Immunology - Exam 1 (Part 4 - ANTIGEN PRESENTATION)

How do we know when SPECIFIC pathogens are present?

Rely on Major Histocompatibility Complex (MHC)

(aka, another name is the Human Leukocyte Antigen (HLA))

What is any substance that elicits a specific response by B or T lymphocytes since its a foreign protein, polysaccharide or lipid, and can be compontents of cell walls, capsule, flagella, toxins, pollen, blood cell surface molecules, and egg whites?

Antigen

What is an antigen that a given B cells receptors recognize?

Cognate antibody

What is a component of antigen that antibodies interact with?

Antigenic determinant (epitope)

What is part of the antiboyd that recognizes and attaches to the epitope?

Paratope

What are molecules that bind to protein framgents created in the cell or phagocytosed in the cell and bring them to the surface of the cell, presenting antigens to lymphocytes?

MHC (Major histocompatibility complex)

aka - HLA gene in humans

What cells present antigens, including dendritic cells, macrophages, experienced B cells, and neutrophils?

Antigen presenting cells (APC)

CD4 is a ______ T cell, while CD8 is a ________ T cell?

CD4 = Helper T cell

CD8 = Cytotoxic T cell

What are normal protein turnover machinery in the cytoplasm?

Proteasomes

Which type of MHC is where cells constantly break down proteins created within the cell and present them on the cell surface, where almost all cells fo the body can do this and it allows us to see what is being made IN the cell?

MHC I

Which type of MHC is special cells that eat protein (phagocytosis) outside of the cell, break it down, and present the fragments on the cell surface, where ONLY antigen presenting cells (APCs) can do this and allus us to see what is happening OUTSIDE the cell?

MHC II

Does MHC I or II display endogenous proteins/peptides and must fit within the MHC? Which displays extracellular proteins/peptides, where the proteins are larger AA in length?

Endogenous = MHC I

Exogenous = MHC II

DUring antigen presentation by MHC I, endogenous proteins are constantly broken down into fragments, these fragments are presented on the surface and regularly updated for what cell to constantly inspect?

Cytotoxic Lymphocytes (CTLs, Killer T cells, CD8) constaly inspect the presented fragments

What three things does Major Histocompatibility Complex I present?

1) Ordinary cellular proteins (enzymes or structural proteins)

2) Proteins encoded by viruses

3) Parasitic proteins

T/F: Almost every cell in the body expresses MHC II molecules

FALSE

-- almost every cell expresses MHC I

What is the function of proteasomes?

Breaking down defective, old, or useless proteins into peptides, then further into single AA for later use

Some of the peptides that were broken down in proteasomes are brought to the endoplasmic reticulum where they are attached to what? What are these peptides carried by to reach the ER?

Attached to MHC I

-- carried by specific transport proteins (TAP 1 & TAP 2)

Once the peptide is bound to the MHC I molecules, forming the peptide-MHC I complex), where is it transported?

Cell surface

How many MHC I genes are there? What chromosome are they located on?

6 MHC I genes (3 from mom, 3 from dad)

-- on chromosome 6

NOTE: There are hundreds of gene cariants for HLA A, B, and C, allowing an ability to bind many different kinds of peptides

Each MHC I protein pairs with what to form Complete MHC molecules?

another protein (beta2 microglobulin)

MHC I molecules have a groove (closed at both ends) in which a peptide must fit, anchoring at both ends and bulging in center, making most peptides bound to MHC I molecules ________ amino acids long

8-11 amino acids

What cells inspect MHC I peptides that are displayed?

Killer T cells (Cytotoxic Lymphocytes (CTLs))

Antigen presenting cells eat extracellular proteins that are contained within a phagosome, and are involved with which type of antigen presentation?

MHC II

Where are MHC II molecules made and where do they get injected?

Made in cytosol

- injected into endoplasmic reticulum

What is the special protein that protects the binding area of the MHC II?

Invariant Chain Protein

Once the invariant chain-MHC II complex is released into an endosome, it fuses with what? Why?

Phagosome (with extracellular protein)

-- break down this extracellular protein with enzymes to produce protein fragments (peptides)

Is the MHC II complex or the invariant chain protein broken down by enzymes within the endosome during protein fragmentation? Which is preserved?

MHC II preserved

Invariant chain protein broken down

After the extracellular protein fragments (peptides) load on MHC IIs, the MHCII-peptide is transported to the cell surface to do what?

Display peptide for Th cells (CD4)

T/F: MHC II molecules are closed at both ends

FALSE

- open at both ends

Most peptides bound to MHC II molecules are ________ AA long, with the peptide anchored at the center and the ends allowed to hang over?

13-25 AA

What are the three types of MHC II Antigen presenting cells?

1) Activated Dendritic cells

2) Activated microphages

3) Activated B cells

What is the two functions of APCs?

1) Provide high levels of MHCs required for T cell activation

2) Provide co-stimulatory molecules required for T cell activation (MHC I -- CTLs; MHC II -- Th cells)

What cell are ALL white blood cells, all made in bone marrow, must migrate out to various sites of the body and must be activated before they can function?

APCs (Antigen presenting cells)

T/F: In normal tissue, dendritic cells can take in four times their volume of extracellular fluid per hour (wine tasting).

TRUE

Dendritic cells in their resting state are NOT very good antigen presenting cells, but can present some _______ (costimulation)?

B7

NOTE: not very good to virgin T cells that require extensive receptor crosslinking and co-stimulation

What type of cell are resting dendritic cells due to the fact they are found all over the body and beneath epithelial cells, and they are the 1st cell on the scene?

Sentinel cells

What are two signals that activate dendritic cells?

1) Chemical signals form cells engaged in battle

2) Recognition of "common molecular patterns"

When activating dendritic cells, what are the two chemical signals from cells engaged in battle?

1) Cytokine (TNF from macrophages or neutorphils)

2) Dying cells

When activating dendritic cells, which "common molecular pattern" is receptors of the innate immune system that recognize common molecular patters on a pathogen surface, not a single pathogen, including TLR, LPS (CD14) receptor, scavenger receptor, glucan receptor?

Pattern Recognition Receptors (PRRs)

When activating dendritic cells, which "common molecular pattern" is molecules associated wtih groups of pathogens that are NOT shared by the host cells, and are recognized by cells of the innate immune system?

Pathogen Associated Molecular Patterns (PAMPs)

-- LPS, RNA of viruses, DNA of bacteria

Once activated, activated dendritic cells do what 3 functions?

Eat much more, resulting in:

1) MHC II loaded with antigens

2) More MHC I expression

3) More B7 expression (co-stimulatory proteins)

Dendritic cells stay in the tissue for about 6 hours, and then travel where? (TQ)

Leaves area though lymphatic system to nearest lymph node to bring new of the battle

Once Dendritic cells are activated, they act as sentinel cells that sample antigens in tissue, bringing samples to the lymph nodes and presenting antigens to naive T cells, but they are short lived.... Why?

We don't want old news still being presented in lymph nodes; allow new DCs to present

T/F: Activated dendritic cells don't do most of the killing, but will do some killing.

FALSE

-- don't do any killing; phagocytose (taste) antigens and then get others to do the killing

Activated macrophages are also sentinel cells, but how do they differ form dendritic cells?

Macrophages located in areas of body exposed to outside world and DONT travel like DC

-- Function in garbage collection, antigen presenting, and then KILLING

Activated dendritic cells activate ______ while Activated macrophages re-stimulate _________.

DC = naive T cells

Macrophages = experienced T cells

Activated macrophages only express enough MHC and co-stimulatory molecules to function as APCs after what three things?

1) Activation by cytokines (IFN-gamma)

2) Recognizing patterns (Toll-like receptor recognition)

3) complement detection

What other cell can serve as APCs since they express high levels of MHC II and B7, have BCR with a high affinity for their antigen, concentrate antigen for presentation, and ensures that Th cells have the MHC IIs and B7 to be activated?

Experienced Activated B cells

(Memory B Cells)

T/F: The time for a B cell to capture the antigen and present it on the cell surface on a n MHC II complex is a slow process.

FALSE

-- VERY FAST PROCESS (30 minutes)

MHC Summary:

MHC I

-- present peptides (protein) to CTLs (CD8 cells)

-- expressed in almost every kind of cell

-- displays proteins made INSIDE cell (Endogenous antigen)

MHC II

-- present peptides (protein) to Helper T cells (CD4 cells)

-- expressed exclusively on cells of immune system (APCs)

-- Advertise what is happening OUTSIDE cell (Exogenous antigen)

What is the exception to MHC1 and MHC2 antigen processing, where exogenous peptides can actually be presented by MHCI and activates CTLs?

Cross-presentation

Experiments with graft rejection in genetically diverse mice vs genetically identical mice found that genes responsible for rejection were located on a particular chromosomes, showing that MHC genes used for antigen presentation are the very same genes responsible for tissue rejection and helped us coin what term in transplant biology?

Histocompatibility

Summary on Antigen Presentation (Inside vs Outside cell):

If invader is OUTSIDE cell:

-- antibodies mark them for destruction

-- marked and/or destroyed by complement system

-- eaten by professional phagocytes

-- Use MHC II and helper T cells for this process

If invader is INSIDE cell:

-- MHC I presentation shows CTLs what going on inside infected cells

-- can't hide inside of cells as easily