6.3 Defence Against Infectious Disease
6.3 Defence Against Infectious Disease
Essential Idea:
The human body has structures and processes resist the
continuous threat of invasion by pathogens
The Flu
At the end of this topic, you should be able to explain this video. We will come back here at the
end as part of a workshop.
https://www.youtube.com/watch?v=Rpj0emEGShQ
What is a disease?
-A particular abnormal
condition that negatively
affects the structure or
function of all or part of an
organism,
-External or internal stimuli
Pathogens
Abiotic factors
Nutrition
Genes/Expression
Classification
of Diseases
Infectious
(flu)
Noninfectious
Social
(alcoholism)
Mental illness
(schizophrenia
)
(cancer)
Categories
of disease
Eating
disorder
Inherited
(hemophilia)
Degenerative
(arthritis)
(anorexia)
Deficiency
(rickets)
Infectious Diseases
Caused by pathogens
Pathogens: a disease causing agent that disrupts the normal physiology of the
infected organism. Pathogens can be cellular (e.g. parasites, protozoa,
bacteria) or acellular (viruses and prions)
Lines of Defense
3 Lines of defense
Surface Barriers
The skin and mucous membranes form a primary defence against pathogens that cause infectious disease
Skin
•Protects external structures when intact
(outer body areas)
•Consists of a dry, thick and tough
region composed predominantly
of dead surface cells
•Contains biochemical defence agents
(sebaceous glands secrete chemicals
and enzymes which inhibit microbial
growth on skin)
•The skin also secretes lactic acid and
fatty acids to lower the pH (skin pH is
roughly ~ 5.6 – 6.4 depending on body
region)
Surface Barriers
The skin and mucous membranes form a primary defence against pathogens that cause infectious disease
Mucous Membranes
Protects internal structures (i.e. externally
accessible cavities and tubes – such as the
trachea, oesophagus and urethra)
Consists of a thin region of living surface
cells that release fluids to wash away
pathogens (mucus, saliva, tears, etc.)
Contains biochemical defence agents
(secretions contain lysozyme which can
destroy cell walls and cause cell lysis)
Mucous membranes may be ciliated to aid in
the removal of pathogens (along with
physical actions such as coughing /
sneezing)
Lysozymes (muramidases) are a family of enzymes with antimicrobial activity characterized by the ability to
damage the cell wall of bacteria.
Lines of Defense
1. First Line of Defense
•The primary defence against infectious disease are the surface barriers that prevent pathogens from entering the body
•These surface barriers include intact skin (protect external boundaries) and mucous membranes (protect internal
boundaries)
•Both the skin and mucous membranes release chemical secretions which restrict the growth of microbes on their surfaces
•If pathogens cannot enter the host body, they cannot disrupt normal physiological functions and cause disea
Clotting
Cuts in the skin are sealed by blood clotting
Blood Clots
Clotting (haemostasis) is the mechanism by which broken blood vessels are repaired when damaged
•Clotting functions to prevent blood loss from the body and limit pathogenic access to the bloodstream when the
skin is broken
2 key components of a blood clot:
•Platelets undergo a structural change when activated to
form a sticky plug at the damaged region
(primary haemostasis)
•Fibrin strands form an insoluble mesh of fibres that trap
blood cells at the site of damage (secondary haemostasis)
Platelets = thrombocytes = cells
Clotting
•
Cuts in the skin are sealed by blood clotting
A biochemical
cascade = signaling
cascade or signalin
g pathway = is a
series of chemical
reactions that
occur within a
biological cell when
initiated by a
stimulus
Clotting
•
Cuts in the skin are sealed by blood clotting
Coagulation factors are proteins in the
blood that help control bleeding
Clotting
•
Cuts in the skin are sealed by blood clotting
The coagulation cascade:
1) Clotting factors cause platelets to become sticky and
adhere to the damaged region to form a solid plug.
2) These factors also initiate localized vasoconstriction to
reduce blood flow through the damaged region.
3) Additionally, clotting factors trigger the conversion of the
inactive zymogen prothrombin into the activated
enzyme thrombin.
4) Thrombin in turn catalyses the conversion of the soluble
plasma protein fibrinogen into an insolube fibrous form
called fibrin.
5) The fibrin strands form a mesh of fibres around the
platelet plug and traps blood cells to form a temporary clot
6) When the damaged region is completely repaired, an
enzyme (plasmin) is activated to dissolve the clot
Clotting
•
Cuts in the skin are sealed by blood clotting
https://www.youtube.com/watch?v=pqo3PDHR924
Clotting
• Causes and consequences of blood clot formation in coronary arteries
Coronary thrombosis = formation of a clot within the blood vessels that supply and sustain the heart tissue
(coronary arteries)
•Occlusion of a coronary artery by a blood clot may lead to an acute myocardial infarction (heart attack)
Clotting
• Causes and consequences of blood clot formation in coronary arteries
Blood clots form in coronary arteries when the vessels are damaged as a result of the deposition of cholesterol
(atherosclerosis)
•Atheromas (fatty deposits) develop in the arteries and significantly reduce the diameter of the lumen (stenosis)
•The restricted blood flow increases pressure in the artery, leading to damage to the arterial wall (from shear
stress)
•The damaged region is repaired with fibrous tissue which significantly reduces the elasticity of the vessel wall
•As the smooth lining of the artery is progressively degraded, lesions form called atherosclerotic plaques
•If the plaque ruptures, blood clotting is triggered, forming a thrombus that restricts blood flow
•If the thrombus is dislodged it becomes an embolus and can cause a blockage in a smaller arteriole
Haemophilia
• Haemophilia is an X-linked recessive condition that impairs the body’s ability to control blood clotting
-More common in males than females (as males are hemizygous and have only one X chromosome)
-normal coagulation cascade is impaired and fibrin formation does not occur
- Haemophiliacs can die from minor injuries (continued loss of blood flow).
- Different types of haemophilia: Haemophilia A (clotting factor XIII deficiency) is more common than haemophilia B
(clotting factor IX deficiency)
Haemophilia
• Haemophilia is an X-linked recessive condition that impairs the body’s ability to control blood clotting
Lines of Defense
3 Lines of defense
Types of Leukocytes
5 distinct classes of leukocytes (white blood cells).
Types of Leukocytes
5 distinct classes of leukocytes (white blood cells).
Neutrophils
•Most abundant type of white blood cell and the first
responder to microbial infection
•They are unable to renew their lysosomes and die after
having phagocytosed a few pathogens (forms the majority
of pus)
•Analogy: Standard police officer – quick to respond to
the situation, but lacks special training or skills and so dies
rapidly
Types of Leukocytes
5 distinct classes of leukocytes (white blood cells).
Eosinophils
•Prominent at the sites of allergic reactions and
parasitic infections (rare in blood but common at
mucous membranes)
•Do not phagocytose pathogens but instead release
chemical products which perforate cell membranes
•Consequently, they function as the primary
response to large multicellular parasites (e.g.
helminth infections)
•Analogy: Fumigator – specialised to deal with
pests / parasites (e.g. helminths) by releasing
chemical products
Types of Leukocytes
5 distinct classes of leukocytes (white blood cells).
Basophil
•Basophils are chiefly responsible for initiating
inflammatory responses by releasing the chemicals
histamine and heparin
•Functionally they are similar to mast cells, however they
circulate in the bloodstream whereas mast cells are
localised
•Because they promote inflammation, they are common
contributors to allergic responses
•Analogy: Fireman – the leukocyte involved when a
region is inflamed (‘in flames’)
Types of Leukocytes
5 distinct classes of leukocytes (white blood cells).
Monocyte
•Monocytes are the largest type of leukocyte and share
phagocytosis duties with neutrophils
•They are slower to respond than neutrophils but are
longer lasting, as they can renew their lysosomes for
continued digestion
•Monocytes will differentiate into two types of cells in
response to pathogenic infection – macrophages and
dendritic cells
•Macrophages will remain in the tissue and phagocytose,
whereas dendritic cells present antigen fragments to
lymphocytes
•Analogy: Riot police (macrophage) – slower to respond
than standard police but better prepared and survives for
longer
•Analogy: Signalman (dendritic cell) – identifies the
pathogen and sends signals to the appropriate special
forces (lymphocytes)
Types of Leukocytes
5 distinct classes of leukocytes (white blood cells).
Lymphocyte
•Lymphocytes are responsible for the production of
antibodies which target specific antigens present on
pathogens
•They are more common in the lymphatic system than
blood and are slowest to respond (requiring antigen
presentation)
•Lymphocytes include B cells (which become antibodysecreting plasma cells) and T cells (which mediate B cell
activity)
•Lymphocytes are also involved in the destruction of virusinfected body cells (via cytotoxic T cells and natural killer
cells)
•Analogy: Special forces / superheroes – takes longest to
mobilise but specially trained to target specific pathogens
Types of Leukocytes
5 distinct classes of leukocytes (white blood cells).
Prevalence of Leukocytes
The relative proportions of the different
types of white blood cells are:
• Neutrophils (roughly 60 – 70%)
• Lymphocytes (roughly 20 – 30%)
• Monocytes (approximately 1 – 6%)
• Eosinophils (approximately 1 – 3%)
• Basophils (less than 1%)
Lines of Defense
3 Lines of defense
Phagocytes
• Ingestion of pathogens by phagocytic white blood cells gives non-specific immunity to disease
innate immune system = non-specific 2 key properties:
•It does not differentiate between different types of pathogens (non-specific)
•It responds to an infection the same way every time (non-adaptive)
•Phagocytic white blood cells (Leukocytes) that engulf and digest foreign bodies (do NOT produce antibodies)
•Other components of the innate immune system include inflammation, fever and antimicrobial chemicals
(complement proteins)
neutrophil phagocytosing anthrax bacilli (orange)
Phagocytes
• Ingestion of pathogens by phagocytic white blood cells gives non-specific immunity to disease
innate immune system = non-specific 2 key properties:
•It does not differentiate between different types of pathogens (non-specific)
•It responds to an infection the same way every time (non-adaptive)
Pathogen Recognition
Phagocytes recognize molecular
structures that are common to
many groups of pathogenic
microbes (pathogen-associated
molecular patterns (PAMPs).:
pattern recognition receptors
•peptidoglycan, found in bacterial cell walls;
•flagellin, a protein found in bacterial flagella;
•lipopolysaccharide (LPS) from the outer membrane of gramnegative bacteria;
•lipopeptides, molecules expressed by most bacteria; and
•nucleic acids such as viral DNA or RNA.
Phagocytes
• Ingestion of pathogens by phagocytic white blood cells gives non-specific immunity to disease
•Phagocytic leukocytes Neutrophils-Macrophages circulate in the blood and move into the body tissue
(extravasation) in response to infection
•Damaged tissues release chemicals (e.g. histamine) which draw white blood cells to the site of infection (via
chemotaxis) Basophils (also release histamine)
•Pathogens are engulfed when cellular extensions (pseudopodia) surround the pathogen and then fuse to form an
internal vesicle
•The vesicle is then fused to a lysosome (forming a phagolysosome) and the pathogen is digested
•Pathogen fragments (antigens) may be presented on the surface of the phagocyte in order to stimulate the third
line of defence
Phagocytes
• Ingestion of pathogens by phagocytic white blood cells gives non-specific immunity to disease
Phagocytes
• Ingestion of pathogens by phagocytic white blood cells gives non-specific immunity to disease
Phagocytes…when it fails
Protozoans of the genus Leishmania are one example. These obligate intracellular parasites are flagellates transmitted to
humans by the bite of a sand fly. Infections cause serious and sometimes disfiguring sores and ulcers in the skin and other
tissues (Figure 4). Worldwide, an estimated 1.3 million people are newly infected with leishmaniasis annually.[
The parasite will lyse the
macrophage and be
engulfed by other
phagocytes, spreading
the infection
Phagocytes
Inflammation
The inflammatory response is the non-specific way in which the body responds when a pathogen
damages body tissue
•When tissue damage occurs, mast
cells (localised)
and basophils (circulating) release a
chemical called histamine.
•vasodilation and increases capillary
permeability
•Side effects:
Increased blood flow = redness and
heat
increased permeability = releases
fluids and causes swelling and
sensitivity to pain..
Fever
A fever is an abnormally high temperature associated with infection and is triggered by the
release of prostaglandins
•Reduce growth rate of microbes (via the inactivation of microbial enzymes)
•Increase metabolic activity in body cells and activate heat shock proteins to strengthen the immune response
A fever occurs when activated leukocytes release pro-inflammatory chemicals called cytokines to start a
chemical cascade.
Lines of Defense
3 Lines of defense
Lymphocytes
• Production of antibodies by lymphocytes in response to particular pathogens gives specific immunity
adaptive immune system = , which is specific in its response
•It can differentiate between particular pathogens and target a response that is specific to a given pathogen
•It can respond rapidly upon re-exposure to a specific pathogen, preventing symptoms from developing
(immunological memory)
Humoral Immunity (body fluids)
pathway by which antibodies are
produced by B lymphocytes to
target exogenous antigens
Cell-mediated Immunity
Pathway that does not result in
antigen production but instead
targets endogenous antigens
Lymphocytes
• Production of antibodies by lymphocytes in response to particular pathogens gives specific immunity
Lymphocytes
• Production of antibodies by lymphocytes in response to particular pathogens gives specific immunity
Lymphocytes
• Production of antibodies by lymphocytes in response to particular pathogens gives specific immunity
•B lymphocytes (B cells) are antibody-producing cells that recognize and target a particular pathogen
fragment (antigen)
•Helper T lymphocytes (TH cells) are regulator cells that release chemicals (cytokines) to activate specific B
lymphocytes
1) Phagocytic leukocytes engulf a
pathogen (some will present the
digested fragments (antigens) on
their surface)
2) Antigen-presenting cells
(dendritic cells) migrate to the
lymph nodes and activate
specific helper T lymphocytes.
Lymphocytes
• Production of antibodies by lymphocytes in response to particular pathogens gives specific immunity
•B lymphocytes (B cells) are antibody-producing cells that recognize and target a particular pathogen
fragment (antigen)
•Helper T lymphocytes (TH cells) are regulator cells that release chemicals (cytokines) to activate specific B
lymphocytes
3) Helper T cells release cytokines to activate the
particular B cell capable of producing antibodies
specific to the antigen.
4)The activated B cell will divide and differentiate to
form short-lived plasma cells that produce high
amounts of specific antibody
5) A small proportion of activated B cell (and
activated TH cell) will develop into memory cells to
provide long-lasting immunity
Lymphocytes
• Production of antibodies by lymphocytes in response to particular pathogens gives specific immunity
The cytokines prime the maturation of B cells, which become plasma cells and produce
antibodies to neutralize the pathogen. CD8+ cytotoxic T cells, on the other hand, directly kill
infected cells.
Once the adaptive
immune system has
vanquished the invader,
a pool of long-lived
memory T and B cells
are made. These
memory
lymphocytes remain
dormant until the
next time they
encounter the same
pathogen.
Lymphocytes
• Production of antibodies by lymphocytes in response to particular pathogens gives specific immunity
Antigen: An antigen is a substance that the body recognizes as foreign and that will elicit an immune response
Antibody: An antibody is a protein produced by B lymphocytes (and plasma cells) that is specific to a given
antigen
•Antibodies are made of 4 to form Y-shaped molecules
•The ends of the arms are where the antigen binds –
these areas are called the variable regions and differ
between antibodies
Lymphocytes
• Production of antibodies by lymphocytes in response to particular pathogens gives specific immunity
Antigen: An antigen is a substance that the body recognizes as foreign and that will elicit an immune response
Antibody: An antibody is a protein produced by B lymphocytes (and plasma cells) that is specific to a given
antigen
•Each type of antibody recognizes a
unique antigen, making antigenantibody interactions specific (like
enzymes and substrates)
Lymphocytes
• Production of antibodies by lymphocytes in response to particular pathogens gives specific immunity
Lymphocytes
• Production of antibodies by lymphocytes in response to particular pathogens gives specific immunity
CTL, T-killer cells, cytotoxic T lymphocyte, cytotoxic T cell, etc
Main Idea: B cells produce antibodies that will help OTHER leukocytes destroy infected cells and pathogens.
Self vs Non-Self
• Every organism has unique molecules on the surface of its cells
The immune system has the capacity to distinguish between body cells (‘self’) and foreign materials (‘non-self’)
Self vs Non-Self
• Every organism has unique molecules on the surface of its cells
MHC I vs MHC II
An evolutionary explanation
is that females are
attracted to males with
MHC alleles different
from their own, to provide
their offspring with a
stronger immune system.
Females not using
hormonal contraceptives
were more attracted to the
scent of males with
dissimilar MHCs.
MHC I = all nucleated cells
MHC II = antigen presenting cells
Antibiotics
• Antibiotics block processes that occur in prokaryotic cells but not in eukaryotic cells
• Viruses lack a metabolism and cannot therefore be treated with antibiotics
Antibiotics = compounds that kill or inhibit the
growth of microbes (specifically bacteria) by
targeting prokaryotic metabolism
Viruses do not possess a metabolism, have
to be treated with antiviral agents
•Because eukaryotic cells do not possess these features, antibiotics will target the pathogenic bacteria and not the
infected host!!!
Antibiotics
• Some strains of bacteria have evolved with genes that confer resistance to antibiotics and some strains of
bacteria have multiple resistance
•Antibiotics can be narrow spectrum (effective against specific bacteria) or broad spectrum (effective
against many bacteria)
Resistance factors:
•Genes (trait)
•Rapid rate of
reproduction (spread)
•Bacterial conjugation
(horizontal gene transfer)
Antibiotics
• Some strains of bacteria have evolved with genes that confer resistance to antibiotics and some strains of
bacteria have multiple resistance
Antibiotics
• Some strains of bacteria have evolved with genes that confer resistance to antibiotics and some strains of
bacteria have multiple resistance
https://www.youtube.com/watch?v=plVk4NVIUh8
Antibiotics
• Some strains of bacteria have evolved with genes that confer resistance to antibiotics and some strains of
bacteria have multiple resistance
Antibiotics
• Florey and Chain’s experiments to test penicillin
on bacterial infections in mice
The first chemical compound found to have antibiotic properties
was penicillin, which was identified by Alexander Fleming in 1928
Antibiotics
• Florey and Chain’s experiments to test penicillin on bacterial infections in mice
HIV Infection
• Effects of HIV on the immune system and methods of transmission
The Human Immunodeficiency Virus (HIV) is a retrovirus that infects helper T cells, disabling the body’s
adaptive immune system
•It causes a variety of symptoms
and infections collectively classed
as Acquired ImmunoDeficiency Syndrome (AIDS)
Effects of HIV
•HIV targets helper T lymphocytes.
•Infected helper T cells reproduce.
•T lymphocytes are destroyed (lysogenic
cycle)
•Reduction of helper T cells
•Antibodies are unable to be produced
•Lowered immunity
•Body becomes susceptible to infections
HIV Infection
• Effects of HIV on the immune system and methods of transmission
The Human Immunodeficiency Virus (HIV) is a retrovirus that infects helper T cells, disabling the body’s
adaptive immune system
HIV Infection
• Effects of HIV on the immune system and methods of transmission
The Human Immunodeficiency Virus (HIV) is a retrovirus that infects helper T cells, disabling the body’s
adaptive immune system
HIV Infection
• Effects of HIV on the immune system and methods of transmission
Transmission of HIV
•HIV is transmitted through the exchange of body fluids (including unprotected sex, blood transfusions,
breastfeeding, etc.)
•The risk of exposure to HIV through sexual contact can be minimised by using latex protection (i.e. condoms)
•A small minority of people are immune to HIV infection (they lack the CD4+ receptor on TH cells that HIV
requires for docking)
•HIV is a global issue, but is particularly prevalent in poorer nations with poor education and health systems
Transplants
Transplants
Transplants