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Kat's Pathology > Immune Response to Infection/Primary Immune Deficiencies > Flashcards

Immune Response to Infection/Primary Immune Deficiencies Flashcards

1
Q

What are the external epithelial route of entry for bacteria (3)

A

External surface
Wounds and abrasions
Insect bites

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2
Q

What are the mucousal surface routes of entry for pathogens (3)

A

Airways.
Gastrointestinal tract.
Reproductive treats.

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3
Q

What are the skin barriers to infection (3)

A

Tightly packed keratinised cells
Physiological factors
Sebacious glands

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4
Q

What are the skin physical barriers to infection (2)

A

Low pH

Low O2

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5
Q

What are the skin sebacious gland barriers to infection (3)

A

Hydrophobic oils repel water and microorganisms
Lysozomes destroy structural integrity of bacterial cell wall
Ammonia and defensins have anti-bacterial properties

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6
Q

What are the mucosal surface barriers to infection (2)

A

Secreted mucous

Cilia

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7
Q

How do secreted mucouses protect the mucosal surfaces from infection (4)

A

Physical barrier to trap invading pathogens.
Secretory IgA prevents bacterai and viruses attaching to and penetrating epithelial cells.
Lysozome and antimicrobial peptides directly kill invading pathogens
Lactoferrin acts to starve invading bacteria of iron

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8
Q

How do the cilia protect the mucosal surfaces from infection

A

Cilia directly trap pathogens and contribute to removal of mucous, assisted by physical manoeuvers such as sneezing and coughing

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9
Q

How do commensal bacteria protect us from pathogens (2)

A

Compete with pathogenic microorganisms for scarce resources

Produce fatty acids and bactericidins that inhibit the growth of many pathogens

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10
Q

What are the cells of the innate immune system (4)

A

Polymorphonuclear cells - neutrophils, eosinophils, basophils
Monocytes and macrophages
Natural killer cells
Dendritic cells

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11
Q

What are the soluble components of the innate immune system (3)

A

Complement
Acute phase proteins
Cytokines and chemokines

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12
Q

How do the cells of the innate immune system protect us from pathogens (5)

A

Essentially identical responses in all individuals
Cells express receptors that allow them to detect and home to sites of infection
Cells express genetically encoded receptors (pattern recognition receptors) that allow them to detect pathogens at site of infection
Cells have phagocytic capacity that allows them to engulf the pathogens
Cells secrete cytokines and chemokines to regulate immune response

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13
Q

How do polymorphonuclear cells react to/combat infection (7)

A

Migrate rapidly to site of injury
Express receptors for cytokines/chemokines - to detect inflammation
Express pattern recognition receptors – 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

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14
Q

Where are polymorphonuclear cells produced

A

Bone marrow

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15
Q

What constitutes polymorphonuclear cells (4)

A

Neutrophils
Eosinophils
Basophils/Mast cells.

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16
Q

What are the mononuclear cells of he innate immune system (2)

A

Monocytes and macrophages

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17
Q

What happens to monocytes during an infective process

A

Monocytes are produced in the bone marrow, circulating in the blood.
They migrate to tissues where they differentiate to macrophages.

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18
Q

What are the macrophages of the liver

A

Kupffer cells

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19
Q

What are the macrophages of the kidneys

A

Mesangial cells

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20
Q

What are the macrophages of the bone

A

Osteoclas

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21
Q

What are the macrophages of the spleen

A

Sinusoidal lining cell

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22
Q

What are the macrophages of the lung

A

Alveolar macrophage

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23
Q

What are the macrophages of the CNS

A

Microglia

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24
Q

What are the macrophages of connective tissues

A

Histiocyte

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25
Q

What are the macrophages of the skin

A

Langerhan cells

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26
Q

What are the macrophages of the joints

A

Macrophage like synoviocytes

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27
Q

How do macrophages combat infection (7)

A

Present within tissue
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

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28
Q

How are phagocytes recruited to the area of injury

A

Cellular damage and bacterial products trigger the local production of inflammatory cytokines and chemokines

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29
Q

How do cytokines recruit phagocytic cells

A

Cytokines activate vascular endothelium enhancing permeability

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30
Q

How do chemokines attract phagocytic cells

A

Chemokines attract phagocytes (macrophages are already present in peripheral sites)

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31
Q

How are micro-organisms recognised during an immune response (2)

A

Pattern recognition receptors (e.g. toll-like receptors, mannose receptors) recognise generic motifts known as pathogen-assocaited molecular patterns (PAMPs) such as bacterial sugars, DNA, RNA
Fc receptors for Fc portion of immunoglobulin to allow recognition of immune complexes.

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32
Q

What role do opsonins play in endocytosis of pathogenic products

A

Opsonins act as a bridge between the pathogen and the phagocyte receptors

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33
Q

What roles do opsonins play in endocytosis (3)

A

Antibodies binding to Fc receptors.
Complement Complement binding to complement receptors
Acute phase proteins (eg. CRP)

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34
Q

How is a phalogysosome formed (2)

A

Phagosome and lysosome fuse to form phagolysosome

Protected compartment in which killing of the organism occurs

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35
Q

How are the organisms killed in the phagolysosome (2)

A

Oxidative killing

Non-Oxidative killing

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36
Q

What is involved in oxidative killing of organisms (3)

A

NADPH oxidase complex converts oxygen into reactive oxygen species - superoxide and hydrogen peroxide
Myeloperoxidase catalyses production of hydrochlorous acid from hydrogen peroxide and chloride
Hydrochlorous acid is a highly effective oxidant and anti-microbial

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37
Q

What is involved in non-oxidative killing of organisms (3)

A

Release of bacteriocidal enzymes such as lysozyme and lactoferrin into the phagolysosome

Enzymes present in granules
Each has a unique antimicrobial spectrum
Results in broad coverage against bacteria and fungi

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38
Q

What happens to the neutrophil after phagocytosis has occurred

A

Process of phagocytosis depletes neutrophil glycogen reserves and is followed by neutrophil cell death

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39
Q

What occurs when neutrophils die (3)

A

As the cells die, residual enzymes are released, causing liquefaction of closely adjacent tissue.
Accumulation of dead and dying neutrophils within infected tissue results in the formation of pus
Extensive localised formation of pus causes abscess formation

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40
Q

What products are involved in opsonisation (3)

A

Antibodies
Complement components
Acute phase proteins

41
Q

Where are natural killer cells

A

Present within blood and may migrate to inflamed tissue

42
Q

What do natural killer cells express (2)

A

Express inhibitory receptors for self-HLA molecules that prevent inappropriate activation by normal self
Express a range of activatory receptors including natural cytotoxicity receptors that recognise heparan sulphate proteoglycans

43
Q

What do natural killer cells do (3)

A

Integrate signals from inhibitory and activatory receptors
Cytotoxic - kill ‘altered self’ as in malignant or virus infected cells
Secrete cytokines to regulate inflammation – promote dendritic cell function

44
Q

Where are dendritic cells normally found

A

Peripheral tissues

45
Q

What do dendritic cells express (3)

A

Express receptors for cytokines and chemokines - to detect inflammation
Express pathogen recognition receptors – to detect pathogens
Express Fc receptors for Ig - to detect immune complexes

46
Q

Are dendritic cells capable of phagocytosis

A

Yes

47
Q

What occurs after a dendritic call has phagocytosed (3)

A

Upregulate expression of HLA molecules
Express costimulatory molecules
Migrate via lymphatics to lymph nodes – mediated by CCR7

48
Q

What do dendritic cells do in the lymph nodes

A

Present processed antigen to T cells in lymph nodes to prime the adaptive immune response

49
Q

What immuno-regulatory functions do dendritic cells have

A

They express cytokines to regulate the immune response

50
Q

How do antigens reach the lymph nodes

A

Via lymphatic system

51
Q

How does the lymphatic system return to the blood

A

Via the thoracic duct

52
Q

What are the components of the adaptive immune resoponse (3)

A 
Humoural immunity (B lymphocytes and antibodies) 
Cellular immunity (T lymphocytes - CD4 and CD8 T cells) 
Soluble components (cytokines and chemokines)
53
Q

What are the key characteristics of the adaptive immune system (4)

A

Wide repertoire of antigen receptors
Exquisite specificity
Clonal expansion
Immunological memory

54
Q

What primary lymphoid organs are involved in lymphocyte development (2)

A

Bone marrow

Thymus

55
Q

What is the role of the bone marrow in adaptive immunity (2)

A

Both T and B lymphocytes are derived from haematopoietic stem cells
Site of B cell maturation

56
Q

What is the role of the thymus in the adaptive immune system (2)

A

Site of T cell maturation

Most active in the foetal and neonatal period, involutes after puberty

57
Q

What secondary lymphoid organs are involved in lymphocyte development (3)

A

Anatomical sites of interaction between the naive lymphocytes and microorganisms

Spleen
Lymph nodes
Mucosal associated lymphoid tissue

58
Q

What is the process of T cell maturation (3)

A

Arise from haematopoietic stem cells in bone marrow.
Exported as immature cells to the thymus where they undergo selection
Mature T lymphoctes enter the circulation and reside in the secondary lymphoid organs

59
Q

What are the two pain subsets of T cells (2)

A

CD8+

CD4+

60
Q

What HLA class do CD8+ T cells recognise

A

HLA class I

61
Q

What HLA class do CD4+ T cells recognise

A

HLA class II

62
Q

What is the ideal selectivity level for HLA molecules by T cells

A

Intermediate affinity

Approximately 10% of original cell produced

63
Q

What is the role of CD4+ T cells (2)

A 
Recognise peptides presented on HLA class II molecules 
Immunoregulatory functions via cell:cell interactions and expression of cytokines
64
Q

What are the main CD4+ T cell subsets (5)

A

Th1 - help CD8 T cells and macrophages
Th17 - help neutrophil recruitment and enhance generation of autoantibodies
Treg - IL-10/TGF beta expressing. CD25+Foxp3+
TFh - follicular helper cells
Th2 - helper T cells

65
Q

What are the roles of CD8+ T cells (5)

A

Sopecialised cytotoxic cells
Recognise peptides derived from intracellular proteins in associated with HLA class I
Kill cells directly (perforin and granzymes, express Fas ligand)
Secrete cytokines (IFNgamma, TNFalpha)
Particularly important in defence against viral infections and tumours.

66
Q

What is meant by T cell memory

A

Response to successive exposures to antigen is qualitatively and quantitively different from that of first exposure - faster response

67
Q

What do Th1 cells express/secrete (3)

A

Express CD4

Secrete IFNgamma and IL2

68
Q

What do Treg cells express 92)

A

Foxp3

CD25

69
Q

What is important that B cells do not do

A

Recognition of self - selected against this

70
Q

What are the two responses that B cells have

A

Early IgM response

Later high affinity IgG, IgA, IgE secreting plasma cells and memory cells

71
Q

How is the more specific B cell response conducted (3)

A

Dendritic cells prime CD4+ T cells.
CD4+ T cells help B cell differentiation - requires CD40L:CD40 interaction (occurs in lymphoid tissue).
B cell proliferation, somatic hypermutation and isotype switching to produce specific immunoglobulins

72
Q

What are immunoglobulins

A

Soluble proteins made up of 2 heavy and 2 light chains

73
Q

What does the heavy chain of the immunoglobulin determine

A

Antibody class (IgM, IgG, IgA, IgE, IgD)

74
Q

What area is the antigen recognised by in the immunoglobulin

A

Antigen is recognised by the antigen binding regions (Fab) of both heavy and light chains

75
Q

What determines the response to the antigen in the immunoglobulin

A

Constant region of the heavy chain (Fc)

76
Q

What are the functions of antibodies (3)

A

Identification of pathogens and toxins
Interact with other components of the immune response to remove pathogens (Fc mediated)
Particularly important in defence against bacteria

77
Q

How does the secondary B cell response differ from the primary B cell response (4)

A

The lag time between antigen exposure and the production of antibody is decreased (to 2-3 days)
The titre of antibodies produced is greatly increased
The response is dominated by IgG antibodies of high affinity
The response may be independent of help from CD4+ T lymphocytes

78
Q

Where are pre-B cells found

A

In the bone marrow

79
Q

What is IgA

A

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

80
Q

What is the germinal centre

A

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

81
Q

What is the complement system

A

> 20 tightly regulated, linked proteins
When triggered, enzymatically active other proteins in a biological cascade, resulting in a rapid, highly amplified response

82
Q

Where are the compliment proteins produced

A

Liver

83
Q

What are the three pathways of complement activation (3)

A

Classical (C1,2,4)
Alternative
MBL (C4,2)

84
Q

What is the key shared step of all three complement pathways

A

C3

85
Q

What is the final compliment pathway

A

C5-0

86
Q

What is formed at the end of the compliment pathway

A

Membrane attack complex

87
Q

What are the steps involved in the classical compliment pathway (4)

A

Formation of antibody-antigen immune complexes
Results in change in antibody shape – exposes binding site for C1
Binding of C1 to the binding site on antibody results in activation of the cascade
Dependent upon activation of acquired immune response (antibody)

88
Q

What steps are involved in the MBL (mannose binding lectin) pathway of the complement system (3)

A

Activated by the direct binding of MBL to microbial cell surface carbohydrates
Directly stimulates the classical pathway, involving C4 and C2 but not C1
Not dependent on acquired immune response

89
Q

What steps are involved in the alternative pathway of the compliment system (3)

A

Directly triggered by binding of C3 to bacterial cell wall components
eg lipopolysaccharide of gram negative bacteria, teichoic acid of gram positive bacteria
Not dependent on acquired immune response
Involves factors B, I and P

90
Q

What does activation of C3 do in the compliment pathway (2)

A

It is the major amplification step in the complement cascade
It triggers the formation of the membrane attack complex via C5-9

91
Q

What does the membrane attack complex do

A

Punches holes in bacterial membranes

92
Q

What are the roles of the complement system (6)

A

Increases vascular pearmeability and cell trafficking to site of inflammation
Opsinisation of immune complexes keeps them soluble
opsonisation of pathogens to promote phagocytosis
Activates phagocytes
Promotes mast cell/basophil degranulation
Punches holes in bacterial membrane.

93
Q

How is the complement system activated

A

Antibody binding to antigen

Binding to Fc receptors on macrophages and natural killer cells

94
Q

What are cytokines (3)

A

Small protein messengers
Immunomodulatory function
Autocrine or paracrine dependent action

95
Q

What are some examples of cytokines (6)

A

IL2, IL6, IL10, IL12, TNF-alpha, TGF-beta

96
Q

What are chemokines (2)

A

Chemotactic cytokines - i.e. chemoattractants

Direct recruitment/homing of leukocytes in an inflammatory response

97
Q

What are CCL19 and CCL21

A

Ligands for CCR7

Important in directing dendritic cell trafficking to lymph nodes

98
Q

What are some other examples of chemokines (3)

A

RANTES
IL8
MIP1 alpha and beta

Kat's Pathology (105 decks)

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