Innate Immune System Flashcards
Innate immune system
Factors determining the outcome of the host-
pathogen relationship -
Infectivity is the ability of the pathogen to establish itself in the host
3 immune deficient patients - 1) elderly 2) patients 3) pregnant woman
Immune system -
Cells and organs that contribute to immune defences against infectious and non-infectious conditions (self vs non-self)
Infectious disease -
When the pathogen succeeds in evading and/or o
Different types of immune response
Innate immunity - immediate protection - fast (within seconds), has a lack of superficial and memory
Adaptive immunity - slow (days) has specificity, allows for immunological memory, can change in intensity depending on the exposure to the pathogen
Innate immune response
The innate response acts as the first line of defence - uses physical barriers e.g. the skin and mucous membrane (in the mouth, GI tract, respiratory tract and urinary tract) and bronchial cilia (in lung - expell out all the trapped microbes in the mucous)
Biological barriers - only if they stay in the correct place - Normal flora (Non pathogenic microbes, these ‘barriers are placed in strategic locations e.g. Nasopharynx, Mouth/Throat, Skin, GI tract, Vagina (lactobacillus spp) - Absent in internal organs/tissues
Benefits - Compete with pathogens for attachment sites and resources
Produce antimicrobial chemicals Protection
Synthesize vitamins (K, B12, other B vitamins) + Immune maturation
Chemical barriers - low pH (skin = 5.5, stomach = 1-3, vagina = 4.4), antimicrobial molecules (IgA (tears saliva and mucous membrane) lysosome (sebum, perspiration and urine) mucous (the mucous membrane), beta defensins (in the epithelium) and gastric acid and pepsin)
Physiological barriers -expelling microbes out e.g. diarrhoea (from food poisoning), vomiting (from food poisoning, hepatitis and meningitis), coughing (pneumonia) and sneezing (sinusitis)
Examples of normal flora that inhabit and clinical problems
The skin - Staphylococcus aureus (week 1, case 1) Staphylococcus epidermidis Streptococcus pyogenes Candida albicans Clostridium perfringens
The nasopharynx - Streptococcus pneumoniae Neisseria meningitidis Haemophilus species These could all become pathogenic if they ‘get into’/inhabit the wrong place in the body
Clinical problems start when:
-Normal flora is displaced from its normal location to sterile location
Breaching the skin integrity - Skin loss (burns), Surgery, IV lines, Skin diseases, Injection drug users Tattooing/body piercing
Fecal-oral route - Foodborne infection
Fecal-perineal-urethral route - Urinary tract infection (women)
-Normal flora is displaced from its normal location
Poor dental hygiene/dental work - Dental extraction, Gingivitis, Brushing/Flossing
Common cause of harmless bacteraemia
Spleen is the main defence against blood borne pathogens
Second line of defence
The body makes use of Phagocytes and Chemicals which trigger the inflammatory pathway, which leads the production of factors that will contain and clear the infection
Microbes - Exogenous - don’t already have these microbes
Endogenous - already have these microbes on the surface of skin but get under skin due to lesions
Phagocytes-microbes interaction - recognition process and killing process of infectious microbes
Main phagocytes - Macrophages -
Pathogen recognition
Microbial structures - produce Pathogen associated molecular patterns (PAMPS) -
Phagocytes have a pathogen recognition receptors (PRRS) e.g. Toll like receptors that recognises these PAMPS and become activated
Opsonisation of microbes : Certain types of Coating proteins called opsonins bind to the microbial surfaces leading to enhanced attachment of phagocytes and clearance of microbes
Examples of Opsonins: Complement proteins - C3b and C4b Antibodies - IgG and IgM Acute phase proteins C-reactive protein (CRP), mannose-binding Leviton (MBL)
These are essential in clearing these encapsulated bacteria :
Neisseria meningitidis
Streptococcus pneumoniae
Haemophilus influenzae b
Therefore after coating of pathogen by Opsonins, this leads to engulfment of the pathogen by Phagocytes which leads to the Degradation of infectious microbes
Phagocyte IC killing mechanism
1) chemotaxis and adherence of microbe to phagocyte
2) Ingestion of microbe by phagocyte
3) Formation of a phagosome
4) Fusion of the phagosome with a lysosome to form a phagolysosome
5) Digestion of ingested microbe by enzymes
6) Formation of residual body containing indigestible material
7) Discharge of waster materials
The IC mech of breaking down ingested microbes -
Oxygen-dependent pathway (respiratory burst) Toxic O2 products for the pathogens: Hydrogen peroxide, Hydroxyl radical, Nitric oxide, Singlet oxygen, Hypohalite
Oxygen-independent pathways - Lysozyme,
The complement system
Complement pathways
20 serum proteins
Most important C1-C9 - C3a and C5a used for recruitment of phagocytes, C3b and C4b used in opsonisation of pathogens, C5 - C9 used to kill pathogens
2 activating pathways
Alternative pathway Initiated by cell surface microbial constituents (endotoxins on E. Coli)
MBL pathway Initiated when MBL binds to mannose containing residues of proteins found on many microbes (Salmonella spp. Candida albicans)
Antimicrobial actions of macrophage derived cytokines such a as TNFalpha, IL-1/6
Systemic actions -
Liver (opsonins)
CRP
MBL (-> complement activation)
Bone marrow
Neutrophil mobilization
Hypothalamus
Increased body temperature
Local inflammatory actions -
Blood vessels undergo vasodilation and increase their Vascular permeability
They also express adhesion molecules -> attraction of neutrophils
Summary of the innate immune response
1) Innate barrier breached entrance and colonisation of the pathogens
2)Complement, mast cells and macrophage activation (PRR),
phagocytosis (opsonins) ,
cytokines and chemokine production
3)Vascular changes (vasodilation/ Vascular permeability
Chemoattraction (neutrophils and monocytes)
4) Hypothalamus
fever
liver - acute phase response
5) Redness, heat, swelling and pain - local inflammation
Clinical problems start when phagocytosis is reduced
Decrease spleen function - due to
Asplenic patients
Hyposplenic patients
Decrease neutrophil number (1.8 109/l) - could be due to
Cancer chemotherapy
Certain drugs (phenytoin)
Leukaemia and lymphoma
Decrease neutrophil function - could be due to
Chronic granulomatous disease (No respiratory burst)
Chediak-Higashi syndrome (no phagolysosomes formation)
