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99 Cards in this Set

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When does adaptive immunity become active after an infection?
Days 1-5
When is innate immunity active?
Always - from hours 0-6
What are the 5 phases in an adaptive immune response?
RaeDM
-Recognition
-Activation
-Elimination
-Decline
-Memory
What are the 2 branches of adaptive immunity?
-Cell-Mediated
-Humoral
What does cell-mediated immunity function to combat?
Intracellular pathogens
What is cell-mediated immunity mediated by?
T lymphocytes
With what 3 other cell types do T cells interact during cell mediated immunity?
-Phagocytes
-Infected host cells
-B cells
What are 2 ways that intracellular microbes get that way, get into cells?
1. Phagocytosis, surviving phagolysosomes, and getting out into the cytoplasm
2. Bind receptor and getting into the nonphagocytic cell's cytoplasm
How can phagocytosed microbes survive within the cytoplasm of a cell?
By surviving the phagolyososomal enzymes and either staying within vacuoles or escaping.
3 bugs that can survive phagolysosomes:
-Mycobacteria
-Listeria monocytogenes
-Legionella pneumophila
What fungus can survive phagolyosomes?
Cryptococcus neoformans
What 2 protozoa can survive phagolysosomes?
-Leishmania
-Trypanosoma cruzi
What can bind a cell surface receptor to infect a cell?
-All viruses
-All rickettsiae
-Plasmodium falciparum and Cryptosporidium parvum
After T cells are born in the marrow, where do they go?
To the thymus for maturation
After naive T cells undergo pos and neg selection in the thymus where do they go?
To peripheral lymphoid organs for immne surveillance.
What capability does a naive T cell have? What can't it do?
-Capable of antigon recognition
-Not able to eliminate pathogen
What does antigen recognition result in in T cells?
1. Clonal Proliferation
2. Differentiation into effector cells
How is T-cell immune surveillance different than for B cells?
T cells circulate between the bloodstream and peripheral lymphoid organs; B cells just stay sequestered in lymph organs.
What are the different peripheral lymph organs that T cells circulate to?
-Spleen
-Lymph nodes
-Mucosal sites - skin, lungs, etc
What tells T cells where to go?
Homing addresses
What are the address ligands on vascular endothelial cells that homes T cells to skin?
-E selectin
-CCL17
After being homed to the correct endothelial site and diapedesis, how do T cells home to the actual keratinocytes in skin?
Via interaction of
T cell: CCR10
Keratinocytes: CCL27
What are CCL17, CCR10, and CCL27 all examples of?
Chemokines
What is the homing receptor for T cells to get to the gut?
MAdCAM-1 ( on epithelium)
What ligands on Tcells bind to the MAdCAM-1 receptor at gut epithelium?
-L-selectin
-alpha4/Beta7
(both bind simultaneously)
After binding to the proper endothelial site and diapedesis, how do gut-homing T cells bind to the proper epithelial sites?
Via more chemokines
What is required for Tcell activation?
1. Recognition of an APC-associated antigen within a peripheral lymphoid organ
2. Costimulatory signal
What happens when T cells are activated?
They secrete IL-2
What is IL-2 critical for?
Subsequent clonal proliferation.
What are the effector functions of effector Th cells?
-Activation of macrophages
-Activation of B cells
-Activation of other cells
What are the effector functions of effector Tc cells?
-Killing of infected target cells
-Macrophage activation
When during an immune response does antigen processing occur in APCs?
This is going on during the innate immune response
What molecules on Tcells are involved in antigen recognition?
-TCR binds Ag + MHC components
-CD4 or CD8 bind MHC
How do T cells bind APC's with enough affinity?
Chemokines get produced during the innate immune response that enhance integrin binding.
Once in lymphoid tissue, do naive T cells find and bind their appropriate Ag right away?
No; they transiently sample many different APC/peptides
What happens when during the sampling process in a peripheral lymph node, a Tcell encounters its appropriate Ag?
LFAI:ICAMI binding affinity increases substantially!
When a microbe enters the body, what is the first step in activating cell-mediated immunity?
Phagocytic cells engulf it and then travel to peripheral lymphoid tissues to act as APCs
What activates Tcells?
1. Ag presentation
2. Costimulatory 2nd signal
When activated what do Tcells secrete?
Il-2
What does IL-2 do?
Causes clonal proliferation
What is the general effector function of CD4+ T cells?
To secrete cytokines and help
What type of antigens are recognized by Thelper cells?
Extracellular
What is the general effector function of CD8+ T cells?
To lyse cells that are infected
What type of antigens are recognized by Tcytotoxic cells?
Intracellular, cytoplasmic
What needs to happen in order for a naieve T cell to be stimulated and activated?
It has to bind two or more TCR/CD receptors simultaneously
What are the 2 families of TCR?
1. alpha/beta (most common)
2. Gamma/delta
What does the alpha/beta receptor recognize?
Protein antigens
What does the gamma/delta receptor recognize?
lipids
What are the 2 molecules that are involved in signal transduction for Tcells?
-CD3
-weird snake thing
What is CTLA-4?
A signal transduction molecule on T cells that causes negative regulation at the end of an immune response
What are the 2 adhesion molecules on Tcells that are involved in Tcell activation?
-LFA-1
-VLA-4
What is the ligand for LFA1 and what cells express it?
ICAM1; on APCs and Endothelial cells
What is the ligand for VLA4 and what cells express it?
VCAM1; only on endothelium.
What are the signals that increase integrin affinity during Recognition?
-TCR induced signals
-Chemokine releases during innate immune responses
What happens if one of the 2 necessary signals for Tcell activation is missing?
Tcell anergy
But the result of both signals being present leads to:
Tcell activation and IL-2 secretion
What is a case in which the B7 costimulatory signal would be absent?
If an APC was resting, deficient of the molecule B7
What takes an APC out of resting, to express B7?
Activation by microbes or the innate immune response.
What does APC activation refer to?
The increase expression of B7 costimulators, and secretion of cytokines
What is one cytokine that active APCs secrete?
IL-12
Where are immature, B7 devoid dendritic cells found?
In peripheral tissues - you don't want presentation happening out there.
Where are mature B7 positive dendritic cells found?
In lymphoid tissue, where you do want antigen presentation to occur!
What is necessary for macrophages to express B7?
Expression of bacterial protein
When would macrophages not express B7 protein?
When they eat nonbacterial (maybe self?) protein. you don't want that to start off a reaction.
Rather than engulfing microbes how do Bcells get hold of antigens?
By binding to specific antigens with their surface Ig's.
What happens once Bcells bind to microbes via surface Ig's?
Antigen is processed and presented via Class II MHC to present along with B7 to Tcells.
When after T-cell activation does clonal proliferation begin?
1-2 days after activation
What changes to allow for the start of proliferation?
The IL-2 receptor affinity on Tcells increases
What will produce a greater progeny of clones in response to activation; a CD4 or CD8 Tcell?
CD8 expands 10,000X
CD4 only expands 100-1000X
What happens after clonal expansion during cell-mediated immunity?
Differentiation into effector T lymphocytes and memory cells.
What happens to these differentiated T cells?
They migrate out from the lymphoid tissue, back to the site of infection.
How do the Tcell clones know where to go?
Because of a chemokine trail left by the innate immune response
What type of response gets rid of virus infected cells?
CTL's cause apoptosis
What type of response gets rid of intracellular bacteria?
TH1 cells
What type of response gets rid of extracellular bacteria?
B cells
What is the main gist of how CD4+ Thelper cells work?
They express CD40L which binds to CD40 on APCs which provides an amplification signal to maintain the immune response.
What APCs have CD40?
All of them; macrophages, dendritic cells, and b-lymphocytes
What does CD40L binding CD40 on APCs result in?
It amplifies the immune response and activates macrophages and Bcells.
Which subset of Thelper cells gives its amplification signal to macrophages? B cells?
Th1 - activates macrophages

Th2 - activates B cells
How exactly do Th1 cells activate macrophages?
1. By binding CD40L to CD40
2. By producing IFN-y
How exactly do Th2 cells activate B cells?
1. By binding CD40L to CD40
2. By producing IL-4, 5, and 10
What are three results of Th1 secreted IFN-y?
1. Stimulates IgG1/3 Ab production to bind APC Fc receptors (opsonization)
2. Activates complement
3. Stimulates B7 expression
What types of pathogens is the Th1 subset directed agains?
Intracellular microbes ingested by phagocytes
What types of pathogens is the Th2 subset directed against?
Protozoa, helminths, parasites.
What does IL-4 secreted by Th2 cells do?
Causes Bcells to make IgE which will result in mast cell degranulation.
What does Il-5 secreted by Th2 cells do?
Activates eosinophils
What tells Th cells whether to become Th1 or Th2 subsets in the first place?
Signals during naieve cell activation.
What is the signal for Tcells to become Th1? Th2?
Th1: IL-12 secreted by APCs

Th2: Il-4 secreted by "other cellular sources".
What is the function of the IL-10 secreted by Th2 cells?
It inhibits macrophage activation
What disease takes advantage of the fact that Th2 activation can tone down Th1 activity?
Crohn's disease
What activates Th2 subsets that in turn deactivate macrophage activity and prevents chronic tissue damage?
Trichuris suis (a parasite)
What is the effector function of Tc cells?
They cause apoptosis of virus infected cells.
How do Tc cells cause apoptosis?
By secreting perforins and granzymes
What is the other fraction of Tcells that differentiate during an immune response?
Memory cells
What immune response resolves and aids in wound healing after an infection is successfully eradicated?
Innate
Do memory T cells do anything?
No, but they retain the capability to produce cytokines and kill infected cells.
How long does it take for an immune response to completely resolve after an infection is eradicated?
1-2 weeks
What type of immune response is it when APCs are activated in response to antigen exposure?
Innate
What happens when APCs are activated?
Increased expression of B7