhance the response.
o Primary Components:
* Physical barriers: Skin, mucosal membranes.
* Cellular components: Neutrophils, macrophages, dendritic cells (DCs), natural killer (NK) cells, mast cells, eosinophils.
* Soluble factors: Complement proteins, cytokines, acute-phase proteins.
o Function: Provides an immediate line of defense; activates and shapes the adaptive immune system.
Topic 1: Basic Components of the Immune System
TLO 1.1: List the main characteristics of the innate and adaptive immune systems
- Adaptive Immunity:
o Speed of Response: Slower on first exposure (days to weeks), but quicker on subsequent exposures.
o Specificity: Highly specific to individual antigens and epitopes.
o Memory: Long-lasting immunologic memory ensures faster and more robust responses on re-exposure.
o Primary Components:
* Cellular components: B and T lymphocytes (Helper T cells, Cytotoxic T cells, Regulatory T cells).
* Humoral components: Antibodies (immunoglobulins).
o Function: Eliminates or neutralizes specific pathogens, provides long-term protection.
TLO 1.2: Contrast the differences between passive and active immunity, using examples
- Active Immunity:
o Definition: Immunity generated by the individual’s own immune system in response to exposure to an antigen.
o Mechanism: Involves B-cell and T-cell activation, clonal expansion, and formation of memory cells.
o Duration: Often long-lasting (years to lifelong).
o Examples:
* Natural: Infection with a pathogen (e.g., recovery from measles confers immunity).
* Artificial: Vaccination (e.g., administration of an inactivated or attenuated pathogen).
TLO 1.2: Contrast the differences between passive and active immunity, using examples
- Passive Immunity:
o Definition: Immunity conferred by transferring antibodies or immune cells from an immune individual to a non-immune individual.
o Mechanism: Does not require the recipient’s immune system to mount its own response; relies on exogenous antibodies/cells.
o Duration: Temporary; protection wanes as transferred antibodies degrade (weeks to a few months).
o Examples:
* Natural: Maternal IgG crossing the placenta or IgA in breast milk.
* Artificial: Administration of intravenous immunoglobulins (IVIG) or monoclonal antibodies.
TLO 1.3: Compare the primary and the secondary immune response to an antigen
- Primary Immune Response:
o Exposure: Occurs upon the first contact with a particular antigen.
o Lag Phase: Longer delay before a detectable immune response (often 5–7 days or more).
o Peak Response: Generally lower magnitude of antibody titer and effector cell function.
o Isotypes: Initial antibody is typically IgM, followed by class switching to other isotypes (IgG, IgA, etc.).
o Memory: Priming of memory B and T cells occurs.
TLO 1.3: Compare the primary and the secondary immune response to an antigen
- Secondary (or Anamnestic) Immune Response:
o Exposure: Occurs upon subsequent contacts with the same antigen.
o Lag Phase: Much shorter due to presence of memory cells.
o Peak Response: Higher and more rapid production of antibodies (often dominated by IgG, especially in serum).
o Higher Affinity: Antibodies have undergone affinity maturation, leading to stronger binding and greater efficacy.
o Clinical Relevance: Underpins the principle of booster vaccinations.
TLO 1.4: List several important morphologic features and functional activities of cells involved in the innate and adaptive immune response: B and T lymphocytes, natural killer cells, neutrophils, mast cells, eosinophils, monocytes, macrophages, and dendritic cells
- B Lymphocytes:
- B Lymphocytes:
o Morphology: Small lymphocytes with large nucleus, sparse cytoplasm; have surface immunoglobulin (B-cell receptor).
o Function: Produce antibodies, present antigen to helper T cells, differentiate into plasma cells (antibody-secreting) and memory B cells
TLO 1.4: List several important morphologic features and functional activities of cells involved in the innate and adaptive immune response: B and T lymphocytes, natural killer cells, neutrophils, mast cells, eosinophils, monocytes, macrophages, and dendritic cells
- T Lymphocytes (T cells):
- T Lymphocytes (T cells):
o Morphology: Similar to B cells in appearance but with T-cell receptors (TCRs).
o Subsets:
* Helper T Cells (CD4⁺): Coordinate immune response via cytokine secretion.
* Cytotoxic T Cells (CD8⁺): Kill virus-infected or tumor cells.
* Regulatory T Cells: Modulate and suppress excessive immune responses to maintain tolerance.
TLO 1.4: List several important morphologic features and functional activities of cells involved in the innate and adaptive immune response: B and T lymphocytes, natural killer cells, neutrophils, mast cells, eosinophils, monocytes, macrophages, and dendritic cells
- Natural Killer (NK) Cells:
- Natural Killer (NK) Cells:
o Morphology: Larger granular lymphocytes with cytotoxic granules.
o Function: Kill virus-infected cells and tumor cells without prior sensitization; recognize “missing-self” (lack of MHC I) or stressed cells.
TLO 1.4: List several important morphologic features and functional activities of cells involved in the innate and adaptive immune response: B and T lymphocytes, natural killer cells, neutrophils, mast cells, eosinophils, monocytes, macrophages, and dendritic cells
Neutrophils
- Neutrophils:
o Morphology: Granulocytes with multilobed nucleus and abundant cytoplasmic granules.
o Function: First responders to acute bacterial infection; phagocytic; release reactive oxygen species and granule enzymes to kill pathogens.
TLO 1.4: List several important morphologic features and functional activities of cells involved in the innate and adaptive immune response: B and T lymphocytes, natural killer cells, neutrophils, mast cells, eosinophils, monocytes, macrophages, and dendritic cells
- Mast Cells:
- Mast Cells:
o Morphology: Tissue-resident cells with abundant granules containing histamine and other mediators.
o Function: Crucial in allergic reactions (Type I hypersensitivity); degranulation triggered by cross-linking of surface-bound IgE.
TLO 1.4: List several important morphologic features and functional activities of cells involved in the innate and adaptive immune response: B and T lymphocytes, natural killer cells, neutrophils, mast cells, eosinophils, monocytes, macrophages, and dendritic cells
Monocytes
- Monocytes:
o Morphology: Large leukocytes in circulation with kidney-shaped nucleus.
o Function: Differentiate into macrophages or dendritic cells upon entering tissues; phagocytic and cytokine-producing.
TLO 1.4: List several important morphologic features and functional activities of cells involved in the innate and adaptive immune response: B and T lymphocytes, natural killer cells, neutrophils, mast cells, eosinophils, monocytes, macrophages, and dendritic cells
Macrophages
- Macrophages:
o Morphology: Tissue-resident phagocytes derived from monocytes; have pseudopods and large vacuoles.
o Function: Phagocytosis and digestion of pathogens, antigen presentation to T cells, release of inflammatory cytokines.
TLO 1.4: List several important morphologic features and functional activities of cells involved in the innate and adaptive immune response: B and T lymphocytes, natural killer cells, neutrophils, mast cells, eosinophils, monocytes, macrophages, and dendritic cells
- Dendritic Cells (DCs):
- Dendritic Cells (DCs):
o Morphology: “Stellate” cells with dendritic processes; found in tissues interfacing with the external environment.
o Function: Professional antigen-presenting cells (APCs); capture antigen in periphery and migrate to lymph nodes to activate T cells.
Topic 2: Antigen and Antibody
TLO 2.1: List the origins of antigens to which the immune system may respond
1. Exogenous Antigens
- Endogenous Antigens
- Autoantigens
- Alloantigens
- Xenoantigens
- Exogenous Antigens: Enter the body from outside (bacteria, viruses, fungi, allergens, toxins).
- Endogenous Antigens: Generated within cells due to infection (intracellular pathogens) or abnormal cellular proteins (tumor antigens).
- Autoantigens: The body’s own molecules that can trigger autoimmunity under certain conditions.
- Alloantigens: Antigens from other members of the same species (e.g., blood group antigens, transplanted organ antigens).
- Xenoantigens: Antigens from different species (e.g., pig heart valves in xenotransplantation).
TLO 2.2: Name the structural features and biologic properties of the different immunoglobulin classes
1. IgG:
2. IgA:
3. IgM:
4. IgE:
5. IgD:
- IgG:
o Structure: Monomer; four subclasses (IgG1–IgG4).
o Properties: Crosses the placenta (maternal-fetal immunity), opsonization, complement activation, neutralization of toxins/viruses. - IgM:
o Structure: Pentamer (5 monomers linked by J chain).
o Properties: First antibody produced during primary response; highly efficient in complement activation and agglutination. - IgA:
o Structure: Monomer in serum; dimer in secretions (linked by J chain and secretory component).
o Properties: Found in mucosal areas (GI tract, respiratory tract), breast milk; protects mucosal surfaces by neutralizing pathogens. - IgE:
o Structure: Monomer.
o Properties: Binds to mast cells and basophils; involved in Type I hypersensitivity and defense against parasites. - IgD:
o Structure: Monomer.
o Properties: Primarily membrane-bound on naive B cells; role in B-cell activation is less well-defined compared to other isotypes.
What cells produce IL-10 to induce peripheral tolerance of T and B cells? (Single choice)
Th1
Th2
CTLs
Treg
NK
I don’t know
Treg
TLO 2.3: Describe a range of diagnostic tests based on antigen-antibody interaction, indicating the general principle of each test
- ELISA (Enzyme-Linked Immunosorbent Assay):
- Western Blot:
- Immunofluorescence (Direct and Indirect):
- Flow Cytometry:
- Agglutination Tests (Latex Agglutination, Hemagglutination):
- ELISA (Enzyme-Linked Immunosorbent Assay):
o Principle: Detects antigen or antibody via enzyme-labeled secondary antibody and a colorimetric reaction.
o Applications: Quantification of hormones, antibodies (e.g., HIV test), detection of specific proteins in serum. - Western Blot:
o Principle: Proteins separated by electrophoresis, transferred to a membrane, and probed with specific antibodies; visualization by enzyme or chemiluminescence.
o Applications: Confirmatory test for HIV, detection of specific protein expression. - Immunofluorescence (Direct and Indirect):
o Principle: Fluorescently labeled antibodies bind to specific antigens in tissues or cells and are visualized under a fluorescence microscope.
o Applications: Autoantibody detection (e.g., in lupus), viral antigen detection, research staining. - Flow Cytometry:
o Principle: Cells are tagged with fluorescent antibodies to cell-surface or intracellular antigens, then passed through a laser beam for analysis of fluorescence.
o Applications: Immunophenotyping (CD4 counts in HIV), identification of abnormal cell populations in leukemia/lymphoma. - Agglutination Tests (Latex Agglutination, Hemagglutination):
o Principle: Visible clumping occurs when particulate antigen binds to specific antibodies.
Antibodies
Antibodies
Attach to antigens → Antibody-antigen complex
Attach to toxins (antigens) → Neutralise toxins
Attach to receptors → Disrupt the function
Attach to pathogens → Clump together → “Agglutination”
Act as opsonins → Present to phagocytes
Antibody-dependent cell-mediated cytotoxicityAttach to antigens → Antibody-antigen complex
Attach to toxins (antigens) → Neutralise toxins
Attach to receptors → Disrupt the function
Attach to pathogens → Clump together → “Agglutination”
Act as opsonins → Present to phagocytes
Antibody-dependent cell-mediated cytotoxicity
TLO 2.4: Explain the terms monoclonal antibodies (mAbs), hybridoma, fully human, humanized, and chimeric
Monoclonal Antibodies (mAbs) Antibodies produced by a single clone of cells, designed to target a specific antigen with high specificity and uniformity.
Hybridoma A cell line created by fusing an antibody-producing B cell with a myeloma (cancer) cell, allowing for the continuous production of monoclonal antibodies.
Fully Human Antibodies made entirely from human genetic material, reducing the risk of immune reactions when used in humans.
Humanized Antibodies that are mostly human, but contain small parts derived from non-human sources (e.g., mouse), engineered to reduce immune reactions.
Chimeric Antibodies that are part human and part non-human (e.g., mouse), with the variable regions from the non-human source and constant regions from humans.
1. Monoclonal Antibodies (mAbs): o Definition: Uniform antibodies derived from a single B-cell clone, each recognizing the same epitope. o Advantages: High specificity, consistent batch-to-batch reactivity. 2. Hybridoma: o Definition: A cell line produced by the fusion of an antibody-producing B lymphocyte with a myeloma cell, creating an immortalized cell line that secretes monoclonal antibodies. 3. Fully Human Antibodies: o Definition: Antibodies with both variable and constant regions derived entirely from human immunoglobulin sequences (generated via transgenic mice or phage display). 4. Humanized Antibodies: o Definition: Mostly human antibody framework with complementarity-determining regions (CDRs) from a non-human (e.g., mouse) source. 5. Chimeric Antibodies: o Definition: Antibodies where the variable regions (heavy and light) are from one species (often mouse) and the constant region from another (human).
TLO 2.5: List several examples of mAbs application in clinical medicine
- Cancer Therapy:
- Autoimmune Diseases:
- Transplant Rejection Prevention:
- Infectious Diseases:
- Cancer Therapy:
o Rituximab (anti-CD20) for certain B-cell malignancies (e.g., non-Hodgkin lymphoma).
o Trastuzumab (anti-HER2) for HER2-positive breast cancer. - Autoimmune Diseases:
o Infliximab (anti-TNF-α) for rheumatoid arthritis, Crohn’s disease.
o Natalizumab (anti-integrin) for multiple sclerosis. - Transplant Rejection Prevention:
o Basiliximab (anti-IL-2 receptor) used to prevent acute rejection. - Infectious Diseases:
o Palivizumab (anti-RSV F protein) for high-risk infants against respiratory syncytial virus.
Topic 3: Antigen Presentation and Recognition; Cytokines
TLO 3.1: Describe the main structural features of the class I and class II MHC gene products
- Class I MHC (HLA-A, -B, -C in humans):
- Class II MHC (HLA-DP, -DQ, -DR in humans):
Topic 3: Antigen Presentation and Recognition; Cytokines
TLO 3.1: Describe the main structural features of the class I and class II MHC gene products
1. Class I MHC (HLA-A, -B, -C in humans):
o Structure: Consists of a heavy α chain (three domains: α1, α2, α3) non-covalently associated with β2-microglobulin.
o Peptide-Binding Groove: Formed by α1 and α2 domains.
o Expression: All nucleated cells (and platelets).
o Presentation: Presents endogenous (intracellular) peptides to CD8⁺ T cells.
2. Class II MHC (HLA-DP, -DQ, -DR in humans):
o Structure: Composed of two chains (α and β), each with two domains (α1, α2 and β1, β2).
o Peptide-Binding Groove: Formed by α1 and β1 domains.
o Expression: Primarily on professional antigen-presenting cells (APCs) like dendritic cells, macrophages, B cells.
o Presentation: Presents exogenous (extracellular) peptides to CD4⁺ T cells.
TLO 3.2: Explain the genetic basis of MHC polymorphism and polygeny, and their significance for the functioning of the immune system
- Polymorphism:
pathogens.
2. Polygeny:
- Significance:
TLO 3.2: Explain the genetic basis of MHC polymorphism and polygeny, and their significance for the functioning of the immune system
1. Polymorphism:
o Definition: Multiple variants (alleles) of each MHC gene in a population.
o Result: Increases the range of peptides that can be presented by the population as a whole; enhances survival against diverse pathogens.
2. Polygeny:
o Definition: Multiple MHC genes encoding different class I and class II molecules in each individual (e.g., HLA-A, -B, -C for class I and HLA-DP, -DQ, -DR for class II).
o Result: Each individual co-expresses several MHC molecules, broadening peptide presentation.
3. Significance:
o Immune Defense: High MHC diversity makes it less likely that a single pathogen can evade the entire human population.
o Transplantation: MHC polymorphisms contribute to graft rejection.
TLO 3.3: Describe the concept of MHC restriction
The principle that T cells recognize antigens only when they are presented by the host’s own MHC molecules.
- Definition: T cells recognize antigenic peptides only when presented on self-MHC molecules.
- CD8⁺ T cells: Require peptide presented on class I MHC of the host.
- CD4⁺ T cells: Require peptide presented on class II MHC of the host.
- Clinical Implication: T cells generally do not respond to peptide antigens presented by non-self MHC, complicating allograft acceptance.