Download Overview of the Immune System

Introduction
Smallpox Eradication
THE IMMUNE SYSTEM
The Invaders
The Defender
Overview of the Immune System
Overview of your immune system
• First line of defense: Physical barriers that viruses, bacteria must
cross
– skin covers ~2 m2
– Mucous membranes that line digestive, respiratory, reproductive tracts
cover ~400 m2
• Second line of defense: Innate immune system (germline-encoded
receptors -- no adaptation to specific pathogens)
– Macrophages (Greek for “big eater”), neutrophils, natural killer (NK) cells
– Cytokines -- hormone-like proteins that mediate inflammation,
Complement proteins
• Third line of defense (vertebrates only): Adaptive immune system
(adapts to defend against specific pathogens using variable
receptors)
– B cells make antibodies that vary -- can make an antibody specific for
any new antigen
– T cells mediate cellular responses using variable receptors (T cell
receptors; TCRs)
COMPONENTS OF THE IMMUNE
SYSTEM
Cellular components of the immune system
Lymphocytes
Phagocytes
Granulocytes
Others
B-cell
Mononuclear phagocyte
Basophil
Platelets
T-cell
Neurtrophil
Mast cell
Large granular lymphocyte
Eosinophil
Antibodies
Cytokines
Complement
Inflammatory mediators
Soluble mediators of the immune system
Immune cells and other blood cells made in bone marrow -all are descendents of self-renewing stem cells
Make variable antibodies
Membrane-bound variable T cell receptors
Kill cells that are missing self proteins
Phagocyte
Phagocyte
Note these are
adult stem cells,
NOT embryonic
stem cells.
p. 4 “How the Immune System Works” by Lauren Sompayrac
Innate Immunity
• Initial response to microbes
• Stimulates adaptive immune response
• Components are directed by adaptive
immune response to remove foreign
material
The innate immune system responds more
quickly than adaptive immune system.
Why is a quick response important?
• Starting with one bacterium that doubles every
thirty minutes --> 100 x 1012 bacteria in one day
• 100 x 1012 bacteria equivalent to ~100 liters of a
dense culture
• Total volume of blood in human ~5 liters
• VERY important to check a bacterial infection
quickly!
Three components of the innate
immune system
• Phagocytes (cells) (e.g., macrophages)
• Complement proteins
• Natural killer (NK) cells
Innate immune receptors recognize features common to many
pathogens. Receptors are employed by all cells of a given cell
type. Response does not lead to immunological memory.
Adaptive immune receptors are antigen specific. Antigen
receptors of adaptive immune system are clonally
distributed on individual lymphocytes. Response can lead to
immunological memory.
Macrophages can engulf and digest bacteria
Macrophage
about to eat a
bacterium
http://www.biochemweb.org/neutrophil.shtml
p. 4 “How the Immune System Works” by Lauren Sompayrac
Question
Which component of bacteria serves
as a very potent stimulant of the
innate immune system?
1)
Ribosomes
2)
Proteins
3)
Carbohydrates
4)
DNA
5)
RNA
6)
Plasmids
Question
Carbohydrates on viruses strongly
activate the innate immune system.
1)
True
2)
False
Complement system
• Ancient system (found in invertebrates such as
sea urchins)
• ~20 different proteins that work together to
destroy invaders and recruit immune cells
• Activated three different ways
– “Classical” pathway: by antibodies bound to pathogen
(vertebrates only)
– “Alternative” pathway: by bacterial surfaces
– Lectin activation pathway: by binding of mannose-binding
lectin (MBL) to yeast, bacteria, parasites or viruses (e.g.,
HIV)
• Activation of complement system is tightly
regulated because end results can be dangerous
The three pathways of complement activation converge
Figure 2-18
Combination of adaptive and innate
immune responses
Innate immunity
Innate immunity
Binding of mannose-binding
lectin, a plasma protein, initiates
lectin pathway of complement
activation.
MBL discriminates self
carbohydrates from
non-self carbohydrates by
recognition of a particular pattern
of sugar residues
Figure 2-11
Figure 2-35 part 3 of 3
One of the end results of complement activation -- the membrane
attack complex kills a cell
Electron micrographs of ~100 Å diameter membrane attack
complex channels
Laboratory uses of complement:
isolate one population of cells by
killing off another population
Example:
Have mixture CD4 T-cells and CD8 T-cells
Want only CD8 T-cells
Add anti-CD4 antibody to mixture of T cells. It binds.
Now add complement, and CD4 T-cells will be killed,
leaving you with CD8 T-cells only.
Question
Which type of pathogen is easier for the innate
immune system to deal with: bacteria or viruses?
1)
Bacteria
2)
Viruses
So far, we’ve talked only about active
recognition of features of pathogens…
But pathogens have also developed ways to remove some of the
cell’s critical proteins, often so that they can escape detection
by the immune system.
For example, in the adaptive immune system, T lymphocytes
(T cells) recognize viral fragments (peptides) bound to MHC
proteins.
It’s hard for a virus to hide out in a cell if the cell surface MHC
proteins contain viral fragments that can be recognized by T
cells.
What’s a virus to do?
Get rid of the host MHC proteins!
For every strategy a virus comes up with,
the immune system (usually) has an answer…
Natural killer cells recognize cells that
do not express adequate levels of MHC
proteins on their surface.
They respond to “missing self”.
Natural killer (NK) cells
• Can kill tumor cells, virus-infected cells, bacteria, parasites,
fungi in tissues
• Identify targets based on “missing self”
– Two types of NK receptors: inhibitory and activating
– If inhibitory receptor recognizes a self protein (a class I MHC
molecule) on a target cell, the NK cell is turned OFF even if activating
receptor binds a ligand on the same target cell
– If activating receptor binds a ligand, but inhibitory receptor does not
(target cell has down-regulated class I MHC proteins), NK cells kill
– Many virally-infected cells and tumor cells down-regulate expression of
class I MHC molecules (NK cells important for preventing cancers)
The immune cells we’re talking about are
called white blood cells.
This means they are in the ____.
How do they get to a site of infection?
Figure 1-7
Figure 1-5
Antibody
Secretion
Activation of
T and B cells,
Macrophages,
Inflammation
Target Cell
Lysis
Phases of Adaptive Immune
Responses
• Recognition
• Activation
• Effector
• Homeostasis
Figure 1-10
Activation
Figure 2-13
Figure 2-14
Figure 2-16
Figure 2-18
Figure 2-19
Figure 2-20
Antigens
Figure 3-4
Figure 3-8