Transcript Symbiosis and Host Defenses

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 host
Opportunistic parasite/pathogen- can be parasitic under
certain circumstances
Virulence Factor-structural or physiological characteristics
that contribute to the effect that we call disease
Endosymbiosis
Ancestral symbiotic
event between primitive
cells
What are the possible costs or benefits to each
organism involved?
How does that affect the evolutionary process?
Selective pressure
Host fitness
Symbiont
fitness
No change
up
up
up
down
up
Relationship is commensal
Relationship is mutual
Relationship is parasitic
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 defenses
Cytoplasm
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
Lysosome containing
digestive chemicals
Phagocytosis of
invader
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’
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
•
“Remembering”
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
Binds to antigen here
Y
Cell with antibody as
cell-surface receptor
Basic structure of and antibody
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
Cell-mediated Immunity
Helper T cell
Y
antigen
Antibody in the form of
T-cell surface receptor
*
MHC
class II
Macrophage presenting
antigen in MHC II protein
Helper T cells are activated.
They differentiate into Th1 or
Th2 cells which stimulate
intracellular destruction of
antigen (Th1) or stimulate B
cells (Th2)
Cell-mediated Immunity
Cytotoxic T cell
Y
antigen
Antibody in the form of
T-cell surface receptor
*
MHC
class I
Infected cell presenting
antigen in MHC I protein
Cytotoxic T cell are
stimulated to attack
infected cells
Prodromal
period
incubation
Phases of Infection
acme
decline
invasive
Convalescence
period
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