Host Defence Mechanisms ✅ Flashcards
What type of barriers are there that prevent infection before it comes into contact with the immune system?
- Mechanical
- Biochemical
- Microbiological
Give a mechanical barrier to infection
Skin
Give a biochemical barrier to infection
Bile acid
Give a microbiological barrier to infection
Host flora
What is the main anatomical structure of the immune system?
The lymphoreticular system
What does the lymphoreticular system include?
- Bone marrow
- Lymph nodes
- Tonsils
- Thymus
- Peyer’s patches
- Appendix
- Spleen
What is the function of the bone marrow in the immune system?
Produces all cells of the immune system
What is the function of the thymus in the immune system?
This is where T cells mature
What do the cells forming the immune system differentiate from?
Stem cells
Which cells differentiated from stem cells form part of the immune system?
- Monocytes
- Neutrophils
- Thymus
- Bone marrow
What do monocytes develop into?
Tissue macrophages
What functions do tissue macrophages carry out?
- Phagocytosis
- Chemotaxis
What is attracted by chemotaxis caused by tissue macrophages?
Neutrophils
What is the function of neutrophils?
Phagocytosis
What can the immune system be divided into?
- Innate
- Adaptive
What does the innate immune system include?
- Antigen non-specific immune cells
- Receptors
- Soluble effector molecules
Give 2 soluble effector molecules in the innate immune systerm
- Cytokines
- Complement
What is the purpose of the innate immune system?
It provides a rapid response to broad range of pathogens
What is the limitation of the innate immune system?
It may not completely eradicate pathogens
What kind of pathogens is it particularly difficult for the innate immune system to eradicate?
Intracellular pathogens
What recognises invading pathogens in the innate immune system?
- Macrophages
- Dendritic cells
How do macrophages and dendritic cells recognise invading pathogens in the innate immune system?
Using receptors called pattern recognition receptors (PRRs)
What do pattern recognition receptors detect?
Classes of molecules common to groups of pathogens called pathogen-associated molecular patterns (PAMPs)
What pattern associated molecular patterns (PAMPs) do gram -ve bacteria have?
Lipopolysaccharide
What pattern recognition receptor detects lipopolysaccharide?
TLR4
TLR = toll-like receptor
What PAMPs do gram +ve bacteria have?
Peptidoglycan cell wall
What PRR detects the peptidoglycan cell wall?
TLR2
What PAMPs do viruses have?
Double-stranded RNA
What PRR recognises double stranded RNA?
TLR3
What PAMP do intracellular pathogens have?
Pathogen RNA
What PRRs recognise pathogen RNA?
NLRP3 (nucleotide-binding oligomerisation domain (NOD)-like receptor pyrin domain containing 3)
What PAMPs do fungi have?
Beta-glucan
What PRR recognises beta-glucan?
Dectin-1
What happens once macrophages and dendritic cells have detected PAMPs?
They become activated and take up the pathogen by phagocytosis
What do activated macrophages initiate?
An acute inflammatory response
What is the purpose of the initiation of an acute inflammatory response by activated macrophages?
To attract neutrophils and specific antigen-presenting cells
What does the inflammatory cascade initiated by activated macrophages consist of?
- Pro-inflammatory cytokines
- Chemokines
- Lipids
- Complement
Give 3 pro-inflammatory cytokines involved in the innate immune response?
- IL-1ß
- IL-6
- TNF-⍺
Give a chemokine involved in the innate immune response
IL-8
Give 2 lipids involved in the innate immune response
- Prostaglandins
- Leukotrienes
What is the effect of complement in the innate immune response?
- Can lyse pathogens directly
- Can opsonise pathogens
What is the purpose of opsonisation of pathogens by complement in the innate immune response?
Assist phagocytosis by macrophages and neutrophils
What does the adaptive immune system consist of?
- T cells
- B cells
What do B and T cells provide?
Cell-mediated and antibody-mediated immunity
What produces T cells?
The thymus
What can T cells be divided into?
- T-helper cells
- T-cytotoxic cells
What do antigen-presenting cells do?
Carry antigens to regional lymph nodes
What do antigen-presenting cells do at regional lymph nodes?
Present antigen on major histocompatibility complex (MHC) class II receptors to T-cell receptors
What does the presentation of antigen on MHC class II receptors to T-cell receptors lead to?
Activation and proliferation of T-helper cells
What do activated T-helper cells do?
Secrete cytokines that activate T-cytotoxic cells and activate B cells
What do activated T-cytotoxic cells do?
Recognise and kill altered host cells, such as virus infected cells
What produces B cells?
The bone marrow
What do B cells do when they encounter antigen?
Clonally expand and terminally differentiatiate into plasma cells
What do plasma cells do?
Produce antibody
What do activated T-helper cells develop into?
- T-helper type 1 cells
- T-helper type 2 cells
- Th17
- T-regulatory cells
What do T-helper type 1 cells do?
- Produce pro-inflammatory cytokines
- Activate T-cytotoxic cells, macrophages, and B cells
What pro-inflammatory cytokines are produced by T-helper type 1 cells?
- IL-2
- IFN-γ
What do B cells activated by T-helper type 1 cells produce?
Oponising antibody (IgG)
What do T-helper type 2 cells do?
- Produce anti-inflammatory cytokines
- Favour humeral response
What anti-inflammatory cytokines are produced by T-helper type 2 cells?
- IL-4
- IL-15
What molecules are involved in the humeral response favoured by T-helper type 2 cells?
- IgM
- IgA
- IgE
What do Th17 cells produce?
- IL-17
- IL-22
What is the role of Th17 cells?
Important role in tissue inflammation and mucosal/epithelial defences against fungal and bacterial infections
What is the role of T-regulatory (Tregs) cells?
- Shutting down immune responses in antigen-specific manner
- Preventing autoimmunity
How do Tregs cells prevent autoimmunity?
Induce apoptosis of T-effector cells
How is the ability of the adaptive immune response to distinguish between antigens achieved?
By the enormous diversity of T and B cell receptors
How is the diversity of T and B cell receptors generated?
By random association of genes for the constant parts of the receptor chains with one of a large number of variable, diversity and joining (VDJ) region genes
How many unique antigen receptors are produced by VDJ genes?
10^14 - 10^18
What happens to the antigen-specific affinity of T-cell receptors throughout the immune response?
It stays high
What happens to the antigen-specific affinity of B-cell receptors and antibodies over time?
They undergo affinity maturation
What is affinity maturation?
The process whereby the immune system generates antibodies of higher affinities during a response to antigen
Which type of antibody is produced early in the immune response?
IgM
Why is IgM produced early in the immune response?
It has a high binding capacity
What is the limitation of IgM?
It has a low antigen affinity and avidity
What is produced later in the immune response?
IgG, IgE, or IgA
Why does the immune response later switch to IgE, IgG, or IgM?
They have a higher affinity
What do T-helper cells secrete?
Cytokines
What is the effect of cytokines secreted by T-helper cells?
Coordinates local and systemic immune response
What local immune responses do cytokines coordinate?
Recruitment and activation of macrophages
What systemic immune response do cytokines cause?
Fever
What immune cells are active against intracellular organisms?
- Cytotoxic T cells
- NK cells
How to cytotoxic T cells and NK cells kill intracellular organisms?
By inducing apoptosis
How do cytotoxic T cells and NK cells induce apoptosis?
Through the performin-granzyme system
What is the role of T-helper cells?
Amplifying and shutting down the immune response
What adaptive immune response predominates in the early phase of the immune response?
Pro-inflammatory (Th1)
What causes innate and adaptive immune responses to shut down?
An increase in the specificity of the humeral and cytotoxic response, shifting to a Th2-type response involving Tregs cells
What happens to T and B cells after the immune response is complete?
A proportion form long-lived memory cells
What is the purpose of memory cells?
Capable of mounting a faster and more efficient secondary response
When do cells of the adaptive and innate immune system develop?
Early in fetal life
Describe the immune state of a fetus?
Overall immunosuppressed state with Th2 bias and predominance of Tregs cells
Why is the fetus in an overall immunosuppressed state?
Due to the high tolerance required for maternal antigens in utero
To what extent are foetuses capable of mounting an immune response?
They can recognise foreign antigens and mount adaptive responses, but may be ineffective in clearing infections
What can result from ineffective clearance of infection by the foetal immune system?
Congenital infection
What protects the foetus from infection?
The placental barrier
When does materno-fetal IgG transfer begin?
Around 17 weeks gestation
When do fetal IgG levels reach half of the maternal level?
30 weeks
When do fetal IgG levels reach full maternal levels?
Close to term
What is the implication of fetal IgG levels not reaching maternal levels until near term?
Infants born prematurely are highly susceptible to infection
What happens to transferred maternal IgG after birth?
It declines and virtually disappears by 6 months of age
What happens to overall IgG levels after birth?
The infant’s own IgG increases, but there is a low point around 3-6 months
What is the result of an infant being immunologically naive?
Symptomatic infections are more frequent and severe in the early years than at older ages
When is there a further period of immunosuppression in a child?
In early adolescence
Why is there a temporary period of immunosuppression in early adolesnce ?
Associated with the onset of sex hormone secretion
