Microbiology week 3

What is a pathogen?

• A microorganism that can cause damage/ disease

• Some organisms may have specific mechanisms that allow them to cause damage, known as virulence factors

What is a virulence factor?

A virulence factor is something that helps the organisms cause the damage/ disease to the host cell

Adhesins- Help the organism adhere to host epithelial cells

Evasins & Impedins- Help the organism evade the host immune system

Invasins-Help the organism invade host tissues

Toxins- Help the organism cause damage direct to the host tissues

Host defenses

Exterior defenses- most of the infectious agents encountered by an individua; are prevented from entering the body by a variety of biochemical and physical barriers. The body tolerates a variety of commensal organism which compete effectively against pathogens.

Respiratory tract

Nose- Specialised hairs vibrissae filter large particles

Abrupt airflow changes due to the structure of the nasopharynx

Cough reflex

Respiratory epithelium from nose to terminal bronchioles are covered with beating cilia, covered in mucus

Alveoli containing IgA, complement components and alveolar macrophages.

Different organisms found in the upper respiratory tract

Urinary tract

• Mucosal

Urothelial secretion of cytokines and chemokines

Mucopolysaccharide lining

Mucosal IgA

Men- prostatic secretions contain bactericidal zinc and urethra is longer

• Urine

Acidic pH

High urine osmolality

Urinary inhibitor of adherence

Competitive inhibitor of attachment to urothelial cells

Flushing action of urine flow

GI tract

Mouth

• Flow of liquids

• Saliva - lysozyme

• Normal bacterial flora

Oesophagus

• Flow of liquids

• Peristalsis

Stomach

• Acid pH

Small intestine

• Flow of gut contents

• Peristalsis

• Mucus/ bile

• Secretory IgA

• Lymphoid tissue - Peyer’s patches

• Shedding and replacement of epithelium

• Normal flora

Large intestine

• Normal flora

• Peristalsis

• Shedding and replication of epithelium

• Mucus

Vaginal flora- protects female reproductive tract

How do microorganism invade the body

1st line of defence- innate immune system

• Skin

• Mucosa membrane

2nd line

• phagocytes

• complements

3rd line- adaptive

• lymphocytes

• antibodies

• Memory cells

How do they invade the 1st line of defence

• Failures in the system- breaks to the skin, lack of normal flora

• Number of pathogens are high= overwhelming

• Resistance to pH changes

• Adhesion despite flow of liquids

How do they invade the 2nd line of defence

• Avoidance- physical barrier

• Cryptococcus neoformans- thick capsule

• Granuloma stops immune system detecting foreign body

• Interference

• CMV has a homologue of UL18- inhibits cytokine production

• Cytokine- stimulate the immune response

How do they invade the 3rd line of defence

• Concealment- the organism surrounds itself with host cells- stops antigens being detected, conceal their receptor antigens

• Chlamydia- exist within the host cell- mimic host antigens- immune system won’t identify chlamydia cells

• Antigenic variation- changes the shape of surface antigens the pathogen induces a series of innate responses in place of the host developing an effective adaptive responses

• Influenza virus- changes surface antigens

• Immunosuppression- organisms can supress the immune system

• less monocytes - impaired lymph proliferation

Trypanosomes and Leishmaniasis- organism can change antigen on their surface

Defects in host defence mechanism

• two types of immune deficiency states affect the host’s ability to fight infection

• Primary immune deficiency- genetic origin. most are recognised during infancy

• Acquired immune deficiency (secondary)- caused by another disease such as cancer, HIV infection or chronic disease. or exposure to a drug that is toxic to the immune system

Immune-mediated damage

Damage/disease can be caused by the pathogen but can also be caused by the immune response.

Excessive stimulation of the innate immune system can lead to dangerous or potentially fatal symptoms, a microbial-induced example of this is sepsis

Sepsis and septic shock

• when some gram-negative bacterial lyse, a component of their cell wall- lipopolysaccharide (LPS) cause excessive cytokine secretion by macrophages

S- slurred speech or confusion

E-extreme shivering or muscle pain

P-passing no urine (in a day)

S-severe breathlessness

I-it feels like you’re going to die

S-skin mottled or discoloured

Treatment can bypass host defenses

Influenza virus

Antigenic variation

• Principle is by constantly changing the shape of surface antigens the pathogen induces a series of innate responses in place of the host developing an effective adaptive response.

Hemagglutinin (HA)

Neuraminidase (NA)

Eight ribonucleotide segments each contain viral RNA surrounded by nucleoprotein and associated with RNA transcriptase

Antigen variation

• Two types of influenza virus, designated type A and type B- public health concern

• Can not be differentiated by symptoms- differentiated in lab only

• Many subtypes of flu A with different variants of HA and NA, most of these subtypes only circulate in birds

• Occasionally a new subtype of flu A virus emerges that has a HA to which humans haven’t been exposed to previously - ANTIGENIC SHIFT

• HA and NA of type A and type B viruses continually change by mutation to produce new strains- ANTIGENIC DRIFT