T Helper and Cytotoxic cells

Question 1

T helper 1 cells (derived from, produce)

Answer 1

• derived from Th0 by IL-12 and IFNgamma
• produce IL-2 and IFNgamma
• orchestrate a cell mediated immune response
  upregulate NK cells and Th1
  activate cytotoxic T cells
  B cells switch to IgG3

Question 2

T helper 2 cells (derived from, produce)

Answer 2

• derived from Th0 by IL-4
• produce IL-4 and IL-5
  orchestrate humoral immune response
• influence Ig isotype to IgG1, IgG2, IgG4, IgA, IgE
• influence plasma v memory B cell differentiation
• eosinophil and basophil recruitment

Question 3

T helper 17 cells (derived from, produce)

Answer 3

• derived from Th0 by IL-6, TGFbeta, IL-23
• produce IL-17 and IL-22
  involved in autoimmune diseases
• antifungal
• increases the production of neutrophils
• involved in gut inflammation

Question 4

T regulatory cells (derived from, produce)

Answer 4

• derived from Th0 by TGFbeta
• produce IL-10 and TGFbeta
  -10% of CD4 T cells
  natural tregs
  induced tregs
• regulate T cell activation
• characterized by CD25 and Fox P3

Question 5

Follicular T cells (derived from, produce)

Answer 5

• derived from Th0 by IL-6 and IL-21
• produce IL-21
• located in germinal centers
• CD4 and PD-1
  -activate B cells to make antibodies
• required for germinal center B cells to undergo somatic hypermutation
• important for germinal center B cells differentiation into plama cells and memory cells

Question 6

Infections are resolved by specific Th responses
Th1:

Answer 6

IFN-gamma, IL-2
type 1 immunity

Question 7

Infections are resolved by specific Th responses
Th2:

Answer 7

IL-4, IL-5, IL-13
type 2 immunity

Question 8

Diseases resolving via type 1 immune responses

Answer 8

tuberculosis
chlamydia
leprosy
intracellular parasites
HIV

Question 9

diseases resolving via type 2 immune responses

Answer 9

pneumococcal pneumonia
diptheria
meningococcal disease
helminth (worms)

Question 10

Diseases caused by type 1 immune responses

Answer 10

silicosis
delayed hypersensitivites
contact hypersensitivities like jewelry
poison ivy

Question 11

Diseases caused by type 2 immune responses

Answer 11

allergies
asthma
lupus

Question 12

Activation of CD8 CTL

Answer 12

-main function of CTL is cytotoxicity
aka killer T cells or T killer cell
- recognize endogenously produced antigens in association with HLA class I
- endogenously derived Ag are mostly tumor Ag and Ag from intracellular pathogens

Question 13

CD8 on CTL are co-receptors that

Answer 13

stabilize and enhance the binding of TCR with HLA class I and possess foreign peptide
- CD8 binds the alpha3 domain of the HLA class I molecules

Question 14

IL-2 is required to signal CD8 to proliferate and differentiate into

Answer 14

CTL effectors
- IL2 is normally provided by the CD4 T helper cell
CTL makes its own IL-2 once activated

Question 15

killing by CTL occurs by two pathways

Answer 15

1. granule-mediated killing
2. fas-fasL killing mechanism

Question 16

granule mediated killing mechanism

Answer 16

after attaching to the target cell, the CTL mobilizes cytoplasmic granules toward the target by actin filament formation (released through exocytosis directly onto target)
- perforin is major constituent that binds and polymerizes forming a transport membrane
- second effect is the induction of apoptosis mediated by other granular contents and secreted cytokines
a. cytokines include TNFbeta and TNFalpha
b. granzymes and granulysin are released and are internalized in cells through perforn pores

Question 17

fas ligand killing mechanism

Answer 17

• fas ligand binds to fas on target cell
• caspases activation induces target cell apoptosis

Question 18

“kiss of death” or “lethal hit”

Answer 18

• unidirectional - only target cell is killed
• after brief binding episode, the CTL releases from target and moves on to another target cell
• hours later, target dies
• a single CTL may deliver multiple lethal hits before dying

Question 19

Natural Killer Cells

Answer 19

-large granular lymphocytes found in blood and secondary lymphoid cells (innate immune system and have no memory)
- CD56 and CD16 but no T cell markers
- recognize the “lack of self” through low-level HLA expression
- possess killer inhibitor receptors (KIRs) that bind HLA class I molecules and when engaged killing is inhibited
- HLA class I expression is suppressed in host cell, KIRs are not sufficiently engaged and killing is allowed
- similar to CTL with perforins, granzymes
can be positively influenced by IL-2 and IFN gamma and can produce IFN gamma

Question 20

Macrophage cytotoxicity

Answer 20

upon activation with IFNgamma alone or in combo with other signals, macrophages have been shown to be cytotoxic
two mechanisms are known:
1) TNF alpha release and induction of apoptosis
2) production of O2 and N2 radicals

Question 21

antibody-dependent cell-mediated cytotoxicity

Answer 21

killer cells for ADCC can be either monocytes/macrophages, eosinophils, neutrophils, or NK cells
- mediated by Ab binding to surface of target cell and binds bc targets cells have foreign antigen on receptor