Transcript T cell mediated response

Hmmm
A
B
C
D
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Final
Jeopardy
5$
5$
5$
5$
C1 $100
Which of the following acute-phase protein levels is/are increased in human plasma
after acute inflammation?
A.
C-reactive protein
B. HSP Fo
C. Chaperonics
D. Fibrinogen
E. Albumin
F.
a,b,c, and d only
G. all of the above
C1 $100
Which of the following acute-phase protein levels is/are increased in human plasma
after acute inflammation?
A.
C-reactive protein
B. HSP Fo
C. Chaperonics
D. Fibrinogen
E. Albumin
F.
a,b,c, and d only
G. all of the above
Acute Phase Reactants
Increased:
- C reactive protein
(opsonin, activates
complement)
- Amyloid
- Haptoglobin
- Fibrinogen
- Ceruloplasmin
- Alpha 1-antitrypsin
- C3 complement
Most potent stimulus
Decreased:
-
Albumin
Prealbumin
Transferrin
C1 $200
Neutrophils are attracted to areas of inflammation and injury. Homing to areas of
injury requires the neutrophils to adhere to endothelium in the affected area. This
process is mediated by which of the following molecules?
A.
TNF
B. L-selectin
C. IL-2
D. NO
C1 $200
Neutrophils are attracted to areas of inflammation and injury. Homing to areas of
injury requires the neutrophils to adhere to endothelium in the affected area. This
process is mediated by which of the following molecules?
A.
TNF
B. L-selectin
C. IL-2
D. NO
Selectin:
-
1st step in transmigration (Rolling adhesion)
L-selectin (Leucocytes) binds to E-selectin
(Endothelium) and P-selectin (Platelets)
Beta-2 Intergin:
CAMs:
-
-
On leucocytes and platelets
Binds ICAM, VCAM etc.
Anchoring adhesion and
transendothelial migration
On endothelial cells
Binds Beta-2 integrin
Anchoring adhesion and
transendothelial migration
C1 $300
Natural Killer cells:
A. Are restricted by MHC
B. Require previous exposure to antigens
C. Require antigen presentation by APCs
D. Recognize cells that lack self-MHC
E. Are not a part of the body’s natural immune-surveillance for cancer
F. Are a type of T cell
C1 $300
Natural Killer cells:
A. Are restricted by MHC
B. Require previous exposure to antigens
C. Require antigen presentation by APCs
D. Recognize cells that lack self-MHC
E. Are not a part of the body’s natural immune-surveillance for cancer
F. Are a type of T cell
Natural Killer Cells (NK Cells)
• Activated by IL-2
• NOT involved in T cell receptor & antigen-MHC recognition
• Attack cells with low expression of MHC (missing self) : Viral
infections?
• Attack cells with bound antibody (Have Fc receptor)
C1 $400
Which of the following is NOT an oxidant generated in inflammation:
A.
Superoxide anion radical (O2-)
B.
C.
D.
E.
Hydrogen Peroxide (H2O2)
Hydroxyl radical (-OH)
Hypochlorous acid (HOCL-)
Superoxide dismutase and Catalase
C1 $400
Which of the following is NOT an oxidant generated in inflammation:
A.
Superoxide anion radical (O2-)
B.
C.
D.
E.
Hydrogen Peroxide (H2O2)
Hydroxyl radical (-OH)
Hypochlorous acid (HOCL-)
Superoxide dismutase and Catalase
Oxidative Burst Kills bacteria
NADPH Oxidase pathway generates reactive oxygen species
Oxidants:
-
Superoxide anion radical (O2)
Hydrogen peroxide (H2O2)
Hydroxyl Radical (OH)
Hypocholorous Acid (HOCl)
Cellular defenses against oxidants:
-
Superoxide anion radical (O2) ------- Superoxide Dismutase
Hydrogen peroxide (H2O2)
------- Catalase, Glutathione peroxidase
Hydroxyl Radical (OH)
------- CANNOT be eliminated
Hypocholorous Acid (HOCl)
- Primary mechanism of injury for O2 radicals:
- DNA damage
- RBCs:
- Have antioxidant properties
- Have Superoxide dismutase and Catalase
- Chronic Granulomatous Disease:
- Enzyme defect in PMNs and macrophages
- Leads to decreased superoxide radical formation
C1 final
Steve is on the million dollar question in “Who wants to be a Millionare’. He is
phoning a friend and its you…… Guess the correct mechanism of action for the
drug below?
A. Glucocorticoids stimulate phospholipase and prostaglandin synthesis
B. ASA reversibly and non-selectively inhibits COX and inhibits prostaglandin
synthesis
C. Celebrex is a selective COX2 inhibitor which only acts at inflamed tissues
and decreases incidence of ulcers (But causes increased incidence of CVS
S/E)
D. NSAIDs are nonreversible COX inhibitors that are both nonselective
(Ibuprofen, Naproxen) and selective (Celebrex)
E. I quit this residency %&%$#$
Timer
C1 final
Steve is on the million dollar question in “Who wants to be a Millionare’. He is
phoning a friend and its you…… Guess the correct mechanism of action for the
drug below?
A. Glucocorticoids stimulate phospholipase and prostaglandin synthesis
B. ASA reversibly and non-selectively inhibits COX and inhibits prostaglandin
synthesis
C. Celebrex is a selective COX2 inhibitor which only acts at inflamed tissues
and decreases incidence of ulcers (But causes increased incidence of CVS
S/E)
D. NSAIDs are nonreversible COX inhibitors that are both nonselective
(Ibuprofen, Naproxen) and selective (Celebrex)
E. I quit this residency %&%$#$
Lipid inflammatory mediators
Steroids
inhibit
ASA
inhibits
irreversibly
COX2
inhibitors
selectively
inhibit only
inflamed
tissues.
Decreased
ulcer risk.
Have CVS
S/Es
Lipid mediator impact on inflammation
C2 $100
T cells recognize only those antigens associated with surface major histocompatibility
complex molecules by specialized antigen-presenting cells. Antigen presenting cells
do NOT include:
A.
Dendritic cells
B. B cells
C. Endothelial cells
D. Macrophages
E. I give up
C2 $100
T cells recognize only those antigens associated with surface major histocompatibility
complex molecules by specialized antigen-presenting cells. Antigen presenting cells
do NOT include:
A.
Dendritic cells
B. B cells
C. Endothelial cells
D. Macrophages
E. I give up
C2 $200
MHC complex:
A. Class I activates CD8 cells
B. Class II activates CD4 cells
C. Class I is present on all nucleated cells while Class II only on B cells and
APC
D. Class I activates cytotoxic T cells while Class II stimulates antibody
formation
E. All of the above
C2 $200
MHC complex:
A. Class I activates CD8 cells
B. Class II activates CD4 cells
C. Class I is present on all nucleated cells while Class II only on B cells and
APC
D. Class I activates cytotoxic T cells while Class II stimulates antibody
formation
E. All of the above
C2 $300
Which activation sequence is completely TRUE?
A. Viral protein  bound to class I MHC  cell surface  recognized by CD4
T cells
B. Bacteria  endocytosed  bound to class I MHC  cell surface
recognized by CD4 T cell and B cells  Activation of B cells into plasma
cells and memory B cells
C. Macrophage (APC) Helper T cell Killer T cell, NK cells, memory T cell,
cytotoxic T cell
D. Macrophage (APC) B cells forms memory B cells (actively releases
antibody) and plasma cells (for future response)
C2 $300
Which activation sequence is completely TRUE?
A. Viral protein  bound to class I MHC  cell surface  recognized by CD4
T cells
B. Bacteria  endocytosed  bound to class I MHC  cell surface
recognized by CD4 T cell and B cells  Activation of B cells into plasma
cells and memory B cells
C. Macrophage (APC) Helper T cell Killer T cell, NK cells, memory T cell,
cytotoxic T cell
D. Macrophage (APC) B cells forms memory B cells (actively releases
antibody) and plasma cells (for future response)
C2 $400
Which of the following IS true?
2-4a (Type a clue in the
form of a statement)
A. Supressor T cells (CD8) have no role in regulating CD4 and CD8 cells
B. Cytotoxic T cells (CD8) recognize and attack non-self antigens attached to
MHC class II receptors
C. Defect in cell mediated immunity leads to infection with intracellular
pathogens (TB, viruses)
D. Intradermal skin test (TB skin test) is used to test antibody-mediated immunity
C2 $400
Which of the following IS true?
A. Supressor T cells (CD8) have no role in regulating CD4 and CD8 cells
B. Cytotoxic T cells (CD8) recognize and attack non-self antigens attached to
MHC class II receptors
C. Defect in cell mediated immunity leads to infection with intracellular
pathogens (TB, viruses)
D. Intradermal skin test (TB skin test) is used to test antibody-mediated immunity
C2 $500
Which of the following is NOT true?
A.
Helper T cells (CD4) release IL2 which causes B cells to mature into plasma
cells
B. Helper T cells (CD4) release IL4 which causes cytotoxic T cell maturation
C. Th1 and Th2 helper cells both predominantly release proinflammatory cytokines
D. Helper T cells (CD4) are involved in delayed type hypersensitivity (by attracting
inflammatory cells by chemokine secretion)
C2 $500
Which of the following is NOT true?
A.
Helper T cells (CD4) release IL2 which causes B cells to mature into plasma
cells
B. Helper T cells (CD4) release IL4 which causes cytotoxic T cell maturation
C. Th1 and Th2 helper cells both predominantly release proinflammatory cytokines
D. Helper T cells (CD4) are involved in delayed type hypersensitivity (by attracting
inflammatory cells by chemokine secretion)
The immune systems share cells and some functions
-
-
Nonspecific
Not long
lasting
These cells +
complement
-
Specific
Has memory
T & B cells
T Cells
• Helper T cells (CD4):
• Releases:
• IL-2  Activated cytotoxic T cells and NK cells (Th1)
• IL-4  Activates B cells into plasma and memory cells (Th2)
• IFN-gamma  Potentiates macrophage bactericidal property
• Cytotoxic T cells (CD8):
• Attacks cells damaged, infected or dysfunctional
• T cell receptor attaches to MHC Class I with bound antigen  releases
perforin + granulysin (pores in cell membrane and lysis) + releases
granzymes (causes apoptosis)
Monocytes are activated and mature into tissue Macrophages
Monocyte Phagocytosis for MHC I/II presentation to CD8 and CD4 T cells
MHC I
- Interact with CD8 (T cytotoxic cells)
- Found on ALL nucleated cells
- Present endogenous antigen (viruses
or cytosolic proteins)
MHC II
- Interact with CD4 (T helper cells)
- Found only on APCs (dendritic,
macrophages, B cells)
- Present exogenous antigen
(phagocytosed bacterial products)
-
Activated by Th2 cells
IL-4
10% become memory cells
- Secrete IgG, not IgM
Eosinophils and Basophils
Worms
C3 $100
Activation of the classical complement pathway is caused by which of the following
stimuli?
A.
Mannose
B. Microbial cell surfaces
C. Interleukin-2
D. Antigen-antibody complexes
C3 $100
Activation of the classical complement pathway is caused by which of the following
stimuli?
A.
Mannose
B. Microbial cell surfaces
C. Interleukin-2
D. Antigen-antibody complexes
C3 $200
Which of the following regarding complement activation is NOT true:
A. Alternate pathway is activated by antigen-antibody complex
B. Classic pathway is activated by direct binding of pathogen to C1
C. Factors C1, C2 and C3 are found only in the classic pathway
D. Endotoxin and bacteria activate the alternate pathway leading to C3 activation
E. Factors B, D and P are found only in the alternate pathway
C3 $200
Which of the following regarding complement activation is NOT true:
A. Alternate pathway is activated by antigen-antibody complex
B. Classic pathway is activated by direct binding of pathogen to C1
C. Factors C1, C2 and C3 are found only in the classic pathway
D. Endotoxin and bacteria activate the alternate pathway leading to C3 activation
E. Factors B, D and P are found only in the alternate pathway
C3a, C4a, C5a (Anaphylatoxins)
Bronchoconstriction, vascular
permeability, activate mast cells
and basophils
C3b and C4b: Opsonization
C5b-9b (MAC): Insert into
pathogen cell mebrane or
cells infected with bacteria 
makes hole  cell lysis
C3 $300
Antibody functions include:
A. IgA and IgD fix complement
B. IgA and IgG are opsonins
C. All have a variable region recognized by only viruses
D. All have a constant region recognized by PMNs and macrophages
C3 $300
Antibody functions include:
A. IgA and IgD fix complement
B. IgA and IgG are opsonins
C. All have a variable region recognized by only viruses
D. All have a constant region recognized by PMNs and macrophages
C3 $400
Which of the following is TRUE regarding antibodies:
A. IgM is the initial antibody produced after exposure to antigen
B. IgG is the most abundant antibody in the body, can cross placenta and protects
the newborn
C. IgA is found in secretions, Peyers patches in gut, breast milk and helps prevent
microbial adherence and invasion in gut
D. IgE is involved in allergic reactions, parasitic infections
E. IgD is a membrane bound receptor on T cells
F. A, B, C and D ONLY
C3 $400
Which of the following is TRUE regarding antibodies:
A. IgM is the initial antibody produced after exposure to antigen
B. IgG is the most abundant antibody in the body, can cross placenta and protects
the newborn
C. IgA is found in secretions, Peyers patches in gut, breast milk and helps prevent
microbial adherence and invasion in gut
D. IgE is involved in allergic reactions, parasitic infections
E. IgD is a membrane bound receptor on T cells
F. A, B, C and D ONLY
Antibody Mediated Phagocytosis of Bacteria
• IgM:
• Primary immune response (first antibody made)
• Activates complement AND opsonin for phagocytosis
• Does NOT cross placenta
• Lack of IgM after splenectomy leads to OPSS
• IgG:
• Most common Ab overall
• Secondary immune response
• Activates complement AND opsonin for phagocytosis
• Crosses placenta (protection in newborn)
• Type II and III Hypersensitivity reaction
• IgE:
• Type I Hypersensitivity reaction and parasitic infection
• IgA:
• Mucosal immunity (Found in secretions)
• Plasma cells release IgA  Taken up by epithelial cells and released on
mucosal luminal surface  IgA bids to pathogen to prevent its adherence to
mucosal cells
C3 $500
Match the 2 columns below for the type of hypersensitivity reaction:
A. Type I
SLE
B. Type II
Asthma, allergic reactions
C. Type III
ITP, acute hemolytic reactions
D. Type IV
Graft versus host disease
C3 $500
Match the 2 columns below for the type of hypersensitivity reaction:
A. Type I
Asthma, allergic reactions
B. Type II
ITP, acute hemolytic reactions
C. Type III
SLE
D. Type IV
Graft versus host disease
• Type I:
• Asthma, allergic reactions (lymphazurin blue), anaphylaxis
• Requires re-exposure
• IgE mediated (Antigen interacts with IgE bound to mast cells and basophils)
• Histamine mediated response, Bradykinin causes pain
• Type II:
• ITP, acute hemolytic reactions, hyperacute rejection
• IgG or IgM mediated (activates either cell mediated immunity OR activates
complement)
• Type III:
• SLE, serum sickness (anivenom)
• Antigen-antibody complexes (IgG mediated) deposit in vessel walls and
induce inflammation (Antibodies NOT bound to cell surface as in Type II)
• Type IV:
• Graft versus host disease, chronic rejection, PPD test, contact dermatitis
• T cell mediated response (Antibody independent), takes 2-3 days
C4 $100
Apoptosis is characterized by which of the following?
A.
loss of cell membrane integrity
B. Inflammation
C. DNA fragmentation
D. cytokine production
C4 $100
Apoptosis is characterized by which of the following?
A.
loss of cell membrane integrity
B. Inflammation
C. DNA fragmentation
D. cytokine production
C4 $200
Cellular injury from oxidants may be manifested by which of the following?
A.
Cell membrane lipid peroxidation
B. DNA strand breaks
C. Cytoskeletal disassembly
D. Depletion of adenosine triphosphate
E. a,b, and c only
F. all of the above
C4 $200
Cellular injury from oxidants may be manifested by which of the following?
A.
Cell membrane lipid peroxidation
B. DNA strand breaks
C. Cytoskeletal disassembly
D. Depletion of adenosine triphosphate
E. a,b, and c only
F. all of the above
Apoptosis vs Necrosis
C4 $300
You are participating in a race……..
You overtake the second person
What position are you in?
C4 $300
2nd place
C4 $400
Match the 2 columns below for the predominant cell type by day s/p injury:
A. 1st hour
Macrophages
B. Days 0-2
Fibroblasts
C. Days 3-4
Platelets
D. Days 5 and on
PMNs
C4 $400
Match the 2 columns below for the predominant cell type by day s/p injury:
A. 1st hour
Platelets
B. Days 0-2
PMNs
C. Days 3-4
Macrophages
D. Days 5 and on
Fibroblasts
C4 $500
Which of the following is the KEY cell and the KEY factor in wound healing?
A. Macrophage, PDGF (Platelet derived Growth Factor)
B. Platelet, PDGF
C. Macrophage, PAF (Platelet Activating Factor)
D. Fibroblast, FGF (Fibroblast Growth Factor)
E. PMNs, EGF (Epidermal Growth Factor)
F. Macrophage, TGF-B
C4 $500
Which of the following is the KEY cell and the KEY factor in wound healing?
A. Macrophage, PDGF (Platelet derived Growth Factor)
B. Platelet, PDGF
C. Macrophage, PAF (Platelet Activating Factor)
D. Fibroblast, FGF (Fibroblast Growth Factor)
E. PMNs, EGF (Epidermal Growth Factor)
F. Macrophage, TGF-B
Wound Healing
• Predominant cell:
• Macrophage
• Predominant growth factor:
• PDGF
• Predominant cytokines:
• IL-1 and TNF alpha
• Order of cell arrival in wound:
• Platelets  PMNs (day 0-2)  Macrophages (day 3-4) 
Fibroblasts (day 5 on)
C5 $100
Aspirin and non-steroidal anti-inflammatory drugs interfere with platelet function via
their activity against which enzyme?
A.
Thromboxane synthase
B. Nitric oxide synthase
C. Phospholipase C
D. Mitogen-activated protein kinase
C5 $100
Aspirin and non-steroidal anti-inflammatory drugs interfere with platelet function via
their activity against which enzyme?
A.
Thromboxane synthase
B. Nitric oxide synthase
C. Phospholipase C
D. Mitogen-activated protein kinase
C5 $200
Platelets have a wide array of functions in inflammation. Which of the following is/are
among these?
A.
Synthesis and release of vasoactive eicosanoids
B. Release of chemotactic factors
C. Adherence to and coating of bacterial and tumor cells
D. Increase of vascular permeability
E. Phagocytosis of bacteria
F. a,b,c, and d only
G. all of the above
C5 $200
Platelets have a wide array of functions in inflammation. Which of the following is/are
among these?
A.
Synthesis and release of vasoactive eicosanoids
B. Release of chemotactic factors
C. Adherence to and coating of bacterial and tumor cells
D. Increase of vascular permeability
E. Phagocytosis of bacteria
F. a,b,c, and d only
G. all of the above
Platelets
• Tissue Injury  exposed collagen
•  PAF released from endothelium  recruits platelets, leucocytes 
PDGF released by platelets  PMN and macrophage recruitment
•  Tissue factor released from endothelium  activates clotting
cascade  fibrin crosslinks platelets  Platelet plug formed
•  vasoconstriction from platelet and endothelial TXA2
•  Platelets release histamine  vasodilation (late)  Edema and
leucocyte migration
• PDGF: KEY growth factor in wound healing
• Chemotactic
• Activates inflammatory cells and fibroblasts
• Angiogenesis and accelerates wound healing
• TGF-beta: Immunosupressive
Platelets do more than induce coagulation cascade
Platelets Crosstalk with the immune system
C5 $300
Nitric oxide is ubiquitous signaling molecule, active in many aspects of inflammation.
The effects of NO are transient, in part because of rapid inactivation. Which of the
following molecules is involved in inactivation of NO?
A.
Copper
B. Hemoglobin
C. L-arginine
D. Citrulline
C5 $300
Nitric oxide is ubiquitous signaling molecule, active in many aspects of inflammation.
The effects of NO are transient, in part because of rapid inactivation. Which of the
following molecules is involved in inactivation of NO?
A.
Copper
B. Hemoglobin
C. L-arginine
D. Citrulline
C5 $400
TNF alpha is responsible for all the following except:
A. Principally produced by macrophages
B. Increases cell adhesion molecules (ICAM, selectins)
C. Is a procoagulant
D. Causes cachexia in cancer patients
E. Causes myocardial excitement in high concentrations
F. Activated PMNs and other macrophages  Growth factor production  cell
recruitment
C5 $400
TNF alpha is responsible for all the following except:
A. Principally produced by macrophages
B. Increases cell adhesion molecules (ICAM, selectins)
C. Is a procoagulant
D. Causes cachexia in cancer patients
E. Causes myocardial excitement in high concentrations
F. Activated PMNs and other macrophages  Growth factor production  cell
recruitment
C5 $500
Match the following:
A. IL-1
Increases hepatic acute phase proteins
B. IL-6
Chemotaxis of PMNs and angiogenesis
C. IL-8
Released by alveolar macrophages in atelectasis causes
fever (PGE2 mediated)
A. IL-10
Down regulation of immune response
C5 $500
Match the following:
A. IL-1
Released by alveolar macrophages in atelectasis causes
fever (PGE2 mediated)
B. IL-6
Increases hepatic acute phase proteins
C. IL-8
Chemotaxis of PMNs and angiogenesis
D. IL-10
Down regulation of immune response
What do cytokines really do ..………. Simple !!!
Cytokines
• Most produced by Macrophages
• Major cytokine for inflammation IL-1 and TNF
• TNF alpha:
• Procoagulant
• Low concentration  Myocardial excitement
• High concentration  Myocardial depression, MOF
• Cachexia in cancer patients
• IL-1:
• Induces fever (PGE2 mediated)
• NSAIDs  Reduce fever by reducing PGE2 production
• Atelectasis  Fever by release of IL-1 from alveolar macrophages
• IL-6:
Hepatic acute phase protein production
• IL-10:
Downregulates immune response
• IL-15:
Activates NK cells in response to viral infection
Interferons
• Released by Lymphocytes and NK cells in response to viral infection
• Activates cell mediated immunity
• Upregulates MHC expression
• Inhibits viral replication
Questions 1-5
TNF alpha is responsible for all the following except:
A. Principally produced by macrophages
B. Increases cell adhesion molecules (ICAM, selectins)
C. Is a procoagulant
D. Causes cachexia in cancer patients
E. Causes myocardial excitement in high concentrations
F. Activated PMNs and other macrophages  Growth factor production  cell
recruitment
TNF alpha is responsible for all the following except:
A. Principally produced by macrophages
B. Increases cell adhesion molecules (ICAM, selectins)
C. Is a procoagulant
D. Causes cachexia in cancer patients
E. Causes myocardial excitement in high concentrations
F. Activated PMNs and other macrophages  Growth factor production  cell
recruitment
Neutrophils are attracted to areas of inflammation and injury. Homing to areas of
injury requires the neutrophils to adhere to endothelium in the affected area. This
process is mediated by which of the following molecules?
A.
TNF
B. L-selectin
C. IL-2
D. NO
Neutrophils are attracted to areas of inflammation and injury. Homing to areas of
injury requires the neutrophils to adhere to endothelium in the affected area. This
process is mediated by which of the following molecules?
A.
TNF
B. L-selectin
C. IL-2
D. NO
Which of the following is NOT an oxidant generated in inflammation:
A.
Superoxide anion radical (O2-)
B.
C.
D.
E.
Hydrogen Peroxide (H2O2)
Hydroxyl radical (-OH)
Hypochlorous acid (HOCL-)
Superoxide dismutase and Catalase
Which of the following is NOT an oxidant generated in inflammation:
A.
Superoxide anion radical (O2-)
B.
C.
D.
E.
Hydrogen Peroxide (H2O2)
Hydroxyl radical (-OH)
Hypochlorous acid (HOCL-)
Superoxide dismutase and Catalase
Apoptosis is characterized by which of the following?
A.
loss of cell membrane integrity
B. Inflammation
C. DNA fragmentation
D. cytokine production
Apoptosis is characterized by which of the following?
A.
loss of cell membrane integrity
B. Inflammation
C. DNA fragmentation
D. cytokine production
Aspirin and non-steroidal anti-inflammatory drugs interfere with platelet function via
their activity against which enzyme?
A.
Thromboxane synthase
B. Nitric oxide synthase
C. Phospholipase C
D. Mitogen-activated protein kinase
Aspirin and non-steroidal anti-inflammatory drugs interfere with platelet function via
their activity against which enzyme?
A.
Thromboxane synthase
B. Nitric oxide synthase
C. Phospholipase C
D. Mitogen-activated protein kinase