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Immunology > The Life of a T Cell- Responding to an Infection > Flashcards

The Life of a T Cell- Responding to an Infection Flashcards

1
Q

What is the major function of:

  1. CD4 Tcell
  2. CD8 Tcell
  3. NK Tcell
A
  1. release cytokines
  2. cytotoxic killer cells
  3. secrete cytokines rapidly within minutes to hours of stimulation
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2
Q

What dictates the type of cytokine released by DC, macrophages, epithelial cells, NKT cells, etc?

A

the type of pathogen

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3
Q

What cytokine is chronically released in cancer? What cells release it? What does it cause?

A

IL-6 is released by macrophages, endothelial cells, T-cells and it causes the acute liver phase (complement fixation and opsonization)

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4
Q

What cells release TNF? What are the effects?

A

T-cells and macrophages

Inflammation, fever, acute phase

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5
Q

What cells release IL-1? What are the effects?

A

T-cells
macrophages
endothelial cells
epithelial cells

Inflammation, fever, acute phase, Th17 differentiation

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6
Q

If the APC releases the IL-12 cytokine

  1. what transcription factor is activated?
  2. what will the tcell become?
  3. What cytokine is produced?
A
  1. Tbet
  2. Th1
  3. gamma-IFN
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7
Q

If the APC released IL4, IL25:

  1. what TF is activated?
  2. What will the T-cell become?
  3. What cytokine is produced?
A
  1. GATA3
  2. Th2
  3. IL-4, IL5, IL13
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8
Q

If the APC releases the cytokines IL1, IL6, TGFb:

  1. What TF is activated?
  2. What with the T cell become?
  3. What cytokine is produced?
A
  1. ROR
  2. Th17
  3. IL17
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9
Q

If the APC releases IL6 and IL21:

  1. What TF is activated?
  2. What will the T cell become?
  3. What cytokine will be released?
A
  1. ??
  2. Tfh
  3. IL-21
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10
Q

What TF will induce the T cell to become Treg?

A

FOXP3

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11
Q

What 3 things does a Treg cell do?

A
  1. suppress the development and activation of potentially autoreactive cells
  2. regulate pathogen induced inflammatory response
  3. control immune cell homeostasis
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12
Q

What TF is associated with Th17?

A

ROR

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13
Q

What cytokine does Th17 secrete?

What is the function?

A

IL17 which attacks extracellular pathogens in tissue bed and gut (specifically fungal, viral and bacterial)

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14
Q

What TF is associated with Th1?

A

Tbet

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15
Q

What TF is associated with Th2?

A

GATA3

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16
Q

What cytokine induces the TF Tbet?

A

IL12

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17
Q

What cytokine induces the TF GATA3?

A

IL4 and IL25

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18
Q

What cytokines induce the TF ROR?

A

IL1 IL6 TGFb

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19
Q

What cytokines induce the T-cell to become Tfh?

A

IL6 and IL21

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20
Q

What T cell subsets do IL-6 cytokines help induce?

A

Th17 and Tfh

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21
Q

What cytokine is released by Th1?

A

gamma interferon

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22
Q

What cytokines are released by Th2?

A

IL4, IL5. IL13

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23
Q

What is the major role of gamma-IFN?

A

to kill intracellular bacteria

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24
Q

What is the major role of IL4,5,13?

A

help make antibodies

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25
Q

What have the Th2 cells been linked to?

A

allergies and atopy (hypersensitivity)

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26
Q

What are Th17 cells linked to?

A

viral, fungal and bacterial infections

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27
Q

Where would one find Tfh cells?

What do they do?

A

In germinal centers where they support B-cell activation and somatic hypermutation

28
Q

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?

A

toxoplasma.

1/3

It is not usually a problem bc CD4 T cells of the Th1 subset can usually clear it

29
Q

What are the three major functions of gamma interferon released by the Th1 cell?

A
  1. stimulate macrophage
  2. enhance antiviral response
  3. upregulate MHCI so the virally infected cells can be killed by CD8 T-cells
30
Q

Th1 cells are especially important for clearing what type of infection?
What are 4 examples of this type of infection?

A

Intracellular bacteria, virus or parasite

  1. T. gondii
  2. mycobacterium tuberculi
  3. Listeria
  4. influenza
31
Q

When a Th1 cell interacts with a B cell and releases IFN-gamma, what is the result?

A

complement binding and opsonizing antibodies to make phagocytosis of the pathogen easier

32
Q

When Th1 stimulates a neutrophil, what cytokines are released and what is the function?

A

TNF and LT activate the neutrophil to enhance its enzymatic killing

33
Q

When a Th2 cell differentiates in response to IL4 and IL25, what cytokines does it release? What is the function of each?

A

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

34
Q

What are the three things IL5 and IL13 can activate/induce?

A
  1. Isotype switching to IgE
  2. Activate macrophages
  3. activate eosinophils
35
Q

When IL5 and IL13 cause isotype switching to IgE, what does the IgE do?

A

induces mast cell degranulation

36
Q

What T-cell subset releases IL-10? What does IL10 do?

A

IL-10 is released by Treg and is a suppressive cytokine to downregulate the strong response of normal CD4 T cells.

37
Q

What cytokine is necessary for the expansion of CD8 T cells?

A

IL-2

38
Q

When a CD8 T cell sees a foreign antigen in the HLA1 molecule, what happens?

A

It activates and sends an intracellular signal which raises the cells Ca level and releases cytolytic granules like perforin and granzyme

39
Q

What cytolytic granules are released by the CD8 T cell to cause the infected cell to lyse?

A

perforin and granzyme

40
Q

Upon activation by cytokines released from T-cells, what three things do macrophages do?

A
  1. upregulate cell surface proteins (CD40, HLAII, B7)
  2. undergo a respiratory burst to generate reactive oxygen intermediates (NO, superoxides)
  3. release cytokines
41
Q

What helps the macrophage generate reactive oxygen species?

A

NADPH oxidase complex

42
Q

What ROS are produced by macrophages?

What do they do?

A

hydrogen peroxide
nitric oxide
hydroxyl ions
hypochlorite

They are bacteriocidal (kill the bacteria)

43
Q

Which cell types release bacteriocidal free radicals from the NADPH oxidase complex?

A
  1. monocytes
  2. macrophages
  3. neutrophils
44
Q

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?

A

Chronic granulomatous disease- severe bacterial infections

45
Q

In a mycobacterium tuberculosis infection, Th1 and macrophages work together to “wall off” the infection. What is this area called?

A

Caseous granuloma/ causeating granuloma

Th1 and macrophages surround necrotic tissue that had been infected with the bacteria

46
Q

When low levels of TNF are released, what will the 2 local effects be?

A

Local inflammation resulting in:

  1. release of IL-1 and chemokines by endothelial cells
  2. Leukocyte activation
47
Q

When medium levels of TNF are released, what will the 3 systemic effects be?

A
  1. Fever induced by hypothalamus
  2. Acute phase proteins from the liver
  3. Leukocytes released from bone marrow
48
Q

When high levels of TNF are released, what will the 3 effects be?
What will this cause?

A
  1. low output from the heart due to low BP
  2. low resistance in blood vessels
  3. hypoglycemia

Septic shock that causes organ failure

49
Q

What three receptors sense viral RNA in a host cell?

A

TLR4 on the endosome

MDA5, RIG1 in the cytosol

50
Q

When viral RNA is sensed in a host cell happens?

A

RIG/MDA or TLR activate IRF3/7 which transcribed IFNa and IFNb

51
Q

What do IFNa and IFNb do to the infected cell?

A

Upregulate MHCI to increase killing

52
Q

What do IFNa and IFNb do to the uninfected cells adjacent to the cell carrying the virus?

A

express enzymes that block viral replication like PKR16

53
Q

What membrane structures on the influenza virus are targeted by the immune system?

A

Hemaglutinin (H)
Neuraminidase (N)
Nuclear proteins (NP or NPP)

54
Q

What family of viruses does influeza belong to?

A

Orthomyxoviridae

55
Q

What three types can influenza viruses be classified into? What are these classifications based on?
What can these types be subdivided by?

A

A, B and C based on the Nuclear proteins and M proteins (matrix)

They can be subdivided based on H and N

56
Q

How many RNAs does the influenza virus have?

A

8

57
Q

What strain of influenza are we concerned with this year?

A

H7N9

58
Q

What is the first response elicited by the influenza virus getting into the lung epithelia?

A
  1. epithelial cells release FAs, anti-microbial peptides, enzymes (lysozymes proteases)
  2. Normal flora competes with the pathogen
59
Q

If the influenza enters the epithelial cell, what two cytokines are released?
What does each do?

A

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)

60
Q

IL1 and TNF precipitate the development of hypotension in the infected tissue. What is this called?

A

Shock

61
Q

After the influeza virus breaches the mechanical, chemical and microbiological barriers, what happens?

A

Dendritic cells traffic the virus to the LN to be recognized by T-cells

62
Q

How long does it take to get enough CD8 T cells to eradicate the virus?

A

7-10 days

63
Q

Which T cells clonally expand first, CD4 or CD8? Why?

A

CD4 because they produce IL-2 which stimulates their own growth AND the growth of CD8 cells via autocrine and paracrine function

64
Q

What happens to most effector cells after the infection is eradicated?
What do the subset that do not subscribe to this fate become?

A

They die.

A subset become memory T cells and go back to subcapsular area of the LN.

65
Q

When studied with fluorescent tagging, what did scientists notice as a difference between primary and secondary infections?

A

Secondary infections had a more rapid and larger number of antigen specific T cells that entered the lung (for influenza tagging)

66
Q

In an initial infection with influenza, how long did it take for specific T cells to enter the lungs?
The secondary response?

A

7-10 days for primary

5 to 7 days for the secondary response (3 to 5 days earlier than primary)

Immunology (25 decks)

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