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Immunology > Lecture 5: Antigen Capture and Presentation to Lymphocytes > Flashcards

Lecture 5: Antigen Capture and Presentation to Lymphocytes Flashcards

1
Q

What is the difference in the types of antigens B and T cells can recognize?

A

B cells can recognize a variety of macromolecules that are in soluble form or associated with the cell surface.

T-cells can only recognize LINEAR (unfolded) fragments of antigens made inside a host cell and presented on MHCs (major histocompatability complex) of APC.

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2
Q

T-cells can only respond to what kind of antigens?

A

Those produced in or taken up by a host cell.

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3
Q

B-cell humoral immune responses can only respond to what kind of antigens?

A

many types of pathogen cell wall and soluble antigens

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4
Q

Key concepts of cell-mediated immunity.

What cells are involved?
What does the term mean?
What does it protect us against.

A

T-cells are involved in cell-mediated immunity.

Named because immunity to INTRACELLULAR pathogens can be transferred by immune cells from an animal that has recovered from the infection.

T-cell protect us against INTRACELLULAR pathogens.

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5
Q

T-cells help with humeral immune responses, which attacks EXTRACELLULAR pathogens. How?

A

Via T-helper cells.

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6
Q

TCR only recognizes what types of antigens?

A

LINEAR FRAGMENTS bound to MHC of APCs.

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7
Q

Can one T-cell recognize many antigens?

A

NO.

One T-cell can only recognize ONE specific antigen.

But, there are many T-cells, each recognizing different antigens.

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8
Q

When does specificity of T-cells occur?

A

When they are developing in the thymus.

Here, they are eliminated if they react with self or survive if they do not.

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9
Q

CD4+ T-helper respond to what kind of antigens?

A

T-helper cells respond to antigens that are present on MHC Class II molecules, which are present on [dendritic cells, macrophages and B cells].

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10
Q

What are the 2 types of T-helper cells?

A
  1. Th1
  2. Th2

each have different fx based on the cytokines they make.

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11
Q

CD8+ T cells recognize what kind of antigens?

A

Antigens presented on MHC Class I complexes .

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12
Q

What part of MHC Class I and II do [CD8 T-cell] and [CD4 T-helper] cells cells bind to?

A

They differentially bind to non-polymorphic part of MHC Class II and I

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13
Q

CD4 and CD8 are called co-receptors. why?

A

They are involved in signaling.

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14
Q

How do we activate naive T-cells, so that they can carry out their fx?

A
  1. Antigen must be presented to them

2. APC must express co-stimulatory molecules that help to initiate signaling events.

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15
Q

What happens when T-cells are activated?

A
  1. IL-2 causes clonal expansion (proliferation) of the activated T-cell.
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16
Q

What happens when Th1 cells are activated?

A
  1. Makes IFN-y,
    - activating macrophages to get ride of intracellular pathogens.

IFN-y will also help the development of cytotoxic T-cells that will kill the pathogen-infected cell.

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17
Q

What happens when Th2 cells are activated?

A
  1. Makes IL-4, which causes proliferation of B cells.

B cells respond to EXTRACELLULAR pathogens and release antibodies, develop into plasma cells and memory cells.

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18
Q

Describe the T-cell receptor (TCR).

A

TCR is made up of 2 polypeptide chains (alpha and beta).

Each polypeptide has constant and variable regions. Antigens bind at the variable regions.

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19
Q

What happens if a TCR has y and g chains?

A

They have some of the same characteristics but have broader specificity for unconventional antigens like [HSPs and phospholipids].

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20
Q

Describe the TCR Complex

A

TCR (ab dimer or yg dimer) + CD3.

CD3 is a signaling complex made up of (y, g, 2e and 2 zeta)

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21
Q

T-cells that express CD4 bind to what?

A

Nonpolymorphic region of MHC class II on APCs, which restricts Th cells to recognize only antigens on MHC class II.

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22
Q

T cells that express CD8 bind to what?

A

Nonpolymorphic regions of MHC Class I, which restricts killing to cell that have an antigen on MHC Class I.

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23
Q

Do AB and yg T cells have different signaling complexes?

A

No; they’re the same.

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24
Q

CD4 and CD8 recognize what part of the MHC molecule?

A

The invariant part.

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25
Q

What are MHC?

A

Membrane proteins on APCs that display antigens so that T-cells can recognize them .

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26
Q

What cells express MHC Class I receptors?

A

All nucleated cells

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27
Q

What cells express MHC Class II receptors?

A

Professional APCs: dendritic cells, macrophages and B-cells

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28
Q

Do RBC contain MHC Class I Receptors?

A

No, because they do not have a nucleus.

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29
Q

Dendritic cells are APC. What is their function?

A

Dendritic cells present the [antigen and costimulator] to naive T cell.

[Naive T] –> clonal expansion and differentiation –> [effector T-cell].

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30
Q

Macophages are APC. What is their function

A

Macrophages present antigens to CD4+ effector T-cells, which activates the macrophage to kill the pathogen.

This is called cell-mediated immunity.

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31
Q

B-cells are APC. What is their function?

A

B-cell present antigens to effector T cells , which activates the B cell and promotes production of antibodies.

This is called humoral immunity.

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32
Q

MHC Class II are APCs that do what

A

Present antigens to CD4+ helper T-cells

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33
Q

MHC Class I are APCs that do what?

A

Present antigens CD8+ T cells.

34
Q

How to antigens enter our body?

A

They commonly enter through the

  1. Skin
  2. GI tract
  3. Respiratory tract.
    Dendritic cells then capture them and take them to lymph nodes.

If they enter the blood, APCs in the spleen will capture them.

35
Q
  1. _______ DCs capture the antigen, creating a _____________.
  2. The ____________ DC –> LN–> present the antigen to the naive T-cells
A
  1. Tissue resident dendritic cells capture the antigen, creating a activated dendritic cell.
  2. The activated dendritic –> LN–> presents the antigen to the naive T-cell
36
Q

What receptors do TISSUE-RESIDENT dendritic cells have?

A

Fr receptors and mannose receptors

Activated DC do not have these receptors.

37
Q

What are the molecules that are involved in activation of T-cells?

Are they higher in tissue resident dendritic cells or activated dendritic cells?

A

B7, ICAM-1, IL-12.

They are higher in activated dendritic cells.

38
Q

Do class II MHC molcules have a higher half life in tissue resident DC or activated DC?

A

Activated DC.

39
Q

How is IFN-y released and what does it cause?

A

IFN-y can be released by:

  1. NK cells during innate immune reactions
  2. T-cells during adaptive immune responses

It then causes APCs to express MHC class II, which will enhance the activation of CD4+ T cells.

40
Q

NK and T-cells releasing IFN-y stimulates APC cells to express MHC Class II, enhancing the activation of CD4+ T-cells.

Can CD8+ T cells activate the same way?

A

IFN-y and type 1 interferons causes APCs to express MHC class I, which activates CD8+ T-cells.

41
Q

What is the human MHC called?

A

HLA (Human leukocyte antigen).

42
Q

Types of MHC (HLA) molecules?

A

There are

Class I HLA gene
Class II HLA gene

Both are polymorphic.

43
Q

Structure of MHC (HLA) molecules.

A

Class I HLA gene has ONE [polymorphic alpha heavy chain] attached to [non-polymorphic B2 microglobin]. The polymorphic heavy chain forms the groove where antigens bind. They are expressed on all nucleated cells.
*the alpha chain is glycolsylated.

Class II HLA genes has [1 polymorphic alpha chain + 1 polymorphic beta chain] that both form the binding groove for antigens.
-both alpha and beta chains are glycosylated.

44
Q

How big of peptides does MHC class I and Class II bind?

A

MHC Class I- binds peptides that have 8-10 AA

MHC Class II- binds peptides that have 10-20 AA.

45
Q

MHC show co-dominant expression; meaning that both alles of the MHC gene are expressed. Why is this significant?

A

This creates a variety of different MHC molecules

46
Q

MHC are polymorphic; meaning that many different alleles are present in the population. Why is this significant?

A

This makes sure that we can respond to different types of pathogens.

47
Q

What type of antigens bind to MHC Class I molecules?

A

Intracellular pathogens that have infected hosts and go to the surface.

Presented to CD8+ T cells
This is an endogenous pathway.

48
Q

What type of antigens bind to MHC Class II molecules?

A

Extracellular pathogens from the environment

Presented to CD4 T-helper cells.

49
Q

How do TCR recognize antigens so that they can bind?

A

The TCR will simultaneously recognize

  1. AA on the antigen
  2. parts of the MHC molecule that is displaying the antigen

Antigens (peptides) have anchor residues that bind in pockets of MHC. These residues vary for different MHC alleles. Thus, ONE MHC complex can bind many different antigens with the same anchor residue.

50
Q

Can 1 MHC bind many peptides?

A

1 MHC can bind many different peptides that have the same anchor residue.

51
Q

Where are the polymorphic residues of class I and class II MHC molecules locates?

A

In the peptide binding clefts and alpha-helices around the cleft.

52
Q

Why can MHC Class II molecules bind bigger peptides (antigens)?

A

The the peptide-binding cleft in Class II is open.

53
Q

What is the site of peptide loading of MHC I and MHC II?

A

MHC I- endoplasmic reticulum

MHC II- specialized vesicles

54
Q

What breaks down the antigen so that it can be presented to class II MHC?

A

Endosomal and lysosomal proteases

55
Q

What breaks down the antigens so that it can be presented to class I MHC?

A

Cytoplasmic proteasome

56
Q

Class II MHC pathway:

A
  1. Extracellular antigens are ingested by APC into endosomal and lysosomal vesicles, where they are degraded into peptides.
  2. Class II MHC (+ CLIP) are made and transported to the endosome.
  3. (Class II MHC + CLIP) are then transported to the same endosomal and lysosomal vesicle.
  4. CLIP is then removed by HLA-DM, allowing the antigens to bind with class II MHC molecules in the vesicles
  5. [Antigen-MHCII] complex are transported to the surface and expressed
57
Q

What is CLIP?

A

Class II invariant chain peptide

58
Q

What is the function of HLA-DM?

A

HLA-DM makes sure that fragments of antigen that are most important to cause an immune response are displayed. It does so by:

  1. Dissociating CLIP from peptide binding groove of MHC II
  2. Stabilizes the empty MHC II
  3. Helps the antigen bind into the open groove.
59
Q

Class I MHC Pathway

A
  1. Antigens can enter the cytoplasm of cells by endogenous synthesis or infected cells that are ingested but whose antigens are transported into the cytosol.
  2. Cytoplasmic antigens are then unfolded, ubiquinated and degraded by proteosomes.
  3. The peptides that are made are then transported by TAP (transporter assx with antigen processing)–> the ER, where they are broken down even more.
  4. Newly made class I MHC are stabilized by chaperones and attached to TAP via [linker protein tapasin].
    - Being near TAP allows them to receive peptides that are brought into the ER.
  5. [antigen+ class I MHC complex] are then transported to the surface of the cell and recognized by CD8+ T cells.
60
Q

What if the antigen is a virus. How are they taken up by the cell and presented on class I MHC?

A

Process is called cross-presentation.

Fragments of cells infected intracellular microbes are ingested by dendritic cells.

The antigens are the transported into the cytosol and processed so that they can be presented on MHC Class I molecules to CD8 T cells

61
Q

Can we present extracellular antigens via the class 1 pathway?

A

Yes. SO to dendritic cells.

62
Q

What is the process by where extracellular antigens are presented on class I MHC vesicles?

A

Cross-presentation pathway.

63
Q

What are immunodominant peptides?

A

When antigen is degraded in APCs, many smaller peptides are made. However, only some are chosen to be presented onto the MHC molecule.

Structural constraints, like length and anchor resides, on peptide binding to MHC molecules are the reason why some people cannot respond to certain antigens.

64
Q

Do complex protein antigens have a unlimited number of immunodominant peptides?

A

No. We have a limited number of immunodominant peptides . Hence, why we have 6 HLA alleles.

65
Q

What is a result of MHC being polymorphic?

A

Some people may not have MHC molecules that can bind any peptide from a specific antigen.

Thus, they would be considered NON-RESPONDERS to that antigen.

66
Q

In the class II MHC pathway, the purpose is to present antigen peptides to CD4 T helper cells, which then do what?

A
  1. activate macrophages, killing the phagocytosed antigen

2. activate B cells, which make antibodies against extracellular microbes

67
Q

In the class I MHC pathway, the purpose is to present antigens peptides to CD8 T-cells, which thendo what?

A

kill infected cells

68
Q

Having a class 1 and class II MHC pathway allows our immune system to do what?

A

Respond to extracellular and intracellular pathogens in different ways.

69
Q

Extracellular pathogens (even ingested viruses)

  • Captured and ingested by ______
  • Presented on class ___ MHC molecules?
  • Recognized by what kind of T-cells?
A

DCs/macrophages

Class 2 MHC molecules
Recognized by CD4+ helper T cells

70
Q

CD4+ helper cells affect B cells how?

A

cause them to make antibodies, which can then go and attack extracellular pathogens.

71
Q

Can phagocytes or antibodies killl intracellular viruses and other pathogens that can survive and replicate in the cytoplasm of host cells?

A

No.

72
Q

Cytosolic pathogens

-Presented on class __ MHC molecules?
-Recognized by what kind of T-cells?
What do these T-cells then do?

A

1
CD8+ T cells
Kill the infected cells and eradicate the infection; this being the most effective mechanism to eliminate cytoplasmic pathogens

73
Q

What kind of antigens to B cells recognize?

A

those expressed on microbial surfaces or soluble forms (secreted toxins)

74
Q

What is the mechanism by which B cells secrete antibodies

A
  1. B cells recognize antigens on the microbial surface or soluble form.
  2. This allows them to begin to secrete Ab.
  3. Ab then enter circulation, bind to Ag and neutralize and eliminate them.
75
Q

B-cell receptors and antibodies recognize Antigens in what form?

A

in their native form, without any processing

76
Q

What are NTK cells specific for?

A

Lipids displayed by ClassI-like CD1 erceptors

77
Q

ygt cells recognize what kind of molecules?

A

a variety. fx and significance is poor and not understood

78
Q

CD8+ T-cells are going to recognize _________ pathogens on MHC Class ____ receptors

A

INTRACELLULAR pathogens

I

79
Q

CD4+ T-cells are going to recognize _______ pathogens on MHC Class ____ receptors

A

EXTRACELLULAR

2

80
Q

Loading onto MHC I Receptor

A

Old peptides will be broken down into peptide fragments in the cytoplasm via [proteosomes]

TAP1 and TAP2 will then move the fragments into the ER.

Fragments in the ER will be loaded onto MHC1

Then be presented on the cell surface

Immunology (12 decks)

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