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L1 - Overview of The Immune System

The immune system protects the body from infection through various cells and mechanisms. Sentinel cells like dendritic cells and macrophages detect pathogens in tissues. Lymphocytes including B cells, T cells, and NK cells help eliminate infections. B cells produce antibodies, while T cells direct immune responses. The immune system has both innate and adaptive arms, with adaptive immunity providing stronger and longer-lasting protection against specific pathogens through memory responses.

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29 views32 pages

L1 - Overview of The Immune System

The immune system protects the body from infection through various cells and mechanisms. Sentinel cells like dendritic cells and macrophages detect pathogens in tissues. Lymphocytes including B cells, T cells, and NK cells help eliminate infections. B cells produce antibodies, while T cells direct immune responses. The immune system has both innate and adaptive arms, with adaptive immunity providing stronger and longer-lasting protection against specific pathogens through memory responses.

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suhiermai3
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We take content rights seriously. If you suspect this is your content, claim it here.
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Overview of the immune

system
What does the immune system do?
• It protects us from infections with:
– 208 viruses
– 538 bacteria
– 317 fungi
– 287 worms
– 57 parasitic protozoa (CDC numbers)
• It promotes normal functioning of the body (tissue
cleanup, wound repair)
• It removes abnormal cells including malignant ones
• But the immune system can also cause disease when it
is not doing the right thing (allergies, autoimmunity,
transplant rejection, etc.)
The players
• Sentinel cells in tissues
– Dendritic cells, macrophages, mast cells
• Circulating phagocytes and granulocytes
– Neutrophils, monocytes, eosinophils, basophils
• Lymphocytes: cells which can recognize particular
pathogens (but also can cause allergies and
autoimmune diseases)
– B lymphocytes: antibodies
– T lymphocytes: cell-mediated immunity
– (also innate lymphoid cells, NK cells, etc.)

• Tissue cells (epithelial cells, endothelial cells, etc.)


Immune sentinel cells in the tissues: dendritic
cells

Green= dendritic cells


Blue= nuclei of all cells

Langerhans cells (epidermal dendritic cells) in the skin


WJ Mullholland et al. J. Invest. Dermatol. 126: 1541, 2006.
Inflammatory mediators
are made in response to
detection of infection or
injury or dendritic cell

Inflammatory mediators:
-Lipids (prostaglandins, etc.)
-Proteins (cytokines/chemokines)
TNF
Others
Cytokines
• “Cytokines”: soluble protein mediators secreted by immune cells
(mostly) and act on other cells (“cyto”) to regulate their activity
(“kine”)

• Name of a cytokine often doesn’t reflect its most important


function (example: TNF stands for “tumor necrosis factor”)

• many cytokines are called “interleukins” (IL-1, IL-2, etc.)

• Cytokines that direct migration of cells are called “chemotactic


cytokines” or “chemokines”
Cytokines and Inflammation
• Pro-inflammatory cytokines are many, but especially
important: TNF, IL-1, and IL-6
• TNF and IL-1 signal to endothelial cells to make them:
– Leaky to fluid (influx of plasma; containing antibodies,
complement components, etc.)
– Sticky for leukocytes, leading to influx of leukocytes
• IL-6 promotes adaptive immune responses; systemic
effects
Leukocyte recruitment to sites of
inflammation

or DC
The neutrophil is the immune system’s
first responder
• Neutrophils are typically the first white blood
cells to come into a site of acute inflammation

Video:
Lammermann et al. Nature 498: 371-5, 2013.
Phagocytosis and Killing of Microbes

Abbas et al. Fig. 2-17


Innate Immunity vs. Adaptive immunity
• Innate immunity utilizes evolved recognition
mechanisms and is surprisingly effective, but changes
little based on life experience
• In innate immunity, limited numbers of distinct receptors;
recognize highly conserved features of classes of
microbes.
• Adaptive immunity learns from previous experience and
hence can protect better upon a second infection by the
same agent.
• Adaptive immunity has a very large number of distinct
“antigen receptors” of T and B lymphocytes; generated by
DNA rearrangements in each developing lymphocyte;
clonal selection of lymphocytes that recognize an infecting
agent
FIGURE 1-2 Types of

adaptive immunity.

In humoral immunity, B

lymphocytes secrete

antibodies that prevent

infections and eliminate

extracellular microbes.

In cell-mediated immunity,

helper T lymphocytes activate

macrophages to kill

phagocytosed microbes, or

cytotoxic T lymphocytes

directly destroy infected cells.


Antigen receptor gene rearrangement:
Many different antibodies are created by
combinations of gene segments
Adaptive Immunity: Antibodies I
• A molecule that induces the production of an antibody is
called an “antigen”
• A few B cells that recognize the infectious agent become
activated, each multiply to form a “clone”.
• These progeny then become antibody-secreting factories.
(plasma cells)
The Clonal Selection Hypothesis

Generation of lymphocytes of
many specificities

Clonal deletion to remove self-


reactive lymphocytes

Clonal selection to expand


pathogen-reactive lymphocytes
during an immune response
FIGURE 1-4 Specificity, memory, and contraction of adaptive immune responses. Antigens X and Y

induce the production of different antibodies (specificity). The secondary response to antigen X is more

rapid and larger than the primary response (memory). Antibody levels decline with time after each

immunization (contraction, the process that maintains homeostasis). The same features are seen in cell-
Antibody responses proceed in two phases

Goodnow et al, Nature Immunol. 2010


Adaptive Immunity: Antibodies II

• Rapid production of lower affinity antibody made by short-


lived plasma cells
• Slower “germinal center response”  selection for
higher affinity  gives rise to long-lived plasma cells
Antibodies bind antigens

Two protein
components: heavy
chain and light chain;
can come in 5 varieties
of heavy chains:
IgM, IgG, IgA, IgE, IgD
Antibodies can be directly protective or can promote immune
protective mechanisms via other cells or molecules

neutralization activation of complement


Adaptive Immunity: Antibodies III
• “Active immunity” (infection, vaccination)
• “Passive immunity”: maternal transfer of IgG across
placenta; injection of antibodies to protect against
infections, toxins; IVIG for immunodeficiency
• “Monoclonal antibodies” for passive immunity, therapy,
diagnosis. All identical  more standardized therapeutic
or diagnostic.
• To work well as therapy, need to make as human as
possible; many new MAb therapeutics in the last 10
years. Most are to treat cancers or to suppress immune
responses
Monoclonal antibodies used in
medicine
Standardized, unlimited reagents for diagnosis or therapy

Some representative examples. This list is rapidly expanding in recent years


CD Nomenclature
• Structurally defined leukocyte surface
molecule that is expressed on cells of a
particular lineage (“differentiation”) and
recognized by a group (“cluster”) of
monoclonal antibodies is called a member of a
cluster of differentiation (CD)
• CD molecules (CD antigens, CD markers) are:
• Identified by numbers
• Used to classify leukocytes into functionally
distinct subpopulations, e.g. helper T cells
are CD4+CD8-, CTLs are CD8+CD4-
• Often involved in leukocyte functions
• Antibodies against various CD molecules are
used to:
• Identify and isolate leukocyte
subpopulations
Recognition of antigen by the TCR

The TCR of CD4+ and CD8+


T cells recognizes MHC-bound
peptide + portions of the MHC.

Other T cells (gd T cells, NKT


cells) recognize non-peptide
antigens
Peptides are bound to MHC molecules and
presented to T cells

MHC=major histocompatability complex.


HLA=human leukocyte antigen
Killer T cells and Helper T cells

killing Microbe evades


Killing
helper

cytokines
Adaptive Immunity: Anatomy of the response
• Naïve T cells and B cells recirculate between lymph
nodes, spleen, and the blood.
• Antigen is taken to the lymph node either by the flow of
lymph or is carried by a maturing dendritic cells that
migrate along the lymphatics.
• The dendritic cell presents antigen to naïve T cells in the
lymph node.
Role of costimulation in T cell activation
Immune responses are tailored to the
type of infection
• Defense against extracellular microbes: IgM, IgG and Th17
• Defense against microbes that survive and replicate inside
phagocytes (macrophages and monocytes): “type 1 immunity”
(Th1)
• Defense against viruses:
– early defense: innate mechanisms that restrict virus replication
(interferon, etc.)
– Adaptive immune defense: antibodies which block virus
infection of cells (“neutralizing antibodies”) plus cytotoxic T
cells
• Defense against worms and biting insects: “type 2 immunity” (IgE,
Th2), Manifestations include: sneezing, coughing, itching, diarrhea,
tears, etc. (allergies and asthma mostly involve this type of immune
response)

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