Adaptive Immunity

1,2, & 3

Why is Adaptive Immunity important?

1) Improved control of infectious disease

2) Immunological memory

3) Protection by Vaccination

How do B cells recognize antigens?

1) B cell encounters its antigen

2) BCR binds directly to a specific part of the antigen

3) The B cell can process the antigen

4) When appropriate, the B cell becomes activated

5) Eventually differentiates into a plasma cell that produces antibodies

How do T cells recognize antigens?

1) T cells recognize processes peptides antigens presented on MHC through TCRs

2.1) CD 4 cells recognize peptides on MHC 2 brought by DCs, macrophages, or B cells

2.2) CD 8 cells recognize peptides on MHC 1 which is expressed on nearly all nucleated cells

What are the key differences between B vs T cell Ag recognition?

• B bind directly; T don’t

• B = no MHC, T = need MHC

• B epitopes are 3D/linear and extracellular, T epitopes are linear and intracellular

• B can rec. proteins, lipids, or carbs; T can only rec. proteins

When & Where do T cells recognize thier antigens?

Naive T cells recognize at secondary organs, before initial activation

Effector T cells recognize in infected tissues and after activation

Why do T cells need antigen capture and processing?

T cells cannot recognize a native antigen directly. It needs to have an APC to capture, process, and present the antigen

How do APCs capture and process antigens as MHC 2?

1) DCs engulf antigen

2) antigen is broken down into peptide fragments

3) DC displays peptide on it’s surface

4) DC travels through afferent lymphatics to a draining lymph node

5) A native CD4 T cell recognizes the peptide; TCRs process, with the appropriate costimulation and cytokine signals, the T cell is activated and begins clonal expansion

How do APCs capture and process antigens as MHC 1?

1) DC engulfs antigen

2) Antigen is broken down

3) Peptides are presented internally

What are the main functions of DCs?

• antigen capture, processing, and presentation

• T cell activation

• Cytokine Secretion

Where are immature DC found?

peripheral tissue

Where are mature DCs found?

lymph nodes

Besides DCs being APCs, what other APCs are there?

Macrophages and B cells

How do Macrophages function as APCs?

1) Engulf and destroy pathogens

2) present antigens to effector CD4 cells

3) usually within tissues

How do B cells function as APCs?

1) Recognize specific antigens through BCR

2) present antigens to helper T cells

3) Found in lymphiod follicles and other tissues

What are the 3 key signals DCs have to have to activate T cells?

1) Signal 1 - TCR binds to peptide-MHC ( recognition)

2) Signal 2 - CD28 on T cell binds B7 on DC (costimulation)

3) Signal 3 - DC secretes cytokines (guides T cell differentiation)

What is cross-presentation?

A DC can capture an extracellular antigen and present it on MHC 1 to CD8 T cells. This helps initiate CD8 responses against viruses or tumors, even when the DC is not infected

What does it mean that MHC is the most polymorphic gene?

There are many different alleles of MHC genes within the human population.

Why is MHC gene polymorphism important?

different MHC alleles have slightly different structures, especially in thier peptide-binding grooves

How does MHC gene polymorphism affect organ transplantation?

People have different HLA alleles, the immune system can recognize transplanted tissue as foreign

How are MHC genes polygenic?

each individual has different genes that encode for the same MHC molecules

How are polygenic MHC genes important?

If a virus infects your body, each HLA might present a different viral peptide, since we have multiple MHC genes your cells can display a broader variety of peptides to T cells

What does it mean that MHC molecules are codominantly expressed?

The MHC alleles inherited from BOTH parents are expressed on your cells. expressing both allows your cellls to present a wider range of pathogen peptides

What are the 3 key structures of MHC class 1?

1) One alpha heavy chain

2) Beta-2-microglobulin

3) Peptide-binding groove

How are MHC 1 molecules made?

1) The alpha chain is synthesized by ribosomes on the rough ER

2) In the ER, it folds and associates with B2m

3) Viral proteins are degraded into smaller peptides by the proteasome in the cytoplasm

4) Peptides are transported to the ER via TAP

5) In the ER, a suitable peptide binds to the peptide-binding groove of MHC 1

6) MHC 1 coplex travels through the Golgi and into the plasma mem.

What happens to the production of MHC 1 molecules if TAP is defective?

• Peptides can’t effectively enter the ER

• MHC 1 cannot be loaded normally

• Fewer stable MHC 1 complexes

What are the 3 main structures of MHC 2?

1) One alpha chain

2) One beta chain

3) Peptide-binding groove

How are MHC 2 molecules made?

1) The alpha and beta chain are synthesized and assembled in the ER

2) The travels from the ER to the Golgi, and into the endosomal pathway

3) Extracellular antigens are captured and processed

4) enymes break down the chain leaving a small fragment called CLIP in the binding groove

5) HLA-DM removes CLIP and allows an antigen peptide to bind to MHC 2

6) MHC 2 complex transported to the plasma mem

What is a BCR?

An immunoglobulin attached to the B cell membrane

What is a secreted antibody?

An antibody is the secreted form of an immunoglobulin produced by a B cell. They are the soluble & secreted form of BCR

What are the 5 classes/isotypes of antibodies?

IgA, IgD, IgE, IgG, and IgM

What are the 4 different polypeptide chains of an antibody molecule?

• 2 IDENTICAL heavy chains - 1 Vh and 3-4 Ch domains

• 2 IDENTICAL light chains - 1 Vh and 1 Ch domains

How are the chains of antibody molecules joined together?

They are joined by disulfide bonds to create a Y-shaped antibody, creating 3 regions

What are the 3 different regions of an antibody molecule?

1) Fab - antigen binding

2) Fc - effector functions

3) Hinge - flexibility

What does the Fab region consist of?

Contains the entire VL chain attached to Vh and connected to the first Ch

Where is the Hinge located?

between the Fab and Fc region

What is the function of IgA?

muscosal immunity

What is the function of IgD?

Naive B cell antigen receptor

What is the function of IgE?

Defense against helminthic parasites

What is the function of IgG?

Opsonization, complement activation

What is the function of IgM?

Native B cell antigen receptor

What is an Isotope?

denotes a difference in constant chains. Aids is diagnosing of immunodificiencies.

What is an Allotype?

differ in short streches of amino acids along L or H constant chains

What are Idiotypes?

stretches of amino acids unique to each Ab

What is affinity?

strength of one antigen-binding interactions

What is Avidity?

Overall binding strength when mulitple binding interactions occur together