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Adaptive Immune SystemAngela Mitchell
BIO4222013
mitcheam@email.unc.edu
“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?
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