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Unit 3 AOS 2

Chapter 6-Pathogens

Responding to antigens

Germ theory of disease

Specific microbe causes specific infectious diseases

Microbe- (bacteria, archaea, protists, fungi with cellular structure)

All body fluids are sterile

Pathogenic-disease causing microbes

Infection by pathogen-infection by pathogen causes disease in one or specific hosts

Infection –occurs when pathogenic bacteria, microbes or viruses gain entry to the human body and
multiply

Disease-occurs only after organs/cells are damaged by infection and specific symptoms are visible

Incubation period-interval between person exposure to pathogen and onset of disease symptoms in that
person

Asymptomatic carriers-people who carry infection yet show no signs of disease

Infectious disease-illness caused by a specific infectious agent or its toxic product that results from the
transmission of that products from an infected person, animal or reservoir susceptible to either directly or
indirectly through an intermediate plant or animal host.

Non infectious diseases

 Environmental diseases
 Nutritional deficiency
 Inherited diseases

Transmissible diseases

 Direct transmission
 Vectors (animals)
 Airborne particles/droplets
 Zoonotic diseases

Cellular and non-cellular pathogens

 Bacteria
 Viruses
 Fungi
 Protozoa
 Prions

Bacteria
 Prokaryotic
 Double stranded DNA

Shapes:

 Cocci-round
 Bacilli-elongated
 Vibrio (oval)

Gram +/- (staining)

Gram negative-red/pink (lipopolysaccharide)-allows bacteria to expel/exclude bacteria/antibiotics

Gram positive-dark blue (peptidoglycan cell wall)-normally susceptible to antibiotics e.g.


penicillin/sulfonamide

Bacterial toxins

Exotoxins Endotoxins
 Soluble proteins produced by bacteria  Toxins derived from lipid portion of
as part of metabolism and released lipopolysaccharide-gram – bacteria
into surroundings  Released only after bacteria die and
 Damage without presence of bacteria outer membrane breaks down
 Generally produced by gram positive  Salmonella typhi
bacteria  Neisseria meningitis
 Clostridium Tetani
 Vibrio cholera
 Streptococcus pyogene

Bacterial capsules

 Capsules increase virulence of bacteria

Anaerobic/Aerobic

Obligate anaerobes Facultative anaerobes Obligate aerobes


 Only produces  Respires  Require
energy in the anaerobically oxygen to to
absence of and reproduce
oxygen aerobically  Tuberculosis

 Spores make bacteria resistant to antibiotics
Nutritional needs

 Different types of bacteria have different nutritional needs

Viruses
 Non cellular, no metabolic activity cannot produce independently of the host cell
 Non living pathogens
 Contain genetic material-either DNA/RNA which is self replicating once inside host cell

Virion-viruses outide of the host cell

Viruses have preferred target cells which they replicate

Way which viruses cause disease

 Alter DNA of host cells


 Host cells show morphological changes which lead to symptoms
 Replicate through budding

Structure of viruses

1. All viruses contain single/double stranded DNA/RNA


2. Capsid surrounds genetic material (protein shell)
Nucleuocaspid- combination of capsid plus surrounding material

Naked viruses-complete structure comprised of nucleocaspid

Enveloped viruses-viruses which have additional envelope surrounding capsid e.g. AIDS

Structure of virus

Spikes-glycoprotein

Genetic material of viruses


Genomes of different viruses are comprised of single/double stranded DNA/RNA
Viruses release by lysis/budding

Enveloped viruses-budding
Naked viruses-lysis

Prions (pertinacious infection)

Prions-infectious particles made of proteins lacking nucleic acids

Normal and harmful prions

Secondary structure-of the protein involved determines if the protein is harmful or not

Nucleotide base sequence of two proteins identical

Reproduction of prions

Normal PrPc protein can be transformed into harmful prion through contact with Prpsc prion

Chain reaction started when contact is made

Each new prion can create other prions

Prion diseases

BSE (bovine spongiform encephalopathy) (Mad cow diesease)


Harmful prions aggregate in nerve cells of cattle, damaging brain tissue

Human prion diseases

CJD Transmission-somatic transmission/ conversion of PrPc into PrPsc

Types of CJD

 Sporadic
 Familial-PRPN gene
 Iatrogenic-acquired trough medical procedures
 Use of prion contaminated surgical instruments
Iatrogenic CJD
 Use of human growth hormone
 Use of gonadotrophin
 Prion infected grafts of brain tissue
 Transfusion of prion infected blood
Variant CJD
 Causal link between consumption of BSE infected cattle
 Form of human BSE

Self/ Non self-Identification

Immune system has ability to


 Identify self/non self-foreign antigens
 Recognize ‘self’ cells

An antigen as a unique molecule or part of a molecule that initiates an immune response including the
distinction between non-self-antigens, self-antigens and allergens

Antigens-any molecule which can stimulate a specific immune response

Immunogen-any a molecule which can generate an immune response

All antigens are immunogens however not all immunogens are antigens

Autoantibodies-causes autoimmune disease

Self-antigen-

Non self-antigen- produces abnormal immune response- autoantibodies

Invading cellular and non-cellular pathogens as a source of non-self-antigens, and preventative


strategies including physical, chemical and microbiological barriers in animals and plants that keep them
out

Distinguishing between self and non self

HLA markers (human leucocyte antigens)

Class I HLA markers-found on all nucleated cells of the body


Class II HLA Markers-found on T cells and B cells (Class II MHC markers)

Transplantation and tissue typing

-HLA marker typing must be conducted before a transplant top reduce the chance of rejection by the
receiver

-non self-antigens on a donor organ can stimulate the receiver’s immune system to reject the transplant.
Immunosuppressive drugs must be taken to prevent this.

Transplant types

 Tissue transplants
 Organ transplants

1. Biologically related people


 For two biologically related people, the chance of the two having identical
 matching HLA markers is as follows:
 for monozygous (identical) twins or triplets: 100 per cent
 for siblings (brothers and sisters): 25 per cent or

The characteristics and roles of components (macrophages, neutrophils, mast cells, dendritic cells,
complement proteins) of the innate (non-specific) immune response to an antigen including the steps in
the inflammatory response

Immunity-resistance against infectious diseases

Neutrophils
Macrophages
Mast Cells
Dendritic Cells
Complement
proteins

 All cells of the immune system are derived from bone marrow
 Lymphocytes B and T cells
Innate immunity (nonspecific/natural immunity)

First line of defence-physical and chemical barriers to entry of pathogens

 epithelial tissues
 mucous membranes –cilia in brochus traps dust by wafting mucus towards back of throat for
digestion in acidic stomach environment
 Intact skin
 Natural flora-(non-pathogenic bacteria which compete with pathogenic bacteria for resources and
nutrients to prevent growth)

Second line of defence-immune cells, dendritic cells, macrophages

 Phagocytic cells (neutrophils and macrophages)


 Natural killer cells
 Complement proteins
 Interferons secreted by infected cells

Extracellular pathogens-macrophages-phagocytosis

 Neutrophils-circulate in the bloodstream


 Macrophages-concentrated in the tissues of epithelial layers

Phagocytosis process

1.pathogen identified by pattern recognition receptor (PRR’s bind to non specific molecular patterns found
on pathogens)

2.pathigen enclosed in phagosome


3.lysosomes fuse with phagosome

4.digestion

5.excytosis of indigestible material

Intracellular pathogens-neutrophils-degranulation

Natural killer (NK cells) release granzymes and perforin into target cells forming pores and breaking
down protein)

Recognition of pathogen infected cells b NK cells

 All cells in body contain ligand which can bind to ‘kill’ receptors on NK cells
 Virus infected cells suppress expression of HLA I markers
 Inhibition of kill receptor is not triggered
 Granzymes released

Third line of defence(Specific Immunity)-immune cells and specific antibodies

 Comes into action only if second line of defence fails

Inflammatory response process

The role of the lymphatic system in the immune response including the role of secondary lymphoid
tissue (with reference to lymph nodes) as the site of antigen recognition by lymphocytes, and as a
transport system for antigen presenting cells including dendritic cells

Role of the Lymphatic system in the immune response

 Primary lymphoid organs (B cells and T cells develop)

Primary lymphoid tissue

 Bone marrow
 Thymus

Secondary lymphoid tissue

 Spleen
 Lymph nodes (adaptive immune response) (B and T cells mature and develop into effector cells)
 Located alongh blood vessels to allow B and T cells to exit and enter via arteries

-Site where foreign antigen s and activate B and T cells

-swell when infections occur

-trap cancer cells in the area

Lymph nodes as a site of antigen recognition and transport system for dendritic cells
The characteristics and roles of components of the adaptive (specific) immune response including the
actions of B lymphocytes and their antibodies (including antibody structure) in humoral immunity, and
the actions of T helper and T cytotoxic cells in cell-mediated immunity. Immunity

Adaptive Immunity (specific/acquired immunity)


Actions of B lymphocytes and their antibodies (Antibody structure)

B cells are

Humoral immunity

Actions of Cytotoxic and helper T cells

The difference between natural and artificial immunity, and active and passive strategies for acquiring
immunity vaccination programs and their role in maintaining herd immunity for a particular disease in
the human population

Means of gaining immunity

Natural Immunity Artificial Immunity


Production of antibodies by a person in response Artificial Passive
to exposure to a particular antigen. Deliberate and artificial introduction of a disabled
pathogen or its toxin to the body
B-memory cells and T cells are produced and react
quickly if another encounter occurs with the same Vaccines are used to activate the immune system
organism. to produce antibodies against specific c disease-
causing organisms without actually causing the
Natural Active Immunity disease (attenuated viruses)
After an infection without any artificial
intervention Artificial Natural Immunity

Active-the antibodies are made by the immune Snakebite-anti-venom


system of the infected person.
Antibodies injected into people who any be at risk
Natural passive immunity of contracting a disease, collected from people
who have already been expose to disease e.g. Hep.
Antibodies produced in one person and introduced A.
into another person can provide immunity to that
person

Developing fetus receives maternal antibodies


across the placenta from its mother. These
antibodies (immunoglobulin G [IgG]) provide
important protection for the fetus and the
newborn baby because the baby’s immune system
does not mature fully until after birth.

Vaccines
-Primary response and secondary response

Mass Vaccines

 Eradication of small pox


 Eradication of polio-almost completely eradicated through vaccination programs which prevent
virus from finding a host

Vaccines have reduced regional incidences of infectious diseases

Herd immunity-indirect protection of populations from infection where that protection is created by the
presence of the immune individuals in the population for individuals, which are not vaccinated.

On the road to the eradication of poliomyelitis


The deficiencies and malfunctions of the immune system as a cause of human diseases including
autoimmune diseases (illustrated by multiple sclerosis), immune deficiency diseases (illustrated by HIV)
and allergic reactions (illustrated by reactions to pollen)

Autoimmune diseases

 Allergies
 Autoimmune disorders

Autoimmune disorders

Body produces autoantibodies, that is antibodies that attack the body’s own cells

Autoimmune diseases (MS)-autoantibodies attack myelin that forms an insulating sheath around nerve fi
bres in the brain and spinal cord

When myelin is destroyed, nerve fibres are destroyed and transmission of impulses is affected

Symptoms

 Numbness
 Lack of coordination
 Unsteady gait
 Slurred speech

Type 1 diabetes

 Type 1 diabetes is most commonly the result of an attack by a person’s immune system in which
autoantibodies destroy the insulin-producing (islet) cells of the pancreas
 Insulin producing cells of the liver

Systemic lupus erythematosus (SLE)

Multisystem autoimmune disease that affects almost all organs of the body, including heart, kidneys and
brain. Common symptoms of SLE include sensitivity to sunlight, rashes (typically on the face), fever, and
fatigue.

Allergies: when harmless becomes harmful

Allergy-person’s immune system reacts abnormally to substances, which are harmless to most people

Allergens-substances, which cause an allergic response in people

Testing for allergens


The Allergic reaction

Action:

Mast Cells

Antibodies (immunoglobulin Ig E)

Sensitisation to allergen

Potential allergens, such as an antigen on airborne pollen cells, are inhaled and become lodged on the
mucous membrane lining the airways. Cells of the immune system identify this antigen as non-self, and an
immune response is activated

IgE antibodies attach to surface receptors of mast cells

Mast cells that are coated with IgE antibodies are primed

Step 1 Activation of mast cells

IgE antibodies on the primed mast cells recognise the allergen and bind to it

Allergen binds to Ig E antibodies and mast cells activate and degranulate, releasing histamine

Release of histamine results in increased blood flow to the region causing redness, increased permeability
of blood vessels causing sneezing, coughing, runny eyes
Step 2-Migration of more immune cells causing inflammatory response

Mast cells produce chemical messengers that signals various circulating immune cells to attack the allergen

Accumulatulation of immune cells causes inflammation and tissue response and recruit more immune cells
to area

Anaphylaxis-allergic reaction affects nervous, cardiovascular and respiratory systems disease

Acquired Immunodeficiency-results from viral uinfection of T helper cells-produces more copies of virus

Acquired through direct contact with body fluids

Immune deficiency diseases (HIV)-Retrovirus that carries information in fragments of single stranded RNA
targets T-helper cells and takes charge of them, using them to make copies of the viral RNA and the viral
proteins

T cell count when infected by HIV Retrovirus

HIV replication

1. Fushion-viral particle binds to CD4 receptor


2. Enrtry-viral DNA and viral reverse transcriptase enter cytoplasm of host cell
3. Copying DNA-reverse transcriptase uses RNA to make copies of DNA complementary to viral DNA
4. Insertion-double stranded DNA moves into T helper cell-inserts into DNA of host cell
5. Transcription of DNA-T helper cell stops its own activities
6. Translation of viral RNA-copies of viral RNA move into cytoplasm where viral RNA is translated to
produce viral proteins-enzymes reverse transcriptase, protease, integrase
7. Translation of viral RNA-copies of viral RNA move into cytoplasm where viral RNA is translated to
produce viral proteins
8. Enveloping and release-new viral praticles are released from T helper cells.
9. Each virus which buds out is coated by phospholipid bi-layer

The use of monoclonal antibodies in treating cancer

Treating cancers-monoclonal antibodies block the growth of new blood vessels to malignant tumours
by binding to growth factor VEGF in cancer cells.

Malignant tumour cannot continue growing withous supply of blood and oxygen

Signalling immune cells attack cancers - The attached antibody acts as a signal that attracts immune
cells to the cancer- immune cells begin eliminating these white blood cells, including the leukemic cells

Blocking signals for cell division-monoclonal antibody binds to HER 2 receptors (receive signals from
growth factors to continue to divide uncontrollably), preventing signal reception.

Conjugated monoclonal antibodies-MAbs joined to a second molecule, such as a chemotherapy drug


or a radioisotope particle.

Fucntions

1. Delivering anticancer drugs to cancer cells


2. Delivering radioisotopes to cancer cells

Producing monoclonal antibodies

1. Mouse is injected with antigen X , B cell production activated, repeat injections (boosters) given
2. Spleen removed, placed in culture medium and separated, B cell mixture is produced
3. B cells are mixed with mouse tumour cells. Some B cells fuse with tumour cells and form
hybridomas
4. Unfused cells die, leaving only hybridoma cells
5. Individual hybrodoma cells are cultured and allowed to divide repeatedly
 Each clone cell is screened for presence of required antibody , clones which produce antibodies
against antigen X are identified
 Selected clones grown in mass culture and antibodies harvested as required

B cells cannot divide, but by fusing a B cell with a tumour cell that can divide indefinitely, a non-stop
factory with an antibody production line