The Life of a T Cell- Responding to an Infection Flashcards
What is the major function of:
- CD4 Tcell
- CD8 Tcell
- NK Tcell
- release cytokines
- cytotoxic killer cells
- secrete cytokines rapidly within minutes to hours of stimulation
What dictates the type of cytokine released by DC, macrophages, epithelial cells, NKT cells, etc?
the type of pathogen
What cytokine is chronically released in cancer? What cells release it? What does it cause?
IL-6 is released by macrophages, endothelial cells, T-cells and it causes the acute liver phase (complement fixation and opsonization)
What cells release TNF? What are the effects?
T-cells and macrophages
Inflammation, fever, acute phase
What cells release IL-1? What are the effects?
T-cells
macrophages
endothelial cells
epithelial cells
Inflammation, fever, acute phase, Th17 differentiation
If the APC releases the IL-12 cytokine
- what transcription factor is activated?
- what will the tcell become?
- What cytokine is produced?
- Tbet
- Th1
- gamma-IFN
If the APC released IL4, IL25:
- what TF is activated?
- What will the T-cell become?
- What cytokine is produced?
- GATA3
- Th2
- IL-4, IL5, IL13
If the APC releases the cytokines IL1, IL6, TGFb:
- What TF is activated?
- What with the T cell become?
- What cytokine is produced?
- ROR
- Th17
- IL17
If the APC releases IL6 and IL21:
- What TF is activated?
- What will the T cell become?
- What cytokine will be released?
- ??
- Tfh
- IL-21
What TF will induce the T cell to become Treg?
FOXP3
What 3 things does a Treg cell do?
- suppress the development and activation of potentially autoreactive cells
- regulate pathogen induced inflammatory response
- control immune cell homeostasis
What TF is associated with Th17?
ROR
What cytokine does Th17 secrete?
What is the function?
IL17 which attacks extracellular pathogens in tissue bed and gut (specifically fungal, viral and bacterial)
What TF is associated with Th1?
Tbet
What TF is associated with Th2?
GATA3
What cytokine induces the TF Tbet?
IL12
What cytokine induces the TF GATA3?
IL4 and IL25
What cytokines induce the TF ROR?
IL1 IL6 TGFb
What cytokines induce the T-cell to become Tfh?
IL6 and IL21
What T cell subsets do IL-6 cytokines help induce?
Th17 and Tfh
What cytokine is released by Th1?
gamma interferon
What cytokines are released by Th2?
IL4, IL5. IL13
What is the major role of gamma-IFN?
to kill intracellular bacteria
What is the major role of IL4,5,13?
help make antibodies
What have the Th2 cells been linked to?
allergies and atopy (hypersensitivity)
What are Th17 cells linked to?
viral, fungal and bacterial infections
Where would one find Tfh cells?
What do they do?
In germinal centers where they support B-cell activation and somatic hypermutation
What is the common infection that is caused by the parasite T. gondii?
How many people worldwide have been infected with these?
What is it usually not a problem?
toxoplasma.
1/3
It is not usually a problem bc CD4 T cells of the Th1 subset can usually clear it
What are the three major functions of gamma interferon released by the Th1 cell?
- stimulate macrophage
- enhance antiviral response
- upregulate MHCI so the virally infected cells can be killed by CD8 T-cells
Th1 cells are especially important for clearing what type of infection?
What are 4 examples of this type of infection?
Intracellular bacteria, virus or parasite
- T. gondii
- mycobacterium tuberculi
- Listeria
- influenza
When a Th1 cell interacts with a B cell and releases IFN-gamma, what is the result?
complement binding and opsonizing antibodies to make phagocytosis of the pathogen easier
When Th1 stimulates a neutrophil, what cytokines are released and what is the function?
TNF and LT activate the neutrophil to enhance its enzymatic killing
When a Th2 cell differentiates in response to IL4 and IL25, what cytokines does it release? What is the function of each?
IL-4 is secreted to enable to b-cell to secrete Ig
IL13 and IL5 enhance isotype switching to IgE and also activate eosinophils and macroohages
What are the three things IL5 and IL13 can activate/induce?
- Isotype switching to IgE
- Activate macrophages
- activate eosinophils
When IL5 and IL13 cause isotype switching to IgE, what does the IgE do?
induces mast cell degranulation
What T-cell subset releases IL-10? What does IL10 do?
IL-10 is released by Treg and is a suppressive cytokine to downregulate the strong response of normal CD4 T cells.
What cytokine is necessary for the expansion of CD8 T cells?
IL-2
When a CD8 T cell sees a foreign antigen in the HLA1 molecule, what happens?
It activates and sends an intracellular signal which raises the cells Ca level and releases cytolytic granules like perforin and granzyme
What cytolytic granules are released by the CD8 T cell to cause the infected cell to lyse?
perforin and granzyme
Upon activation by cytokines released from T-cells, what three things do macrophages do?
- upregulate cell surface proteins (CD40, HLAII, B7)
- undergo a respiratory burst to generate reactive oxygen intermediates (NO, superoxides)
- release cytokines
What helps the macrophage generate reactive oxygen species?
NADPH oxidase complex
What ROS are produced by macrophages?
What do they do?
hydrogen peroxide
nitric oxide
hydroxyl ions
hypochlorite
They are bacteriocidal (kill the bacteria)
Which cell types release bacteriocidal free radicals from the NADPH oxidase complex?
- monocytes
- macrophages
- neutrophils
If a patient has a mutation in a protein in the NADPH oxidase complex, what disorder will they develop and what will be the presentation?
Chronic granulomatous disease- severe bacterial infections
In a mycobacterium tuberculosis infection, Th1 and macrophages work together to “wall off” the infection. What is this area called?
Caseous granuloma/ causeating granuloma
Th1 and macrophages surround necrotic tissue that had been infected with the bacteria
When low levels of TNF are released, what will the 2 local effects be?
Local inflammation resulting in:
- release of IL-1 and chemokines by endothelial cells
- Leukocyte activation
When medium levels of TNF are released, what will the 3 systemic effects be?
- Fever induced by hypothalamus
- Acute phase proteins from the liver
- Leukocytes released from bone marrow
When high levels of TNF are released, what will the 3 effects be?
What will this cause?
- low output from the heart due to low BP
- low resistance in blood vessels
- hypoglycemia
Septic shock that causes organ failure
What three receptors sense viral RNA in a host cell?
TLR4 on the endosome
MDA5, RIG1 in the cytosol
When viral RNA is sensed in a host cell happens?
RIG/MDA or TLR activate IRF3/7 which transcribed IFNa and IFNb
What do IFNa and IFNb do to the infected cell?
Upregulate MHCI to increase killing
What do IFNa and IFNb do to the uninfected cells adjacent to the cell carrying the virus?
express enzymes that block viral replication like PKR16
What membrane structures on the influenza virus are targeted by the immune system?
Hemaglutinin (H)
Neuraminidase (N)
Nuclear proteins (NP or NPP)
What family of viruses does influeza belong to?
Orthomyxoviridae
What three types can influenza viruses be classified into? What are these classifications based on?
What can these types be subdivided by?
A, B and C based on the Nuclear proteins and M proteins (matrix)
They can be subdivided based on H and N
How many RNAs does the influenza virus have?
8
What strain of influenza are we concerned with this year?
H7N9
What is the first response elicited by the influenza virus getting into the lung epithelia?
- epithelial cells release FAs, anti-microbial peptides, enzymes (lysozymes proteases)
- Normal flora competes with the pathogen
If the influenza enters the epithelial cell, what two cytokines are released?
What does each do?
IL-1- activate vascular endo, increase local temp, activate cells
TNF- increase vascular permeability, activate integrin, fluid and protein release into tissue
(IFN, IL-6, IL-8)
IL1 and TNF precipitate the development of hypotension in the infected tissue. What is this called?
Shock
After the influeza virus breaches the mechanical, chemical and microbiological barriers, what happens?
Dendritic cells traffic the virus to the LN to be recognized by T-cells
How long does it take to get enough CD8 T cells to eradicate the virus?
7-10 days
Which T cells clonally expand first, CD4 or CD8? Why?
CD4 because they produce IL-2 which stimulates their own growth AND the growth of CD8 cells via autocrine and paracrine function
What happens to most effector cells after the infection is eradicated?
What do the subset that do not subscribe to this fate become?
They die.
A subset become memory T cells and go back to subcapsular area of the LN.
When studied with fluorescent tagging, what did scientists notice as a difference between primary and secondary infections?
Secondary infections had a more rapid and larger number of antigen specific T cells that entered the lung (for influenza tagging)
In an initial infection with influenza, how long did it take for specific T cells to enter the lungs?
The secondary response?
7-10 days for primary
5 to 7 days for the secondary response (3 to 5 days earlier than primary)
