10.6 Intro Flashcards
B lymphocytes make up the (humoral/cellular) arm of the adaptive immune system
B lymphocytes make up the humoral arm of the adaptive immune system
Organs and tissues of the immune system that contain the developing lymphocytes (ie bone marrow and thymus) are called the (central/peripheral) immune system
Organs and tissues of the immune system that contain the developing lymphocytes (ie bone marrow and thymus) are called the central immune system
* Sometimes called primary vs secondary
Organs and tissues of the immune system that contain the more mature cells to activate in host defense (including spleen, lymph nodes, and MALT) are called the (central/peripheral) immune system
Organs and tissues of the immune system that contain the more mature cells to activate in host defense (including spleen, lymph nodes, and MALT) are called the peripheral immune system
MALT stands for _
MALT stands for mucosal-associated lymphoid tissue
* Includes: tonsils, adenoids, appendix, Peyer’s pathches, other mucosal lymphoid tissues
The thymus is an important site for (T cell/ B cell) maturation; it can be seen in neonates near _
The thymus is an important site for T cell maturation; it can be seen in neonates near right upper chest
* Called a sail sign
(True/ False) Lymph carries red blood cells
False; Lymph does not carry red blood cells
* Only carries white blood cells and plasma
Three roles of the lymphatic system
- Collect and drain excess fluid from surrounding tissue and to return it to the vascular system
- Absorb fat from the villi of the small intestine
- Act as a conduit for immune cells to get back into circulation
Lack of proper function of lymphatic drainage results in a collection/backup of lymph called _
Lack of proper function of lymphatic drainage results in a collection/backup of lymph called lymphedema
* Can result from problems associated with infection, blockage, and malignancy
A particular disease related to blockage of lymphatic drainage can result from a parasitic infection spread by mosquitos called _
A particular disease related to blockage of lymphatic drainage can result from a parasitic infection spread by mosquitos called filariasis
We have physical barriers like _ and _ to keep pathogens out
We have physical barriers like skin and mucous membranes to keep pathogens out
We have chemical agents that are secreted to exert a wide range of antimicrobial effects; two examples are _ and _
We have chemical agents that are secreted to exert a wide range of antimicrobial effects; two examples are low pH and hydrolytic enzymes
We have certain physical actions that keep pathogens away; for example urination prevents colonization of the urethra; the respiratory and GI tracts are coated with _
We have certain physical actions that keep pathogens away; for example urination prevents colonization of the urethra; the respiratory and GI tracts are coated with sticky mucus
_ cells engulf bacteria and fungi; they increase reactive oxygen species in what is called “oxidative burst”
Neutrophils engulf bacteria and fungi; they increase reactive oxygen species in what is called “oxidative burst”
_ cells are associated with parasitic infection
Eosinophils are associated with parasitic infection
- “Mast cells are tissue resident cells and uniquely required for immediate hypersensitivity.
Basophils are largely circulating cells, but home to areas of allergic inflammation during the late phase response. Eosinophils are resident to the GI tract, but also home to allergic inflammatory sites.”
_ cells are associated with hypersensitivity and release of histamine
Basophils are associated with hypersensitivity and release of histamine
- Mast cells are tissue resident cells and uniquely required for immediate hypersensitivity. Basophils are largely circulating cells, but home to areas of allergic inflammation during the late phase response. Eosinophils are resident to the GI tract, but also home to allergic inflammatory sites.
_ cells have granules containing vasoactive amines like histamines and proteases that will kill bacteria
Mast cells have granules containing vasoactive amines like histamines and proteases that will kill bacteria
- Mast cells are tissue resident cells and uniquely required for immediate hypersensitivity. Basophils are largely circulating cells, but home to areas of allergic inflammation during the late phase response. Eosinophils are resident to the GI tract, but also home to allergic inflammatory sites.
_ are cells that recognize stress or infected cells and kills them by secreting INF-gamma
Natural killer cells are cells that recognize stress or infected cells and kills them by secreting INF-gamma
_ cells are involved in phagocytosis, antigen presentation, and the initiation of T-cell response
Dendritic cells are involved in phagocytosis, antigen presentation, and the initiation of T-cell response
_ cells are considered WBC lymphocytes but are actually part of the innate immune system
Natural killer cells are considered WBC lymphocytes but are actually part of the innate immune system
Bacterial infections will be fought off by 4 components of the immune system _ , _ , _ , and _
Bacterial infections will be fought off by 4 components of the immune system
* Complement
* Neutrophils
* Macrophages
* Dendritic cells
Parasitic infections are fought off by _
Parasitic infections are fought off by eosinophils
Fungal infections are fought off primarily by _ but also _
Fungal infections are primarily fought off by neutrophils but also macrophages
Viral infections are fought off by 5 components of the immune system
Viral infections are fought off by:
1. Complement
2. Interferons
3. NK cells
4. Dendritic cells
5. Macrophages
_ are the microbial molecules that are present on invading cells that stimulate the innate immune system to act
Pathogen-associated molecular patterns (PAMPs) are the microbial molecules that are present on invading cells that stimulate the innate immune system to act
The _ recognize and bind PAMPs
The pattern recognition receptors (PRRs) recognize and bind PAMPs
One of the best studied PAMP is the _ of gram-negative bacteria that stimulates the PRR _
One of the best studied PAMP is the LPS of gram-negative bacteria that stimulates the PRR TLR4
Pattern recognition receptors (PRRs) can either be _ or _ (location)
Pattern recognition receptors (PRRs) can either be secreted/circulating or transmembrane/intracellular
_ is a special protein complex that recognizes products of dead cells, microbes, and crystals; it activates IL-1
Inflammasome is a special protein complex that recognizes products of dead cells, microbes, and crystals; it activates IL-1
_ is a cytokine induced by macrophages and T cells that acts on:
* Endothelial cells to induce inflammation and coagulation
* Hypothalamus to induce fever
* Liver to synthesize acute-phase proteins
* Muscle to induce catabolism
* Cells to undergo apoptosis
* Stimulation of neutrophils
Tumor necrosis factor (TNF) is a cytokine induced by macrophages and T cells that acts on:
* Endothelial cells to induce inflammation and coagulation
* Hypothalamus to induce fever
* Liver to synthesize acute-phase proteins
* Muscle to induce catabolism
* Cells to undergo apoptosis
* Stimulation of neutrophils
_ is a cytokine released by macrophages and endothelial cells that triggers inflammation/coagulation (endothelial cells), fever (hypothalamus), acute phase proteins (liver), and TH17 differentiation (T cells)
IL-1 is a cytokine released by macrophages and endothelial cells that triggers inflammation/coagulation (endothelial cells), fever (hypothalamus), acute phase proteins (liver), and TH17 differentiation (T cells)
_ is a cytokine released by NK cells and T lymphocytes that works to activate macrophages and stimulates some antibody responses
Interferon-gamma is a cytokine released by NK cells and T lymphocytes that works to activate macrophages and stimulates some antibody responses
The three main, pro-inflammatory cytokines are _ , _ , and _
The three main, pro-inflammatory cytokines are TNF-alpha , IL-6 , and IL-1
* Involved in initial inflammation and onset of fever
_ is a cytokine that tells the liver to synthesize acute-phase proteins and tells the B cells to begin proliferation of antibody-producing cells
IL-6 is a cytokine that tells the liver to synthesize acute-phase proteins and tells the B cells to begin proliferation of antibody-producing cells
* Ex: C-reactive protein is one of the acute phase protein produced by the liver
(Innate/ Adaptive) immunity is activated by PAMPs binding to phagocytic cells
Innate immunity is activated by PAMPs binding to phagocytic cells
_ are low MW, soluble proteins that serve as the chemical messengers for regulating innate and adaptive immune systems
Cytokines are low MW, soluble proteins that serve as the chemical messengers for regulating innate and adaptive immune systems
Cytokines that travel in the bloodstream to activate distant tissues are considered _
Cytokines that travel in the bloodstream to activate distant tissues are considered endocrine
* Autocrine: self
* Paracrine: adjacent
The three main endogenous pyrogens are cytokines _ , _ , and _
The three main endogenous pyrogens are cytokines TNF-alpha , IL-1 , and IFNs
_ are special cytokines that move cells
Chemokines are special cytokines that move cells
* Abbreviation: CXCL
_ is the important chemokine involved in the recruitment of neutrophils
CXCL8 is the important chemokine involved in the recruitment of neutrophils
Otherwise known as IL-8
_ is the important chemokine involved in recruiting naiive T cells
CXCL2 is the important chemokine involved in recruiting naive T cells
_ is a special chemokine that activates and recruits macrophages
CCL2 is a special chemokine that activates and recruits macrophages
* Also called monocyte chemoattractant protein 1 (MCP-1)
_ is a chemokine that helps inhibit overactivation/ inflammation by T cells; it stimulates regulatory T cells and the differentiation of TH17
TGF-beta is a chemokine that helps inhibit overactivation/ inflammation by T cells; it stimulates regulatory T cells and the differentiation of TH17
* Prevents the dangerous cytokine storm
CD4 and CD8 T cells secrete cytokine _ which is involved in the survival, proliferation, and differentiation of effector and regulatory T cells
CD4 and CD8 T cells secrete cytokine IL-2 which is involved in the survival, proliferation, and differentiation of effector and regulatory T cells
CD4 and mast cells secrete the cytokine _ which is involved in B cell switching to IgE
CD4 and mast cells secrete the cytokine IL-4 which is involved in B cell switching to IgE
CD4 and mast cells secrete the cytokine _ which is involved in activation of eosinophils
CD4 and mast cells secrete the cytokine IL-5 which is involved in activation of eosinophils
CD4 cells, CD8 cells, and NK cells secrete cytokine _ which is involved in the activation of macrophages
CD4 cells, CD8 cells, and NK cells secrete cytokine IFN-gamma which is involved in the activation of macrophages
CD4 cells (and others) secrete cytokine _ which is involved in the stimulation of acute inflammation
CD4 cells (and others) secrete cytokine IL-17 which is involved in the stimulation of acute inflammation
CD4 and other cells of the innate immune system secrete cytokine _ which stimulates the inhibition of T cell activation and differentiation of regulatory T cells
CD4 and other cells of the innate immune system secrete cytokine TGF-beta which stimulates the inhibition of T cell activation and differentiation of regulatory T cells
_ cells are the primary cells involved in tissue healing
Macrophages are the primary cells involved in tissue healing
* Once signaled by infection resolution, macrophages can produce anti-inflammatory signals as well as signaling tissue-healing cells to arrive at damaged tissues
* They can also phagocytose dead tissues to allow for new, healthy tissue to grow
Drugs that inhibit _ are being developed for the treatment of inflammatory disorders like rheumatoid arthritis, psoriasis, and Crohn disease
Drugs that inhibit TNF-α are being developed for the treatment of inflammatory disorders like rheumatoid arthritis, psoriasis, and Crohn disease
What is the risk to using drugs that inhibit TNF-alpha for treatment of inflammatory disorders?
The risk is that the patient could become immunocompromised
* Reactivation of tuberculosis and hepatitis has been seen with use of these drugs
The three main functions of complement are _ , _ , and _
The three main functions of complement are “OIL”:
opsonization , inflammation , and lysis
Complement activation helps to attach substances or antibodies to invading organisms to help phagocytosis; this is called _
Complement activation helps to attach substances or antibodies to invading organisms to help phagocytosis; this is called opsonization
Complement activation triggers _ by activating mast cells and basophils which dilate blood vessels; then inflammatory phagocytic cells will come in to remove the invading organism
Complement activation triggers inflammation by activating mast cells and basophils which dilate blood vessels; then inflammatory phagocytic cells will come in to remove the invading organism
After opsonization and inflammation, the complement system generates proteins that can penetrate the invading cell’s cell wall to induce _
After opsonization and inflammation, the complement system generates proteins that can penetrate the invading cell’s cell wall to induce lysis
The three complement pathways are _ , _ , and _
The three complement pathways are alternative , lectin , and classical
* Usually initiated in this order but we can have all three of these happening at the same time
_ , _ , and _ are three complement proteins that are anaphylatoxins that promote vasodilation through the release of histamines
C3a , C4a, and C5a are three complement proteins that are anaphylatoxins that promote vasodilation through the release of histamines
* These are revving everything up
* Think anaphylaxis
In addition to having the ability to release histamines and promote vasodilation, _ (complement protein) also increases neutrophil chemotaxis
In addition to having the ability to release histamines and promote vasodilation, C5a (complement protein) also increases neutrophil chemotaxis
Deficiencies in complement proteins that form MAC (C5b-9) can increase susceptibility to _
Deficiencies in complement proteins that form MAC (C5b-9) can increase susceptibility to gram-negative bacteria like Neisseria meningitidis
Complement proteins _ make up the membrane attack complex (MAC)
Complement proteins C5b-9 make up the membrane attack complex (MAC)
Complement protein _ is helping with opsonization
Complement protein C3b is helping with opsonization
Activation of the classical pathway requires interaction with _
Activation of the classical pathway requires interaction with IgG or IgM
Activation of the lectin pathway requires _
Activation of the lectin pathway requires mannose
Activation of the alternative pathway requires _
Activation of the alternative pathway requires microbial surface
Describe the steps of the classical pathway:
Classical pathway:
1. Fc portion of Ig interacts with C1
2. C1 splits C4 and C2
3. C4b2b forms C3 convertase
4. C3 convertase splits C3
5. C4b2b3b forms the C5 convertase
6. C5 convertase splits C5
7. C5b joins MAC
Instead of using C1 to kick off the complement pathway, the lectin pathway uses _
Instead of using C1 to kick off the complement pathway, the lectin pathway uses mannose-binding lectin (MBL)
* MBL take the place of C1 and splits C4
The alternative pathway relies on the presence of complement protein _ floating around which will join Bb to form C3 convertase
The alternative pathway relies on the presence of complement protein C3 floating around which will join Bb to form C3 convertase
_ is a protease inhibitor that downregulates C1q and C1s activation in the classical pathway; this prevents C1 activation from getting out of control
C1 inhibitor is a protease inhibitor that downregulates C1q and C1s activation in the classical pathway; this prevents C1 activation from getting out of control
C1-inhibitor deficiency causes uncontrolled C1 activation and leads to excessive vasoactive peptides like _
C1-inhibitor deficiency causes uncontrolled C1 activation and leads to excessive vasoactive peptides like bradykinin
* This is called hereditary angiodema
_ is a C1-inhibitor deficiency that causes excessive vasoactive peptides (bradykinin)
Hereditary angidema is a C1-inhibitor deficiency that causes excessive vasoactive peptides (bradykinin)
_ helps to down-regulate C3 convertase in the alternative pathway
Decay-accelerating factor (DAF) helps to down-regulate C3 convertase in the alternative pathway
* Deficiency can lead to paroxysmal nocturnal hemoglobinuria
Paraxysmal nocturnal hemoglobinuria is a deficiency in _
Paraxysmal nocturnal hemoglobinuria is a deficiency in decay accelerating factor (DAF)
* Usually down-regulates C3 convertase in the alternative pathway
* Without it we get uncontrolled complement activation –> RBC lysis –> PNH
C1 deficiency: increased risk of _
C1 deficiency: increased risk of immune complex disease such as systemic lupus erythematosus (SLE)
C3 deficiency: increased risk of _
C3 deficiency: risk of encapsulated bacteria infection
C2 deficiency: increased risk of _
C2 deficiency: increased risk of immune complex disease (SLE)
C1-inhibitor deficiency:
C1-inhibitor deficiency: excessive vasoactive peptides (bradykinin) –> hereditary angiodema
C4 deficiency: increased risk of _
C4 deficiency: increased risk of immune complex disease (SLE)
Deficiency in _ , _ , _ , _ , or _ may lead to increased susceptibility to Neisseria infection
Deficiency in C5b , C6 , C7 , C8 , or C9 may lead to increased susceptibility to Neisseria infection
* We call this a terminal complement deficiency
The three main cytokines that act as endogenous pyrogenes are _ , _ , and _
The three main cytokines that act as endogenous pyrogenes are IL-1 , IFNs , and TNF-alpha
Direct binding of C3 to the cell surface of a microbe is the activating step of _ pathway
Direct binding of C3 to the cell surface of a microbe is the activating step of alternative pathway
Prevention of the cleavage of C2 and C4 is caused by _
Prevention of the cleavage of C2 and C4 is caused by C1 esterase inhibitor
The main function of IgA is _
The main function of IgA is mucosal immunity
* IgA will be present in the mucosa like in our noses to fight off pathogens like respiratory pathogens, for example
* IgA is technically the most abundant immunoglobulin in the body because we have so much mucosa
IgA is found in _ form
IgD, IgE, and IgG are all found in _ form
IgM is found in _ form
IgA is found in dimer form
IgD, IgE, and IgG are all found in monomer form
IgM is found in pentamer form
The immunoglobulin that has a pentamer form is _
The immunoglobulin that has a pentamer form is IgM
IgM is primarily responsible for _
IgM is primarily responsible for activation of complement
The main Ig involved in helminth defensea and mast cell degranulation (allergies) is _
The main Ig involved in helminth defensea and mast cell degranulation (allergies) is IgE
What are the key functions of IgG?
What is the purpose of increasing expression of endothelial adhesion molecules during acute inflammatory response to infection?
By increasing the endothelial adhesion molecules, we make it easier to hold onto neutrophils in the site of infection
_ is an important ligand found on T helper cells that enables class switching (plasma cells)
CD40L is an important ligand found on T helper cells that enables class switching (plasma cells)
Th17 cells secrete IL-17 to activate _ cells
Th17 cells secrete IL-17 to activate neutrophils
Treg cells suppress the immune response by secreting _ or _
Treg cells suppress the immune response by secreting IGF-beta or IL-10
Macrophages stimulate CD4+ cells to become Th1 cells by secreting _ cytokine
Macrophages stimulate CD4+ cells to become Th1 cells by secreting IL-12
Macrophages stimulate CD4+ cells to become Th2 cells by secreting _ cytokine
Macrophages stimulate CD4+ cells to become Th2 cells by secreting IL-4
In response to IL-12 secretion by the macrophages, Th1 cells secrete _ to activate the macrophages
In response to IL-12 secretion by the macrophages, Th1 cells secrete IFN-gamma to activate the macrophages
* IFN-gamma will stimulate macrophages but also CD8+ cells
(Th1/ Th2) help trigger cell-mediated response
Th1 help trigger cell-mediated response
(Th1/ Th2) help trigger humoral-mediated response
Th2 help trigger humoral-mediated response
The _ region determines antibody isotype
The Fc region (constant region) determines antibody isotype
Which is the Fc region?
5 is the Fc region
1 corresponds to the Fab region.
2 corresponds to the antigen-binding region.
3 corresponds to the complement-binding region.
4 corresponds to the hinge region.
Complement proteins and macrophages will bind to _ region of antibodies
Complement proteins and macrophages will bind to Fc region of antibodies
_ is the primary antibody produced upon initial immune system exposure to a foreign antigen
IgM is the primary antibody produced upon initial immune system exposure to a foreign antigen
* IgE, IgG, and IgA can only be produced once the B cell undergoes isotype switching
Somatic hypermutation and isotype switching occur in the _
Somatic hypermutation and isotype switching occur in the lymph node
VDJ and VJ recombination of B cells occurs in the _
VDJ and VJ recombination of B cells occurs in the bone marrow (while B cells are maturing)
Which cytokine promotes class switching to IgG?
IL-4
(IgG and IgE)
The most abundant immunoglobulin in the blood is _
The most abundant immunoglobulin in the blood is IgG
* Crosses the placenta
IgE cross-linking activates _ cells
IgE cross-linking activates mast cells –> type I hypersensitivity reaction
The most prevalent antibody in the blood is _
The most prevalent antibody in the blood is IgG
The most prevalent antibody in the body is _
The most prevalent antibody in the body is IgA
* Because the body has so much mucosa
VDJ recombination in B cells occurs early on in the maturation of B cells in the _
VDJ recombination in B cells occurs early on in the maturation of B cells in the bone marrow
* Recombination process involving the DNA in the B cells that codes for antibody structure
* Allows us to have diversity in Fab regions
Ig light chains do not have _ segments
Ig light chains do not have Diversity (D) segments
* They undergo VJ recombination
The enzymes that mediate somatic recombination are _
The enzymes that mediate somatic recombination are RAG-1 and RAG-2: these are VDJ recombinase enzymes
A deficiency in RAG-1/ RAG-2 can lead to a complete lack of T and B cells called _
A deficiency in RAG-1/ RAG-2 can lead to a complete lack of T and B cells called SCID
The two naiive B cell antigen receptors are _ and _
The two naiive B cell antigen receptors are IgD and IgM
Within V regions, we have hyper-varible sequences that encode residues that contact the antigen; these are called _
Within V regions, we have hyper-varible sequences that encode residues that contact the antigen; these are called complementarity-determining regions (CDRs)
After clonal expansion of B cells, we can move into differentiation which included “perfecting” the B cells via processes like _ and _
After clonal expansion of B cells, we can move into differentiation which included “perfecting” the B cells via processes like isotype switching and affinity maturation
The primary antibody response involves _ (immunoglobulin)
The primary antibody response involves IgM (immunoglobulin)
* Does not peak for about 7-10 days
Unlike the primary antibody response, the second antibody response is dominated by _ (immunoglobulin)
Unlike the primary antibody response, the second antibody response is dominated by IgG (immunoglobulin)
* And antibody levels peak much earlier, in about 4-5 days
Mast cell degranulation is mediated by _ (immunoglobulin)
Mast cell degranulation is mediated by IgE (immunoglobulin)
The primary immunoglobulin involved in opsonization is _
The primary immunoglobulin involved in opsonization is IgG
The two primary immunoglobulins that activate complement are _ and _
The two primary immunoglobulins that activate complement are IgM and IgG
The primary immunoglobulin involved in transport across epithelium is _
The primary immunoglobulin involved in transport across epithelium is IgA