The Immune system

The Immune system is the body’s defense system

• Against:– Bacteria– Viruses– Protists– Other living invaders– Toxins– Foreign debris– Cancerous cells

• The immune system is complex

• Defends against threats known and unknown

Elements of the Immune system

• Many lines of defense, for many kinds of threats

• Skin• Blood• Thymus• Spleen• Lymphatic system• Mucous membranes• Bone marrow

Innate vs. Adaptive immunity

Innate Immunity• Non-specific• Defends against known

invaders• Skin, lysozyme• Pre-existing• Cannot adapt to changing

threats

Adaptive Immunity• Mechanisms which fight

specific invaders• For unknown threats• Responsive• Requires time to build

defense (days)• Cannot anticipate threats• Remembers previous

threats

Humoral vs. Cell-mediated Immunity

Cell- Mediated Immunity• Live cells kill invaders• Innate: Phagocytic cells

(e.g. macrophages, neutrophils)

• Adaptive: B lymphocytes and T lymphocytes create specific responses to unique invaders

Humoral immunity• Proteins in blood

(“humors”) • Innate- complement

system, clotting factors, cytokines, etc.

• Adaptive: Antibodies

Blood is a mixture of cells and plasma

• ~55% Plasma• ~45% Red blood cells• <1% White blood cells and

platelets (“buffy coat”)

Human Blood after centrifugation

Blood plasma

• Water• Nutrients• Solutes- Na+, Cl-,

wastes, CO2, etc.• Contains humoral

immune elements• Some innate immunity

All blood cells are part of the hematopoetic stem cell lineage

Hematopoetic stem cells differentiate into all blood cells

• Pluripotent- able to become any one of many cell types

• Includes T cells, B cells, macrophages, etc.

Red blood cells carry oxygen and CO2

• Lose nucleus in development

• Short-lived, no repair• Packed solid with

hemoglobin• Membranes designed to

maximize surface area• Facilitate gas transfer

Hemoglobin• The oxygen-carrying

protein • Heterotetrameric protein• 2 alpha subunits, 2 beta• Each subunit holds a

Heme group• Each heme holds an Fe++

ion• Each Fe++ can bind an O2

Hemoglobin binding curve

• In areas of High O2 (e.g., lungs)- binds O2 very well (picks up O2)

• In areas of Low O2 (e.g., muscles) binds O2 poorly (drops off O2)

• Myoglobin binds O2 in muscle & organ tissues

Platelets assist with blood clotting

• Recruit plasma protein fibrinogen to a cut

• They release clotting factors

• Clotting factors convert fibrinogen to fibrin

• Fibrin net prevents blood loss

• The liquid part of blood is called • A) water. • B) plasma. • C) serum. • D) extrastitial fluid. • E) anionic fluid.

White blood cells come in a great variety of types

Elements of Innate Immunity

Lysozyme- an innate enzymatic defense

• Enzyme that cuts bacterial cell walls

• Also cuts chitin, a constituent of fungal cell walls and arthropod exoskeleton

• Found in mucous, tears, egg whites

Complement- humoral defense against non-specific invaders

• A biochemical cascade• Non-specific• Signalling pathway to

cause cell lysis• Also Recruitable by

adaptive immune system

Interferons are nonspecific anti-viral signalling molecules

Phagocytic white blood cells devour bacteria

• Which of the following, produced by virus-infected cells, diffuses to neighboring cells to help them fight a viral infection?

• A) lysozyme • B) interferon • C) histamine • D) antigen • E) interleukin-2

The Inflammatory response

Keeping the body safe comes at a cost

• Inflammation implicated in heart disease, etc.

• Gum inflammation linked to heart attacks

The lymphatic system collects lymph and houses white blood cells in nodes

Adaptive Immunity contains humoral and cell-mediated components

Adaptive Immunity is learned, and has memory

Antibodies- the Key component of humoral adaptive immunity

• Two light chains, two heavy chains

• Each contains a variable region and a constant region

Antigen- anything which can be bound by an antibody

B Cells- the source of

antibodies

Clonal selection musters B-cell defense forces against specific antigens

Adaptive Immunity is learned, and has memory

Immune cells are the only cells with different DNA

• VDJ recombination of light and heavy chains generate antibody diversity

• Change is permanent• A form of Russian Roulette

for the cell• Successful recombination

creates a binding antibody- cell survives

• Unsuccessful- cell is destroyed

• Finding a good cell takes time

Bound antibodies are the mark of death for invaders

Breast milk contains maternal antibodies

• Infants have no acquired immunity

• Mother’s acquired immunity is transferred to the baby through nursing

• Passive immunity• Is not retained by the

baby

Vaccination gives the body active immunity

• An antigen sample is given to a person

• Person’s immune system mounts a response to the antigen

• Antigen can be deactivated/destroyed virus particles, etc.

• No waiting time for body to develop 2o immune response

Antibodies can be used as therapy

• Some growth factors are overactive in certain cancers

• Antibody binds to growth factors, or their receptors

Polyclonal Antibodies

• From multiple B cells• Bind to different

epitopes of an antigen

Monoclonal antibodies

• Obtained from a single B cell

• Bind to a single epitope

• A single B cell is fused to a myeloma cell

• Myeloma cells are immortal

Mouse antibodies can be humanized

• Constant regions of mouse antibody are gradually replaced with human sequences

Fluorescent antibodies can be used in scientific experiments

• Fluorescent molecules can be linked to antibodies

• Antibodies show us where proteins exist in vivo

In an ELISA, Horseradish Peroxidase is linked to a 2o antibody

Indirect ELISATo detect the presence of an antibody

Wash BlockWash

Substrate

Primary Antibody Secondary Antibody

Home pregnancy tests utilize antibodies

• The transfer of antibodies from breast milk to an infant is an example of __________ immunity.

• A) nonspecific • B) passive • C) humoral • D) active • E) cell-mediated

T cells are the primary cell-mediated adaptive immune response

Major Histocompatibility Complex (MHC or HLA)

• MHCI Found on all cells, recognized by TC cells

• MHCIIFound on B cells and Macrophages

recognized by TH cells

When presented with antigen, Helper T cells recruit other immune cells

• The basic function of T cells is to identify and destroy invaders in our

• A) blood or lymph. • B) interstitial fluid. • C) cells. • D) immune system. • E) brain.

CD4 on the surface of TH cells is the site of HIV binding

Any known stage of the HIV life cycle is a potential point for therapy

Protease inhibitors prevent formation of HIV capsids

AZT is a nucleoside analog reverse transcriptase inhibitor

AZT Thymine

Cytotoxic T cells destroy infected body cells

In Autoimmune disease, the immune system attacks the self

Allergies are immune responses to harmless antigens

• A substance that can elicit an immune response is called a(n)

• A) complement. • B) interferon. • C) histamine. • D) antibody. • E) antigen.

• Which one of the following statements about HIV is false?

• A) The genome of HIV consists of RNA. • B) HIV attacks helper T cells. • C) New HIV are produced inside helper T cells. • D) HIV is transmitted by body fluids transporting

infected cells. • E) Some antibiotics have proven effective in

combating the spread of AIDS.

• Which type of immune response is always disadvantageous to a person?

• A) cell-mediated • B) inflammatory • C) humoral-mediated • D) autoimmune • E) All immune responses are advantageous.