Immuno 1: Response to immune infection Flashcards
What are the different aspects of immune protection?
Anatomical barriers - skin, oral mucosa, resp epithelium, intestine
Complement
Innate immunity (macrophages, granulocyte and NK cells)
Adaptive immunity (B, T cell)
NB - this decreases in speed but increases in specificity and memory as you go down these layers
What are the different components of the innate immune response and what is involved in these?
Cellular component:
- Polymorphic cells - neutrophils, eosinophils and basophils (From BM)
- Monocytes + macrophages (From BM)
- NK cells
- Dendritic cells
Soluble component:
- Complement
- Acute phase proteins
- Cytokines and chemokines
What do polymorphic cells in the innate immune response use to recognise immune complexes and attach to them?
The Fc component
Difference between macrophages and neutrophils?
Macrophages = resident cells stay within a tissue
Neutrophils = Mobile and will move to sites of acute inflammation
Describe the process of phagocytosis
Pathogen taken into phagosome
Phagosome fuses with lysosome ->phagolysosome
Here you can get oxidative / non-oxidative killing
Describe how oxidative killing occurs in phagocytosis?
Oxidative killing via reactive oxygen species produced by NADPH oxidase and myeloperoxidase
Describe how non-oxidative killing occurs in phagocytosis?
Non-oxidative killing – lysozymes and lactoferrin
What happens at the end of phagocytosis?
Phagocytosis depletes neutrophil glycogen reserves –> cell death –> enzyme release –> pus formation
Macrophages persist and present antigens to T cells - e.g. the IL-12-IGNγ pathway
What are NK cells?
These are cytotoxic lymphocytes that are part of the innate immune response
Have inhibitory receptors for self-HLA
Have activating receptors for heparan sulfate proteoglyclans (found basically everywhere in the body)
Hence this is a equilibirum that gets shifted in altered self-cells that dont display self-HLA hence get killed
What are the functions of NK cells?
Kill ‘altered self’ cells – malignant or virus infected
Secrete cytokines to regulate inflammation
What are complements?
There are a combination of 20+ proteins produced by the liver and are involved in the innate immune system
(can be low in people w/ liver failure)
What are the different complement pathways and what are they activated by? what happens after activation?
Classical pathway (C1, C2, C4) - Ag-Ab complexes (MAIN)
Mannose binding lectin / MBL pathway (C2, C4) - Bacterial cell wall
Alternative pathway (directly onto C3) - Microbiol cell surface carbs (MAIN)
Converge on C3 convertase which activates final common pathway (C5-9)
What do dendritic cells do?
- Present processed antigen to T cells in lymph nodes to prime the adaptive immune response
- Dendritic cells travel to LN via lymphatics
- Ag from infection reach LN via lymphatics
- Lymphocytes return to blood via thoracic duct and enter LN from blood
What does the adaptive immune response involve?
Cells component:
- B lymphocytes + antibody = Humoral immunity
- T lymphocytes (CD4, CD8) = Cellular immunity
Soluble components:
- Cytokines + Chemokines
What organs are involved in the adaptive immune response?
Primary lymphoid organs (Development + maturation) - Hematopoietic stem cells (B &T cells) - Thymus (T cell maturation) - BM (B cell maturation)
Secondary lymphoid organs (Where immune response occurs) - Spleen - Lymph nodes - Mucosal associated lymphoid tissue
Describe the process of lymphoid development
Arise from haematopoetic stem cells
T cells:
• Exported as immature T cells to the thymus where undergo selection
• Mature T lymphocytes enter the circulation and reside in secondary lymphoid organs
B cells:
• Exported as IgM B cells these can undergo isotype switching OR
• Become mature IgM plasma cells
Describe how T cell selection works? (1/2)
This depends on the T cell’s affinity for HLA
- Low affinity for HLA = not selected due to lack of reactivity (can’t protect v infection)
- Intermediate affinity for HLA = POSITIVE SELECTION (10% of original cells)
- High affinity for HLA = NEGATIVE SELECTION to avoid autoreactivity (ie AI conditions)
Describe how T cell selection works (2/2)
What applies to all T cells?
T cells with intermediate affinity for HLA I –> differentiate as CD8+ T cells
T cells with intermediate affinity for HLA II –> differentiate as CD4+ T cells
NB - all T cells are CD3+
How are the HLA classes named?
HLA I normally has 1 letter after it
HLA II normally has 2 letters after it (eg HLA-DR27)
What is the 1st stage in B cell selection
This is when they mature and develop in the BM:
- No recognition of self in BM = Survive
- Recognise of self in BM = negative selection to avoid autoreactivity
What are the two phases of the B cell response?
- T cell independent i.e. no T cell help – produce only IgM (Usually acute infection) -> IgM secreting plasma cell
- T cell dependent i.e. T cell help allows isotype switching to produce IgG and IgA (Germinal centre reaction)
Describe the T cell dependent aspect of the B cell response
- Dendritic cells prime CD4+ T cells
- CD4+ T cell help for B cell differentiation
Requires CD40L:CD40 - B cell proliferation
Somatic hypermutation
Isotype switching to IgG, A , E
What do CD4+ T cells do?
CD4+ T helper cells – cytokines encourage development along different lines
TGFβ stimulates development into Treg cells – CD25+ and Foxp3+
What do CD8+ T cells do?
CD8+ cytotoxic T cells
- Directly cytotoxic through perforin, granzymes and expression of Fas ligands
- Indirectly cytotoxic through cytokine secretion
What can happen when B cells get engaged by antigens?
Develop as IgM plasma cells
Undergo germinal centre reaction (somatic hypermutation and class switching) to produce IgG, IgE or IgA
What are IgG, IgA and IgM as types of molecules?
IgG is a monomer, IgA is a dimer and IgM is a pentamer
Which cells mastermind the transition from innate to adaptive immunity?
Macrophage Complement T helper cells Dendritic cells Memory B cells
Dendritic cells
