Immune response to infection Flashcards
What are the body’s constitutive barriers to infection?
External epithelium
Mucous membranes
How does the skin stop entry of pathogens?
- tightly packed keratinised cells > physically blocks entry
- low pH, low O2 tension
- sebaceous glands (produce oils, lysozyme, ammonia)
How does mucous stop entry of pathogens?
- acts as physical barrier
- contains secretory IgA, which binds to pathogens and prevents their entry
- contains lysozyme
- contains lactoferrin (starves invading bacteria of iron)
How do commensal bacteria stop entry of pathogens?
Compete with bacteria for scarce resources
What are the components of the innate immune system?
Cells
- PMN cells e.g. neutrophils, basophils, eosinophils;
- monocytes n macrophages
- NK cells
- dendritic cells
Soluble components
- cytokines, chemokines
- complement
- acute phase protein
What is the innate response like in different individuals?
It is the SAME in ALL individuals
Describe the production and maturation of PMN cells
Produced in BM
Migrate to site of injury
Describe function of PMN cells
Express receptor of cytokines > detect inflamm
Express PRP > detect pathogen
Express Fc receptor for Ig > detect immune complex
Capable of phagocytosis and oxidative/non-ox killing
How do macrophages differ from PMN in function?
Same
Except they can also process antigens and present them to T cells
What re the 5 steps of phagocytic action?
- Phagocyte recruitment
- Recognition of microorganisms
- Endocytosis with opsonisation
- Formation of phagolysosome
- Oxidative killing
What happens with phagocyte recruitment?
Cellular damage triggers production of cytokines and chemokine
- cytokines enhance permeability of vasc endothelium
- chemokine attract phagocytes
What happens with recognition of microorganisms?
PRRs like toll like receptor recognise motifs such as PAMPs > they bind
What happens in opsonisation?
Opsonins act as a bridge between pathogen and phagocyte’s receptors
How is a phagolysosome formed?
Pathogen is uptakes into phagosome Phagosome fuses with a lysosome to form a phagolysosome Killing of pathogen can occur via: - oxidative mechanism - non-oxidative mechanism
How does oxidative killing work?
NADPH oxidase converts oxygen into reactive oxygen species, into hydrochlorous acid, which does the killing
How does non-oxidative killing work?
Release of bactericidal enzymes e.g. lactoferrin, lysozyme
What happens after killing of pathogen?
Death of the phagocyte > residual enzymes released > liquefaction of adjacent tissue > accumulation of dead/dying neutrophils > pus formation
What are the two receptors on NK cells that a normal cell binds to to survive?
The activating receptor and the inhibitory receptor
What is the receptor on NK cell that a target cell binds to to die?
The ACTIVATING receptor only
What is the process of maturation for a monocyte?
Monocyte produced in bone marrow
To target tissue > becomes macrophage > phagocytosis
What are the components of an acquired immune response=?
B lymphocytes (antibodies) T lymphocytes (CD4, CD8+) Cytokines, chemokines
What is a primary lymphoid organ?
An organ involved in lymphocyte development
What are the 2 primary lymphoid organs?
Bone marrow (both B and T cells produced, only B cells mature here) Thymus (T cell maturation)
What are secondary lymphoid organs?
Sites of interaction between naive lymphocytes and microorganisms
- Spleen
- Lymph nodes
- MALT
What are the 4 key features of the adaptive immune response?
- Wide repertoire of antigen receptors
- High specificity
- Clonal expansion
- Immunological memory
What happens to T cells in the thymus?
They undergo +/-ve selection before being exported to the periphery
CD4+ recognises peptides from HLA II
CD8+ recognises peptides from HLA I
What affinity must T cells in the thymus display to survive?
INTERMEDIATE affinity for HLA
low affinity > they die (FAS triggers apoptosis)
high affinity > they die (auto reactivity)
What are CD4+ cells also known as?
Helper T cells
Because they HELP development of B cells and of CD8+ T cells
What do Th1 Cells produce?
INFgamma, TNF alpha and IL2
What are T regulatory cells?
Subset of lymphocytes that express Foxp3 and CD25
What occurs in B cell maturation?
They exist in the periphery as IgM B cells
They undergo a germinal centre reaction to differentiate into plasma cells producing IgG, IgE, IgM
What is the germinal centre reaction dependent on?
CD4+ T helper cells
CD40L:CD40
What do B cells undergo after the germinal centre reaction?
Somatic hypermutation Isotope switching (from IgM to IgG/E/A)
What are immunoglobulins made up of?
2 heavy chains, 2 light chains
What part of the immunoglobulin determines the antibody class?
The heavy chain
What part of the antibody recognises the antigen?
Fab (antigen binding region), made up of both heavy and light chains
What part of the antibody determines the effector function?
The constant region of the heavy chain
What are the TWO KEY functions of antibodies
- Identification of pathogens (Fab mediated)
- Interaction with other components of the immune response to remove pathogens (Fc mediated)
What is the benefit of B cell memory?
It decreases the lag time between antigen exposure and antibody production to 2-3 days max
What is the function of IgA?
Divalent antibody present within mucous
Helps provide a constitutive barrier to infection
What are IgM secreting plasma cells?
Cells generated rapidly following antigen recognition
Not dependent on CD4 T cell help
What are IgG secreting plasma cells dependent on ?
dependent on the presence of CD4 T cell help for generation
Where is the complement produced?
In the liver
What is the function of the complement?
Produce a rapid highly amplified response
By activating other proteins in a biological cascade
What are the three pathways for complement activation?
Classical
Mannose Binding Lectin
Alternate
What is the classical pathway activated by?
how does it work?
By immune complexes
Formation of antibody-antigen immune complex > conformation change in antibody shape»_space; exposes binding side for C1
C1 binding to antibody results in activation of cascade
What is the mannose binding lectin (MBL) pathway activated by?
DIRECT binding of MBL to microbial cell surface carbohydrates
This stimulates the classical pathway involving C4 and C2 (not C1)
How is the alternative pathway activated by?
By binding C3 to bacterial cell wall components
What factors does the alternate pathway involve?
B, I, P
How does the complement pathways work
C3 triggers the formation of a membrane attack complex via C5-9
This complex makes holes in the membranes
What pathways cause cleavage of C3?
classical
MBL
alternate
What is C9?
Part of the final common pathway resulting in generation of the membrane attack complex
What are chemokine?
Subset of cytokines
They are CHEMOTACTIC - are CHEMOATTRACTANTS
list complement functions
increase vascular permeability and cell trafficking to sites of inflammation
Opsonisation of immune complexes to keep them soluble
Opsonisation of pathogens to promote phagocytosis
Activation of phagocytes
Promote mast cell/basophil degran
Punches holes in bacterial membranes
