Angela Mitchell BIO422 2013 [email protected].

Adaptive Immune SystemAngela Mitchell

BIO4222013

[email protected]

“Jobs” of the Immune System

Recognize that invaders are present◦ Recognize that these are different than self

Recruit more cells/factors to fight invaders Kill the invaders Block any toxins produced by the invaders Learn from past encounters to increase

future effectiveness

“Jobs” of the Immune System

Overview of Host Response to Pathogens

Time Course of an Immune Response

Levels of the Immune Response

Levels of the Immune Response

Antigen: the molecule recognized by the response

The epitope is the specific part of the antigen recognized

Each adaptive immune cell can only recognize one epitope

Adaptive Responses Are Specific to Individual “Epitopes”

Epitopes are small parts of antigens

Figure 24.2

Can an antigen have more than one epitope?◦ Yes, almost always

Can an epitope have more than one antigen?◦ No (almost always…)

You found two adaptive immune cells that respond to pilin. Are these cells specific for the same epitope?◦ No necessarily: they could respond to two different

epitopes on the same antigen

Concept Questions

Adaptive Immune response relies on lymphocytes: B and T cells

Two Branches of Adaptive Response

Cellular Immunity Humoral Immunity

Main cells are T cells Useful against

intracellular pathogens

B cells and antibodies Useful against

extracellular microbes and toxins

Cellular Immune Response

T cell Mediated Immunity

Roles of T cells in Host Defense

CD8+

CD4+

T cell receptor Recognizes small parts of proteins

“presented” on MHC molecules MHC is present on antigen presenting cells

How do T cells recognize antigen?

MHCI is present on all nucleated cells◦ CD8+ cytotoxic T cells recognize MHCI

MHCII is present on professional antigen presenting cells pAPCs◦ CD4+ helper T cells recognize MHCII

Two types of MHC: MHCI and MHCII

Figure 24.20

Intracellular antigens are processed and displayed on MHCI for CD8+ cytotoxic T cells

Figure 24.21

Extracellular antigens are processed and displayed on MHCII for CD4+ helper T cells

Figure 24.21

Professional antigen presenting cells Dendritic cells, macrophages, and B cell Offer activating signals to T cells—primes for

activity, causes proliferation

Initial recognition by pAPCs

Cytotoxic T cells: CD8+ T cells◦Recognize antigens on MHCI◦Releases granules to kills target cells

Helper T cells: CD4+ T cells◦Recognize antigens on MHCII◦Secrete cytokines to activate other cells◦Two major types: Th1 and Th2

Types of T cells

CD8+ Cytotoxic T cells

Death of cells infected with virus or cytoplasmic bacteria, cancer cell, etc.

CD4+ Helper T cells (Th)

Th1 cells: activate phagocytes

Th2 cells: activate B cells

What do cytotoxic T cells recognize?

A. Exogenous peptides on MHCIB. Endogenous peptides on MHCIC. Exogenous peptides on MHCIID. Carbohydrates on bacteria cellsE. Endogenous peptides on MHCII

Concept Question

T helper 1 cells (Th1) are important for defense from…

A. Extracellular pathogensB. Fungi onlyC. Viruses onlyD. Cytoplasmic pathogensE. Phagocytosed/Endosomal pathogens

Concept Question

Review From FridayEpitopes and AntigensMHCI and MHCIIActivation of T cells

Epitopes are small parts of antigens

Figure 24.2

Every T cell has a different T cell receptor specific to a different epitope◦ Your body can make about 10^18 different T cell

receptors Developmental processes kill T cells that

cannot recognize your MHC and that recognize self peptides

Initial T cell recognition of a peptide without an innate immune response (inflammation) does not activate the T cell

Specificity of T cell (B and) activation

Initial response of T cells (cytotoxic and helper): proliferation and activation

Croft. 2003. Nat Rev Immun. 3: 609.

MHCI presents cytoplasmic (endogenous) peptides to Cytotoxic T cells

CD8+ Cytotoxic T cells

Death of cells infected with virus or cytoplasmic bacteria, cancer cell, etc.

MHCII presents endosomal (exogenous) peptides to Helper T cells

CD4+ Helper T cells (Th)

Th1 cells: activate phagocytes

Th2 cells: activate B cells

Cell Type Cytotoxic T cell Th1 Helper T cell Th2 Helper Tcell

Type of MHC MHCI MHCII MHCII

Location of MHC All nucleated cells Professional antigen presenting cells

Professional antigen presenting cells

Location of antigen

Endogenous—within the cytoplasm of the cell

Exogenous—present in the phagosome

Exogenous—present in the phagosome

Type of epitope Small linear peptide

Small linear peptide

Small linear peptide

Response to initial recognition

Proliferate and activate to effector

Proliferate and activate to effector

Proliferate and activate to effector

Activated cell recognizing epitope releases

Granules—perforins, granzymes

Cytokines Cytokines

Which… Kill the target cell Activate phagocytes (WBC) to kill phagocytosed microbes

Activate B cells to proliferate, produce antibodies, and develop memory

T cell summary

Humoral Immune Response

B cell Mediated Immunity

Defense from extracellular pathogens and toxins

Recognize antigen in native form

B cells Produce Antibodies

Activation of B cells B cell receptor (BCR)

recognizes antigen◦ Membrane bound

antibody Th2 cells help

activation and are required for memory

B cell differentiates to plasma cell, which produces antibodies

Antibody Structure Immunoglobulins (Ig) “Y” shaped proteins 4 polypeptides linked by

disulfide bonds◦ Two identical heavy chains◦ Two identical light chains

Has variable and constant regions

Variable regions are responsible for recognizing the epitope

Antibody Structure

Figure 24.7

Structure of Different Antibody Types

Functions of Antibodies

Functional Activity IgM IgD IgG IgA IgE

Neutralization + ++ ++

Phagocytosis + +++ +

Natural killer cell killing

++

Mast cell activation + +++

Complement activation

+++ +++ +

Location BCR &Serum

BCR (minor)

Serum & tissue

Mucus & tissue

Mast cells

Types of Antibodies

Basophile activation?

B cells recognize _____ with membrane bound_____.

A. Peptides only MHCsB. Whole antigens MHCsC. Peptides only AntibodiesD. Carbohydrates only TLRsE. Whole antigens Antibodies

Concept Question

Immunological Memory

Secondary responses to infectionVaccination

Timing of Adaptive Response

Immunological Memory

Secondary Immune Response

Small populations of B and T cells retained from first exposure

Survive for a long time

Begin faster than first response Stronger than first response

Vaccinations take advantage of memory responses

Memory Responses

Vaccines allow for high levels of pre-existing immunity due to memory

Figure 24.13

Deliberate induction of an immune response to a pathogen by introducing a dead or non-pathogenic (attenuated) form of the pathogen

Vaccination began with Edward Jenner (around 1796)

◦ Observation that people exposed to cowpox did not get smallpox◦ Exposed a boy to cowpox (vaccinia) and the boy did not get sick with smallpox

Vaccination

Smallpox vaccine led to the eradication of smallpox

Now many vaccines!

When you’re exposed to a pathogen for the second time, your innate and adaptive immune responses will be

A. Innate and adaptive both faster and strongerB. Adaptive faster and stronger but innate only

fasterC. Innate and adaptive both faster onlyD. Innate the same, adaptive both faster and

strongerE. Innate the same, adaptive faster only

Concept Question

AllergiesThe roles of IgE and mast cells

Symptoms or disease caused by immune activation by a normally harmless antigen (known as an allergen)

Allergies are mediated by IgE and mast cells

What is an allergy?

Allergies are mediated by IgE and mast cells

50% of people in developed countries have allergies◦ There are less allergies in the developing world.

Some families have high rates of allergies Environmental factors: the hygiene

hypothesis◦ Lower levels of childhood disease, especially

parasite infections◦ Immune system is not “trained” correctly◦ Therefore, the immune system responds

inappropriately to harmless antigens

Why are allergies increasing?

The hygiene hypothesis

Nature Reviews Immunology 2001 (1) 69-75 

Immune System Summary

Adaptive Immune System

A

BC

What types of adaptive responses would be best at fighting the listeria at A, B, and C?