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A daptive I mmune S ystem. Angela Mitchell BIO422 2013 mitcheam@email.unc.edu. “Jobs” of the Immune System. “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

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a daptive i mmune s ystem

Adaptive Immune System

Angela Mitchell

BIO422

2013

mitcheam@email.unc.edu

jobs of the immune system1
“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
adaptive responses are specific to individual epitopes
Adaptive Responses Are Specific to Individual “Epitopes”
  • 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
concept questions
Concept Questions
  • 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
two branches of adaptive response
Two Branches of Adaptive Response
  • Main cells are T cells
  • Useful against intracellular pathogens
  • B cells and antibodies
  • Useful against extracellular microbes and toxins

Cellular Immunity

Humoral Immunity

cellular immune response
Cellular Immune Response

T cell Mediated Immunity

how do t cells recognize antigen
How do T cells recognize antigen?
  • T cell receptor
  • Recognizes small parts of proteins “presented” on MHC molecules
  • MHC is present on antigen presenting cells
two types of mhc mhci and mhcii
Two types of MHC: MHCI and MHCII
  • 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

Figure 24.20

intracellular antigens are processed and displayed on mhci for cd8 cytotoxic t cells
Intracellular antigens are processed and displayed on MHCI for CD8+ cytotoxic T cells

Figure 24.21

initial recognition by papcs
Initial recognition by pAPCs
  • Professional antigen presenting cells
  • Dendritic cells, macrophages, and B cell
  • Offer activating signals to T cells—primes for activity, causes proliferation
types of t cells
Types of T cells
  • 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
cd8 cytotoxic t cells
CD8+ Cytotoxic T cells
  • Death of cells infected with virus or cytoplasmic bacteria, cancer cell, etc.
cd4 helper t cells th
CD4+ Helper T cells (Th)

Th1 cells: activate phagocytes

Th2 cells: activate B cells

concept question
Concept Question

What do cytotoxic T cells recognize?

  • Exogenous peptides on MHCI
  • Endogenous peptides on MHCI
  • Exogenous peptides on MHCII
  • Carbohydrates on bacteria cells
  • Endogenous peptides on MHCII
concept question1
Concept Question

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

  • Extracellular pathogens
  • Fungi only
  • Viruses only
  • Cytoplasmic pathogens
  • Phagocytosed/Endosomal pathogens
review from friday
Review From Friday

Epitopes and Antigens

MHCI and MHCII

Activation of T cells

specificity of t cell b and activation
Specificity of T cell (B and) activation
  • 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
initial response of t cells cytotoxic and helper proliferation and activation
Initial response of T cells (cytotoxic and helper): proliferation and activation

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

cd8 cytotoxic t cells1
CD8+ Cytotoxic T cells
  • Death of cells infected with virus or cytoplasmic bacteria, cancer cell, etc.
cd4 helper t cells th1
CD4+ Helper T cells (Th)

Th1 cells: activate phagocytes

Th2 cells: activate B cells

humoral immune response
Humoral Immune Response

B cell Mediated Immunity

b cells produce antibodies
B cells Produce Antibodies
  • Defense from extracellular pathogens and toxins
  • Recognize antigen in native form
activation of b cells
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
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
types of antibodies
Types of Antibodies

Basophile activation?

concept question2
Concept Question
  • B cells recognize _____ with membrane bound_____.
    • Peptides only MHCs
    • Whole antigens MHCs
    • Peptides only Antibodies
    • Carbohydrates only TLRs
    • Whole antigens Antibodies
immunological memory
Immunological Memory

Secondary responses to infection

Vaccination

memory responses
Memory Responses
  • 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
vaccination
Vaccination
  • 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

concept question3
Concept Question
  • When you’re exposed to a pathogen for the second time, your innate and adaptive immune responses will be
    • Innate and adaptive both faster and stronger
    • Adaptive faster and stronger but innate only faster
    • Innate and adaptive both faster only
    • Innate the same, adaptive both faster and stronger
    • Innate the same, adaptive faster only
allergies
Allergies

The roles of IgE and mast cells

what is an allergy
What is an allergy?
  • Symptoms or disease caused by immune activation by a normally harmless antigen (known as an allergen)
  • Allergies are mediated by IgE and mast cells
why are allergies increasing
Why are allergies increasing?
  • 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
the hygiene hypothesis
The hygiene hypothesis

Nature Reviews Immunology 2001 (1) 69-75