Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pathology by week > W2 - The immune response to infection > Flashcards

W2 - The immune response to infection Flashcards

1
Q

Which two routes of entry are there for pathogens?

A

External epithelia
Mucosal surfaces

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the constitutive barriers to infection of the skin?

A
  1. tightly packed keratinised cells
  2. low pH
  3. Low oxygen tension
  4. Sebaceous glands:
    - hydrophobic oils repel water and microorganisms
    - lysozyme destroys bacterial cell wall
    - ammonia and defensins have anti-bacterial properties
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the constitutive barriers to infection of mucosal surfaces?

A
  1. Secreted mucous
    - Physical barrier
    - Secretory IgA prevents bacteria and viruses attaching to and penetrating epithelial cells.
    - Lysozyme and antimicrobial peptides
    - Lactoferrin starves invading bacteria of iron.
  2. Cilia
    - traps pathogens
    - removal of mucous, assisted by physical manoeuvres such as sneezing and coughing.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the constitutive barriers to infection of in the gut?

A

Resident bacteria - outcompete pathogenic microorganisms and produce fatty acids and bactericidins that inhibit pathogen growth

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

List the cells of the innate immune system

A
  1. Polymorphonuclear cells - Neutrophils, eosinophils, basophils
  2. monocytes + macrophages
  3. NK cells
  4. DCs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

List the soluble components of the innate immune system

A

Complement
Acute phase proteins
Cytokines and chemokines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Where are polymorphonuclear cells made?

A

BM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the actions of polymorphonuclear cells?

A

Express receptors for cytokines/chemokines - to detect inflammation

Express pattern recognition receptors (PRR) – to detect pathogens

Express Fc receptors for Ig - to detect immune complexes

Capable of phagocytosis / oxidative & non-oxidative killing – particularly neutrophils

Release enzymes, histamine, lipid mediators of inflammation from granules

Secrete cytokines and chemokines to regulate inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the special names of tissue resident macrophages of the:
liver
kidney
bone
spleen
lung
neural tissue
connective tissue
skin
joints

A

Liver Kupffer cell
Kidney Mesangial cell
Bone Osteoclast
Spleen Sinusoidal lining cell
Lung Alveolar macrophage
Neural tissue Microglia
Connective tissue Histiocyte
Skin Langerhans cell
Joints Macrophage-like synoviocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the actions of macrophages?

A

Express receptors for cytokines and chemokines - to detect inflammation

Express pattern recognition receptors –to detect pathogens

Express Fc receptors for Ig - to detect immune complexes

Capable of phagocytosis / oxidative and non-oxidative killing

Secrete cytokines and chemokines to regulate inflammation

Capable of presenting processed antigen to T cells!!!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the functions of cytokines and chemokines?

A

Cytokines - activate vascular endothelium enhancing permeability

Chemokines - attract phagocytes
(note that macrophages are already present at peripheral sites)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Give examples of PRRs and name what they see

A

Toll-like receptors (TLRs) and mannose receptors see generic motifs called PAMPs (bacterial sugars, RNA, DNA)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Endocytosis is facilitated by _______

A

Opsonisation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Name 3 opsonins of the immune system

A
  1. Antibodies binding to Fc receptors
  2. Complement components binding to complement receptors
  3. Acute phase proteins eg C reactive protein (CRP)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Explain oxidative killing of microbial species

A

NADPH oxidase complex coverts O2 to a ROS - superoxide and hydrogen peroxide

myeloperoxidase catalyses production of hydrochlorous acid (HOCl-) from hydrogen peroxide (H2O2) and Cl-

Hydrochlorous acid is a highly effective oxidant!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Explain non-oxidative killing of microbial species

A

Release of bactericidal enzymes (lysozyme and lactoferrin) into phagolysosome –> broad coverage against bacteria and fungi

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Phagocytosis by which cell results in its death?

A

Neutrophil

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Explain what happens following neutrophil cell death?

A

Residual enzymes are released > liquefaction of close by tissue > accumulation of dead/dying neutrophils results in pus formation > extensive pus can become abscess formation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q
  1. Oxidative killing
  2. Pathogen recognition
  3. Opsonisation
  4. Non-oxidative killing

A. Is mediated by Toll like receptors which recognise pathogen associated molecular patterns

B. May be mediated by antibodies, complement components or acute phase proteins and facilitates phagocytosis

C. Describes killing mediated by reactive oxygen species generated by action of the NADPH oxidase complex

D. May be mediated by bacteriocidal enzymes such as lysozyme

A
  1. C
  2. A
  3. B
  4. D
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Where are NK cells normally found?

A

Present within blood and may migrate to inflamed tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How do NK cells function when they interact with other cells?

A
  1. Express inhibitory receptors for self-HLA molecules that prevent inappropriate activation by normal self
  2. Express activatory receptors including natural cytotoxicity receptors that recognise heparan sulphate proteoglycans

Integrate signals from inhibitory and activatory receptors

normally inhibitory > activatory

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What happens if NK cells see altered self cells?

A
  1. Cytotoxic - kill ‘altered self’ as in malignant or virus infected cells
  2. Secrete cytokines to regulate inflammation – promote dendritic cell function
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What will an infected/malignant cell do to signal to an NK cell?

A

Downregulate HLA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Where are DCs normally found?

A

Reside in peripheral tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

How do immature DCs function?

A
  • Express receptors for cytokines and chemokines - to detect inflammation
  • Express pathogen recognition receptors (PRRs)– to detect pathogens
  • Express Fc receptors for Ig - to detect immune complexes
  • Capable of phagocytosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What do DCs (matured) do after phagocytosis?

A
  1. Upregulate expression of HLA
  2. Express costimulatory molecules
  3. Migrate via lymphatics to LNs – mediated by CCR7
  4. Present processed antigen to T cells in LNs to prime adaptive immune response
  5. Express cytokines to regulate the immune response
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

How do lymphocytes and lymph return to blood?

A

via thoracic duct

28
Q

Which cell bridges the innate and adaptive immune system?

A

DCs

29
Q

Which innate immune cells are capable of phagocytosis?

A

Neutrophils, macrophages, DCs, NK (sometimes)

30
Q
  1. Neutrophils
  2. Natural Killer Cells
  3. Dendritic cells
  4. Macrophages

A. Derived from monocytes and resident in peripheral tissues

B. Polymorphonuclear cells capable of phagocytosing pathogens and killing by oxidative and non-oxidative mechanisms

C. Lymphocytes that express inhibitory receptors capable of recognising HLA class I molecules and have cytotoxic capacity

D. Immature cells are adapted for pathogen recognition and uptake whilst mature cells are adapted for antigen presentation to prime T cells

A
  1. B
  2. C
  3. D
  4. A
31
Q

What are the cells of the adaptive immune system - humoral, cellular, and soluble components?

A

‘Humoral’ immunity = B lymphocytes and antibody

‘Cellular’ immunity = T lymphocytes
CD4 T cells
CD8 T cells

Soluble components = Cytokines and chemokines

32
Q

Where are T and B lymphocytes derived from? Where does each mature?

A

Derived from BM
B cells - BM
T cells - thymus

33
Q

When is the thymus most active? when does it involute?

A

Foetal and neonatal period;
involutes after puberty

34
Q

What are primary and secondary lymphoid organs?

A

Primary - Organs involved in lymphocyte development

Secondary - Anatomical sites of interaction between naïve lymphocytes and microorganisms

35
Q

Examples of secondary lymphoid organs

A
  • Spleen
  • LNs
  • Mucosal associated lymphoid tissue (MALT)
36
Q

CD8 T cells recognise peptide presented by HLA (MHC) _____________
CD4 T cells recognise peptide presented by HLA (MHC) _____________

A

Class I
Class II

37
Q

Describe which T cells are positively and which are negatively selected for?

A

Intermediate affinity for HLA = POSITIVE SELECTION (10% of cells) –> if affinity for HLA Class I then become CD8 T cells, if for HLA Class II, then become CD4 T cells

Low affinity for HLA = NEGATIVE SELECTION to avoid inadequate reactivity

High affinity for HLA = NEGATIVE SELECTION to avoid autoreactivity

38
Q

What is the function (2-step) of CD4 T cells?

A

T helper cells

  1. Recognise
    - peptides derived from extracellular proteins
    - presented on HLA Class II molecules (HLA-DR, HLA-DP HLA-DQ)
  2. Immunoregulatory functions via cell-cell interactions and expression of cytokines
    - Provide help for development of full B cell response
    - Provide help for development of some CD8+ T cell responses
39
Q

Describe the following CD4 T cell subsets:

  • TH1
  • TH17
  • Treg
  • Tfh
  • TH2
A
  • TH1 = help CD8 T cells and macrophages
  • TH17 = help neutrophil recruitment, enhance generation autoantibodies
  • Treg = IL-10/TGF-beta expressing, CD25+ FOXP3+
  • Tfh = follicular helper T cells assist in B cell response
  • TH2 = Helper T cells
40
Q

What is the function of CD8 T cells?

A 
Cytotoxic T cells 
1. Recognise peptides derived from intracellular proteins in association with HLA class I (HLA-A, HLA-B, HLA-C)
  1. Kill cells directly
    - Perforin (pore forming) and granzymes
    - Expression of Fas ligand
  2. Secrete cytokines eg IFNg TNFa
  3. Particularly important in defence against viral infections and tumours
41
Q
  1. Th1 cells
  2. CD8 T cells
  3. T follicular helper (Tfh) cells
  4. T regulatory cells

A. Express receptors that recognise peptides usually derived from intracellular proteins and expressed on HLA class I molecules

B. Subset of lymphocytes that express Foxp3 and CD25

C. Subset of cells that express CD4 and secrete IFN gamma and IL-2

D. Play an important role in promoting germinal centre reactions and differentiation of B cells into IgG and IgA secreting plasma cells

A
  1. C
  2. A
  3. D
  4. B
42
Q

How does central tolerance for B cells take place?

A

No recognition of self in BM = survive!!

Recognition of self in BM = negative selection to avoid autoreactivity

43
Q

Germinal Centre reaction in LN requires ____________ cells

A

CD4 T cells

44
Q

The early antibody response at initial antigen encounter of B cells is ____

A

IgM

45
Q

Summarise the events that happen at the germinal centre

A
  1. DCs prime CD4+ T cells
  2. CD4+ T cells help B cell differentiation (via CD40L:CD40 interaction)
  3. B cell proliferation + somatic hypermutation + isotype switching
46
Q

What is isotype switching?

A

Following positive selection, B cells will undergo somatic hypermutation and isotype switching from IgM to IgG, IgA or IgE

47
Q

What are immunoglobulins?

A

Soluble proteins made up of 2 heavy and 2 light chains

48
Q

Which chain determines the ab class?

A

heavy chain

49
Q

What are the Fab and Fc regions?

A

Fab is made of heavy and light chains and recognises the antigen

Fc (constant) is made of the heavy chain and has an effector function

50
Q

What components of the immune system can the Fc region interact with?

A
  1. Complement
  2. Phagocytes
  3. NK cells
51
Q

What are the main differences between primary and successive exposure to antigens?

A
  1. Lag time is decreased (to 2-3 days)
  2. [antibody] response is greatly increased
  3. response is dominated by IgG
  4. response may be independent of help from CD4+ T cells
52
Q
  1. Pre-B cells
  2. IgA
  3. IgG secreting plasma cells
  4. IgM secreting plasma cells

A. Exist within the bone marrow and develop from haematopoietic stem cells

B. Cell dependent on the presence of CD4 T cell help for generation.

C. Are generated rapidly following antigen recognition and are not dependent on CD4 T cell help

D. Divalent antibody present within mucous which helps provide a constitutive barrier to infection

A
  1. A
  2. D
  3. B
  4. C
53
Q
  1. Primary lymphoid organs
  2. Thoracic duct
  3. Thymus
  4. Germinal centre

A. Area within secondary lymphoid tissue where B cells proliferate and undergo affinity maturation and isotope switching

B. Include both the bone marrow and thymus; sites of B and T cell development

C. Carries lymphocytes from lymph nodes back to the blood circulation

D. Site of deletion of T cells with inappropriately high or low affinity for HLA molecules and of maturation of T cells into CD4+ or CD8+ cells

A
  1. B
  2. C
  3. D
  4. A
54
Q

How many proteins are in the complement cascade?

A

20

55
Q

Where are complement proteins produced?

A

Liver

56
Q

Complement proteins are present in circulation as __________ molecules

A

INACTIVE

57
Q

How do complement proteins activate?

A

When triggered, they ENZYMATICALLY active each other in a biological cascade –> rapid, highly amplified response

58
Q

Name the 3 pathways of complement activation

A
  1. Classical Pathway
  2. Mannose Binding Lectin (MBL) pathway
  3. Alternative pathway
59
Q

Describe the classical pathway and its key components

A

C1, 2, and 4 lead to C3

  • includes C1 binding to ab-ag complex, and this results in activation of the cascade
  • hence is dependent on ACQUIRED ADAPTIVE immune response
60
Q

Describe the MBL pathway and its key components

A

C2, C4 and MBL complex lead to C3
- includes MBL binding to microbial cell surface oligosaccharides (carbs)

61
Q

Describe the alternative pathway and its key components

A

Directly triggered by binding of C3 to bacterial cell wall components

  • involves factors, B, I, and P
62
Q

Summarise end result of all complement pathways

A

Classical, MBL, and alternative all lead to C3 –> go into final common pathway (C5-C9) –> Membrane Attack Complex (MAC)

63
Q

What does the membrane attack complex (MAC) do?

A

Causes lesions (punch holes) in the bacterial membranes

64
Q

Other than MAC formation, what are 3 other effects of complement activation?

A
  1. Increases vascular permeability and cell trafficking to site of inflammation
  2. Opsonisation of immune complexes keeps them soluble
  3. Opsonisation of pathogens to promote phagocytosis
  4. Activates phagocytes
  5. Promotes mast cell/basophil degranulation
65
Q
  1. C3
  2. C1
  3. C9
  4. MBL

A. Binding of immune complexes to this protein triggers the classical pathway of complement activation

B. Cleavage of this protein may be triggered via the classical, MBL or alternative pathways

C. Binds to microbial surface carbohydrates to activate the complement cascade in an immune complex independent manner

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

A
  1. B
  2. A
  3. D
  4. C
66
Q

What are cytokines? Give examples

A

Small protein messengers that have an immunomodulatory function

  • may signal in an autocrine or paracrine dependent fashion
  • Examples: IL-2, IL-6, IL-10, IL-12, TNF-alpha, TGF-beta
67
Q

What are chemokines? Give examples of specific ones

A

chemokines =chemotactic cytokines = i.e., chemoattractants

  • direct recruitment/homing of leukocytes in an inflammatory response
  • CCL19 and CCL21 (chemokine) are ligands for CCR7 = direct DC trafficking to LNs
  • Other examples: IL-8, RANTES, MIP-1a/b

Pathology by week (70 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions