Acquired immunity T cells Flashcards

1
Q

Antigen presenting cells

A

Function
* present antigens to T cells
* carry class II MHC
* release factors necessary for T cell activation (ex IL-12)

Types
* dendritic cells (best)
* B cells
* selected macrophages
* monocytes
* keratinocytes

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2
Q

MHC (major histocompatability complex) proteins

A
  • coded by a number of genes located as a cluster on a part of a chromosome
  • inherited as “block”, high mutation rate
  • surface proteins
  • easily detected on leukocytes (LA- leukocyte antigen)
  • bind to processed antigenic peptides
  • 3 classes (I, II, III)
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3
Q

MHC classes

A

I: present on all nucleated cells (cytotoxic CD8 T cells recognize these which become associated with foreign antigens)
II: present on selected cells (APCs) binds CD4 T cells
III: complex components ans sex limited proteins (soluable serum proteins, TNF)

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4
Q

number of MHC class I, II and amount of immune response

A

increase number of MHC class I, II
increased immune response

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5
Q

MHC and antigen presentation

A

antigens taken in by APC are “chopped” into small pieces and presented on their surface by MHC proteins

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6
Q

processing and presentation of exogenous proteins

A
  1. antigen phagocytosed
  2. antigen “chopped” to MHC class II peptide level
  3. peptide binds to MHC class II
  4. processed antigen class II is presented
  5. CD4 T cell binds to class II MHC

(only APC can have class II MHC)

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7
Q

processing and presenting of endogenous antigens

A

ex: viral infected cells (all nucleated cells have MHC class I, can be infected)
1. viral protein infects cell
2. viral particle chopped
3. protein fragment binds MHC class I
4. MHC class I presented
5. CD8 T cells bind to MHC I

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8
Q

lymphocytes

A
  • located in blood, lymph, lymphoid tissue
  • 5-15um
  • most of cell contains nucleus (thin rim of cytoplasm)
  • look alike, but different characteristic surface proteins, functions
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9
Q

CD4+ cells

A

helper T cells
4 types:
* Th-1
* Th-2
* Th-17
* Treg

Bind class II MHC

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10
Q

perforins

A

in granules of CD8 cells
polymerize within target cells to form membrane attack complex (MAC) with hole in center
granzymes enter through hole in center of MAC and trigger apoptosis of target cell

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11
Q

CD8+ cells can destroy cells via:

A
  • perforins: polymerize within target cells to form membrane attack complex (MAC) with hole in center, granzymes enter through hole in center of MAC and trigger apoptosis of target cell
  • Fas-Fas: ligand interaction leads to death of target cell
  • secrete TNFbeta: causes apoptosis
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12
Q

CD8+ cells

A

cytotoxic T cells
bind class I MHC
destroy abnormal (infected: virus/intracellular bacteria, non infected: tumors/foreign grafts)
have granules that contain perforins move to destroy abnormal cells
secrete TNFbeta
Fas-Fas ligand interaction leads to death of target cell

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13
Q

T cell receptors

A
  • antigen recognition
  • alpha beta
  • gamma delta
  • all T cells
  • determines specificity of T cells
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14
Q

CD3 T cell surface marker

A

signal transduction, all T cells

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15
Q

CD28 and CD40L T cell surface marker

A

co stimulatory, on activated T cells

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16
Q

cytokine receptors

A

IL-2, INFgamma

17
Q

alpha, beta T cell receptors

A

expressed by CD4, CD8

18
Q

thymocytes

A

Developing lymphocytes in the thymus [IMMATURE], lack CD4 and CD8
turn into:
T CELLS: Mature lymphocytes which have emigrated from the
thymus to the secondary lymphoid organs
* gain both CD4 and CD8 in thymus
* either CD4 or CD8 is inactivated

19
Q

T cell selection in thymus

A
  • Majority of developing T cells die within the thymus.
  • Only those cells that are competent leave the thymus.
  • Cells that dieinclude defective cells, cells that react with self-antigens (Negative selection) etc. Most of emigrated T cells (Positive Selection)
  • 95% die
20
Q

cortex of thymus

A

most immature immigrants from bone marrow

21
Q

medulla of thymus

A

mature thymocytes ready to exit thymus
mature T cells

22
Q

where do mature T cells reside

A
  • paracortex of lymph node
  • periarteriolar lymphoid sheath (PALS) in spleen
23
Q

Th-1

A

Type of CD4 (helper) T cell
* Participate in Delayed Type Hypersensitivity (DTH)
* primarily secrete IFN-g, IL-2
* intracellular infections

24
Q

Th-2

A

Type of CD4 (helper) T cell
* Help other cells (eg. B or Tc) by secreting Interleukin
* secrete IL-4, IL-6, IL-10 which promote B cell functions, suppress Th-1
* extracellular infections

25
Q

Th-17

A

Type of CD4 (helper) T cell
* Regulation of Inflammatory response (VERY inflammatory)
* IL-17, IL-22, TNF-a
Physiological Effects:
* Protective in infections
* Recruits monocytes and neutrophils
* Upregulates pro-inflammatory chemokines & cytokines: MCP-1, IL- 6, IL-8, ICAM-1 expression

Pathological Effects:
* Increased in autoimmune diseases- RA, Multiple Sclerosis

26
Q

Treg

A

Type of CD4 (helper) T cell
* Regulation of immune response by suppressing it
* Primarily secrete TGF
* loss of regulatory cells induces autoimmune disease, can be used to treat autoimmune disease

27
Q

Conditions for T cell activation

A
  1. T cells DO NOT recognize FREE ANTIGEN (Ag). An antigen MUST be MEMBRANE BOUND (eg. on APC)
  2. T Cells recognize only processed antigens. (Processing takes place in antigen presenting cells).
  3. The processed antigen MUST ASSOCIATE with another protein molecule, Major Histocompatibilty Complex **(MHC) ** molecules, present on the membrane of cells (eg. APC).
  4. Antigen presenting cells ** secrete IL-1 or other factors IL-12** which are necessary for activation of T cells.
  5. Activation of T cells require at least 2 signals. First, is the primary signal that is antigen-specific (delivered through TCR/CD complex) and a second, co-stimulatory signal (delivered through membrane interactions of CD28 on T cells with CD80/86 on APC and/or CD40L on T cells with CD40 on APC, and/or cytokines e.g. IFNg)
28
Q

T cell vs B cell recognition of antigen

A

T cells recognize peptide sequence
B cells recognize the shape of an epitope

29
Q

How many signals do T cells need for activation?

A

TCR will now recognize this presented antigen. This is FIRST SIGNAL.
Activation of T cells require SECOND SIGNAL or CO-STIMULATORY SIGNALS.

The molecular contacts between T cells and APC are delivered through interactions of :
CD28 on T cells with B7 molecules on APC and/or CD40L on T cells and CD40 on APC.

30
Q

How many signals do T cells need for activation?

A

TCR will now recognize this presented antigen. This is FIRST SIGNAL.
Activation of T cells require SECOND SIGNAL or CO-STIMULATORY SIGNALS.

The molecular contacts between T cells and APC are delivered through interactions of :
CD28 on T cells with B7 molecules on APC and/or CD40L on T cells and CD40 on APC.

31
Q

Th1 differentiation cytokines

A

*IL-12 -It leads to a bias in clonal expansion of Th-1-type of cells.
*IL-18
*IL-27
(Th-1 cells are important in immunity against intracellular
infections and are also involved in inflammatory conditions.)

32
Q

Th2 differentiation cytokines

A
  • IL-4 and IL-10 inhibit Th1 and default response is generation
    of Th-2 response.
33
Q

IFNgamma and macrophages

A

Activated Th1 CD4 cells secrete IFNgamma
IFNgamma activates macrophage to kill intracellular pathogen

34
Q

Interfero Gamma (IFNgamma)

A
  • Activates Macrophages, NK
  • Critical for immunity against intracellular pathogens
  • Enhance MHC Class 1 & 2 molecule
  • secreted from Th-1, blocks Th-2
35
Q

IL- 4

A
  • Stimulates B cells (IgE) (important in allergies/helminths)
  • extracellular pathogens
  • Stimulates T helper 2/Inhibits Th1
36
Q

IL-5

A
  • eosinophil growth & activation factor
  • Stimulates B (enhances IL-4-mediated IgE)
  • Important in IgA (mucosal immunity)
37
Q

IL-6

A
  • Promotes fever
  • Promotes B cell functions
38
Q

IL-10

A
  • Inhibits Th-1 responses
  • Promotes some Th2 & B cell functions
39
Q

Regulatory cells may be involved in:

A

ex: Treg cells (CD4 T cells)
* pregnancy: local immune suppression to maintain normal state
* allergies: decrease regulatory cells (desensitization = increase regulatory cells
* cancer
* viral diseases: increased regulatory cells can dampen immune response