Lecture 4 new Flashcards
Define the immune system:
Cells and organs that contribute to immune defences against infectious and non-infectious conditions (cancer)
Define infectious disease:
When the pathogen succeeds in evading and/or overwhelming the host’s immune defences
What is infectivity?
Ability of microorganisms to establish itself within the host or on the host
What are the roles of the immune system?
PCRR
Pathogen recognition- cell surface and soluable receptors
Containing/eliminating infection (killing and clearance mechanisms)
Regulating itself- minimum damage to host, otherwise you develop autoimmune
Remembering pathogens- prevent the disease from recurring
What are the two types of defence?
Innate immunity
- fast
- lack of specificity
- lack of memory
- no change in intensity
Adaptive immunity
- slow
- specific
- immunologic memory
- changes in intensity
What are the 1st line defences? (innate immunity)
Barriers to stop pathogen entering
- physical barriers
- physiological barriers
- chemical barriers
- biological barriers
What are the physical barriers?
- skin
- mucous membranes of mouth/ resp tract/ GI tract/ urinary tract
- bronchial cilia (beat to expel trapped microbes in mucous)
What are the physiological barriers?
- diarrhoea (food poisoning)
- vomiting (food poisoning/hepatitis/meningitis)
- coughing (pneumonia)
- sneezing (sinusitis)
What are the chemical barriers?
Low pH: skin 5.5, stomach 1-3, vagina 4.4 Antimicrobial molecules: -IgA (tears/saliva/mucous membrane) -lysozyme (sebum/perspiration/urine) -mucous (mucous membrane) -beta-defensins (epithelium) -gastric acid and pepsin (endopeptidase)
What are biological barriers?
Normal flora
-non pathogenic microbes (found in nasopharynx, mouth, throat, skin, GI tract, vagina)
Where are normal flora absent?
In internal organs/tissues
What are the benefits of normal flora?
-compete with pathogens for attachment sites and resources
-produce antimicrobial chemicals
-synthesise vitamins K, B12, and other B vitamins
-immune maturation
(normal flora can become pathogenic)
Give some examples of normal flora that inhabit the skin:
- staphylococcus aureus
- staphylococcus epidermidis
- streptococcus pyogenes
- candida albicans
- clostridium perfringens
Give some examples of normal flora that inhabit the nasopharynx:
- streptococcus pneumoniae
- neisseria meningitidis
- haemophilus species
How is normal flora displaced from its normal location?
Breaching skin integrity
- skin loss (burns)
- surgery
- IV lines
- skin diseases
- injection drug users
- tattooing/body piercing
Fecal-oral route
-foodbourne infection
Fecal-perineal-urethral route
-UTI in women
Poor dental hygiene/dental work
- dental extraction
- gingivitis (gum disease)
- brushing/flossing
What is the perineum?
The space between the anus and scrotum in the male and between the anus and the vulva in the female
What are some high risk patients susceptible to serious infections?
- asplenic/hyposplenic patients
- patients with damaged/prosthetic valves
- patients with previous infective endocarditis (infection of of the endocardium- the inner lining of the heart)
What may cause normal flora to overgrow and become pathogenic when host is immunocomprimised?
- diabetes
- AIDS
- malignant diseases
- chemotherapy
What conditions cause the flora in mucosal surfaces to be depleted by antibiotic therapy?
- severe colitis (intestine): clostridium difficile
- thrush (vagina): candida albicans
What are the second lines of defences that contain and clear the infection?
- phagocytes
- chemicals
- inflammation
What are the main types of phagocytes?
- macrophages
- monocytes
- neutrohpils (pus)
What is the function of a macrophage?
- present in all organs
- ingest and destroy microbes via phagocytosis
- present microbial antigens to T cells
- produce cytokines/chemokines
What is the function of monocytes?
- present in blood
- recruited at infection site and differentiate into macrophages
What is the function of neutrophils?
- present in blood (60% of blood leukocytes)
- increased during in infection
- recruited by chemokines to site of infection
- ingest and destroy pyogenic bacteria (Staph. aureus, Strep.pyogenes)
What is a pyogenic bacteria?
Bacteria which produces pus
What is the function of basophils/mast cells? (granulocytes)
- early actors of inflammation (vasomodulation)
- important in allergic responses
What is the function of eosinophils?
Defence against multi-cellular parasites (worms)
What is the function of natural killer cells?
Kill all abnormal host cells (virus infected or malignant)
What is the function of dendritic cells?
Present microbial antigens to T cells
How are pathogens recognised?
Microbial structures: PAMPs (pathogen associated molecular patterns) e.g. carbohydrates/lipids/proteins/nucleic acids
Phagocytes: PRRs (pathogen recognition receptors)
(PRRs allow phagocytic cells to detect PAMPs)
Give an example of a PRR:
TLR (toll like receptor)- these bind to various PAMPs and communicate with the nucleus of the phagocyte to ellicit a response
What is opsonisation of microbes?
Opsonins are coating proteins which bind to the microbial surfaces leading to enhanced attachment of phagocytes and therefore clearance of molecules
Give some examples of opsonins:
Complement proteins: C3b/C4b
Antibodies: IgG/IgM (these attach to antigens on the microbe which in turn acts as an opsonin for the opsonin receptor on the phagocyte)
Acute phase proteins: CRP (C-Reactive protein)/ MBL (mannose-binding lectin)
How do phagocytes work?
- recognition (PAMPs & opsonins)
- engulfment
- degradation of infectious microbes
What are the 2 intracellular killing mechanisms of a phagocyte?
1) oxygen dependent pathway (respiratory burst: using oxygen free radicals)
2) oxygen independent pathways (lysozyme)
What is the system of phagocytosis?
- chemotaxis and adherence of microbe to phagocyte
- ingestion of microbe by phagocyte
- formation of phagosome (phagocytic vesicle)
- fusion of phagosome with lysosome to form phagolysosome
- digestion of ingested microbe by enzymes
- formation of residual body containing indigestible material
- discharge of waste materials
Why are you at risk of infection when you have a splenectomy?
The spleen clears encapsulated bacteria such as: Neisseria meningitidis/Streptococcus pneumoniae/Haemophilus influenzae B
What is the complement system?
20 serum proteins
the most important are C1-C9
Give some examples of complements with antimicrobial actions:
They float around in blood. and become activated in presense of pathogen.
C3a/C5a recruit phagocytes
C3b/C4b for opsonisation of pathogens
C5-9: Killing of pathogens & Membrane attack complex (MAC forms transmembrane channels which disrupt the cell membrane of target cells causing lysis and death)
How do cytokines act?
- chemoattraction
- phagocyte activation
- inflammation
