Unit 3: The Adaptive Immune Response

What is the main difference between innate and adaptive immunity?

Innate immunity uses germline-encoded patterns for recognition, while adaptive immunity uses somatically generated receptors.

How quickly does innate immunity respond?

Innate immunity responds within minutes to hours.

How quickly does adaptive immunity respond?

Adaptive immunity takes days to respond initially.

How does the diversity of innate immunity compare with adaptive immunity?

Innate immunity has limited but broad diversity, while adaptive immunity is extremely diverse but specific.

What happens with repeat exposure in innate immunity?

There is typically no memory.

What happens with repeat exposure in adaptive immunity?

The response is faster and stronger because of memory. This is called an anamnestic response.

What are the major players of innate immunity?

• Barriers

• Phagocytes

• NK cells

• Complement

What are the major players of adaptive immunity?

• B cells

• T cells

• Antibodies

What is active immunity?

Active immunity occurs when an immunocompetent individual is exposed to a challenge and produces their own immune response and immune products.

How long can active immunity take to develop?

It may take weeks to develop.

How long can active immunity provide protection?

It can provide lifelong protection.

What is naturally acquired active immunity?

Recovery from an infection.

What is artificially acquired active immunity?

Vaccination

What is passive immunity?

Passive immunity occurs when preformed immune products are given to an individual.

How quickly does passive immunity provide protection?

It provides immediate protection.

How long does passive immunity last?

Passive immunity provides transient, or temporary, protection.

What is naturally acquired passive immunity?

IgG crossing the mother's placenta and IgA in breast milk.

What is artificially acquired passive immunity?

• Intravenous immunoglobulin (IVIg)

• Monoclonal antibody (mAb) therapy.

What is adoptive immunity?

Adoptive immunity is the transfer of immunocompetent cells from one individual to a second individual to establish immunocompetence.

What is one purpose of adoptive immunity?

It can help reconstitute the immune system.

What are examples of adoptive immunity?

Bone marrow transplantation (BMT) and CAR T-cell therapy.

What is hematopoiesis?

Hematopoiesis is how blood cells are produced.

What are the primary lymphoid organs?

The bone marrow and thymus.

What happens in the primary lymphoid organs?

Lymphocytes develop and mature, including a selection process that distinguishes self from non-self.

Where do B cells develop?

B cells develop in the bone marrow.

Where do T cells develop?

T cell progenitors migrate to the thymus, where T cells develop and mature.

What are secondary lymphoid organs?

Organs where mature lymphocytes can encounter antigens and become activated.

What happens to lymphocytes after they mature?

They enter circulation and may stay in specific organs where they can encounter antigens and become activated.

What are examples of secondary lymphoid organs?

Lymph nodes, spleen, and mucosal-associated lymphoid tissue (MALT).

What do lymph nodes do?

They filter lymph fluid from draining tissue.

Where are B cells concentrated in lymph nodes?

B cells are concentrated in follicles and the cortex.

What happens in the lymph node after B cells are activated?

They form germinal centers.

Where are T cells concentrated in lymph nodes?

T cells are concentrated in the paracortex.

What does the spleen filter?

The spleen filters blood.

How is the spleen similar to a lymph node?

It has a similar function to a lymph node but filters blood instead of lymph fluid.

What does MALT stand for?

Mucosal-associated lymphoid tissue.

What is GALT?

Gut-associated lymphoid tissue.

What are examples of GALT?

Peyer's patches, tonsils, and adenoids.

What do M cells do?

M cells deliver antigens from the gut to adaptive immune cells.

What is BALT?

Bronchial-associated lymphoid tissue.

Where is BALT located?

In the respiratory epithelium.

How do lymph nodes organize B- and T-cell encounters?

An antigen is found by an APC, the APC enters the draining lymph node, the APC scans for a matching naïve T cell, the T cell becomes activated, and then clonal expansion and B-cell interaction occur.

What is MHC?

MHC stands for Major Histocompatibility Complex.

What is another name for MHC in humans?

HLA, or human leukocyte antigen.

Where is MHC found?

MHC is found on cells and helps bring small peptide antigens to the cell surface for recognition by T cells.

Where are MHC genes located?

MHC genes are found on the short arm of chromosome 6.

How are MHC genes inherited?

They are inherited as a haplotype, with one chromosome from each parent, and are codominant.

Why does MHC provide a lot of genetic diversity?

There are more than 1.7 billion possible combinations.

What are the three classes of MHC?

Class I, Class II, and Class III.

Where is MHC Class I found?

On all nucleated cells.

What are the major MHC Class I gene loci?

HLA-A, HLA-B, and HLA-C.

What are the minor MHC Class I gene loci?

HLA-E, HLA-F, and HLA-G.

What is special about HLA-G?

HLA-G is part of the placenta.

Where is MHC Class II found?

On antigen-presenting cells (APCs).

What are the MHC Class II isotypes?

HLA-DM, HLA-DO, HLA-DP, HLA-DQ, and HLA-DR.

What is MHC Class III?

MHC Class III is not found on cells and includes complement proteins.

What are some clinical areas where MHC/HLA is important?

Transfusion reactions, platelet compatibility, transplant and graft rejection, and autoimmune diseases.

How can HLA matching help clinically?

HLA matching can help prevent problems with transplants and graft rejection.

What is the basic structure of MHC Class I?

MHC Class I is a glycoprotein dimer made of two non-covalently linked polypeptide chains: an alpha chain and a beta chain.

How many domains does the MHC Class I alpha chain have?

Three

What is special about the MHC Class I beta chain?

It is encoded by a single gene on chromosome 15, does not penetrate the cell membrane, and is essential for alpha-chain folding.

What types of antigens are presented by MHC Class I?

Endogenous antigens, including intracellular pathogens, viruses, and tumor antigens.

What happens to endogenous antigens before they are presented by MHC Class I?

They are degraded by the proteasome into peptides.

Where are the peptides transported after being produced?

They are transported to the rough ER.

Where does the peptide bind to MHC Class I?

Inside the rough ER.

What happens to the peptide-MHC Class I complex after it forms?

It is transported through the Golgi to the cell surface.

What happens when a TCR recognizes a peptide-MHC Class I complex?

The TCR binds the antigen and MHC Class I binds the CD8 co-receptor.

What type of T cell interacts with MHC Class I?

CD8+ T cells.

What does a CD8+ T cell do after recognizing its target?

It lyses the target cell.

What are CD markers?

CD markers are cell-surface proteins used to identify and classify immune cells.

What can CD markers help distinguish?

They can help distinguish immature from mature cells and B cells from T cells.

What is the role of MHC Class I in killing infected or tumor cells?

MHC Class I presents viral or tumor peptides to cytotoxic CD8+ T cells.

How many identical antigen-MHC Class I complexes may be needed to induce a response?

About 10–100 identical antigen-MHC Class I complexes.

What do CD8+ T cells produce to lyse cells?

Perforin and granzyme.

Where is MHC Class II expressed?

On antigen-presenting cells (APCs).

What are examples of cells that express MHC Class II?

Monocytes, macrophages, Kupffer cells, microglia, alveolar cells, dendritic cells, and B cells.

Which APC is the most effective?

The dendritic cell.

What type of antigens does MHC Class II present?

Exogenous antigens.

What is the basic structure of MHC Class II?

It has two non-covalently bound polypeptide chains: an alpha chain and a beta chain.

Where are the MHC Class II alpha and beta chains located?

Both chains are inserted into the cell membrane.

What forms the peptide-binding site in MHC Class II?

The α1 and β1 regions form the peptide-binding site.

What is different about the MHC Class II peptide-binding site?

It is deeper and binds longer peptides.

What happens to an exogenous protein before it is presented by MHC Class II?

The protein is taken up by the cell and endocytosed, then processed into peptides in an endosome.

Where is MHC Class II made?

MHC Class II exists in the rough ER.

What blocks the peptide-binding site of MHC Class II in the rough ER?

The invariant chain.

What happens to MHC Class II after it leaves the rough ER?

It travels through the Golgi and fuses with an endosome.

What happens to the invariant chain?

The endosome cleaves the invariant chain, allowing the peptide to bind to MHC Class II.

What happens after the peptide-MHC Class II complex forms?

It is transported to the cell surface.

What happens when a TCR recognizes peptide-MHC Class II?

The TCR binds the antigen and MHC Class II binds the CD4 co-receptor.

What type of T cell interacts with MHC Class II?

CD4+ T cells.

What happens after MHC Class II activates T cells?

T cells undergo clonal expansion, proliferation, and activation.

What are T cells?

T cells are small lymphocytes about 7–10 µm in size and make up about 75% of circulating lymphocytes.

What markers are associated with T cells?

TCR, CD2, CD3, CD4, and CD8.

What does TCR stand for?

T cell receptor.

What does CD2 recognize?

CD2 is a sheep RBC receptor.

What is CD3?

CD3 is part of the TCR and is involved in intracellular signaling.

What does CD4 act as a co-receptor for?

MHC Class II.

What does CD8 act as a co-receptor for?

MHC Class I.

What does the TCR recognize?

The TCR recognizes a peptide-MHC complex.

Can a TCR bind an antigen without MHC?

No. T cells cannot bind antigen without MHC.