Immuno 1: Response to immune infection

Question 1

What are the different aspects of immune protection?

Answer 1

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

Question 2

What are the different components of the innate immune response and what is involved in these?

Answer 2

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

Question 3

What do polymorphic cells in the innate immune response use to recognise immune complexes and attach to them?

Answer 3

The Fc component

Question 4

Difference between macrophages and neutrophils?

Answer 4

Macrophages = resident cells stay within a tissue

Neutrophils = Mobile and will move to sites of acute inflammation

Question 5

Describe the process of phagocytosis

Answer 5

Pathogen taken into phagosome

Phagosome fuses with lysosome ->phagolysosome

Here you can get oxidative / non-oxidative killing

Question 6

Describe how oxidative killing occurs in phagocytosis?

Answer 6

Oxidative killing via reactive oxygen species produced by NADPH oxidase and myeloperoxidase

Question 7

Describe how non-oxidative killing occurs in phagocytosis?

Answer 7

Non-oxidative killing – lysozymes and lactoferrin

Question 8

What happens at the end of phagocytosis?

Answer 8

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

Question 9

What are NK cells?

Answer 9

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

Question 10

What are the functions of NK cells?

Answer 10

Kill ‘altered self’ cells – malignant or virus infected

Secrete cytokines to regulate inflammation

Question 11

What are complements?

Answer 11

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)

Question 12

What are the different complement pathways and what are they activated by? what happens after activation?

Answer 12

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)

Question 13

What do dendritic cells do?

Answer 13

• 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

Question 14

What does the adaptive immune response involve?

Answer 14

Cells component:

• B lymphocytes + antibody = Humoral immunity
• T lymphocytes (CD4, CD8) = Cellular immunity

Soluble components:
- Cytokines + Chemokines

Question 15

What organs are involved in the adaptive immune response?

Answer 15

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

Question 16

Describe the process of lymphoid development

Answer 16

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

Question 17

Describe how T cell selection works? (1/2)

Answer 17

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)

Question 18

Describe how T cell selection works (2/2)

What applies to all T cells?

Answer 18

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+

Question 19

How are the HLA classes named?

Answer 19

HLA I normally has 1 letter after it

HLA II normally has 2 letters after it (eg HLA-DR27)

Question 20

What is the 1st stage in B cell selection

Answer 20

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

Question 21

What are the two phases of the B cell response?

Answer 21

1. T cell independent i.e. no T cell help – produce only IgM (Usually acute infection) -> IgM secreting plasma cell
2. T cell dependent i.e. T cell help allows isotype switching to produce IgG and IgA (Germinal centre reaction)

Question 22

Describe the T cell dependent aspect of the B cell response

Answer 22

1. Dendritic cells prime CD4+ T cells
2. CD4+ T cell help for B cell differentiation
   Requires CD40L:CD40
3. B cell proliferation
   Somatic hypermutation
   Isotype switching to IgG, A , E

Question 23

What do CD4+ T cells do?

Answer 23

CD4+ T helper cells – cytokines encourage development along different lines

TGFβ stimulates development into Treg cells – CD25+ and Foxp3+

Question 24

What do CD8+ T cells do?

Answer 24

CD8+ cytotoxic T cells

• Directly cytotoxic through perforin, granzymes and expression of Fas ligands
• Indirectly cytotoxic through cytokine secretion

Question 25

What can happen when B cells get engaged by antigens?

Answer 25

Develop as IgM plasma cells​

Undergo germinal centre reaction (somatic hypermutation and class switching) to produce IgG, IgE or IgA​

Question 26

What are IgG, IgA and IgM as types of molecules?

Answer 26

IgG is a monomer, IgA is a dimer and IgM is a pentamer

Question 27

Which cells mastermind the transition from innate to adaptive immunity?

Macrophage
Complement
T helper cells
Dendritic cells
Memory B cells

Answer 27

Dendritic cells