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 Adaptive Immunity Non-specific Defends against known invaders Skin, lysozyme Pre-existing Cannot adapt to changing threats 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 Humoral immunity Live cells kill invaders Innate: Phagocytic cells (e.g. macrophages, neutrophils) Adaptive: B lymphocytes and T lymphocytes create specific responses to unique invaders Proteins in blood (“humors”) Innate- complement system, clotting factors, cytokines, etc. Adaptive: Antibodies

Blood is a mixture of cells and plasma Human Blood after centrifugation ~55% Plasma ~45% Red blood cells <1% White blood cells and platelets (“buffy coat”)

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 ELISA To detect the presence of an antibody Primary Antibody Secondary Antibody Wash Block Wash Substrate

Home pregnancy tests utilize antibodies

Antibodies are A) amino acids. B) lipids. C) carbohydrates. D) proteins. E) nucleic acids.

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 MHCII Found 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 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.