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Micro and Immuno > Antigen Presentation. > Flashcards

Antigen Presentation. Flashcards

1
Q

antigen presenting cells

A

macrophages, dendritic cells, and B cells that process and present foreign pathogen antigens for the purpose of activating T cells and adaptive immune defenses

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2
Q

MHC molecules display…

A

peptides derived from protein antigens

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3
Q

T cells recognize peptide antigens displayed by…

A

MHC molecules on APCs

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4
Q

Major Histocompatibility Complex (MHC)

A

The major histocompatibility complex (MHC) is a group of genes that encode proteins on the cell surface that have an important role in immune response. Their main role is in antigen presentation where MHC molecules display peptide fragments for recognition by appropriate T-cells.

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5
Q

describe the process of how microbial antigens are transported to lymphoid organs where recognition by T cells occurs

A
  • dendritic cells residing in tissues capture microbes and antigens
  • cell-free antigens are drained via lymphatic vessels
  • antigens enter blood stream
  • lymph node collects antigen from tissue
  • blood born antigens are captured by antigen presenting cells in the spleen
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6
Q

the majority of dendritic cells in tissues and lymphoid organs are…

A

classical dendritic cells
(classical DC are in the T cell zone of the lymph nodes to be able to interact)

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7
Q

describe the capture and presentation of antigens by dendritic cells

A
  • immature DC capture protein antigen
  • DC are activated via PRR and migrate to lymph node via chemokine gradient
  • mature DC present antigens to T cells (finish maturation in the lymph node)
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8
Q

what makes dendritic cells the most potent APC for activating naive T cells?

A

They constitutively express Class II MHC and costimulators, and also increases with maturation. They don’t need to be activated to be able to present class II MHC.

(macrophages and B lymphocytes have low or negative levels, or need to be induced)

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9
Q

What determines the specific recognition of antigens?

A

Major histocompatibility complex (MHC) molecules

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10
Q

describe the genes of MHC locus

A
  • human MHC proteins are called human leukocyte antigens (HLA)
  • two sets of highly polymorphic genes: Class I MHC genes and Class II MHC genes (each has its own locus)
  • other nonpolymorphic genes associated with antigen presentation, cytokine, and complement
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11
Q

What are HLA A9 and B15 associated with?

A

These are MHC class I molecules associated with aggressive periodontitis

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12
Q

describe the structure of MHC class I molecules

A
  • membrane proteins containing a peptide-binding cleft at the amino terminal
  • 8-11 AA peptide can be accommodated
  • alpha chain associated with b2-microglobulin with a groove accommodating 8-11 AA: variability in a1 and a2, a3 is invariant
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13
Q

Structure of MHC class II molecules

A
    • membrane proteins containing a peptide-binding cleft at the amino terminal
  • 10-20 AA peptide
  • a and b chain with a groove accommodating 10-30 AA, variability in a1 and b1, a2 and b2 invariant
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14
Q

Describe the MHC I and T cell receptor interaction

A
  • CD8 cells only recognize peptides presented by MHC class I
  • a3 binds CD8 on CD8 cells
  • peptide binds floor of the cleft while TCR binds side and top of cleft
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15
Q

Describe the MHC II and T cell receptor interaction

A
  • CD4 T cells only recognize peptides presented by MHC class II
  • b2 binds CD4 on CD4 T cells
  • peptide binds floor of the cleft while TCR binds side and top of cleft
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16
Q

MHC haplotype

A

The set of MHC alleles on each chromosome inherited from both parents
- 6 different class I
- 6-8 different class II

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17
Q

MHC polymorphism ensures…

A

that a population can deal with microbe diversity (many different alleles present in the population; different individuals are able to respond to different microbial peptides)

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18
Q

Which cells express Class II MHC?

A

Dendritic cells, macrophages, B cells (APCs) and induced by IFNgama. Thus CD4+ helper T lymphocytes will interact with these APCs.

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19
Q

Which cells express Class I MHC?

A

Expressed on all nucleated cells. Thus CD8+ CTLs can kill any type of virus-infected cell

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20
Q

describe the binding structure of peptides to MHC molecules

A

Anchor residues in the peptide anchor the peptide to the groove of MHC molecules. Other residues are recognized by TCR

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21
Q

Features of peptide binding to MHC molecules

A
  • different peptides can bind to the same MHC (not as specific as T cell receptor)
  • one binding cleft = each MHC molecule presents only one peptide at a time
  • one APC displays a large number of different peptides (increases probability of presenting to T cells in lymph node or spleen)
  • T cell receptors only bind peptides (protein antigens) thus not carbs, lipids, etc.
  • peptides are loaded on MHC during MHC assembly
  • loading of peptides stabilizes expression of MHC on cell surface
  • binding lasts for several days to maximize interactions with T cells
22
Q

How are proteins converted into peptides?

A

antigen processing pathways

23
Q

(overview) What is the processing pathway of extracellular and cytosolic protein antigens in MHC Class II?

A

Extracellular proteins are processed in endosome/lysosome and displayed on MHC Class II to CD4 cells

24
Q

(overview) What is the processing pathway of cytosolic protein antigens in MHC Class I?

A

Cytosolic proteins are processed by proteasome and endoplasmic reticulum and displayed on MHC Class I to CD8 cells

25
Q

What may be an extracellular protein that will be used in a class II MHC?

A

A cell that is being phagocytosed, a dead cell containing a molecule like a virus

26
Q

(in-detail) Describe the processing of extracellular proteins for Class II MHC

A
  1. antigen internalization: uptake of extracellular proteins into vesicular compartments of APC
  2. antigen degradation in lysosome: processing of internalized proteins in endosomal/lysosomal vesicles. Biosynthesis and transport of class II MHC molecules to endosomes.
  3. antigen association with Class II molecules: association of processed peptides with class II MHC molecules in vesicles. Expression of peptide-MHC complexes on cell surface.
27
Q

What may be an intracellular protein used in a Class I MHC?

A

Virus in the cytoplasm

28
Q

(in-detail) Describe the processing of intracellular proteins for Class I MHC

A
  1. Protein antigen tagging with ubiquitin
  2. Antigen degradation by proteasome (recognized due to ubiquitin tagging) and transport via TAP in ER
  3. Peptide is loaded onto MHC Class I; antigen association with Class I molecules and surface expression
29
Q

What is the significance of MHC-associated antigen presentation?

A
  • optimization of response to different microbes in different locations (ex1: T cell interacting with macrophage that has phagocytosed an extracellular microbe. The T cell can produce cytokines like interferon-gamma that helps the macrophage to get activated and kill the phagocytosed microbe. Macrophage will ingest the microbe but need a signal to actually kill it. Ex2: Same situation with B cells, except T cell cytokine activates the B cell to make an antibody against the antigen. Ex3: Cytotoxic T cells will be able to kill antigen-expressing target cells once activated by APC)
  • microbes can be extracellular and become intracellular
30
Q

CD4+ cells

A

Helper T cells

31
Q

CD8+ cells

A

Cytotoxic T cells that recognize non-self (viral or malignant) proteins on MHC I of nucleated cells. Release porforins and granzymes to induce apoptosis

32
Q

How are internalized microbial proteins presented to T cells?

A

Processed in the endosome and loaded onto MHC Class II for presentation to CD4 T cells.

33
Q

Describe the inflammatory mechanisms leading to bone loss in periodontitis

A

Mice deficient in MHC Class II-restricted CD4 T cells are resistant to experimental periodontitis, thus activated CD4 T cells mediate destructive inflammation in the periodontium

34
Q

Antigens are transported from _______/_______ to __________ where recognition by T cells occurs

A

tissue/mucosa; lymphoid organs

35
Q

The majority of DC in tissues and lymphoid organs are what?

A

Classical DC

36
Q

Describe the capture and presentation of antigens by DC

A

-Immature DC captures and processes protein antigen
-DC are activated via PRR and migrate to LN via chemokine gradient (upregulate chemokine receptors (CCR7) and costimulatory molecules).
-Mature DC presents protein antigens to T cells

37
Q

Where do peptides bind?

A

IN the cleft (of MHC and TCR)

38
Q

T cell recognizes _______ ________ displayed by MHC molecules on APC

A

peptide antigens

39
Q

How many sets of genes?

A

Two sets of highly polymorphic genes
-Class I MHC genes
-Class II MHC genes

40
Q

Describe the structure of MHC class I molecules

A

-Membrane proteins containing a peptide-binding cleft at the amino-terminal
-Alpha chain associated with beta2-microglobulin

41
Q

Describe the structure of MHC class II molecules

A

-Membrane proteins containing a peptide-binding cleft at the amino terminal
-Alpha and Beta chains

42
Q

_____ T cells only recognize peptides presented by MHC class I

A

CD8

alpha3 (invariant portion of alpha chain) binds CD8 on CD8 T cells

43
Q

_____ T cells only recognize peptides presented by MHC class II

A

CD4

beta2 (invariant portion of beta chain) binds CD4 on CD4 T cells

44
Q

Why is MHC polymorphism important?

A

It ensures that a population can deal with microbe diversity

45
Q

Where is MHC Class II expressed?

A

On APC and induced by IFNgamma

46
Q

Where is MHC Class I expressed?

A

On all nucleated cells

47
Q

What can MHC molecules bind to?

A

Proteins, Lipids, Carbohydrate sugars, and Nucleic acids

48
Q

What can T cells recognize?

A

They can only recognize peptides derived from protein antigens

49
Q

When peptides bind to MHC, how long does binding last?

A

Binding lasts up to days to maximize interaction with T cells

50
Q

Describe processing of extracellular proteins

A

Extracellular proteins (tumor, bacteria) are processed in endosome/lysosome and peptides displayed on MHC Class II to CD4 cells

51
Q

Describe processing of cytosolic proteins

A

Cytosolic proteins (virus, bacteria that escape phagosome) are processed by proteasome and endoplasmic reticulum and peptides displayed on MHC Class I to CD8 cells

52
Q

What is the significance of MHC-associated antigen presentation?

A

Optimization of response to different microbes in different locations
-extracellular –> CD4
-intracellular –> CD8

Micro and Immuno (17 decks)

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