Microbio Week 4 (Exam 2) Flashcards
Any substance that induces a specific adaptive immune response (T and B cells)
Antigen
Examples of antigens
Proteins
Nucleic acids
Lipids
Polysaccharides
Metals
Each microbe possesses many different ___________
antigens
Primary immune response to antigen
First antigen encounter
Secondary immune response to antigen
Second encounter with same antigen
Characteristics of innate immunity
Immediate
Non-specific
No memory
Which type of immunity is always present to block microbe entry?
Innate immunity
Characteristics of adaptive immunity
Delayed
Specific
Has memory
What does adaptive immunity require?
Expansion/differentiation of lymphocytes
What are the 2 types of adaptive immunity?
- Humoral
- Cell-mediated
Which type of adaptive immunity?
Mediated by antibodies; extraceullar microbe
Humoral immunity
Which type of adaptive immunity?
Involves T lymphocytes; intracellular microbe
Cell-mediated immunity
Which type of adaptive immunity?
Blocks infections and eliminate extracellular microbes
Humoral immunity
Which type of adaptive immunity?
Elimination of phagocytosed microbes
Cell-mediated immunity
Which type of adaptive immunity?
Kills infected cells and eliminates reservoirs of infection
Cell-mediated immunity
Adaptive immunity recognizes microbial antigens on _________ or ________ _______ surfaces
microbes; host cell
Describe the steps of clonal selection
- Lymphocyte clones w/ diverse receptors arise in lymph organs
- Clones of mature lymphocytes specific for many antigens enter lymph tissue
- Antigen-specific clones are activated by antigens
- Antigen-specific immune responses occur
How long is the primary memory response?
1-3 weeks
How long is the secondary memory response?
2-7 days
Which memory response mounts larger and more effective responses to repeated antigen exposures?
Secondary memory response
Name some cells involved in innate immunity (immediate response) (6)
Macrophages (WBCs)
NK cells
Dendritic cells
Neutrophils
Eosinophils
Basophils
Name some cells involved in adaptive immunity (delayed response)
B cells
T cells (CD4 & CD8)
Name some cells involved in both innate and adaptive immunity
T cells
NK T cells
Name the type of cell:
Circulates and initiates response upon recognition of antigen
Lymphocyte
Name examples of lymphocytes
T lymphocytes
B lymphocytes
Name the type of cell:
Detects presence of microbes
Antigen-presenting cell
Name examples of antigen-presenting cells
Dendritic cells
Macrophages
B cells
Name the type of cell:
Destroys microbes
Effector cells
Name examples of effector cells
T lymphocytes
Macrophages
Granulocytes
Where do B cells mature?
Bone marrow
Where do T cells mature?
Thymus
Which type of lymphocyte?
Neutralization of microbe, phagocytosis, complement activation
B lymphocyte
Which type of lymphocyte?
Activation of macrophages, inflammation, activation (proliferation/differentiation) of T and B lymphocytes
Helper T lymphocyte
Which type of lymphocyte?
Killing of infected cells
Cytotoxic T lymphocyte
Which type of lymphocyte?
Suppression of immune response
Regulatory T lymphocyte
What type of T/B cell?
Survive for weeks-months and die if no antigen
Naive T/B cell
What type of T/B cell?
Short lived, die when antigen is eliminated
Effector T/B cell
What type of T/B cell?
Survive for long period of time
Memory T/B cell
__________ T cells are more numerous in young people
Naive
__________ T cells are more numerous in old people
Memory
____________ occurs in primary lymph organs
Maturation
____________ occurs in secondary lymph organs
Activation
Name the primary lymph organs
Thymus
Bone marrow
Name the secondary lymph organs
Spleen
Lymph nodes
What does organization of secondary lymph organs enable? (3)
- APCs to concentrate antigens
- Lymphocytes to identify/respond to antigens
- Cells to interact
Where does lymph drain to?
Lymph nodes
Draining of lymph to lymph nodes allows for what 2 things?
- Concentrate antigens
- Sampling of antigens by APCs
Lymph nodes and the spleen have distinct ___ and ___ cell zones
B and T
________ _______ pick up antigens in tissues and migrate to lymph nodes
Dendritic cells
Blood entering the spleen allows for what?
Sampling of antigens by APCs
Activated ___ _________ migrate in tissues to eliminate microbes
T cells
The mucosal immune system is a collection of lymph tissue that is similar in organization as what?
Lymph nodes (tonsils, Peyer’s patch)
How is movement of T and B cells coordinated?
Chemokines and receptors
____ _________ are attracted in __________ in lymph organs
B cells; follicles
____ _________ are attracted ___________, but adjacent to follicles in lymph organs
T cells; outside
How does the immune response to microbes occur? (3 steps)
- Antigen recognition
- Cell activation
- Antigen elimination
Name the 5 phases of the adaptive immune response
- Antigen recognition
- Clonal expansion
- Differentiation in effector cells
- Contraction via apoptosis
- Memory cells
__________ __________ __________ capture antigens and concentrate it in lymph organs where the organization allow them to present it to ____ __________
Antigen presenting cells; T cells
__________ T lymphocytes circulate through lymph organs, whereas ____________ T cells migrate to tissue where inflammation/infection is present
Naive; effector
Lymphocytes divide in response to what?
Antigens
What do lymphocytes become after they divide in response to antigens?
Effector and memory cells
Innate immunity is essential for…?
Effective host defense at early stage of infection
Adaptive immunity is essential for…?
Microbe clearance
Innate immunity varies according to _________ type
microorganism
What are the 2 categories of microorganisms involved in innate immunity?
Extracellular and intracellular
Extracellular or intracellular microorganism?
Accessible to soluble molecules and phagocyte
Extracellular
Extracellular or intracellular microorganism?
Require killing or activation of infected cells
Intracellular
Extracellular or intracellular microorganism?
Complement, macrophages, neutrophils
Extracellular
Extracellular or intracellular microorganism?
Antimicrobial peptides
Extracellular
Extracellular or intracellular microorganism?
NK cells
Intracellular
Extracellular or intracellular microorganism?
Activated macrophages
Intracellular
Innate or adaptive immunity?
Recognizes structures shared by various classes of microbes, but not present on normal host cells
Innate
Innate or adaptive immunity?
Pattern recognition receptors (PRRs) encoded in germline possess limited diversity
Innate
How do cells of the innate immune response identify microorganisms?
Pattern recognition receptors (PRRs) recognize pathogen associated molecular patterns (PAMPs)
Molecules expressed and/or produced solely by microbes and recognized by PRR expressed by immune cells
Pathogen associated molecular patterns (PAMPs)
Pattern recognition receptor (PRR) expression and ligands are __________
redundant
Pattern recognition receptors (PRRs) recognize similar types of ___________
ligands
Where are pattern recognition receptors (PRRs) found in cells?
Localized at plasma + endosomal membrane, and in the cytosol
What are pathogen associated molecular patterns (PAMPs) recognized by?
Toll-like receptors (TLRs)
Where are toll-like receptors (TLRs) expressed on?
Cells of the innate immune system
During toll-like receptor (TLR) signal transduction, recruitment of adaptor proteins, ________ and __________, leads to activation of ________________ factors and ___________ production
MyD88; TRIF; transcription; cytokine
____________ recruits TRIF and triggers IFNa/B production
TLR3
During toll-like receptor (TLR) signal transduction, activation of transcription factors leads to increased expression of cytokines, adhesion molecules, and costimulators. This causes what 2 things to occur?
- Acute inflammation
- Stimulation of adaptive immunity
During toll-like receptor (TLR) signal transduction, activation of transcription factors also leads to production of type 1 interferon. This causes what to occur?
Antiviral state
How many types of inflammasomes are there?
14
Activate inflammatory processes and provides host defense; involved in chronic disease development
Inflammasomes
How is the NLRP3 inflammasome assembly initiated?
By sensing several molecules
(ex: microbial products, inorganic particles, endogenous substances, etc)
What does inflammasome assembly lead to? (4)
Caspase-1 activation
Cleavage of pro-IL1B
Secretion of IL1B
Accumulation of neutrophils + monocytes at site
What are the components of the innate immune system?
Epithelial barriers
Phagocytes
NK cells
Granulocytes
Name the 3 types of barriers of the epithelia
- Physical barrier
- Chemical barrier
- Cellular barrier
Which barrier: physical, chemical, or cellular?
Saliva (oral cavity)
Physical barrier
Which barrier: physical, chemical, or cellular?
Kill microbes by disrupting outer membranes of bacteria and some virus
Chemical barrier
What cell?
Most abundant (1x10^11/day)
Short lived (6 hrs in blood)
No lysosome
Neutrophils
What do neutrophils mediate?
Earliest phase of inflammatory responses
What cell?
10x less abundant than neutrophils
Long lived
Monocytes differentiate into macrophages in tissues
Mononuclear phagocytes
What do macrophages mediate?
Later stages of innate immune response, 1-2 days after infection
What cells divide and persist at inflammation site?
Macrophages
What is the function of classical/M1 macrophages? (2)
- Trigger inflammation
- Kill micobes
Dendritic cells have __________ and __________ capabilities
dendrites; phagocytic
What cells link innate and adaptive immune responses?
Classical dendritic cells
What cells?
Capture and display microbial antigens to naive T lymphocytes
Classical dendritic cells
What cells?
Tune T cell response by secreting cytokines
Classical dendritic cells
What do plasmacytoid dendritic cells produce?
Type 1 interferons (IFNa/B) that have antiviral activities
What cell?
Bind dsRNA via TLR3
Plasmacytoid dendritic cells
What cell?
Do not express somatically rearranged clonally distributed antigen receptors; are NOT phagocytes
NK cells
Inhibitory receptor engagement to MHC class I inhibits _________ cell activation
NK
Signals from ____________ receptors block signals from ____________ receptors
inhibitory; activating
Lack of inhibitory receptor engagement triggers _____________
activation
What happens to NK cell if the inhibitory receptor is engaged?
NK cell = not activated
No cell killing!!
What happens to NK cell if inhibitory receptor is NOT engaged?
NK cell = activated
Killing of infected cell occurs
What cell?
Kill virus-infected cells via perforin/granzyme
NK cells
What cells?
Upon activation, release proteolytic enzymes and substances that contribute to inflammation
Mast cells, basophils, and eosinophils
Name some examples of proteolytic enzymes and substances released by mast cells, basophils, and eosinophils that contribute to inflammation (5)
Histamine
Prostaglandins
Heparin
Leukotrienes
TNFa
What cells?
Important in helping to protect against helminth and bacterial infection
Mast cells, basophils, and eosinophils
Lymphocyte activation requires how many signals?
2
What are the 2 signals involved in lymphocyte activation?
Signal 1 = antigen binding to antigen receptor
Signal 2 = molecules provided by innate cells
4 principal effects of inflammation
- Increase in temp (calor)
- Redness (rubor)
- Swelling (tumor)
- Pain (dolor)
What are 3 mediators secreted in response to bacterial infection?
Histamine
Prostaglandins
TNFa
During an acute inflammatory response, the increased _____________ permeability of mediators leads to influx of _________ _________ and ________ cells. This contributes to swelling, redness, heat, and pain
capillary; plasma proteins; phagocytic
How do cells at the site of infection alert other innate cells of the immune response?
Cytokines attract and activate cells, or induce cellular processes
__________ induce innate cells to produce _________
Microbes; cytokines
Cytokines are produced by __________ cells upon interaction with infectious agents, and activate/mobilize other cells
innate
What is an effect of cytokines on vascular endothelium?
Endothelial wall gains new adhesion proteins specific for interactions with leukocytes
What 3 parts of the body do inflammatory cytokines have an effect on systemically?
- Liver
- Hypothalamus
- Fat, muscle
Liver, hypothalamus, or fat + muscle?
Systemic effect of inflammatory cytokines includes: activation of complement; opsonization
Liver
Liver, hypothalamus, or fat + muscle?
Systemic effect of inflammatory cytokines includes: increased body temp; decreased viral and bacterial replication
Hypothalamus
Liver, hypothalamus, or fat + muscle?
Systemic effect of inflammatory cytokines includes: protein and energy mobilization to generate increased body temp; decreased viral and bacterial replication
Fat + muscle
What cytokines are involved in an abscess?
TNFa and IL1
Name the 4 steps in the recruitment of leukocytes: transmigration
- Rolling
- Integrin activation by chemokines
- Stable adhesion
- Migration through endothelium
What are the 3 liver plasma proteins that serve as acute phase reactants?
SAP
CRP
MBL
What do acute phase reactants function as?
Opsonin, targeting microbes for phagocytosis
Molecules coating microbe surface
Opsonin
Process of marking microbe for ingestion
Opsonization
What do opsonins simultaneously bind to?
Microbe + phagocyte receptor
What do acute phase reactants activate?
Complement
In the complement system, what do all pathways lead to?
Cleavage of C3 into C3b and C3a
What enzyme is responsible for cleavage of C3 into C3b and C3a?
C3 convertase
What is C3b?
Opsonin
What is C3a?
Anaphylatoxin
C3a and C5a induce local inflammatory responses. Name them
Increased vascular permeability
Increased microbicidal activity
Which process triggered by opsonization leads to microbe ingestion?
Phagocytosis
What can we compare phagocytes to?
Pac-man
What cells kill microbes?
Neutrophils
Macrophages
What cells process antigens?
Dendritic cells
Process of ingestion of opsonin-coated or receptor-bound microbes
Phagocytosis
How are microbes killed once phagocytosed?
Production of toxic products
The generation of what is toxic for ingested microbes?
O2-
Reactive oxygen species (H2O2, OCl-, -OH)
NO
Reactive peroxynitrite radicals
What is pus?
Dying neutrophils
Antigens are transported from ___________ to lymph organs where recognition by ____ cells occurs
tissue/mucosa; T
The majority of dendritic cells in tissues and lymph organs are what type?
Classical dendritic cells
What cells capture and process protein antigens?
Immature dendritic cells
Dendritic cells upregulate __________ receptors (CCR7) and ____________ molecules
chemokine; costimulatory
What cells present protein antigens to T cells?
Mature dendritic cells
What determines the specific recognition of antigens by T cells?
MHC molecules
Antigens are displayed by ____ __________ and are recognized by ___ _______
MHC molecules; T cells
T cell receptors on T cells recognize peptide antigens displayed by _____ ___________ on antigen presenting cells
MHC molecules
How many sets of highly polymorphic genes are there? Name them
2
Class I MHC genes
Class II MHC genes
Genes of the MHC locus are highly _________
polymorphic
MHC class I and class II molecules are membrane proteins containing a peptide-binding cleft at the ________ ___________
amino terminal
MHC class I molecules have an ________ chain associated with _______________
alpha; B2-microglobulin
MHC class II molecules have _________ and _________ chains
alpha; beta
CD8 T cells only recognized peptides presented by ….
MHC class I molecules
______ binds CD8 on CD8 T cells
a3
(invariant portion of alpha chain)
CD4 T cells only recognized peptides presented by ….
MHC class II molecules
______ binds CD4 on CD4 T cells
B2
(invariant portion of beta chain)
What ensures that a population can deal with microbe diversity?
MHC polymorphism
What is expressed on APCs and induced by IFNgamma?
MHC class II molecules
What is expressed on ALL nucleated cells?
MHC class I molecules
MHC molecules only bind peptides derived from what?
Protein antigens
T/F: One APC can display multiple peptides
True
How are are proteins converted into peptides?
Antigen processing pathways
Peptide binding to MHC lasts up to ______ in order to maximize interaction with ___ _______
days; T cells
Extracellular proteins (tumor, bacteria) are processed in ______________. Peptides are displayed on MHC class _____ molecules to ______ cells
endosome/lysosome; II; CD4
Cytosolic proteins (virus, bacteria that escape phagosome) are processed by ___________ and _____________ ___________. Peptides are displayed on MHC class _____ molecules to ______ cells
proteasome; endoplasmic reticulum; I; CD8
What is the significance of MHC-associated antigen presentation?
Optimization of response to different microbes in different locations
(extracellular = CD4; intracellular = CD8)
Which inflammatory cytokines affect the liver?
IL-1
IL-6
TNFa
Which inflammatory cytokines affect the hypothalamus and fat + muscle?
IL-1
TNFa
