Immunology Flashcards
1
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Immune System
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Collection of cells, tissues, and molecules that mediate resistance to foreign elements (antigens)
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Immune response
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Coordinated reaction of these cells and molecules to antigens
3
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Immunology
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Study of the immune system, including its responses to microbial pathogens and damaged tissues and its role in disease
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Antigen
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Antibody generator
Molecules that induce an immune response when introduced into the body
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Epitope or antigenic determinant
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Part of an antigen that is actually responsible for inducing the immune response and binding to the products of the immune response (lymphocyte receptors and antibodies)
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Self versus non-self
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The immune system must be able to discriminate foreign elements from components of its own organism
Failure results in autoimmunity
Immune responses should be generated only when components of the immune system come into contact with non-self elements
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Innate Immunity
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Physical barriers
Inflammation
Complement
8
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Adaptive immunity
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Humoral immunity
cellular immunity
9
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Innate Immunity: Activation
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Always active
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Innate Immunity: main cells
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Macrophages, neurophils, NK cells
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Innate Immunity: Response time
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Fast (minutes to hours)
12
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Innate Immunity: specificity
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Structures common to several pathogens
13
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Innate Immunity: Memory
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Absent
14
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Adaptive immunity: Activation
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Only when in contact with antigens
15
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Adaptive immunity: main cells
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T cells and B cells
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Adaptive immunity: Response time
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Slow (days to weeks)
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Adaptive immunity: Specificity
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Specific antigens
18
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Adaptive immunity: Memory
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Present
19
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Physical/ Chemical Barriers
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things like pH of intestinal tract, mucus in respiratory system
Antimicrobial properties-prevent infection from taking place
20
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Recognition of Pathogens
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Pathogen-Associated molecular patterns (PAMPs)
Components that are shared between different types of pathogens and present a molecular composition that differ from self
21
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Recognition of Damage
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Damage-associated molecular patterns (DAMPs)
Released when cells die (intracellular DAMPs) or generated when connective tissue is damaged (extracellular DAMPs)
No DAMPs if cells die of apoptosis
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Pattern Recognition Receptors
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Receptors of innate immunity that recognize PAMPs and DAMPs
Soluble or membrane-bound
signaling phagocytic
23
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Cells of the immune system
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Many share some precursor cells
all start from a stem cell
Some cells will have multiple functions
24
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Neutrophils: Appearance
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Segmented nucleus, granular cytoplasm
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Neutrophils: Location in health
Blood
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Neutrophils: Lifespan
48-72 hours
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Neutrophils: Primary Function
Antimicrobial effectors, particular in acute bacterial infection (innate)
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Neutrophils: Mechanism of Action
Phagocytosis; degranulation; Neutrophil extracellular trap formation
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Eosinophils: Appearance
Characteristic eosinophilic granules
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Eosinophils: Location in health
Blood and tissues lining gastrointestinal tract and airways
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Eosinophils: Lifespan
Days to weeks
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Eosinophils: Primary Function
Antiparasitic effectors, particularly in helminthic infection; some antiviral action; roles in allergy (innate)
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Eosinophils: Mechanism of Action
Degranulation; Limited phagocytosis
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Basophils: Appearance
Characteristic blue-purple basophilic granules
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Basophils: Location
Blood
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Basophils: Lifespan
Days
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Basophils: Primary function
Mediatory of inflammation (innate)
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Basophils: Mechanism of action
Degranulation
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Mast Cells: Appearance
Round nucleus, cytoplasm densely packed with purple granules
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Mast Cells: Location
Tissue, particularly connective tissue surrounding vasculature and nerves, and the lamina propria of the mucosa
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Mast Cells: Lifespan
Weeks to months
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Mast Cells: Primary function
immune surveillance, mediator and amplifier of inflammation and allergy (innate)
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Mast Cells: Mechanism of action
Detection of threats and release of inflammatory mediators via degranulation (vasoactive amines) or synthesis of lipid mediators and cytokines
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Macrophages: Appearance
Round nucleus, clear-vacuolated cytoplasm, irregular cell shape
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Macrophages: Location
Peripheral Tissue
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Macrophages: Lifespan
Months
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Macrophages: Primary function
immune surveillance, moderate antimicrobial capacity, limited antigen presentaion
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Macrophages: Mechanism of action
Detection of threats and release of inflammatory mediators; phagocytosis
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Dendritic Cells: Appearance
Round Nucleus, clear cytoplasm, irregular shape with long branched projections (dendrites)
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Dendritic Cells: Location
Tissues
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Dendritic Cells: Lifespan
Months
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Dendritic Cells: Primary Function
Immune surveillance, antigen processing and presentation (adaptive)
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Dendritic Cells: Mechanism of action
Detection of threats and release of inflammatory mediators; endocytosis and phagocytosis
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Natural Killer (NK) cells: Appearance
Large lymphoid cell, round nucleus, azurophilic cytoplasmic granules
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Natural Killer (NK) cells: Location
Blood, spleen
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Natural Killer (NK) cells: Lifespan
Months
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Natural Killer (NK) cells: Primary function
Destruction of virally infected or abnormal host cells (including tumor cells) (innate)
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Natural Killer (NK) cells: Mechanism of action
Recognition of virally infected or abnormal host cells and targeted release of cytotoxic granules
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Lymphocytes: Appearance
Round nucleus, clear cytoplasm, high N:C ratio
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Lymphocytes: Location
Blood, tissues, secondary lymphoid organs
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Lymphocytes: Lifespan
Weeks to months, years (memory cells)
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Lymphocytes: Types
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T cells (TCR)
B cells (BCR)
Both will have a specific receptor characteristic of that lymphocyte
Their specific epitope
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Complement System
Collection of plasma proteins that are individually inert but can interact in a cascade once they are activated
Attacks the cellular membrane leading to cell death
Act as signaling molecules that recruit immune cells to inflammatory sites
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Cell communication: Receptors
Expressed in the surface of a cell or in intracellular compartments
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Cell Communication: Ligands
Molecules that activate receptors
| Soluble or membrane-bound
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Cell Communication: Cytokines
Proteins with diverse functions such as cell growth, activation
Interleukins- communication between cells
Chemokines- chemotaxis
(kinda start with cell that hasnt figured out its life- depending on whats going on, and what cytokines are present will affect what the cell becomes
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Inflammation: recognition of threat
Pathogen-Associated Molecular Patterns
Damage-associated Molecular Patterns
The first thing that needs to happen. These are what the cells need to recognize
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Sentinel cells
Dendritic cells, Macrophages, Mast cells -> pro-inflammatory and antimicrobial mediators
Sentinel cell exposed to PAMPs, DAMPs, or pro-inflammatory cytokines
detect PAMPs, DAMPs, and release mediators that will activate an inflammatory response- effect macrophages, plasma proteins -> affects complement system
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Sentinel Cell Activation
Upregulation of cellular antimicrobial defenses
| Release of proinflammatory chemokines, lipid mediators, and cytokines
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Inflammation: Mast cells
Vasoactive molecules (histamine, serotonine)
Vasodilation
Increased vascular permeability
All these mediators and leukocytes to get to injury site (usually in tissue) done so by blood
More leukocytes arriving
Increase blood flow (Swelling)- slower velocity
Easier to migrate to tissue
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Systemic consequences: Hypothalamus
Fever, anorexia, sleepiness, depression
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Systemic consequences: Liver
Increases synthesis of acute-phase proteins
| Iron sequestration
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Systemic consequences: Bone
Increases white cell production
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Leukocyte extravasation
Macrophages and dendritic cells, produce cytokines such as that activate the endothelial cells to express selectins and ligands for integrins and to secrete chemokines
Selectins -> rolling
Integrins -> adhesion
Chemokines -> migration
Macrophages in tissue, stimulated by microbes and will produce mediators (cytokines etc) and will have an effect on vessel walls
Mast celss stimulating dilation which helps leukocytes arrive
some cytokines will cause some endothelial cells to express certain molecules (selectins and integrins)
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Leukocyte Chemotaxis
Neutrophils will extend pseudopods to fell around for inflammation site
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Leukocyte kinetics during inflammation
Lymphocytes are present once the adaptive immune system is engaged in the response
Monocytes/Macrophages predominate at later stages of inflammation
Neutrophils predominate during acute inflammation
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Phagocytosis
It is an active process of capturing and ingesting foreign objects/microorganisms by phagocytes- neutrophils and macrophages
Destruction of microorganisms, damaged cells and cellular debris, foreign objects
Induction of cytokine production
Processing and presentation of antigens (macrophages)
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Recognition of microbe
Endocytosis
Phagosome maturation
Fusion of phagosome and lysosome
Killing of bacteria inside the phagolysosome
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Intracellular Killing Mechanism: Oxidative Pathway
Use fo oxygen and glucose increases several fold "respiratory burst"
Reactive oxygen species (ROS)
Reactive nitrogen species (RNS)
Toxic to microorganisms
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Intracellular Killing Mechanism: Non-oxidative
Dependent on the action of the toxic substances present in lysosomes
Cationic proteins: damage the bacterial cell wall
Lysozyme: damages the mucopeptides in the bacterial cell wall
Lectoferrin: Sequestrates iron thus inhibiting bacterial growth
Preoteolytic and hydrolytic enzymes: digest killed bacteria
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Extracellular Killing by NETs
Neutrophil Extracellular Traps
Increase in proinflammatory stimulus
Extrude strands of nuclear DNA and associated proteins into the extracellular fluid
Traps and kills microbes
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Complement System
Collection of circulating and membrane-associated proteins
Many complement proteins are proteolytic enzymes
Activation occurs in a sequential manner
3 pathways:
Alternative pathway
Classical Pathway
Lectin Pathway
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Alternative Pathway
Complement proteins are activation on microbial surfaces (because complement regulatory proteins are not present on microbes, only on host cells)
Activated by innate
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Lectin Pathway
Activated when a carbohydrate-binding plasma protein, mannose-binding lectin (MBL), binds to terminal mannose residues on the surface of glycoproteins
Innate
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Classical Pathway
Activated by antibodies that bind to microbes or other antigens
First described, last to kick in
Adaptive immune system
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Membrane attack complex
How does the complemet system kill cells
Breached the cell membrane of the microbe, allowing water to rush in by essentially punching holes which creates cylindrical pores
Destruction bt osmotic lysis
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Type 1 Interferons
Innate immunity
One of the cytokines
Produced by virus-infected cells and plasmocytoid DCs
Non-specific response to viral infections
IFN-a and IFN-B: inhibit viral replication and induce antiviral state
effects the cells metabolism so it cant synthesize proteins correctly
87
Natural Killer Cells
Recognize and respond to infected and stressed cells
A. killing of the cells
B. Secretion of IFN-y stimulates and activates macrophages.
First line of defense against tumors.
Healthy host cells express self class I major histocompatibility complex (MHC) molecules, which are recognized by inhibitory receptors
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NK cells are activated by infected or mutated cells in which ligands for activating receptors are expressed (often at high levels) and class I MHC expression is reduced
NK cells are checking to make sure the cells have MHC I
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Adaptive Immunity
T and B cells
Will have specific antigen receptors (epitopes)
Driving a much more specific response
89
Antigen processing and Presentation
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Major histocompatibility complex (MHC) molecules
2 types: class 1 MHC
class 2 MHC
These are similar with slight differences. Both are there to help present an antigen to a T cell. Differences are in types of cells that contain them and to which type of T cell theyll present the antigen
T calls can only recognize antigens presented in an MHC molecule- cant do it on their own
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Class I MHC
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All nucleated cells have MHC I- response to intracellular pathogens- important to be able to eliminate pathogen no matter what cell its in
Cytosolic protein- antigen uptake by proteasomes and processed and broken down to peptides. These peptides will bind to class I MHCmolecules on ER. Transported to cell membrane and MHC can present the peptide to T-cells
MHC I presents antigens ONLY to CD8 T cells (cytotoxic T lymphocytes)
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Class II MHC
Break down proteins-pick them up through endocytosis. Use lysosomes to break down then bind to MHC II and transported to membrane and presented to T cells (T helper) doesnt kill it but will stimulate other cells that will ]MHC II presents antigens to CD4 T cells (T helper cells
MHC II expressing cells are professional antigen presenting cells (APCs): dendritic cells, macrophages, B cells
92
Activation of Naive T cells
Always done by a dendritic cell
Dendritic cell will prime and activate naive T cells. Dendritic cell can do MHC I and II so it can activate CD8 (no response after- the cell will just be killed) and CD4 activation
Then they will have proliferation- specific T cell clone
Then Differentiation- effector and memory T cells.
Immature DCs encounter antigens in tissues
Migration to lymphoid tissue and maturation
Antigen presentation by mature DCs in lymph nodes
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Differentiation of activated T Cells
Subsets: CD4+
| CD8+
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CD4+
Th1, Th2, Th17
| Express surface molecules and secrete cytokines that activates other cells
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CD8+
Cytotoxic T lymphocytes (CTLs_
Killing of infected cells
endpoint
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Cellular response: CD4+ Th1 cells
cytokine secretion
causes activation of macrophages and phagocytosis to kill microorganisms
activation of CTLs (CD8+)
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Cellular response: CD8+ CTLs
Induces apoptosis of infected cells
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Humoral response: B cells
Basically the antibody response
Able to recognize antigens independently of MHC presentation
Activated by Th cells or T-independent activation (need Th in order to amount FULL immune response)
B cells only produce IgM, but with Th can do isotype-- switch to do other.
Differentiate between effector (plasma) cells and memory cells( not in T-independent) (plasma might change type of antibody they secrete)
Affinity maturation (not in T-independent) over course of immune response, the antibodies being produced by those cells will become of higher affinity by the epitope than they were in initial stages
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Humoral Response: Immunoglobulins
Isotypes or classes:
IgM (blood), IgG (blood and tissues), IgA (mucous membranes), IgE (epithelial tissue), IgD
Only B cells will produce antibodies so Ig are the B cell receptors themselves
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Isotype Comparasin
Differences in heavy chain structure, monomeric vs polymeric, subclasses, serum concentration, half-life, functions
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Humoral response against microorganisms
B cells will have receptors on membrane and get activated and can produce receptors in soluble form.
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Against microorganisms or toxins:
bind them and neutralize them
Facilitate action phagocytic cells- can cover microbes
Trigger NK cell activation
Antibody dependent cellular cytotoxicity
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Primary and Secondary Ab response
IgM is the major Ab of primary responses. Acute infection. first one to increase because all cells can make IgM
IgG is the major Ab of secondary responses. Chronic infection
