Immune response to infection

Question 1

What are the body’s constitutive barriers to infection?

Answer 1

External epithelium

Mucous membranes

Question 2

How does the skin stop entry of pathogens?

Answer 2

• tightly packed keratinised cells > physically blocks entry
• low pH, low O2 tension
• sebaceous glands (produce oils, lysozyme, ammonia)

Question 3

How does mucous stop entry of pathogens?

Answer 3

• acts as physical barrier
• contains secretory IgA, which binds to pathogens and prevents their entry
• contains lysozyme
• contains lactoferrin (starves invading bacteria of iron)

Question 4

How do commensal bacteria stop entry of pathogens?

Answer 4

Compete with bacteria for scarce resources

Question 5

What are the components of the innate immune system?

Answer 5

Cells

• PMN cells e.g. neutrophils, basophils, eosinophils;
• monocytes n macrophages
• NK cells
• dendritic cells

Soluble components

• cytokines, chemokines
• complement
• acute phase protein

Question 6

What is the innate response like in different individuals?

Answer 6

It is the SAME in ALL individuals

Question 7

Describe the production and maturation of PMN cells

Answer 7

Produced in BM

Migrate to site of injury

Question 8

Describe function of PMN cells

Answer 8

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

Question 9

How do macrophages differ from PMN in function?

Answer 9

Same

Except they can also process antigens and present them to T cells

Question 10

What re the 5 steps of phagocytic action?

Answer 10

1. Phagocyte recruitment
2. Recognition of microorganisms
3. Endocytosis with opsonisation
4. Formation of phagolysosome
5. Oxidative killing

Question 11

What happens with phagocyte recruitment?

Answer 11

Cellular damage triggers production of cytokines and chemokine

• cytokines enhance permeability of vasc endothelium
• chemokine attract phagocytes

Question 12

What happens with recognition of microorganisms?

Answer 12

PRRs like toll like receptor recognise motifs such as PAMPs > they bind

Question 13

What happens in opsonisation?

Answer 13

Opsonins act as a bridge between pathogen and phagocyte’s receptors

Question 14

How is a phagolysosome formed?

Answer 14

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

Question 15

How does oxidative killing work?

Answer 15

NADPH oxidase converts oxygen into reactive oxygen species, into hydrochlorous acid, which does the killing

Question 16

How does non-oxidative killing work?

Answer 16

Release of bactericidal enzymes e.g. lactoferrin, lysozyme

Question 17

What happens after killing of pathogen?

Answer 17

Death of the phagocyte > residual enzymes released > liquefaction of adjacent tissue > accumulation of dead/dying neutrophils > pus formation

Question 18

What are the two receptors on NK cells that a normal cell binds to to survive?

Answer 18

The activating receptor and the inhibitory receptor

Question 19

What is the receptor on NK cell that a target cell binds to to die?

Answer 19

The ACTIVATING receptor only

Question 20

What is the process of maturation for a monocyte?

Answer 20

Monocyte produced in bone marrow

To target tissue > becomes macrophage > phagocytosis

Question 21

What are the components of an acquired immune response=?

Answer 21

B lymphocytes (antibodies)
T lymphocytes (CD4, CD8+)
Cytokines, chemokines

Question 22

What is a primary lymphoid organ?

Answer 22

An organ involved in lymphocyte development

Question 23

What are the 2 primary lymphoid organs?

Answer 23

Bone marrow (both B and T cells produced, only B cells mature here)
Thymus (T cell maturation)

Question 24

What are secondary lymphoid organs?

Answer 24

Sites of interaction between naive lymphocytes and microorganisms

• Spleen
• Lymph nodes
• MALT

Question 25

What are the 4 key features of the adaptive immune response?

Answer 25

- Wide repertoire of antigen receptors - High specificity - Clonal expansion - Immunological memory

Question 26

What happens to T cells in the thymus?

Answer 26

They undergo +/-ve selection before being exported to the periphery CD4+ recognises peptides from HLA II CD8+ recognises peptides from HLA I

Question 27

What affinity must T cells in the thymus display to survive?

Answer 27

INTERMEDIATE affinity for HLA low affinity > they die (FAS triggers apoptosis) high affinity > they die (auto reactivity)

Question 28

What are CD4+ cells also known as?

Answer 28

Helper T cells | Because they HELP development of B cells and of CD8+ T cells

Question 29

What do Th1 Cells produce?

Answer 29

INFgamma, TNF alpha and IL2

Question 30

What are T regulatory cells?

Answer 30

Subset of lymphocytes that express Foxp3 and CD25

Question 31

What occurs in B cell maturation?

Answer 31

They exist in the periphery as IgM B cells | They undergo a germinal centre reaction to differentiate into plasma cells producing IgG, IgE, IgM

Question 32

What is the germinal centre reaction dependent on?

Answer 32

CD4+ T helper cells | CD40L:CD40

Question 33

What do B cells undergo after the germinal centre reaction?

Answer 33

``` Somatic hypermutation Isotope switching (from IgM to IgG/E/A) ```

Question 34

What are immunoglobulins made up of?

Answer 34

2 heavy chains, 2 light chains

Question 35

What part of the immunoglobulin determines the antibody class?

Answer 35

The heavy chain

Question 36

What part of the antibody recognises the antigen?

Answer 36

Fab (antigen binding region), made up of both heavy and light chains

Question 37

What part of the antibody determines the effector function?

Answer 37

The constant region of the heavy chain

Question 38

What are the TWO KEY functions of antibodies

Answer 38

- Identification of pathogens (Fab mediated) | - Interaction with other components of the immune response to remove pathogens (Fc mediated)

Question 39

What is the benefit of B cell memory?

Answer 39

It decreases the lag time between antigen exposure and antibody production to 2-3 days max

Question 40

What is the function of IgA?

Answer 40

Divalent antibody present within mucous | Helps provide a constitutive barrier to infection

Question 41

What are IgM secreting plasma cells?

Answer 41

Cells generated rapidly following antigen recognition | Not dependent on CD4 T cell help

Question 42

What are IgG secreting plasma cells dependent on ?

Answer 42

dependent on the presence of CD4 T cell help for generation

Question 43

Where is the complement produced?

Answer 43

In the liver

Question 44

What is the function of the complement?

Answer 44

Produce a rapid highly amplified response | By activating other proteins in a biological cascade

Question 45

What are the three pathways for complement activation?

Answer 45

Classical Mannose Binding Lectin Alternate

Question 46

What is the classical pathway activated by? | how does it work?

Answer 46

By immune complexes Formation of antibody-antigen immune complex > conformation change in antibody shape >> exposes binding side for C1 C1 binding to antibody results in activation of cascade

Question 47

What is the mannose binding lectin (MBL) pathway activated by?

Answer 47

DIRECT binding of MBL to microbial cell surface carbohydrates This stimulates the classical pathway involving C4 and C2 (not C1)

Question 48

How is the alternative pathway activated by?

Answer 48

By binding C3 to bacterial cell wall components

Question 49

What factors does the alternate pathway involve?

Answer 49

B, I, P

Question 50

How does the complement pathways work

Answer 50

C3 triggers the formation of a membrane attack complex via C5-9 This complex makes holes in the membranes

Question 51

What pathways cause cleavage of C3?

Answer 51

classical MBL alternate

Question 52

What is C9?

Answer 52

Part of the final common pathway resulting in generation of the membrane attack complex

Question 53

What are chemokine?

Answer 53

Subset of cytokines | They are CHEMOTACTIC - are CHEMOATTRACTANTS

Question 54

list complement functions

Answer 54

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