Immunology Quiz 1 PDF

Immunology quiz 1 Introduction to the immune system – Dr. S Crish - Describe what the immune system is and what its functions are, distinguished between types o What the immune system is and what its functions are § Protect against foreign invaders (e.g. path...

Immunology quiz 1 Introduction to the immune system – Dr. S Crish - Describe what the immune system is and what its functions are, distinguished between types o What the immune system is and what its functions are § Protect against foreign invaders (e.g. pathogens) § Manage internal tissues (remove dead cells, kill cancer cells) § Potential for harm (e.g., chronic diseases driven by immune dysfunction) o Innate vs adaptive § Innate – first line of defense First line of defense, active immediately after pathogen entry. Non-specific response: Targets a broad range of pathogens without specificity. Components: o Barriers: § Physical: Skin, mucous membranes, blood-brain barrier § Chemical: Mucus, saliva, tears, gastric acid, and antimicrobial peptides. § Commensal Bacteria: "Good" bacteria in the digestive system outcompete pathogens. § Behavioral: Reflexes like coughing and sneezing. Cellular Response: o Mediated by myeloid-derived cells. § Neutrophils: First responders, perform phagocytosis. § Monocytes/Macrophages: Clean up debris, phagocytose pathogens, and present antigens. § Eosinophils: Target parasites and regulate vascular effects. § Basophils and Mast Cells: Central to inflammation and allergic responses. o Phagocytosis: Neutrophils, macrophages, and other cells engulf pathogens and present antigens to adaptive immune cells. Signaling Molecules: o Complement system activates pathways for pathogen destruction. o Cytokines regulate and modulate the immune response. Key Features: o Rapid but limited response duration. o No memory: Reacts identically to repeat infections. § Adaptive General Characteristics: o Also called acquired immunity. o Specific response to antigens, triggered by initial exposure. o Provides immunological memory, allowing a faster and stronger response upon subsequent encounters. Components: o Lymphocytes (Lymphoid Lineage): § B Cells: Produce antibodies. Can differentiate into plasma cells for immediate antibody production or memory B cells for long-term immunity. § T Cells: CD4+ Helper T Cells (Th): Magnify and coordinate immune responses (e.g., Th1 for cell-mediated immunity, Th2 for humoral immunity). CD8+ Cytotoxic T Cells (Tc): Directly kill infected or cancerous cells.  § Natural Killer (NK) Cells: Bridge innate and adaptive immunity by targeting infected or transformed cells. Signaling Molecules: o Cytokines: Interleukins, interferons, and TNFs play critical roles in communication and activation of adaptive immune cells. Types of Responses: o Humoral Immunity: Mediated by antibodies secreted by B cells. o Cell-Mediated Immunity: Mediated by T cells, targeting intracellular pathogens and abnormal cells. Key Features: o Slower initial response but highly specific. o Immunological memory ensures enhanced responses to repeat exposures. o Pro-inflammatory vs anti-inflammatory § Balance between promoting and resolving inflammation for health § Pro-inflammatory Eats everything up and draws other cells in § Anti-inflammatory Offsets and starts inhibiting pro-inflammatory state Promotes repair, and good proliferation As you get older you have lower levels of anti-inflammatory cells - Define given terms o Antigen – any substance that specifically binds receptor/antibody o Immunogen - an antigen that elicits an immune response o Leukocyte – a white blood cell (WBC) § Lymphocytes § Polymorphonuclear leukocytes § Monocytes § Dendritic cells o Myeloid & lymphoid – distinct cell linages for differentiating immune cells in the bone marrow o Lymphocyte – class of WBC with cell surface antigen receptor, responsible for adaptive response § B cells § T cells o Complement – small proteins made by the liver. Float along until activated by cleavage to do three things § Stimulate phagocytic cells § Drive release of cytokines § Forma attack complex that kills invading pathogens o Phagocytosis § Engulfing of bacteria or debris by certain leukocytes to eliminate external threats § Neutrophils are the first leukocyte to the site of an infection or inflammation § What happens after something is phagocytized? A phagosome (a vesicle filled with the engulfed material) combines with a lysosome to break down engulfed material. This can then present antigens to activate the adaptive immune system. - List the stages of hematopoiesis, differentiating between myeloid and lymphoid lineages o Occurs in the bone marrow – all blood cells occur in the bone marrow o Hematopoietic stem cells differentiate into myeloid or lymphoid lineage cells. o Hematopoiesis – the formation and differentiation of blood cells § Most cells differentiate or mature in peripheral tissues T cells will differentiate in the thymus and be activated in lymph nodes B cells in the spleen and lymph nodes o Stages of hematopoiesis § Serves as the “grandmother: cells of all hematopoietic lineages § Constantly renew and give rise to progenitor cells  Common myeloid progenitor – gives rise to myeloid lineage cells Common lymphoid progenitor – gives rise to lymphoid lineage cells o Myeloid lineage – first responders – innate immune response § Derived from the common myeloid progenitor (CMP) Platelets o Anuclear cytoplasmic fragments of megakaryocytes o Immune related functions § Degranulate (serotonin) à increase blood flow, vascular permeability § Thromboxane A2 à vasoconstriction, platelet aggregation Granulocytes – contain granules with destructive enzymes o Neutrophils - direct harm to pathogens o Eosinophils – antiviral, antiparasitic activity o Basophils - mast cells: inflammation, allergy o Mast cells – vascular permeability, various aspects of inflammatory response, allergy Monocytes – migrate to tissues to differentiate into o Macrophages – destroy pathogens , present antigens, repair tissue o Dendritic cells – link innate and adaptive immunity by presenting antigens to T cells § The adaptive or acquired immune system does not work until it is activated by an antigen Megakaryocytes: fragment into platelets, involved in clotting and immune responses Erythrocytes: red blood cells (not immune cells but produced from myeloid progenitors) o Lymphoid lineage – mediate specific response = adaptive § Derived from the common lymphoid progenitor (CLP) B lymphocytes/ cells o Mature in the bone marrow o Differentiate into plasma cells for antibody production or memory B cells for long-term immunity T lymphocytes/ cells o Universal expression of CD3 § CD4+ Helper T Cells (Th): Magnify and coordinate immune responses Th1 for cell-mediated immunity – help Tc cells Th2 for humoral immunity – help B cells Th17 – activate macrophages Regulatory T cells (Tregs) – regulate response § CD8+ Cytotoxic T Cells (Tc): Directly kill infected or cancerous cells. Natural killer cells (NK) o Recognized and eliminate cells virally infected cells and cancerous cells - Explain what cytokines do – their function, modes of action, classes, and effects o Proteins that mediate effector functions of the immune system (activate and regulate) o Function and modes of action § Activate immune cells, regulate inflammation § Non-covalent, high affinity receptor binding o Classes § Chemokines: Recruit immune cells. § Interleukins (IL): Pro-inflammatory (IL-1), anti-inflammatory (IL-10). § Tumor Necrosis Factor (TNF): Induces fever and acute phase proteins. § Interferons (IFN):  § IFNα, IFNβ: antiviral protein production § IFNγ: macrophage microbicidal activity o Effects § Pleiotropic – induces different biological effects depending on target cell § Redundant – similar effects on target cells § Synergistic – combination of two cytokines activities greater than additive effect § Antagonistic – inhibition of 1 cytokine effect by the action of another § Cascade – 1 cytokine acts on target cell to produce addition cytokines - Describe the plasma protein system and effects o System of inactive enzymes (proenzymes) § 1st proenzyme converted to active enzyme § Substrate of activate enzyme becomes next component § 3 systems in the blood/plasma Complement o Complements antibacterial activity o Proteins are made by hepatocytes in the liver o Different triggers activate 1 of 3 pathways § Classical pathway § MB-lectin pathway § Alternative pathway All of the pathways will produce the same outcomes o When a phagocyte gets triggered it results in the following § Phagocytosis of microbe § Destruction of microbes by leukocytes § Osmotic lysis of bacteria o Opsonization – tagging of cells by C3b o MAC – protein complex that inserts into pathogen cell membrane, inducing lysis Clotting – prevents bleeding and contains infection Kinin – promotes vascular changes during inflammation - Discuss the lymphatic system, its function, and various organs o Lymphatic system § Vascular system transporting lymph and immune cells. § Produces, maintains, and distributes lymphocytes. o Primary lymphoid organs § Where immune cells develop § Bone marrow Site of hematopoiesis (where HSCs live) Where B cells develop ( exit immature) § Thymus 2nd stop in T cell development and maturation o Secondary lymphatic organs § Where immune responses develop Antigens interact with immune cells o Essential for activation of lymphocytes § Lymph nodes, spleen Cortex – B cells Medulla – T cells o Endothelium § Regulate circulating inflammatory components § Damage à platelet adherence Innate Immunity and Complement – Dr. Casali - Be able to discuss the general features that differentiate the specificity and response of innate and adaptive immunity o Innate immunity § More limited § Induces inflammation and antiviral responses § Does not have “memory” § Responses are generalized and mediated via patterns on microbes or viruses § Microbes contain pathogen-associated molecular patterns (PAMPs) Recognized by pattern-recognition receptors (PRRs) on innate immune cells o PAMPs are conserved across microbes § PAMPs are on the actual bacteria, whereas DAMPs are part of the actual host cell, and out response of dying § Damage-associated molecular patterns (DAMPs) from dying/infected host cells also drive innate immune cells via PRRs § Expressed in nearly all immune cells via the GERMLINE § Healthy host cells are not attacked because Don’t express PAMPs or material microbes/viruses do § Innate immune response provides the first line of defense at regions of entry o Adaptive immunity § More specialized Fine tailors for more immune responses § More of an antibody response - How does the innate immune system recognize microbes and damaged cells? o What are some common types of PRRs? These are going to recognize PAMPs and DAMPs § Extracellular – surface Toll-like receptors (TLRs) à bacterial cell walls C-type lection receptors à microbial polysaccharides § Cytosolic NOD-like receptor (NLR) à bacterial cell walls; damaged host cells RIG-like receptor (RLR) à Viral RNA Cystolic DNA sensor à microbial DNA § Endosomal TLRs à various nuclei acids of phagocytosed microbes o TLRs recognize bacterial and viral components § Extracellular – TLRs mostly recognized components of bacterial cell walls Gram – positive bacteria: o Lipopeptides à TLR-1: TLR-2 (TLR2:TLR-6) Gram – negative bacteria: o LPS à TLR-4 Bacterial flagellin à TLR-5 § Endosomal – TLRs mostly recognize nucleic acid components of bacteria or viruses TLR-7 and TLR-8 à ssRNA TLR-3 à dsRNA TLR-9 à unmethylated CpG o TLR signaling triggers acute inflammation and an antiviral state § Signals from all TLR types trigger changes in gene expression in innate immune cells § TLR activation converges on NF-kB or interferon-regulator factor (IRFs) transcription factors § Gene changes enhance inflammation and antimicrobial effects in immune cells o Cystolic receptors can sense viral or microbial DNA  § Cystolic PRPPs mostly recognize non-host nuclei acids, bacterial components and DAMPs § RIG-like receptors (RLRs) mainly sense viral dsRNA or ssRNA components § RLRs activate interferon production and inflammation to induce an antiviral state o Specific cytosolic DNA sensors induce antiviral responses § Specialized cytosolic DNA sensors (CDS) detect microbial or viral dsDNA § Foreign dsDNA activates the enzyme cyclic GMP-AMP synthase (cGAS) to produce cyclic dinucleotides § These cyclic dinucleotides activate the stimulator of interferon gene (STING) protein complex which will then activate IRF3 § STING activation leads to production of interferons and an antiviral and antimicrobial state o NOD-like receptors detect bacterial cell walls and damaged host cells § NOD-like receptors (NLRs) contain a nucleotide oligomerization domain (NOD). § Two main types of NLRs, NOD1 and NOD2, recognize bacterial cell walls. § Promote inflammation via NF-κB activation. o The inflammasome is a NLR that detects PAMPs and DAMPs § NLRP3/inflammasome detects bacterial products and products of host cell damage § Inflammasome assembly activates caspase-1 to produce biologically active IL- 1β and IL-18, leading to acute inflammation. § NLRP3 initiates pyroptosis—a programmed cell death of macrophages. o Other PRRs act similarly to TLRs, but recognize other pathogens § C-type lectin receptors: bind carbohydrates specific to fungal cell walls. § Mannose receptors: recognize terminal mannose on bacterial cells. § N-Formyl methionyl receptor: recognizes bacterial proteins. § Scavenger receptors: binds bacterial lipids. § Engagement leads to phagocytic clearance and inflammation. - Summary o Innate immunity recognizes PAMPs and DAMPs through germline-encoded receptors, yielding limited diversity in contrast to the adaptive immune system. o Common cellular locations for PRRs are extracellular membranes, the cytosol and endosomes on innate immune cells. o TLRs recognize diverse PAMPs, such as bacterial cell walls and nucleic acids from bacteria and viruses. o Activation of TLRs triggers cytokine production associated with inflammation and antiviral responses o The cytosol contains specialized PRRs recognizing nucleic acids, such as RLRs and CDS, and the inflammasome. o CDS recognizes bacterial and viral nucleic acids, resulting in activation of STING and enhanced cytokine production. o The inflammasome recognizes PAMPS, such as bacteria, and DAMPs associated with host cell damage, such as ATP, K+ efflux and reactive oxygen species. o Inflammasome activation promotes IL-1β production. o IL-1β is released from cells undergoing cell death (pyroptosis), leading to acute inflammation - What are the primary components of the innate immune system? o Physical Barriers: Skin, mucous membranes, saliva, and stomach acid. § Epithelium Physical barrier to infection Killing of microbes by locally produced antibiotics Killing of microbes and infected cells by intraepithelial lymphocytes o Innate Immune Cells: Neutrophils, monocytes/macrophages, natural killer (NK) cells. § Characteristics: Monocytes become macrophages upon tissue entry. NK cells target virus-infected cells. § Macrophages Life span is longer than neutrophils  Have prolonged ability to ingest microbes, apoptotic cells, tissue debris, foreign material Major functional activity, large amounts per cell, requires transcriptional activation of cytokine genes o Soluble Proteins and Mediators: § Cytokines: Trigger inflammation, adaptive immunity § Chemokines: Recruit immune cells § Reactive oxygen species, nitric oxide, and complement proteins. The ones in the red boxes are important in basically activating the immune system and targeting these innate immune cells Also need to know for the exam o Summary § Components of the innate immune system consist of physical barriers, innate immune cells and soluble cytokines and species § Barriers such as the skin provide physical blockade of microbes and pathogens, as well as regions inhospitable to pathogens § Common innate immune cells consist of neutrophils and monocytes/macrophages, whose functions, properties and dynamics differ § Activation of immune cells leads to cytokine, chemokine, and soluble mediator production, enhancing inflammation and an antiviral response - How is complement activated, and what effector functions does complement activation achieve? o Complement is a crucial component of the innate immune system, composed of circulating and membrane-associated proteins that work together to defend against pathogens. Complement activation can occur through three distinct pathways, all of which converge on the activation of C3 and lead to various effector functions. o Activation Pathways of Complement  § Alternative Pathway: Trigger: Spontaneous hydrolysis of complement protein C3 or its binding to microbial surfaces. Mechanism: C3b (a fragment of C3) attaches directly to microbial surfaces, initiating a cascade that amplifies the complement response. § Classical Pathway: Trigger: Binding of the complement protein C1 to antibodies that are already bound to microbial surfaces or antigens. Key Feature: This pathway bridges innate and adaptive immunity as it requires antibodies for activation. § Lectin Pathway: Trigger: Recognition of microbial carbohydrates by mannose-binding lectin (MBL) or ficolins in the plasma. Mechanism: MBL binds to mannose or lectins present on microbial surfaces, initiating the complement cascade. o Steps of Complement Activation § Early Steps: C3 Activation: C3 Cleavage: Regardless of the activation pathway, all converge on the cleavage of C3 into: o C3a: Functions as an inflammatory mediator. o C3b: Attaches to microbial surfaces for opsonization and further complement activation. Enzymatic Amplification: The complement system rapidly amplifies the response through enzymatic cascades. § Late Steps: C5 Activation and Membrane Attack Complex (MAC) Formation: C5 Cleavage: C3b promotes the activation of C5, splitting it into: o C5a: A potent inflammatory mediator that recruits immune cells. o C5b: Initiates the assembly of the membrane attack complex (MAC). § MAC Formation: C5b combines with proteins C6, C7, C8, and multiple C9 molecules to form a pore-like structure on the microbial membrane. The MAC causes osmotic lysis of the pathogen. o Effector Functions of Complement Activation § Opsonization and Phagocytosis: C3b binds to microbial surfaces and is recognized by phagocytic receptors, such as CR1 on macrophages. This process tags pathogens for efficient phagocytosis by immune cells. § Complement-Mediated Lysis: The MAC directly lyses pathogens by creating pores in their membranes, leading to cell death via osmotic imbalance. o Stimulation of Inflammation: § C3a and C5a are anaphylatoxins that: Increase vascular permeability. Recruit immune cells, such as neutrophils and monocytes, to the site of infection. Enhance the inflammatory response to combat infection. o Summary § Complement can be activated through three mechanisms: Classical à complement C1 binds to antibody-microbe complex Alternative à complement C3 binds to microbe surface Lectin à plasma mannose-binding lectin recognizes lectins on bacteria. § All three mechanisms converge on C3 activation, which gets cleaved to C3a + C3b. § C3b then activates C5, leading to C5a + C5b production.  § C5b activate C6-C9 and assembly of the MAC. Effector functions of complement include opsonization and phagocytosis, microbe lysis via the MAC and enhanced inflammation due to C3a and C5a production. - What is acute inflammatory response, and how do immune cells eventually arrive at sites of infection/injury? o The acute inflammatory response directs innate immune cells to sites of infection and damage o Leukocytes migrate into infected tissue is four steps § Rolling: tissue production of TNF and IL-1 cause endothelium to increase selectin expression. Leukocyte “rolls” on-off selectins § Integrin activation by chemokines: integrins LFA-1 and VLA-4 become activated by binding to selectin receptors ICAM-1 and VCAM-1 on endothelia à come in contact during “rolling” § Stable adhesion: integrin activation triggers cytoskeletal changes and stabilized immune cell on endothelium. Leukocyte changes dynamics and anchors itself even further to the endothelium § Migration through endothelium: leukocyte enters inflamed tissue, guided by chemokines - How do immune cells clear phagocytosed pathogens and deal with viruses? o Neutrophils and macrophages phagocytose microbes o Occurs mostly via complement o Microbe is ingested into cell in a phagosome o Microbes are killed via reactive oxygen species, lysosomal enzymes and nitric oxide o Viruses are cleared differently than bacteria § Interferons (IFNs) are produced by infected cells or immune cells o IFNs bind to receptors to trigger conditions unfavorable to viruses - Summary o Innate immune defenses consist of the acute inflammatory response, phagocytosis of pathogens and antiviral responses. o Four phases comprise leukocyte honing to sites of injury: rolling, integrin activation, stable adhesion and entry into tissue. o Phagocytosis is triggered by complement and leads to destruction of pathogen via fusion with lysosome containing reactive oxygen species and other mediators. o Interferons promote an antiviral response in infected cells by blocking cell replication and protein production - Clicker questions o Which of the follow is/are true regarding innate immunity? § The receptors used by the innate immune system are encoded by the germline § The innate immune responses are generalized § The innate immune system can detect host-cell damage § All of the above are true o TLRs are present in which cellular compartment(s) of innate immune cells? § Extracellular cell surface § Cell cytoplasm § Endosomes § All of the above are locations for TLRs § None of the above are locations for TLRs o Which of the following is true regarding the inflammasome? § It is located in the endosome § It detects patterns associated with host-cell damage § Activation of the inflammasome results in pyroptosis § Both A and B are true § Both B and C are true o Which of the following best describes the components of the innate immune system? § The epithelium produces localized antibiotics against microbes § Neutrophils differentiates from monocytes § Cytokine production promotes inflammation and adaptive immunity § Both A and B  § Both A and C o Which of the following best describes the classical complement activation pathway? § Mannose receptors are recognized on bacterial cell surfaces § The C3 protein binds to a bacterial cell surface § The C1 protein recognizes an antibody bound to a microbe § None of the above o Which of the following pathways lead to formation of the membrane attack complex? § Classical § Alternative § Lectin § All of the above o Which of the following is the FIRST step in leukocyte migration from the blood to the site of infection? § Integrin activation – 2nd step § Stable adhesion – 3rd step § Leukocyte rolling – 1st step § Leukocyte tethering o When a host cell is infected with a virus, all the following are functions of interferons EXCEPT § Degrade viral genetic material § Block viral protein synthesis § Enhance host-cell replication § Enhance inflammation - Overall summary o The innate immune response is generalized, and innate immune cells recognize pathogens based on PAMPs. o The innate immune system can also detect damaged self-cells through DAMPs. o PAMPs and DAMPs initiate production of cytokines, chemokines and other soluble proteins in innate immune cells via PRRs. o Complement is activated via three pathways, but the effector results are the same—microbes are opsonized and phagocytosed; lysed; and immune cells are recruited to site of infection. o The innate immune system response triggers leukocyte entry into infected tissue, clearance of pathogens and an antiviral response. o Some microbes have evolved to evade the innate immune system.