S2 L2 - Innate Immunity Flashcards
Which groups of people have an increased susceptibility to infection?
- *Key definitions:**
- Immune system
- Infectious disease
Roles of the immune system
Which groups of people have an increased susceptibility to infection?
Elderly people, pregnant, children under 5, immunosuppresed people, patients with damaged or prosthetic valves (especially mouth flora infections)
- *- Immune system:** Cells and organs that contribute to immune defences against infectious and non-infectious conditions
- *- Infectious disease:** When a pathogen succeeds in evading and/or overwhelming the host’s immune defences
- *Roles of the immune system:**
- Pathogen recognition (cell surface and soluble receptors)
- Containing/eliminating the infection (killing and clearance)
- Managing the host response (regulating itself - to minimise damage to host)
- Remembering the pathogen (preventing the disease from recurring)
- *Immune response**
- Split into 2 - I and A
- Name and explain the two ‘types’ of immunity
Innate immunity:
First line defences - 4
Main aim of innate immunity
Innate immunity:
• Fast (within seconds)
• Lack of specificity
• Lack of memory
• No change in intensity
Adaptive immunity:
• Slow (days)
• Specificity
• Immunologic memory
• Changes in intensity
Innate immunity: pic
First line defences -
- Physical
- Chemical
- Physiological
- Biological
Aim:
Prevent entry and limit growth of pathogens
- *Innate barriers:**
- Physical barriers gives examples
- Physiological barriers give examples
- *Physical barriers:**
- Skin
- Mucous membranes (mouth, respiratory tract, GI tract, urinary tract)
- Bronchial cilia
- *Physiological barriers:**
- Diarrhoea
- Vomiting
- Coughing
- Sneezing
Innate barriers:
Chemical barriers
Biological barriers (and benefits of these)
- *Chemical barriers:**
- Low pH e.g. skin is 5.5, stomach is 1-3, vagina is 4.4
- Antimicrobial molecules e.g. IgA (tears, saliva, mucous membrane), lysozyme, mucus (mucus membranes)
Biological barriers:
• Normal flora: Non pathogenic microbes, in Strategic locations
o Nasopharynx
o Mouth/Throat
o Skin
o GI tract
o Vagina (lactobacillus spp)
• Absent in internal organs/tissues
Benefits:
• Compete with pathogens for attachment sites and resources
• Produce antimicrobial chemicals
• Synthesize vitamins (K, B12, other B vitamins)
• Immune maturation
- *Examples of normal flora that inhabit…**
- Skin
- Mouth and nasophranyx
- GI tract
Clinical problems start when…
(list 3/4)
Examples of normal flora that inhabit…
pic
- *Clinical problems start when…**
- Normal flora is displaced from its normal location to sterile location
- Normal flora is displaced from its normal location to another location
- Normal flora overgrows and becomes pathogenic when host becomes immunocompromised
- Normal flora in mucosal surfaces is depleted by antibiotics therapy
- *More detail:**
- Normal flora is displaced from its normal location to sterile location - how could this happen?
- Normal flora is displaced from its normal location
Normal flora is displaced from its normal location to sterile location - how could this happen?
• Breaching the skin integrity:
o Skin loss (burns) o Surgery o IV lines o Skin diseases o Injection drug users o 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:
o Dental extraction o Gingivitis o Brushing/Flossing
- *More detail:**
- Normal flora overgrows and becomes pathogenic when host become immuno-compromised
- Normal flora in mucosal surfaces is depleted by antibiotic therapy
Normal flora overgrows and becomes pathogenic when host become immuno-compromised:
o Diabetes (session 3, case 2) o AIDS o Malignant diseases o Chemotherapy (mucositis)
Normal flora in mucosal surfaces is depleted by antibiotic therapy:
o Intestine -> severe colitis (Clostridium difficile)
o Vagina -> thrush (Candida albicans)
2nd part:
- *Adaptive immunity (second line defence)**
- Aim
- Briefly state steps in this type of immunity
- *Recap on main phagocytes:**
- Macrophages
- Monocytes
- Neutrophils
- Basophils
- Eosinophils
- Natural killer cells
- Dendritic cells
Aim:
Factors that will contain and clear the infection
Briefly state the steps in this type of immunity:
1. Recognition (PAMPs, PRRs and opsonisation)
2. Phagocytosis
3. Complement system
4. Cytokines
Recap on main phagocytes:
pic
- *1. Recognition**
- Two main bits involved here
- Give examples
PAMPs and PRRs:
Microbial structures (PAMPs - Pathogen-associated molecular patterns) - these are carbohydrates, lipids, proteins, nucleic acids
Phagocytes (PRRs - Pathogen Recognition Receptors) - Toll Like Receptors
Example of PAMPs and cognate PRRs:
Gram negative bacteria
PAMPs - Lipopolysaccharides (LPS)
PRRs - TLR4
Gram positive bacteria
PAMPs - Peptidoglycan
PRRs - TLR2
Opsonisation (more on next flashcard)
Opsonisation (continued from last flashcard)
- Aim
- Examples of opsonins
- What infectious diseases are opsonins essential in treating?
Aim:
Opsonisation of microbes - coating proteins called opsonins that bind to the microbial surfaces leading to enhanched attachment of phagocytes and clearance of microbes THEY INCREASE THE RECOGNITION ABILITY OF NEUTROPHILS AND HELP ENHANCE THE ATTACHMENT TO THE MICROBES
Examples of opsonins:
pic
What infectious diseases are opsonins essential in treating? NHS
Neisseria meningitidis
Haemophilus Influenzae
Streptococcus pneumoniae
- *2. Phagocytosis**
- 2 methods of ‘killing’
Oxygen-dependent pathway (respiratory burst)
covered in MEH, uses the enzyme NADPH oxidase
Oxygen-independent pathway
uses lysozymes
pic
- *3. Complement system**
- What is this system
- What’s it really important for…
- Examples of the complement
What is this system:
Works alongside the immune system, gives it a boost!
What’s it really important for…
SOLUBLE RECEPTORS
It is also extremely important if the pathogen has not been recognised by cellular receptors
Examples of the complement
pic
- *4. Cytokines/chemokines**
- What are these/what do they ‘bridge’
- Example of 3, state their specific actions
- Combined actions of cytokines
What are these/what do they ‘bridge’
They provide a key link between the innate immune response and the adaptive immune response.
- TNF-α: the main cytokine used for triggering the inflammatory response and leads to increased permeability of the blood vessel.
- IL-1: Responsible for T and B cell activation.
- IL-6: Stimulates B cell activation, increases production of acute phase proteins (opsonins), also plays a role in stimulating haematopoeisis
Produced by - macrophages
Combined actions of cytokines:
- Increase in CRP (C-reactive protein) and MBL (Mannose binding lectin) produced by the liver - these help with the activation of the complement pathways.
- Neutrophil mobilisation in/from bone marrow.
- Vasodilation, increase in vascular permeability and attracting neutrophils to a particular area.
- Cause the hypothalamus to increase body temperature, making the body temperature unfavourable for bacterial/ viral growth.
Problems arise when…
Decrease spleen function:
o Asplenic patients
o Hyposplenic patients
Decrease neutrophil number
o Cancer chemotherapy
o Certain drugs (phenytoin)
o Leukaemia and lymphoma
- *Decrease neutrophil function**
e. g. o Chronic granulomatous disease (No respiratory burst)…