MCB 100- Lecture 26 Exam 3

What is Adaptive Immunity?

• specific, inducible, acquired upon exposure to pathogen

• cells involved in adaptive immunity—> lymphocytes: T-cells and B-cells

• antibodies

• antigen processing and presentation

• cell-mediated cytotoxicity

Innate Distribution

almost all multicellular eukaryotes

Adaptive Distribution

only in vertebrates—> the adaptive immune system evolved over time

Innate Targets

a limited number of key structures present in many microbes (PAMPs), perhaps 20-50

Adaptive Targets

antigens, which are mostly proteins; different ones number in the billions

• massively diverse

Innate Immune Receptors

pattern recognition receptors, such as toll-like receptors (TLRs)

Adaptive Immune Receptors

T-cell receptors and antibodies

Innate Cellular Presence

almost all cells

Adaptive Cellular Presence

lymphocytes only (highly specialized)

Innate Discrimination

host cells do not contain PAMPs

Adaptive Discrimination

tolerance for self antigens can break down, resulting in autoimmune disease

Innate Immunological Memory

Absent

Adaptive Immunological Memory

present —> molecular record of pathogen exposure

Adaptive Immunity

the body’s ability to recognize and defend itself against distinct invaders (pathogens and irregular host cells) and their products

Five Main Attributes of Adaptive Immunity

• Specificity

• Inducibility

• Clonality

• Unresponsiveness to self

• Memory

Specificity

acts only against specific molecular shapes (antigens) from individual pathogens

Inducibility

only recognition of that specific antigen from a pathogen will initiate the response

Clonality

once induced, many generations of cells with identical response capabilities to a specific pathogen will be generated

Unresponsiveness to Self

self vs non-self recognition- eg response is only to the pathogen and not the host

Memory

once an adaptive response to a pathogen is initiated, the antigen will be remembered for future encounters

The Lymphatic System

composed of lymphatic vessels and lymphoid cells, tissues, and organs

The Lymphatic System Function

screen the tissues of the body for foreign molecules

The Lymphatic System Major Organs

lymph nodes, bone marrow, spleen, thymus, tonsils, intestines (GALT: Gut-associated lymphoid tissue)

Lymphatic Vessels

one-way system that conducts lymph from tissues and returns it to the circulatory system

Lymph

liquid with a similar composition to blood plasma. arises from fluid leaked from blood vessels into surrounding tissues.

Lymphatic Vessels Function

a conduit for immune communication throughout the body

Lymphoid tissues contain

a vast majority of the total immune cells in the body and are the organizing centers for mounting immune responses

Bone marrow and thymus

primary lymphoid organs (locations where all lymphoid cells in the body are formed and mature)

Blood and lymph

are the conduits for adaptive immune communication between tissues

Who is responsible for adaptive immunity?

Lymphocyte

B-cells (antibody production)

T-cells (cell-mediated responses)

B-cells

• develop/mature in the bone marrow

• involved in antibody-mediated functions of the adaptive immune system

T-cells

• develop/mature in the thymus

• involved in cell-mediated functions of the adaptive immune system

Humoral Response

antibodies secreted by B-cells specific to individual antigens

IgG

• oligomeric state: monomer (1)

• function: complement activation, virus and toxin inactivation, and opsonization

• major class of antibody in the bloodstream (80% of Ab in blood/serum, 13.5 mg/mL)

• lower amounts of antibodies

• found in breast milk and colostrum

IgM

• oligomeric state: pentamer (5)

• function: complement activation (1000X better than IgG) and initial adaptive response

• found in breast milk and colostrum

• largest of all antibodies, containing 10 antigen binding sites per molecule which allows high avidity binding

IgA

• oligomeric state: dimer (2)

• function: mucosal immunity (ex. airways, intestines etc) and newborn passive immunity in breastmilk

• found in the highest concentration in breast milk (90%)

• lower amounts of antibodies present

IgD

• oligomeric state: monomer (1)

• function: mucosal homeostasis and not well understood

IgE

• oligomeric state: monomer (1)

• function: inflammation and controlling parasties

Antigen

a substance that interacts with a specific antibody

Immunogen

an antigen that elicits an immune response

Epitope

(antigenic determinant) is the part of antigen recognized by an antibody-binding site

How is antibody diversity generated?

VDJ Recombination

1. Recombination activating gene (RAG) randomly combines one D segment with one J segment

2. RAG randomly combines DJ with V segment

3. Transcription and translation result in a unique BCR for that B cell

Primary Response

• IgM levels rise rapidly, while IgG is slower

• IgM and IgG total response is similar

• IgM and IgG response times during initial antigen exposure

Secondary Response

• Lag period reduced, especially for IgG

• IgG levels are maintained for longer duration

• IgG amounts greater

• IgM levels comparable to the initial response

• IgM and IgG response times during secondary antigen exposure

B-cells Long Term Memory

generation of memory cells that can circulate within the body for many years

B-cells Recognition of Diverse Epitopes

1 X 10^11 (100 Billion) different molecular patterns can be recognized by B-cells during adaptive immunity

B-cells TLRs from Innate Immunity

Recognizing about 20-50 distinct pathogen-associated molecular patterns (PAMPs)

B-cell sustained response

can be weeks to months

B-cells and antibodies

• each b lymphocyte has multiple copies of b cell receptor (BCR)

• each b cell generates a single BCR

• two variable regions of the BCR form the antigen-binding sites

• each BCR recognizes only one epitope

• the entire repertoire of an individual’s BCRs is capable of recognizing millions of different epitopes at any given time

B-cells that secrete antibody are called

plasma cells

Antibodies help clear pathogens in many ways

• neutralization

• opsonization

• agglutination

• antibody-dependent cell-mediated cytotoxicity (ADCC)