Symbiosis, Disease and Host Defenses

An evolutionary arms race

Symbiosis: Organisms ‘living together’

Three types based on effects:

Commensalism- positive for one organism and neutral for the other

Mutualism-positive for both organisms

Parasitism-positive for one negative for the other

Parasite (Greek parasitos, to dine along side of)

As a matter of convention, parasitology usually covers protist and animals even though bacteria and viruses can be parasites . Microbes are often referred to as pathogens even though they are parasitic.

Parasitic Organisms• Overarching questions

– How do parasites affect their hosts?– What makes an efficient parasite?– Why are some organisms parasitic and others are

not?– Why is a particular organisms pathogenic sometimes

but not always?

Obligate parasite- can not live without hostOpportunistic parasite/pathogen- can be parasitic under

certain circumstancesVirulence Factor-structural or physiological characteristics

that contribute to the effect that we call disease

Endosymbiosis

What are the possible costs or benefits to each organism involved?

How does that affect the evolutionary process?

Ancestral symbiotic event between primitive cells

Selective pressure

Relationship is commensal

Relationship is mutual

Relationship is parasitic

Host fitness Symbiont fitness

No change up

up up

down up

A biological arms race?

Parasite increases fitness if:• Continues to benefit from the host by resisting defenses

Host increases fitness if:• Excludes parasite• Destroys parasite outside• Destroys/digests parasite inside

All living things have some defense mechanisms

• Restriction enzymes in bacteria

• Vesicles with chemical defenses in single-celled eukaryotes

• Specialized phagocytic cells in most animals, including arthropods and helminthes

• Pinnacle of host defenses are found in vertebrates (fish, amphibians, reptiles, birds, mammals)

Non-Specific Host Defenses of Vertebrates

Defense “strategies” include:

External (Exclusion)

chemical-sweat, tears

physical-keratinized structures

Internal

cellular-leukocytes other than lymphocytes

chemical and molecular- complement, interferon

inflammation, fever etc..

Note: regulation is important for all internal defense mechanisms

Physical barriers: the human integument

Pathogens subvert physical barriers

Portals of entry include:

Ears

Nose

Mouth

Urogenital tract

Gastrointestinal tract

Wounds

Leukocytes in non-specific defensesCytoplasm Cell name Function

Granular Neutrophils Phagocytic

Eosinophils Phagocytic, antiworm chemicals released

Basophils Release histamine

Agranular Monocytes Fixed macrophage

Phagocytic, guard tissues

Wandering

macrophages

Phagocytic, Circulate in blood and enter tissues upon infection

Dendritic (Langerhanz) cells

Phagocytic, reside in tissues like epidermis

Phagocytic cells are non-specific defenses that destroy invaders

Phagocytosis of invader

Lysosome containing digestive chemicals

Phagolysosome formed

Mechanisms for subverting non-specific defenses

• Structural adaptation-formation of special cell walls, capsules, endospores, cysts

• Physiological adaptations- enzymes that neutralize host chemicals, digest host physical barriers or destroy phagocytes

• Vectors, vehicles, fomites aid in gaining entry into host

Specific Immunity: defensive cells get ‘smarter’

• “Remembering” invaders allows for faster response upon subsequent encounters of that specific invader

• Specific immunity can be divided into two branches– Humoral immunity- antibodies produced by B cells– Cell-mediated immunity- T cells recognized

invaders and stimulate defense mechanisms• Antigen any molecule that generates an immune

response (antibody generating)• Antibody- a protein that can bind to specific antigens

and help with the immune response in various ways

Types of Specific Immunity

• Active- antibodies formed by the host– Natural- host forms antibodies naturally upon natural

exposure to antigen– Artificial- host is artificially exposed to antigen i.e.

immunization, vaccination• Passive-antibodies not made by host

– Natural-Maternal antibodies– Artificial-antibodies from other source (horse, cow

etc..), for example antivenin administered after snake bite

Cells of the Specific Immune System

• B lymphocytes produce antibodies which are special proteins that bind to foreign molecules (antigens) and facilitate an immune response– Plasma cells– Memory B cells

• Natural Killer cells Kill virus- infected cells, bacteria and cancer cells extracellularly

• T lymphocytes differentiate into several types with different immunological functions

– Helper T cells ( TH), CD4 (T4)

– Cytotoxic cells (TC), CD8 (T8)

– Memory T cells

B lymphocytes produce antibodies (immunoglubulins)

• Antibodies are proteins and therefore are synthesized from the instructions in DNA

• Antibodies can be constructed to fit a variety of immunological functions from cell surface receptors to circulation, or excretion

• The sections of DNA that encode the part the antibody that binds to antigen is highly variable allowing the formation of millions of different antigens so antibodies may be formed to any foreign molecule that is complex enough

Antibodies

Basic structure of and antibody

Binds to antigen here

Y

Cell with antibody as cell-surface receptor

Antibodies (immunoglobulins)

IgG-circulating in blood serum, can cross placenta

IgM-first to blood serum, on B cell membrane

IgA-Body secretions, epithelium of GI, Resp, UG tracts

IgD-B cell membrane

IgE-body fluids and skin, affinity for mast cells and basophils, main mediator for type 1 hypersensitivity

B Cells and Humoral Immunity

Countless B cells are produced expressing a variety of antibodies on the cell surface

Whichever B-cell binds to a specific antigen will be produced in greater numbers to mount an immune response

Some of the newly created B cells will become memory cells and the others will become plasma cells produce and secrete various forms of that specific antibody

Overview of Cell-mediated Immunity

• Antigen is processed by non-specific immune cells (e.g. macrophages) which present the antigen at the cell surface

• T cells that have a matching receptor bind to the antigen• If the MHC protein is correct, the T cell is activated and it

divides and differentiates

MHC proteins• made from highly variable gene which makes ‘self’

different for almost all individuals• class I MHC on all body cells • class II MHC only on some immune cells

*

Macrophage presenting antigen in MHC II protein

Y Antibody in the form of T-cell surface receptor

MHC class II

antigen

Helper T cell

Cell-mediated Immunity

Helper T cells are activated. They differentiate into Th1 or Th2 cells which stimulate intracellular destruction of antigen (Th1) or stimulate B cells (Th2)

*

Infected cell presenting antigen in MHC I protein

Y Antibody in the form of T-cell surface receptor

MHC class I

antigen

Cytotoxic T cell

Cell-mediated Immunity

Cytotoxic T cell are stimulated to attack infected cells

Phases of Infection

acme

decline

Convalescence period

Pro

drom

al

perio

d

incu

batio

n

invasive

Immune System Disorders:hypersensitivities

• Hypersensitivities – Type 1 - anaphylactic, immediate, IgE mediated– Type 2- cytotoxic, reaction to cell surface antigens– Type 3- immune complex, persistent antibody-antigen

complexes formed– Type 4 –cell (T cell) mediated, delayed

hypersensitivity

Immune System Disorders: Autoimmunity

• Caused by lack of self recognition-T-cells and/or antibodies act against self tissues

• Triggers of autoimmunity include:– failure of lymphocyte programming process– new self antigens

• mutation in genes• Haptens (incomplete antigen)

– foreign antigens stimulate cross-reactive antibody production

Immune System Disorders: Immunodeficiency and Immunosupression

• Causes may be:– Genetic (SCIDS)– Environmental, Chemical (pollution etc..)– Infections (AIDS)– Psychoneuroimmunological (Severe stress)

Herd Immunity

• Populations of hosts in close proximity may be similarly exposed to diseases (especially crowd diseases)

• The more host there are in the population that are immune to a specific disease, the harder it is for the disease to spread

• Herd immunity can occur naturally as host are exposed over their lifetimes and nature selects for the fittest individuals

• Vaccines can confer artificial herd immunity to limit the spread of disease