Antigen Presentation Flashcards by Jacob Amato

How were Major Histocompatibility Complexes discovered

Due to their importance during tissue rejection

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Major Histocompatibility Complex is encoded where

Human Leukocyte Antigen Complex on Chromosome 6

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What are Major Histocompatibility Complex genes

Polygenic, extremely polymorphic, Codominantly expressed

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Major Histocompatibility Complex molecules are neccessary to

Present Ag to T cells

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Who has MHC Class I

All nucleated cells

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What do MHC Class I display

Endogenous peptides

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What do MHC Class I present to

CD8+ T cells

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Who expresses MHC Class II

on professional antigen presenting cells

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What do MHC Class II present

exogenous peptides

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Who do MHC CLass II present to

CD4+ T cells

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Strucutural difference between Class I and Class II MHC structures

Class I, only in membrane once, where class II enters cell membrane twice

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MHC Peptide Binding region for Class I and Class II

Class I: 8-10 amino acids

Class II: 13-18 amino acids

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The breakdown of macromolecules into amller fragments in order to prepare for presentation to a t cell

Antigen Processing

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4 ways of Ag Processing

Exogenous, Endogenous, Cross-presentation, autophagic

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endogenous pathway

Infection by bacteria, antigen degraded in ctosol, peptide association with MHC Class I, activation of CD8 Tc Cells

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Exogenous Pathway

Internalization by APCs, antigen degradation in endocytic compartment, peptide assocation with MHC class II, Activation of CD4 Th cells

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Cross presentation

Starts in exogenous pathway and ends in endogenous pathway (outside but MHC class I)

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Autophagic

Starts in endogenous pathway and ends in exogenous pathway (inside but MHC class II)

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Naive T Cell Activation

Uses a Dendritic cell to take up antigen, and results in Clonal expansion and differentiation into effector T cells

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Effector T cell activation

Marcrophase presnts, leading to T cell activation and activation of macrophages for Cell-mediated Immunity

And B cell activation and antibody production leading to humoral immunity

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What i contained in the Alpha subunit of MHC Class I

Enter into the membrane and have the peptide binding chain

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Subunits of MHC CLass I

Alpha and Beta subunits both insert into the membrane and also have a peptide binding cleft

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3 types of Antigen Presenting Cells

Mature DC, Macrophages, B cells

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What is the best at presenting to a T cell

Dendritic cells (high MHC II and constimulary molecules)

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What can activate a Naive T cell

Dendritic cells

What are macrophages and B cells good activating

Effector cells and memory T cells

Action of Dendritic Cells

Recognize antigen, Phagocytosis it, activating DC cell. Begins processing, drain through lymphatics , to find the correct T cell, to activate that T cell

Exogenous Pathway

Internatlize antigen by phagocytosis to form phagosome. This fuses with lysosome to bread down antigen. At the same time the RER begins making Class II MHC. Passes throught the SER, Golgi, then heads to Lysosome, to degrade invariant chain. HLA-DM removed clip and peptide from antigen to be presented on the outside of the cell.

What parts are uniquie to the exogenous pathway

Invariant chain, Clip, HLA-DM, MHC II

Endogenous Pathway

Internal peptide has a tag added to it from the Ubiquitin Protein. Tis tells the protein to be degraded by the proteosome. TAP puts these fragments into the endoplasmic reticulum and is loaded into MHC Class I

Cross Presentation pathway

APC ingest and processes virally infected cell. Viral Proteins enter the cytosol and is processes via endogenous pathway(protesome) to activate a CD8 cell via MHC I

Autophagic Pathway

Uses internal stuff and degrades it with lysosome and presented in MHC II

Receptor responsible for antigen recognition on t Cells

T cell Receptor

Alpha Beta T cells recognize

MHC/Ag

Where Alpha-Beta T cells Reside

In secondary Lymphoid tissue

Gamma delta T cells recognize

Processed/unprocessed ligands (innate immune cells)

Where gamma delta T cells are found

Intraepithelial Tissues

Structure of T cell Receptor

1 variable region on each chain(2 total) | 1 constant region on each chain (two total)

The T Cell receptors need to recognize

Peptide + MHC

What helps to start an intracellular chain of events in a T cell Receptor

CD3 (zeta chains)

What recognizes MHC class I

CD8 T Cell

What recognizes MHC Class II

CD4 T cell

What are CD4 T cells | And CD8

Helper T cells | Cytotoxic

How TCR Complex is activated

MHC interacts with T cell receptor. CD4 or CD8 recognizes when this becomes activated and this activates Lck which phosphorylates tyrosines in ITAMs

Can a TCR undergo VDJ recombination

Yes

V(D) J recombination occures where

In the Variable region

HOw T cell and B cell development is similar

Begin in bone marrow V(D)J recombination of variable region of TCR leads to antigenic diversity At one point cells express both CD4 and CD8 Undergo positive and negative selection

What do T cell development begin with

NK/T precursor cell

Where do T cells (thymocytes) move to finish development

leave bone marrow to go to thymus

What molcules of T cell development are involved in Establishing central tolerance

MHC molecules

Can Somatic hypermutation occur in T cells

Role of Rag genes

do V(D)J recombination

What surface molecules are expressed by T cell stem cells

Adhesion molecules

Does Recombination of V(D)J occure during stem cell stage of T cells

1st tell cell stage in the thymus

Pro-T cell

When does the Beta Chain first recombo for T-cell

At the end of the Pro-T cell

When the Beta chain recombo for T cells end and alpha begins

Pre-T (alpha at the end)

DOuble positive T cell

full T receptor and CD4 and CD8

When T cells go through positve and negative selection

Double possitive

What separates Single possitve T cell

when it only recognizes as a CD4 or CD8 cell

Negative selection

Dies because reacts to much to MHC

Cell involved in Naive T cell activation

Dendritic Cells

Naive T cell activation steps

Dendritic cells process antigen, present to a CD4 T cell and co-stimulatory factors

The Best epitope of activating a T Cells

immunodominant

Steps of signalling T cells

- Ag recognition - Costimulation(IL-2 needed to activate) - Cytokines - Differentiation (cytokines)

B7 is related to

Found on the antigen presenting cells to adhere to CD28 for signal transduction via costimulation

IL-2 is needed for

Survial, proliferation, and differentiation of T cells

Roll of CD4 T cell

Activation of Macrophages, B cells, and others, plus inflammation

Roll of CD8 T cells

Killing of infected cells, macrophage activation

CD4 subsets

Subsets of Helper T cells that match for which type of problem you have

FUnction of Th1 helper t cells

T help for Tc response against intracellular pathogens (activate macrophages) (IFN7)

Function of Th2 helper t cells

T cell for B cell responses against extraceullar pathogens and humoral activation (IL-4)

Th17 roll

Inflammation and mucosal immune response(antimicrobial peptides), recruit nutrophils (IL-17)

Treg roll

Peripheral tollerance, make sure immune response does not get out of control (IL-10)

The Cytotoxic Cells

CD8 T cells

Ctokines needed for CD8 T cells

IL-2, IL-12, and type 1 IFN

interaction of cytotoxic T Lymphocytes

Interacts with Anitgen bound to MHC class 1. GRanule exocytosis to kill target. Releases and taget cell dies

What is left after Contraction of Immune system

Memory T cells