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

Immune Response to Infection/Primary Immune Deficiencies Flashcards

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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
What are the macrophages of the skin
Langerhan cells
26
What are the macrophages of the joints
Macrophage like synoviocytes
27
How do macrophages combat infection (7)
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
28
How are phagocytes recruited to the area of injury
Cellular damage and bacterial products trigger the local production of inflammatory cytokines and chemokines
29
How do cytokines recruit phagocytic cells
Cytokines activate vascular endothelium enhancing permeability
30
How do chemokines attract phagocytic cells
Chemokines attract phagocytes (macrophages are already present in peripheral sites)
31
How are micro-organisms recognised during an immune response (2)
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.
32
What role do opsonins play in endocytosis of pathogenic products
Opsonins act as a bridge between the pathogen and the phagocyte receptors
33
What roles do opsonins play in endocytosis (3)
Antibodies binding to Fc receptors. Complement Complement binding to complement receptors Acute phase proteins (eg. CRP)
34
How is a phalogysosome formed (2)
Phagosome and lysosome fuse to form phagolysosome | Protected compartment in which killing of the organism occurs
35
How are the organisms killed in the phagolysosome (2)
Oxidative killing | Non-Oxidative killing
36
What is involved in oxidative killing of organisms (3)
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
37
What is involved in non-oxidative killing of organisms (3)
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
38
What happens to the neutrophil after phagocytosis has occurred
Process of phagocytosis depletes neutrophil glycogen reserves and is followed by neutrophil cell death
39
What occurs when neutrophils die (3)
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
40
What products are involved in opsonisation (3)
Antibodies Complement components Acute phase proteins
41
Where are natural killer cells
Present within blood and may migrate to inflamed tissue
42
What do natural killer cells express (2)
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
What do natural killer cells do (3)
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
Where are dendritic cells normally found
Peripheral tissues
45
What do dendritic cells express (3)
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
Are dendritic cells capable of phagocytosis
Yes
47
What occurs after a dendritic call has phagocytosed (3)
Upregulate expression of HLA molecules Express costimulatory molecules Migrate via lymphatics to lymph nodes – mediated by CCR7
48
What do dendritic cells do in the lymph nodes
Present processed antigen to T cells in lymph nodes to prime the adaptive immune response
49
What immuno-regulatory functions do dendritic cells have
They express cytokines to regulate the immune response
50
How do antigens reach the lymph nodes
Via lymphatic system
51
How does the lymphatic system return to the blood
Via the thoracic duct
52
What are the components of the adaptive immune resoponse (3)
``` Humoural immunity (B lymphocytes and antibodies) Cellular immunity (T lymphocytes - CD4 and CD8 T cells) Soluble components (cytokines and chemokines) ```
53
What are the key characteristics of the adaptive immune system (4)
Wide repertoire of antigen receptors Exquisite specificity Clonal expansion Immunological memory
54
What primary lymphoid organs are involved in lymphocyte development (2)
Bone marrow | Thymus
55
What is the role of the bone marrow in adaptive immunity (2)
Both T and B lymphocytes are derived from haematopoietic stem cells Site of B cell maturation
56
What is the role of the thymus in the adaptive immune system (2)
Site of T cell maturation | Most active in the foetal and neonatal period, involutes after puberty
57
What secondary lymphoid organs are involved in lymphocyte development (3)
Anatomical sites of interaction between the naive lymphocytes and microorganisms Spleen Lymph nodes Mucosal associated lymphoid tissue
58
What is the process of T cell maturation (3)
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
What are the two pain subsets of T cells (2)
CD8+ | CD4+
60
What HLA class do CD8+ T cells recognise
HLA class I
61
What HLA class do CD4+ T cells recognise
HLA class II
62
What is the ideal selectivity level for HLA molecules by T cells
Intermediate affinity | Approximately 10% of original cell produced
63
What is the role of CD4+ T cells (2)
``` Recognise peptides presented on HLA class II molecules Immunoregulatory functions via cell:cell interactions and expression of cytokines ```
64
What are the main CD4+ T cell subsets (5)
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
What are the roles of CD8+ T cells (5)
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
What is meant by T cell memory
Response to successive exposures to antigen is qualitatively and quantitively different from that of first exposure - faster response
67
What do Th1 cells express/secrete (3)
Express CD4 | Secrete IFNgamma and IL2
68
What do Treg cells express 92)
Foxp3 | CD25
69
What is important that B cells do not do
Recognition of self - selected against this
70
What are the two responses that B cells have
Early IgM response | Later high affinity IgG, IgA, IgE secreting plasma cells and memory cells
71
How is the more specific B cell response conducted (3)
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
What are immunoglobulins
Soluble proteins made up of 2 heavy and 2 light chains
73
What does the heavy chain of the immunoglobulin determine
Antibody class (IgM, IgG, IgA, IgE, IgD)
74
What area is the antigen recognised by in the immunoglobulin
Antigen is recognised by the antigen binding regions (Fab) of both heavy and light chains
75
What determines the response to the antigen in the immunoglobulin
Constant region of the heavy chain (Fc)
76
What are the functions of antibodies (3)
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
How does the secondary B cell response differ from the primary B cell response (4)
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
Where are pre-B cells found
In the bone marrow
79
What is IgA
Divalent antibody present within mucous which helps provide a constitutive barrier to infection
80
What is the germinal centre
Area within secondary lymphoid tissue where B cells proliferate and undergo affinity maturation and isotope switching
81
What is the complement system
>20 tightly regulated, linked proteins When triggered, enzymatically active other proteins in a biological cascade, resulting in a rapid, highly amplified response
82
Where are the compliment proteins produced
Liver
83
What are the three pathways of complement activation (3)
Classical (C1,2,4) Alternative MBL (C4,2)
84
What is the key shared step of all three complement pathways
C3
85
What is the final compliment pathway
C5-0
86
What is formed at the end of the compliment pathway
Membrane attack complex
87
What are the steps involved in the classical compliment pathway (4)
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
What steps are involved in the MBL (mannose binding lectin) pathway of the complement system (3)
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
What steps are involved in the alternative pathway of the compliment system (3)
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
What does activation of C3 do in the compliment pathway (2)
It is the major amplification step in the complement cascade It triggers the formation of the membrane attack complex via C5-9
91
What does the membrane attack complex do
Punches holes in bacterial membranes
92
What are the roles of the complement system (6)
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
How is the complement system activated
Antibody binding to antigen | Binding to Fc receptors on macrophages and natural killer cells
94
What are cytokines (3)
Small protein messengers Immunomodulatory function Autocrine or paracrine dependent action
95
What are some examples of cytokines (6)
IL2, IL6, IL10, IL12, TNF-alpha, TGF-beta
96
What are chemokines (2)
Chemotactic cytokines - i.e. chemoattractants | Direct recruitment/homing of leukocytes in an inflammatory response
97
What are CCL19 and CCL21
Ligands for CCR7 | Important in directing dendritic cell trafficking to lymph nodes
98
What are some other examples of chemokines (3)
RANTES IL8 MIP1 alpha and beta

Kat's Pathology (105 decks)

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