Unit 3 - Adaptive Immunity

Antigen

Any molecule that immune system responds to as harmful/foreign

B Cell

Secretes antibodies which neutralize and helps innate cells engage in killing

T Cell

Induces apoptosis and helps innate cells kill

What are the professional APC?

• Dendritic Cells

• Macrophages

• B Cells

Constant Region

Base of antibody that determines what the antibody does

Variable Region

Tips of the antibody that differs for every antibody

Epiptope

Portion of the antigen that’s directly bounds by a B or T cell receptor

Linear Epiptope

Binds to sequential amino acids in order

Confirmational/Discontinuous Epiptopes

Binding of amino acids aren’t in order of protein, probably because it’s folded

T Cell Receptor

Binds to processed antigens from APCs has either aB or yD chain

Antigen Presenting

1. Protein is taken in and broken down

2. Small peptide chunk is presented on MHC1

3. T cells bind to MHC and peptide chunk

Helper T Cells (CD4 T Cell)

GIve signals to help other cells perform their function

Cytotoxic Cells (CD8 T Cell)

Directly kills infected or mutated host cells by detecting antigen on MHCI and acts as a co-receptor for T cell to bind properly

T_FH Cells

Follicular helper cells that activate B cells and usually activate in all modules

Plasma Cells

Activated B cells that bind to bacterium and differentiates to make antibodies

Antibodies

Binds, neutralizes and tags for destruction by immune cells

Adaptive Immune Cells

Lives in lymph nodes in an organized structure

Germline Theory

1 gene, 1 antibody

Somatic Diversification Theory

Combining smaller genes together makes diversity (Cohn and Tonegawa)

B Receptor/Immunoglobulin/Antibody

Has two identical heavy and light chains that binds to whole antigen in its natural conformation

Onlu _________ express MHC II

APCs

Every B or T receptor is made up of

• V1-V40

• D1-D23

• J1-J6

VDJ Recombination

1. D and J are spliced together

2. V subunit with its promoter is spliced with DJ

3. All subunits are palced beside a constant region

Light Chains

Contains just V and J subunits

TCR a and y chain similar to

Light chain

TCR B and D chain similar to

Heavy chain but with different B constant regions

Rag

Recombines genes

Junctional Diversity

Diversity generated from V and J sticky ends being sealed by random bases

Tdt

Places random nucleotides to increase diversity until they match

Long Loops

Allow antibody into tight spaced

Short Amino Acids

Helps antibody with steric hindrance

Somatic Hypermutation

Affinity of binding varies (affinity maturation) of B cells as time goes on, point mutated antibodies are selected for the best one

Naive T Cells

Made in lymph nodes that become activated by DC

Development T Cell Pathway

1. Hematopoietic stem cell progenitors differentiate into T cell precursors in bone marrow

2. T Cell precursors travel to the thymus

3. T Cell differentiates and travel to lymphoid tissues for activation

Thymus

Immune organ with an inner looser medulla and outer denser cortex

DiGeorge Syndrome

Developmental disease with no thymus and mature T cells

Nude Mouse

Mutation that has no thumus or T cells

Removing Thymus of neonatal mice

Eliminates T cells

Adding Thymus to Nude Mice

Recovers T cells

What happens to the thymus as we age?

T cell production decreases from thymus being replaced with fat, but doesn’t impact immune system greatly because enough T cells are already generated

Thymocytes

Precursor T cells

CD3^-

Progenitor cell not committed to a T cell lineage

Double Negative

CD4^- CD8^-

Double Positive

CD4⁺ CD8⁺

Single Positive

CD4⁺ CD8^- or CD4^- CD8⁺

How many cells have a aB chain

95%

Where are most yD chains?

Mucosal sites and act like innate immune cells

VDJ Recombination Fail Rate

>66%

Common Cause of T Cell Death

Frameshift mutations change TCR reading frame

TCR Development

1. Progenitor enters medulla and divides

2. RAG genes increase to rearrange VDJ genes to make TCR while moving into cortex (CD3⁺)

3. T cell determines aB or yD (whichever rearranges 1st)

4. If pre TCR can signal, cell survives and divides

5. Re-arrange an a chain to replaces surrogate one before it runs out

CD4 T Cells can specialize into

• T_h1

• T_h2

• T_h17

• T_Fh

T_H1

Activates macrophages

T_H2

Activate cellular and antibody reponse to parasites

T_H17

Enhance neutrophil response

Where is the adaptive immune system activated?

• Adenoid

• Tonsil

• Lymph node

• Spleen

• Peyer’s patch in small intestine