MICR 3230 Midterm Exam | Questions and Answers (Complete Solutions)

MICR 3230 Midterm Exam | Questions and Answers (Complete Solutions) What is immunity? The state of protection against foreign pathogens or substances (antigens) How do you generate immunity without disease? Immunization What does immunization do? Prepares the immune system for eradication of the antigen What is herd immunity? Vaccination/protection of a critical mass of people What is humoral immunity? Combats pathogens via antibodies What are antibodies produced by? B cells 2 types of humoral immunity: Passive & active What is cell-mediated immunity mediated by? T lymphocytes How does cell-mediated immunity work? Eradicates pathogens, clear infected self-cells, aid other cells in immunity Humoral & cell-mediated immunity rely on: Surface receptors of B and T cells Receptors are randomly generated by: Gene segment rearrangements in the cells B cells that encounter antigen produce: Specific antibodies T cells: Bind antigens/specific peptides presented by APCs General gist of humoral immunity: BCR binds antigen Antigen internalized B cell produces antibodies General gist of cell-mediated: TCR binds antigen T cell produces cytokines OR TCR binds antigen Antigen internalized Infected cells recognized by APCs & lysed 4 major categories of pathogens: Viruses Bacteria Fungi Parasites What is pathogen recognition? An interaction b/w foreign organism & recognition molecule expressed by host Ligands include: Whole pathogens Antigenic fragments Products secreted by foreign organisms The immune response is: An extra-/intracellular cascade of events leading to the labeling & destruction of pathogen after ligand binding Cells that recognize & kill/engulf pathogen labelled: CELLULAR immunity Soluble proteins for labeling & destruction of invaders labelled: HUMORAL immunity Immune responses rely on: Recognition molecules Recognition molecules are: Encoded in DNA - always expressed - PRRs PRRs bind to PAMPs Randomly generated Explain clonal selection: Individual B and T cells have specificity for single antigen Each has many copies of a receptor that only binds to 1 antigen When B or T cell reacts w antigen it's SELECTED & ACTIVATED Activation -- proliferation -- large # of clones Each clone responds to original pathogen Cells not activated are deleted Tolerance ensures: That the immune system avoids destroying host tissue from anti-self antibodies 2 systems that respond to pathogens: Innate Adaptive The innate system: First line of defense Fast but NOT specific Uses inherited recognition molecules & phagocytic cells The adaptive system: Humoral & cell-mediated Slow (5-6 days) Uses randomly generated antigen receptors Highly specific How do the innate & adaptive systems work together? The innate gives out signal molecules (cytokines & chemokines) that direct adaptive response Primary response (memory): First exposure to the antigen Memory lymphocytes left behind after the antigen is cleared Secondary response (memory): Second exposure stimulates the memory lymphocytes Faster, more significant, better response The 2 dysfunctions of immunity are: Overly active/misdirected Immunodeficiency (primary or secondary) What is the microbiome? Commensal organisms that live on & in us causing no harm Pushes to homeostasis An imbalance/dysbiosis leads to inflammation Hematopoietic stem cells have the ability to: Differentiate into many types of blood cells What is hematopoiesis? Highly regulated process by which HSCs differentiate into mature blood cells What are the primary lymphoid organs? Bone marrow & thymus Where immune cells develop from immature precursors What are secondary lymphoid organs? Spleen, lymph nodes, gut & mucosal tissue Where mature antigen-specific lymphocytes first encounter antigen & begin the immune process Hematopoiesis occurs in the: Bone marrow HSCs are constantly: Renewed & directed to differentiate into 2 major types of PROGENITOR CELLS What are the 2 types of progenitor cells? Common myeloid progenitor cells - give rise to RBCs & myeloid cells (granulocytes, monocytes, macrophages, DCs); part of innate immune system Common lymphoid progenitor cells - give rise to WBCs, B & T lymphocytes, innate lymphoid cells, NKs; part of innate & adaptive immune systems Human blood cells' lifespan: RBCs - 120 days Platelets - 5-10 days Monocytes - days to months Basophils - hours to days Lymphocytes - days to years 4 main types of cells develop from common myeloid progenitors: RBCs Monocytes Granulocytes (neutrophils, basophils, eosinophils) Megakaryocytes What do all granulocyte subtypes have? Large nucleus & granules containing cytotoxic enzymes & antimicrobial peptides Granulocytes - neutrophils: Multilobed nucleus Granules contain: Proteases - tissue remodelling, protein degradation Antimicrobial proteins - direct harm to pathogen Protease inhibitors - regulation of proteases Histamine - vasodilation, inflammation Granulocytes - eosinophils: Granules contain: Cationic proteins - induces formation of ROS, vasodilation, basophil degradation Ribonucleases - antiviral activity Cytokines Chemokines - attract leukocytes Granulocytes - basophils/mast cells: Granules contain: Cytokines Lipid mediators Histamine Monocytes function is: Migrate into tissue & differentiate into macrophages Repair/remodel, destroy pathogens, present antigens Differentiate into DCs – ingestors When professional APCs encounter a pathogen (3 steps): 1. Secrete proteins that attract & activate other immune cells 2. Internalize pathogens via phagocytosis, digest pathogenic proteins into peptides, present peptide antigens on membrane surfaces via MHC II molecules 3. Upregulate costimulatory molecules required for optimal activation of T helper cells Macrophages & neutrophils are specialized for: Phagocytosis Macrophages present antigens to ____ via ____: T cells; MHC molecules Immature DCs ___ antigen then ___ & ___: Capture; mature & migrate to present to T cells The most potent APCs are for: Activation of naive T cells The 3 main types of cells that develop from common lymphoid progenitors: B lymphocytes T lymphocytes NK cells Different lymphocytes carry different: Sets of CD molecules What is CD4? Binds to MHC II Signal transduction T helper What is CD8? Binds to MHC I Signal transduction T-cytotoxic Lymphocyte maturation: Naive - newly formed B & T Effector - contact w/ antigen Memory - contact w/ antigen, effector cloned B cells express what receptor? BCR T cells express what receptor? TCR During embryogenesis & the fetal period blood cell formation shifts: Side to side Hematopoiesis begins in the: Yolk sac Fetal HSCs arise near the: Kidney Mature HSCs capable of populating the hematopoietic system can be isolated from: Yolk sac Placenta Fetal liver Postnatally HSCs populate the: Bone marrow Stromal cells facilitate: HSC proliferation Direct migration Stimulate differentiation T cells develop initially in the ___ & then migrate to ___ to mature: Bone marrow; thymus What directs stepwise changes in thymocytes? Microenvironment of the thymic cortex & medulla TCR affinity of binding w/ MHC peptides drive: Positive & negative selection Positive selection = self/non-self recognition w/ intermediate recognition of TCR to MHC Negative selection = self/non-self recognition w/ high affinity binding of TCR to MHC If thymocytes bind to self MHC too strongly they: Are negatively selected & die What are the lymph nodes, spleen & MALT connected by? Blood & lymphatic systems What are the most highly organized parts of the secondary lymphoid organs? Lymph nodes & spleen B cells act in the: Cortex T cells act in the: Paracortex Macrophages & DCs act in the: Innermost lymph node medulla Antigen enters via: Afferent vessel Naive lymphocytes enter by: HEV Lymphocytes exit via: Efferent vessel Lymphocyte cells actively migrate towards: Each other during activation events Lymphoid fibroblastic reticular conduit guides: T cells & APCs toward activation interactions Differentiation takes place in: Follicles B cells - clonal expression - germinal centres CD4+ T helper - helper T cells CD8+ T cells - killer T cells The spleen is the: First line of defence against bloodborne pathogens RBCs compartmentalized into: Red pulp WBCs segregated in: White pulp Bordering white pulp is a: Specialized region of macrophages & B cells = MARGINAL ZONE What is the mucosa associated lymphoid tissue? Layer of defense against infection at mucosal & epithelial layers What is the function of the mucosa associated lymphoid tissue? Organizes responses to antigens that enter mucosal tissues Includes gut associated lymphoid tissues If the antigen breaks through the layer - immune response If an anatomical barrier is breached: Innate RCs recognize the threat – PAMPs DAMPs recognize: Aging, dead, damaged self-structures PRRs recognize: PAMPs & DAMPs Target for clearance Physical & chemical anatomical barriers: Epithelial layers of skin Mucosal/glandular tissue Acidic pH Antimicrobial proteins & peptides Epithelial barriers: Prevent pathogen entry into body Skin, mucosal membrane, acidic pH, enzymes & binding proteins, antimicrobial proteins & peptides What are the PAMP ligands? TLRs CLR RLR NLRs What recognize PAMP ligands? Families of PRRs When signalling pathways are activated they contribute to: Innate/inflammatory responses Toll-like receptors recognize: Many types of pathogen molecules TLR exteriors rich with: Leucine-rich repeats Associated w/ ligand binding of PAMPs & DAMPs TIR domain with: Toll/IL 1 Rc What activates the TLR signal cascade? Ligand (PAMP/DAMP) induced TLR dimerization Where are TLRs located? In the plasma membranes of endosomes & lysosomes After PAMP binding, different TLRs recruit different adaptor proteins to: The Toll/IL-1R domain Different adaptor proteins lead to different events What signalling pathways do TLRs include? NFkB transcription factor activation Interferon regulating factor (IRF) pathways MAP kinase pathway downstream TFs (AP-1) 2 key adaptors recruited to activated TLR domains: MyD88 TRIF MyD88 initiates: Signaling pathway to activate NFkB & MAPK TRIF initiates: Signaling pathway to activate TRAF3 What is the role of adaptors? To bind multiple components, generate scaffold, initiate signaling PM TLR signaling through MyD88 steps: 1. Extracellular binding of lipopeptide & TLR dimerization 2. Adaptor binding & recruitment of kinase 3. Phosphorylation 4. MAP kinase activated OR complex activated MAP - activation of AP 1 Complex - NFkB pathway 5. AP-1 & NFkB move into the nucleus for activation & transcription 6. Production of cytokines, chemokines & anttimicrobials Endosomal TLR signalling through MyD88 & TRIF steps (TRIF PATH): 1. Endosomal binding of dsRNA TLR dimerization 2. Recruit TRIF 3. Kinase activation 4. Phosphorylation 5. NFkB activation & movement into nucleus 6. Transcription 7. Production of cytokines, chemokines & antimicrobials Endosomal TLR signalling through MyD88 & TRIF steps (MyD88 PATH): 1. Endosomal binding of ssRNA & TLR dimerization