Lecture 4 - Innate Immunity Flashcards
What is infectivity?
The ability for a microorganism to infect a host and therefore establish itself
What is virulence?
The ability of a microbe to drive/cause tissue damage
Which 3 groups of people have weak immune systems and are therefore more susceptible to infections?
Elderly people (65yrs +)
Children (less than 5 yrs)
Pregnant women
What is the definition of the immune system?
The cells and organs that contribute to immune defences against infectious and non-infectious conditions
What is an infectious disease?
When the pathogen succeeds in evading and/or overwhelming the hosts immune defences
What are the roles of the immune system?
Pathogen recognition
Containing/eliminating the infection
Regulating itself (ending once infection is gone)
Remembering pathogens (immunological memory)
What principles do vaccines use to work?
Modified version of microbe
Stimulates normal immune response from body
Immunological memory created (preventing illness when infected by actual pathogen)
What are the 2 components to the immune response?
Innate immunity
Adaptive immunity
What is the main difference between innate and adaptive immunity?
Innate immunity provides immediate protection
Adaptive immunity provides long lasting protection
What are the features of the innate immunity giving immediate protection?
Fast/rapid acting
Lack of specificity
Lack of memory
No change in intensity
What are the feature of the adaptive long lasting protection ?
Slow
Specific
immunological memory
Changes in intensity (due to immunological memory, faster and stronger upon repeat infection)
In innate immunity, what are the 4 first lines of defence?
Physical barriers
Physiological barriers
Chemical barriers
Biological barriers
What is the general function of the first lines of defences in innate immunity?
They prevent the entry and limit the growth of pathogens
Prevent microbes getting in
What are the innate physical barriers to infection?
Skin
Mucous membranes
Bronchial cilia
Where are the mucous membranes of the body located?
Mouth
Respiratory tract
GI tract
Urinary tract
What is the function of the Bronchial cilia?
Waft mucus that has trapped pathogens to the back of the oesophagus to be swallowed and destroyed
What are the physiological barriers of innate immunity?
Diarrhoea
Vomiting
Coughing
Sneezing
These usually happen once a pathogen has breached a physiological barrier
What is the general function of the physiological barriers?
Usually trying to expel pathogens from the body
What are the chemical barriers of innate immunity?
Low pH (skin, stomach and vagina)
Antimicrobial molecules:
-(IgA in saliva, tears and mucous membranes)
-Lysozymes
-Mucus
-Beta-defensins
-Gastric acid + pepsin
What are Beta-defensins?
Chemicals with antimicrobial properties
How does IgA (Immunoglobulin A) act as an antimicrobial molecule?
Prevent attachment to host
Antibody that binds to microbe preventing it attaching to the host
What is the biological barrier of the body?
The normal flora of the body
What is meant by the normal flora of the body?
Non pathogenic microbes that are normally present in/on the body
Can cause disease when displaced from intended site
Where is the normal flora of the body normally located?
Skin
All mucosal surfaces
How does the bodies normal flora act as a biological barrier to infection?
Competition
Competes with pathogens for attachment sites and resources
Produce antimicrobial chemicals
Which organ in the body deals with encapsulated bacteria?
Spleen
Where is Staphylococcus aureus normally found and what condition does it cause if it invades the body?
Skin
Invades subcutaneous layer causing:
CELLULITIS
Where is Streptococcus pyogenes normally found and what disease does it cause if it is displaced?
Skin
Scarlet fever
Where is Streptococcus mutans normally found and what disease can it cause if its displaced?
Mouth and nasopharynx
Endocarditis
Where is E.coli normally found and what disease does it cause if its displaced?
GI tract
Food poisoning
How can the normal flora be displaced from its normal location?
Breaching the skin integrity
Fecal oral route
Fecal-perineal-urethral route (UTIs women)
Where is the main portal of entry for microbes into the body?
The mouth
When do problems with normal flora arise?
Normal flora displaced
Overgrowth when host is immunocompromised
Normal flora depleted due to antibiotics
How does Chemotherpy cause problems with the normal flor?
Inflames the mucous membranes (mucositis) allowing normal flora to invade the host
What are the secondary lines of defence in innate immunity that lead to Inflamation?
Phagocytes
Chemicals
What is the function of the secondary line of defence of innate immunity?
They contain and clear the infection
What are exogenous microbe invaders?
Microbes that invade that aren’t normally present in the host
What are endogenous microbe invaders?
Normal flora that breach and invade
What are phagocytes?
White blood cells which first respond to an infection and engulf a pathogen
What are the 3 types of phagocyte?
Macrophage
Monocytes
Neutrophils
What is a macrophage?
Phagocyte only found in tissues and organs
What is the function of a macrophage?
Phagocytosis (ingest and destroy microbes)
Present antigens to T cells (adaptive immunity)
Make cytokines/chemokines
What important clinical marker do cytokines cause elevated levels of?
cRP (c Reactive Protein)
What are monocytes?
Phagocytes found in the blood
They migrate to tissues and differentiate into macrophages
How are neutrophils different to macrophages?
Neutrophils =
Increased levels during infection
+ Shorter lived than macrophages
What are the functions of basophils/mast cells?
Inflammation (histamines)
Allergic reactions
What is the function of eosinophils?
Defence against parasites (multicellular)
What is the function of natural killer cells?
Kill all abnormal host cells
What is the function of dendritic cells?
Present microbial antigens to T cells (important for acquired immunity)
How do phagocytes recognise which microbes are pathogens to be ingested?
PAMPs
PRRs
Where are PAMPs located?
What does it stand for?
On microbes/pathogens
Pathogen Associated Molecular Patterns
Where are PRRs located?
What does it stand for?
On phagocyte
Pathogen Recognition Receptors
How do PAMPs of microbes interact with the PRRs of phagocytes?
The phagocytes PRRs (Pathogen Recognition Receptors) will match the PAMPs (Pathogen-associate molecular patterns) on the pathogen
How is it useful for 1 PRR on a phagocyte to match/recognise multiple PAMPs?
Phagocyte can recognise and phagocytose many different pathogens
What is opsonisation of microbes?
When the host coats microbes in proteins (opsonise) which a phagocyte can recognise leading to enhanced attachement to phagocytes
What can act as opsonins?
Complement proteins (C3b)
Antibodies (IgM and IgG)
Acute phase proteins (C-reactive protein cRP)
If opsonins are not present or non functional, which type of microbes cant be removed?
Encapsulated bacteria:
-Neisseria meningitidis
-Haemophilus influenzae
-Streptococcus pneumoniae
How does phagocytosis take place?
Pathogen recognised
Pathogen binds to phagocyte
Engulfed
Phagosome
Phagolysosome
Digested
How does a phagocyte kill a microbe once its been engulfed in a phagolysosome? (Main mechanism)
Respiratory burst/ Oxygen-dependant pathway
What is involved in the chemical portion of the second line of defence of innate immunity?
Complement system/proteins
Cytokines
What is the complement system?
What organ is the main contributor to producing complement?
Proteins in blood serum which get activated by coming into contact with invading microbes
Liver = main complement producing organ
Which complement proteins attract phagocytes to microbes?
(Chemoattractants)
C3a
C5a *
Which complement protein binds to pathogens (opsonisation)?
C3b
Which complement proteins bind to surface of pathogens and kill the pathogen?
C5
C6
C7
C8
C9
What is the function of cytokines?
Chemoattraction
Activates phagocytes
Inflammation
What systemic affects do cytokines have ini the body?
Liver makes opsonins
Bone marrow mobilises neutrophils
Fever (hypothalamus increases body temp)
How do cytokines cause local inflammation?
Vasodilation
Increased vascular permeability
Innate immune response summarised:
Innate barrier may get breached
Complement proteins made/activated
Macrophages/phagocytes activated
Cytokines made
Vasodilation/vascular permeability
Chemoattraction
Fever
Inflammation
When may phagocytosis be reduced causing problems?
Asplenic/Hyposplenic patients
Neutropenia (chemotherapy, leukaemia, certain drugs)
Decreased neutrophil function (Chronic Granulomatous Disease caused by NAPDH oxidase defect)
Give 2 conditions where neutrophils have decreased function:
Chronic granulomatous disease (no respiratory burst) due to phagocyte NADPH oxidase deficiency
Chediak-Higashi syndrome (No phagolysosome formation)
First line defences and second line defences of innate immunity purpose:
First line = limit entry and growth of pathogens at portals of entry
Second line = contain and eliminate infection
What specific cytokines produced by macrophages stimulate the liver to produce CRP?
IL-1
IL-6
TNF-a (Tumour Necrosis Factor - Alpha))
What is the function of cRP?
What stimulates its production?
Opsonisation
Macrophages producing the cytokines IL-1, IL-6 and TNF-a
What cells produce IL-1, IL-6 and TNF-a?
What do these cytokines do?
Macrophages produce them
These cytokines are pyrogens inducing fever
