Immunology 1 - The immune response to infection/ primary immune deficiencies part 1

Question 1

How is pus formed?

What about abscess formation?

Answer 1

Following phagocytosis, neutrophils die

When they die, they release residual enzymes which causes the liquefication of closely adjacent material

This forms pus

*8abscess formation: if you get extensive localised formation of pus**

Question 2

Recall 2 functions of CD4+ T lymphocytes

Answer 2

Provide help for development of:

1. Full B cell response
2. Some CD8+ T cell responses

Question 3

Which type of plasma cell is dependent on CD4+ T cells for activation?

Answer 3

IgG

Question 4

Which components of complement comprise the classical pathway?

Answer 4

C1 C2 C4

Question 5

Which components of complement comprise the mannose binding lectin pathway?

Answer 5

c4 and c2

Question 6

What is the role of the membrane attack complex formed at the end of the complement pathway?

Answer 6

Makes holes in membranes

Question 7

What is the first class of immunoglobulin to be made in the adaptive immune response?

Answer 7

IgM

Question 8

What is the difference between oxidative and non-oxidative killing?

Answer 8

Oxidative: uses NADPH and hydrochlorous acid
Non-oxidative: uses lysozyme and lactoferrin

Question 9

Which form of HLA is recognised by CD4 cells?

Answer 9

HLA-2

Question 10

Which form of HLA is recognised by CD8 cells?

Answer 10

HLA-1

Question 11

Which cytokines induce development of CD4 T cells into Th1 cells?

Answer 11

IL12 and IFN gamma

Question 12

What is the function of Th1 cells?

Answer 12

‘Help’ CD8 T cell and macropage responses

Question 13

Which cytokines induce development of CD4 T cells into Th17 cells?

Answer 13

IL6 and TGF beta

Question 14

What is the function of Th17 cells?

Answer 14

‘Help’ neutrophil recruitment and enhance generation of autoantibodies

Question 15

Which cytokine induces development of CD4 T cells into Treg cells?

Answer 15

TGF beta

Question 16

Which cytokine induces development of CD4 T cells into follicular T helper cells?

Answer 16

IL6

Question 17

Which type of T cell produces CD25 and FOXP3?

Answer 17

T reg cells

Question 18

By what mechanism do CD8 cells effect their cytotoxicity?

Answer 18

Injection of perforin, which enables granzyme entry
OR
Fas ligand expression

Question 19

Which cytokines are secreted by CD8 T cells?

Answer 19

IFN gamma and TNF alpha

Question 20

How do CD4 cells activate B cells?

Answer 20

Express CD40 ligand, which interacts with CD40 on immature B cell surface, causing the B cell to differentiate

**the ligand is what is needed to activate the recetor; T cell is what is needed to activate the B cell; ligand is on the T cell and the receptor is on the B cell**

Question 21

Recall the 2 processes that B cells undergo to become mature

Answer 21

1. Class switching
2. Somatic hypermutation

Question 22

Which part of an immunoglobulin determines its class?

Answer 22

Heavy chain

Question 23

Which class of immunoglobin forms a pentamer?

Answer 23

IgM

Question 24

Which class of immunoglobulin forms a dimer?

Answer 24

IgA

Question 25

Which portion of an immunoglobulin mediates pathogen identification?

Answer 25

Fab portion

Question 26

Which portion of an immunoglobulin mediates activation of complement/ NK cells?

Answer 26

Fc portion

Question 27

Where is complement produced?

Answer 27

Liver

Question 28

Neutrophils and macrophages: a) site of production b) mechanisms of action COMMON to both

Answer 28

a) produced in the bone marrow (macrophages - called macrophages once in tissue) b) mechanism of action - **receptors for:** pathogens themselves (via pattern recognition receptors), cytokines/chemokines (detect inflammation), immune complexes (via Fc receptor) - **phagocytic killing:** oxidative and non-oxidative

Question 29

How do neutrophils kill pathogens?

Answer 29

Oxidative and non-oxidatvie killing Release: - preformed myeloperoxidase - neurtophil elastase - defensins

Question 30

Difference between monocytes and macrophages

Answer 30

Monocytes- produced in bone marrow When they migrate to tissues they are called macrophages

Question 31

What is the main difference in function between neutrophils and macrophages?

Answer 31

Macrophages can present antigen on their surface following phagocytosis, but neutrophils cannot

Question 32

Which cell surface marker is associated with macrophages?

Answer 32

CD14 Recognises LPS on bacterial cell walls

Question 33

Give two examples of pattern recognition receptor

Answer 33

Toll like receptor Mannose receptor

Question 34

Mode of action of NK cells

Answer 34

* inhibitory receptors: recognise self HLA/MHC I * activatory receptors: recognise heparan sulfate proteoglycans * Loss of inhibitory signals/increase in activatory signals--\>activates NK cells * NK cells kill altered self cells - ie virus infected or malignant * They also secrete cytokines - regulates inflammation and promotes dendirtic cell activity NB: NK cells are lymphocytes

Question 35

What type of cell is a dendritic cell? Describe the changes that occurs in dendritic cells following phagocytosis

Answer 35

Dendritic cells mediate the transition between innate and adaptive immunity. After phagocytosis: 1. Upregulate expression of HLA-1 2. Express costimulatory molecules 3. Migrate via lymphatics to lymph nodes (mediated by CCR7) 4. Process non-self antigen and present it to T cells in lymph nodes to prime the adaptive immune response

Question 38

What are the two types of dendritic cells?

Answer 38

Immature: detecting pathogens and phagocytosis Mature: processing pathogens and presenting to T cells

Question 39

How do antigens and lymphocytes reach the lymph nodes from respecive sites?

Answer 39

Antigens: reach lymph nodes via migration through lymphatics from the infected site Lymphocytes: reach the lymph nodes via the blood After this, lymphocytes and lymph return to the blood via the thoracic duct

Question 40

What are the soluble components of the innate immune system?

Answer 40

1. complement 2. acute phase proteins 3. ferritin

Question 41

What are acute phase proteins?

Answer 41

Proteins secreted by the liver in response to infection Examples: - **IL1/IL6** - pyrogenic - **CRP** - binds to surface of infected cells--\> activates the complement cascade via c1q - **ferritin**

Question 42

What is opsonisation?

Answer 42

Modification of a pathogen to attract it to a NK or phagocytic cell May be mediated by antibodies, complement components or acute phase proteins Enables phagocytosis

Question 43

Summary: which cells of the immune system are phagocytic?

Answer 43

monocytes and macrophages granulocytes dendritic cells i.e. NK cells are not phagocytic !!

Question 44

Describe the process of T cell development: overview

Answer 44

1. T cells start as stem cells in bone marrow 2. Lymphoid progenesis 3. Pre-T cells go out into circulation 4. T cells mature in thymus 5. T cells proliferate 6. T cells undergo positive and negative selection within thymus 7. Mature T cells exported to periphery, reside in secondary lymphoid organs

Question 45

Describe the process of maturation of T cells once in Thymus

Answer 45

* TCR with intermediate affinity for HLA moelcules are selected, whilst those with too low or too high affinity are deleted * These intermediate affinity T cells undergo further differentiation based on whether they have affinity for HLA class 2 or HLA class 1 * Those that bind to HLA class II differentiate into CD4 positvie T cells * Those that bind to HLA class I differentiate into CD8 positive T ccells

Question 46

CD8+ vs CD4+ T cells

Answer 46

* **CD8+ t cells:** detect INTRACELLUAR peptides presented by MHC class I (on APC) * particularly important for viral infections/malignancy * **CD4+ t cells:** detect EXTRACELLULAR peptides presented by MHC class II (on APC) * variety of functions including activation of B cells and development of other T cells

Question 47

Examples of HLA class I and HLA class II molecules

Answer 47

**HLA class 1:** HLA A, HLA B, HLA C **HLA Class II:** HLA-DP, HLA-DQ, HLA-DR \*\*these are expressed on the APC \*\* they present processed peptide to T cells

Question 48

Summary of different CD4+ T cell subsets

Answer 48

Question 49

Function of TH17 cells

Answer 49

* Fungal and bacterial infections * Helps neutrophil recruitment * Enhance generation of autoantibodies

Question 50

Function of Treg cells

Answer 50

* Secrete IL-10 * → inhibit the immune response * T regs express CTLA-4 on cell surface * → directly inhibit T cell activation

Question 51

Function of Follicular helper T cells

Answer 51

* Promotes germinal centre reactions * stimulates differentiation of B cells → IgG (memory B cells) and IgA secreting plasma cells

Question 52

Explain the process of B cell maturation

Answer 52

_Early IgM response_ * they are produced in the bone marrow * they leave the bone marrow as PRO B CELLS or PRE B CELLS * once they are in the peirpheries they become IgM B cells * so when they recognise antigen they are in the IgM state * once they recognise antigen, they differentiate into IgM secreting plasma cells _Germinal centre reaction: Somatic hypermutation and istotype switching_ * IgM secreting plasma cells migrate from the peripheries to the lymph nodes * Here they encounter CD4+ helper T cells that have previously been primed (in the peripheries) by dendirtic cells (by detection of the SAME antigen) * This interaction requires CD40L (T cell) - CD40 (B cell) interaction * IgM producing B cells undergo SOMATIC HYPERMUTATION (the receptor mutates to become high affinity) and class switching (IgM switches to IgG, IgE or IgA) * Now you have HIGH AFFINITY, IgG/IgA/IgG secreting **plasma cells** and **memory cells** leaving the lymph nodes to enter the circulation

Question 53

Structure of antibodies

Answer 53

* two heavy chains * two light chains * FaB portion: light chain + variable region of heavy chain * Fc portion: cosntant region of heavy chain Fab: recognises antigen Fc: effector function; interacts with other components of immune system (complement, phagocytes, NK cells)

Question 54

Function of IgA

Answer 54

* protection of mucosal surfaces via salivary, respiratory, gastrointestinal and lacrimal secretions * blocks pathogenic ligands from binding to epithelial cell surface receptors * IgA is also present in breast milk * providing passive immunity in neonates

Question 55

Which antibody is present in breast milk?

Answer 55

IgA \*think it's SECRETORY

Question 56

FUnction of IgD

Answer 56

* found on the cell surface of immature B cells * IgD provide role in lymphocyte activation

Question 57

Function of IgG

Answer 57

* the most abundant/ common antibody * and occurs in monomer form in the circulation * Subclasses of IgG perform different functions, * IgG2- fighting encapsulated bacteria * IgG also has a role in activating complement proteins \*\*crosses the placenta

Question 58

Function of IgM

Answer 58

* occurs as a pentamer * and has a role in the primary response against pathogens

Question 59

Function of IgE

Answer 59

* is produced in response to parasitic infections, * as well as during type I hypersensitivity reactions * where it is involved in mast cell activation.

Question 60

Difference in B cells between primary and secondary immune response

Answer 60

Primary immune response: early IgM response Secondary immune response: high affinity IgG and memory cell response

Question 61

Main difference between IgM and IgG plasma cells

Answer 61

IgM plasma cells: not dependent on T cell help for generation IgG: dependent on T cell help

Question 62

Is the complement system part of innae or adaptive immune response?

Answer 62

Neither - it just complements the two systems

Question 63

Explain the process of complement activation

Answer 63

Question 64

What activates the classical complement pathway?

Answer 64

Immune complexes Hence it requires activation of the adaptive immune response So it does not occur early \*C1 activates C4 and C2

Question 65

What activates the MBL pathway of complement activation?

Answer 65

* Activated by the direct binding of MBL to microbial cell surface carbohydrates * This directly stimulates the classical pathway involving C4 and C2 (but NOT C1) * This is NOT dependent on the adaptive immune response

Question 66

How does the alternative pathway of complement activation work?

Answer 66

This is directly triggered by binding of C3 to bacterial cell wall components E.g. lipopolysaccharide of Gram-negative bacteria E.g. teichoic acid of Gram-positive bacteria

Question 67

What are the main regulatory factors for the alternative pathway?

Answer 67

Factor H C1 inhibitor --\> prevent the alternative pathway from going into overdrive

Question 68

What is the main amplification step of final common pathway?

Answer 68

Activation of C3 convertase Triggers formation of Membrane attack complex via C5-c9

Question 69

Function of MAC

Answer 69

* attacks membranes * makes holes in membranes * and lyses them * → cell death

Question 70

Functions of the complement system

Answer 70

* Increase vascular permeability and cell trafficking to sites of inflammation * Opsonisation of immune complexes keeps them soluble * Opsonisation of pathogens to promote phagocytosis * pathogens are chemically modified * Activation of phagocytes * Promotes mast cells/ basophil degranulation * Punches holes in bacterial membranes

Question 71

Examples of chemokines

Answer 71

CCL19 and CCL21 are ligands for CCR7 on dendritic cells important in directing dendritic cell trafficking to lymph nodes

Question 72

What is VDJ recombination

Answer 72

VDJ recombination is the process by which T cells and B cells: * randomly assemble different gene segments * and nucleic acids are randomly deleted/ added at the sites of rearrangement Consequence of VDJ recombination: * Potential to create vast array of specificities (10^11- 10^12 receptors) * Generates unique antigen receptors that can collectively recognise many different types of molecule * Auto-reactive cells are likely to be generated * Mechanisms must exist to delete or tolerise these autoreactive cells

Question 73

Primary and secondary lymphoid organs

Answer 73

**Primary:** Bone marrow Thymus **Secondary** SIte of interaction between naive lmphocytes and microorganisms Examples: spleen, lymph nodes, MALT

Question 74

What are the constitutive barriers to infection?

Answer 74

Question 76

What markers are expressed by T memory cells vs naive T cells?

Answer 76

Naive T cells: CD45 RA Memory T cells: CD45 RO

Question 77

What is the difference between central and effector memory T cells?

Answer 77

Question 78

Describe B cell memory

Answer 78