Intro to Immune System and Innate Immunity Flashcards
Cells and structure of immune system Cell migration and cytokines
1
Q
What is immunity defined as?
A
- resistance to infectious disease
2
Q
What is the immune system defined as?
A
- Collection of cells, tissues, and molecules that mediate resistance to infections.
3
Q
What is the most important physiological function of the immune system?
A
- to PREVENT infections
- to ERADICATE established infections
4
Q
What is innate immunity also called?
A
- Natural or native immunity
- Always present in healthy individuals
5
Q
What is adaptive immunity also called?
A
- Specific or acquired immunity
- Adapts based on the pathogen
- Lymphocytes have to differentiate (B and T)
6
Q
Is innate or adaptive immunity phylogenetically older?
A
- Innate is phylogenically older
7
Q
What does the innate immune system consist of ?
A
- Physical barriers (epithelial barrier)
- complement proteins
- Natural Killer Cells
- Phagocytes
- Complement Proteins
- Dendritic Cells
8
Q
What does the adaptive immune system consist of?
A
- Lymphoctyes (B + T) and antibodies (or products)
9
Q
What are antigens defined as and what can they be produced by (2)?
A
- Molecue that binds to an antibody OR TCR
- Produced by microbes or non infectious things`
10
Q
What is one of the most important roles of antibodies?
A
- To stop the microbes in blood and lumen (muscoal organs) from getting into the HOST CELLS and CONNECTIVE TISSUES thus destroying them
11
Q
Can antibodies get into and destroy cells that already have the microbes inside?
A
NO! Cell-mediated immunity now comes in with T cells
12
Q
What is passive immunity and an example of it?
A
- Naive person receives antibodies (or cells) from someone already immune to infection
- E.g. Newborns with placenta and breast milk antibodies
13
Q
Which are the only 2 diseases (pathogens) to be eradicated by vaccination?
A
- Smallpox
- rinderpest
14
Q
Which types of diseases can be a candidate for vaccination (one criteria)?
A
- Diseases with NO intermediate host
15
Q
What is a proper definition for innate immunity?
A
- The system of immunity that can respond with pathogens very quickly and relies on mechanisms that are inbuilt and respond in essentially the same manner with the same exposure to pathogen
16
Q
What is an antigen?
A
- Any substance that is recognised by lymphocytes or antibodies
17
Q
What is the specific term that defines the ability of the immune system to recognise a large number of antigens?
A
-Diversity
18
Q
What is a naiive T lymphocyte known as?
A
- It has all features of a T cell but hasn’t been activated yet.
- It is fully developed and left thymus
19
Q
What is a T cell that is undergoing development in thymus called?
A
- Thymocyte
20
Q
What is the estimated number of naive lymphocytes that can react against an antigen?
A
- 1 in 100 000 cells
21
Q
What are CD4+ T cells known as?
A
- T helper cells
22
Q
What are CD8+ T cells known as?
A
- Cytotoxic T cells
23
Q
What do regulatory T lymphocytes do?
A
- Prevent/limit immune responses
24
Q
Which type of cell is a key link between the adaptive and innate immune responses?
A
- Dendritic cells (present antigen to T cell
25
What do plasmablasts do?
- Produce antibodies, even after infection has gone, to provide immediate protection
26
What do CD4+ T cells produce?
- Cytokines (activates the B cells, macrophages, and other cells, thus 'helping')
27
What do the peripheral lymphoid organs consist of?
- Lymph nodes, Spleen, mucosal and cutaneous immune systems.
28
What is the general function of M cells in the small intestine?
- To transport antigens from the gut lumen to underlying tissues
29
What are lymph nodes?
- Nodular aggregates of lymphoid tissues (encapsulated)
30
What is the B cell zone in the lymph node known as?
- Primary lymphoid follicle
31
What is the T cell zone in the lymph node known as?
- Parafollicular cortex
32
What are two anatomically defined MUCOSAL lymphoid tissues?
- Pharyngeal tonsils
| - Peyer's patches (intestine)
33
When do cutaneous and muscosal tissues come into action in an immune response (general)?
- When the antigens have gone through the epithelia
34
Where are FDCs (Follicular Dendritic Cells-activation of B cells) located?
- In the lymph node follicle
35
Which area of the lymph node are dendritic cells (present antigen to T cell) located?
- Paracortex
36
What is the function of chemokines?
- Attract B cells into the follicles--> bind to CXCR5 receptor on B cells (Naive B cels)
37
What are chemokines for B cells secreted by?
- FDCs (Follicular dendritic cells)
38
What are antibody secreting cells known as?
-Plasmablasts
39
What do CD4 T cells produce that helps activate other cells?
- Cytokines
40
Are effector T cells long or short lived?
- Short lived (die when antigen is eliminated)
41
Can the innate immune system combat microbes upon first infection?
- YES!!
| - Instructs adaptive on how to respond to eraticate microbes
42
Does the innate immune system initiate removal of DEAD tissues and repair?
- YES!!
43
What does the specificity of the innate immune system allow it to recognise?
- PAMPs and DAMPs
44
What does PAMP stand for?
- Pathogen Associated Molecular Pattern
45
What does DAMP stand for?
- Damage Associated Molecular Pattern
46
What are the innate immune receptors encoded by?
- Encoded in the germline (i.e. not much diversity)
47
What are adaptive immune response receptors encoded by?
- Genes from SOMATIC RECOMBINATION of gene segments (much more diversity)
48
What are two effects that extracellular PRRs can have on macrophages?
1. Engulf the pathogen and release lysosomal content which is acidic and kills pathogen
2. Send signals to nucleus to secrete cytokines/interferons (for virus infected cells)
49
Which types of extracellular PRRs (3 types) cause macrophage to engulf the pathogen and release lysosomal content?
- formydyl peptide receptors, mannose receptors, and Scavenger receptors
50
Which type of extracellular PRRs (1 type) allow macrophages to send signals to nucleus to secrete cytokines/interferons?
- TLR
| - Toll Like Receptors (signalling receptors)
51
What are intracellular PRRs that cause release of cytokines or death of cell?
- NOD-like receptors
52
What are the two main types of reactions for the innate immune system?
- Inflammation
| - Antiviral defense
53
Does the innate system remember prior encounters of pathogen?
NO!
54
What are Pattern Recognition Receptors?
- receptors in innate immunity that recognise shared structures (PAMPs) e.g. dsRNA in virus
55
What will the innate immune system do if it identifies DAMPs?
- Eliminate damaged cells and begin tissue repair
56
What does 'clonally distributed' mean?
- Each clone of B & T lymphocytes has different receptor specific for particular antigen
57
what does 'non-clonally distributed' mean?
- IDENTICAL receptors expressed on all cells of certain lineage (e.g. macrophages)
58
Which 4 stages of infection can innate immunity provide protection? (not in chronological order)
1. Portals of entry for microbes (e.g. epithelia, antimicrobial molecules)
2. Tissues: Microbes detected by dendritic cells and macrophages
3. Blood: Complement plasma proteins---> promote microbe destruction
4. Viruses: Inhibit infection of other cells (NKC can kill)
59
What does TLR-2 target and where in cell is it found?
- Bacterial lipoglycans
| - Found on cell surface
60
What does TLR 3,7,8 recognise and where are they found in cells?
- Viral nucleic acids (dsRNA)
| - Found INTRAcellularly in endosomes
61
What does TLR-4 recognise and where in the cell is it found?
- recognises bacterial LPS (endotoxin) --> gram neg. bacterial surface
- found on cell surface
62
What does TLR-5 recognise and where in the cell is it found, as well as where in the body is it found?
- recognises bacterial flagellin (gram neg. bacteria)
- found on cell surface
- Found in epithelial cells in lungs and gut and in dendritic cells in intestine
63
What does TLR-9 recognise and where in the cell is it?
- recognises unmethylated CpG oligonucleotides (more in microbial DNA than mammalian)
- found intracellularly
64
What happens when TLRs recognise something?
- Transcription factors activated
| - expression of genes--> cytokines, enzymes etc. `
65
What is NF-kB (nuclear factor-k-light chain enhancer) and what does it cause?
- Transcription factor that is activated by TLR signals
| - Allows expression of cytokines, Adhesion molecules and IRF (interferon regulating factors)
66
What do IRFs do?
- Stimulate production of antiviral cytokines e.g. Type I interferon
67
What are NOD like receptors and what do they recognise?
- Cytosolic receptors
- Recognise DAMPs and PAMPs in cytoplasm
- have domain
68
What does NOD stand for?
- Nuclear Oligomerization Domain
69
What does NLRP-3 stand for and what does it sense?
- Microbial products--> substances indicating cell damage or death
- Also senses substances in cells and tissues IN EXCESS (e.g. cholesterol crytals, free FAs)
- Nod Like Receptor family Pyurin domain containing-3)
70
What are some signs of a cell that is damaged/dead?
- Released ATP
- Uric acid crystals (from nucleic acids--> purine degradation)
- changes in K+ concentration
71
What is the inflammasome?
- Cytosolic complex of NLRP-3, an adaptor, and Capsase-1
72
What does capsase-1 allow for?
- It is a protease(breaks down proteins)--> Proteolytic processing of pro-inflammatory cytokines (not all)
73
What do RIG like receptors recognise?
- Viral RNA
74
What do Lectin receptors do?
- Recognise carbohydrates
- specific for fungal glycans (dectins)
- Mannose receptors recognise terminal mamnose residues
- Involved in phagocytosis of fungi & bacteria (inflammatory)
75
Which antibiotics do epithelial cells produce?
- Defensins and cathelicidins (kill bacteria)
76
What are the two types of circulating phagocytes?
- Monocytes
| - Neutrophils
77
What are neutrophils also called?
- PMNs (polymorphonuclear leukocytes)
78
What is the PRODUCTION of neutrophils stimulated by?
- Cytokines
79
How are macrophages activated to remove dead tissue?
- Damaged microbes bind to PRR (like TLR or NLR)
80
What do mannose and scavenger receptors mediate? -
- Phagocytic functions of macrophages
81
What is classical Macrophage activation (M1)?
- Innate immune signals (TLRs, IFN-gamma)
| - M1 macrophages destroy microbes and trigger INFLAMMATION
82
Is IFN-gamma made in both innate and adaptive immune responses?
- YES!
83
What is alternative macrophage activation (M2)?
- Induced by CYTOKINES (no TLR signals)
- Il-4 + IL-3
- M2 Macrophages more important for tissue repair and controlling inflammation
84
How do dendritic cells respond to microbes?
- Produce CYTOKINES which initiate inflammation and stimulate adaptive immune response
- Then interact with T cells
85
What are Mast cells and where are they from?
- From bone marrow
| - Cytoplasmic granules (skin and mucosal epithelium)
86
How can most cells be activated?
- Microbial agents binding to TLR (innate)
| OR special antibody dependent mechanism (like in allergic response)
87
What do mast cell granules contain?
- Histamine (vasoactive amines)--> causes dilation
| - Proteolytic enzymes
88
What do proteolytic enzymes do?
- Kill bacteria OR inactivate microbial toxins
89
What are prostaglandins (lipid mediators) and cytokines (TNF) synthesised by?
- Mast cells
90
What do NK cells do and which substances are involved?
- Recognises infected and stressed cells and acts by killing them
- Secretes macrophage activating cytokine IFN-gamma - NK cell releases granule contents and kills infected cell
91
What are 3 NK-activating cytokines?
- IL-15
- Type I IFNs
- IL-12
92
What does IL-15 do specifically?
- Aids with development and maturation of NK cells
93
hat do the type I-IFNs, and IL-12 do with mast cells?
- Enhance the killing actions of mast cells
94
What is activation of NK cells determined by?
- Balance b/w engagement of ACTIVATING INHIBITORY RECEPTORS
95
What is ADCC?
- Antibody Dependent Cellular Cytotoxicity
| - Recognition of a cell coated in antibodies (NK cell then directed to kill it)
96
How does class I MHC expression protect healthy cells from destruction by NK Cells?
- Inhibitory receptors of NK cells block signalling of activating receptors and is specific for MHC I
97
Which cells is MHC I expressed on?
- On all healthy, nucleated cells
98
Where are marginal zone B cells present?
- Edges of lymphoid follicles in spleen and other organs (antibody responses to blood-borne polysaccharide rich microbes)
99
What is the complement system?
- Collection of circulating and membrane associated proteins important in defense against microbes
- lots of complement proteins are proteolytic enzymes
100
What are the 3 pathways for compliment activation?
1. Alternative (complement) pathway
2. Classical pathway
3. Lectin pathway
101
What is a rough description of the alternative complement pathway?
- When complement proteins are activated on microbial surfaces and can't be controlled (due to complement regulatory proteins not being present on microbes)
- INNATE COMPONENT
102
When is the clasical pathway triggered?
Triggered after antibodies bind to microbes or other antigens
- (component of ADAPTIVE IMMUNITY)
103
When is the lectin pathway triggered?
- When mannose-binding lectin (MBL) binds to terminal mannose resiudes (on surface--> glycoproteins of microbes)
- Lectin activates proteins of classical pathway (INNATE IMMUNITY COMPONENT) (because microbial product has NO ANTIBODIES)
104
What do activated complement proteins do?
- Cleaves other complement proteins
105
What is opsonisation?
- Coating the microbe with molecules (such as complement proteins) that are recognised by receptors on phagocytes
106
What are the main cytokines in recruiting blood neutrophils and monocytes to infection sites?
- TNF (Tumor Necrosis Factor)---> from macrophages and T cells
- Interleukin-1
- Chemokines (chemoattractant cytokines)
-
107
Which cytokines induce fever?
- TNF
- IL-1
these act on the hypothalamus
108
What occurs in inflammation: Recruitment of phagocytes to sites of infection and tissue damage?
- Nuetrophils and monocytes migrate to site of infection
| - bind to venular endothelial adhesion molecules (from chemokines in response to DAMPs and PAMPs )
109
What do the cytokines TNF and IL-1 do stimulate?
- Endothelial cells to express two adhesion molecules ; e secretin and p selectin
110
What are integrins and what are they expressed by?
- Integrate EXtrinsic signals into cytoskeletal alterations
| - Expressed by leukocytes
111
Where are inegrins present?
- Low affinity state on UNACTIVATED leukocytes
112
What do deficiencies in integrins and selectin ligands lead to?
- LADs (Leukocyte Adhesion Deficiencies)
| - Defective leukocyte recruitment to sites of infection
113
What does phagocyte oxidase do?
- Converts O2-->O2- (superoxide) ---> toxic if injested to microbe
114
What are 3 actions of Il-1?
1. Inhibition of protein synthesis
2. Degradation of viral RNA
3. Inhibition of viral gene expression ans viron assembly
115
What are primary lymphoid organs?
- Where the immature cells are made
- Thymus (T cells)
- Bone marrow (b cells)
116
What are secondary lymphoid organs?
- Where the actual immune response is generated
| e. g. Spleen and lymph nodes
117
Are NK cells a type of lymphocyte? -
- YES
118
Is the spleen associated with the lymphatics?
- NO!
119
As well as filtering blood, what does the spleen do? -
- Dendritic. T and B cells go there to initiate responses (like lymph nodes) but with blood
120
What do white pulp areas of the spleen contain?
- Lymphocytes
121
What do red pulp areas of the spleen contain?
- RBCs
122
What is the general rough innate immune response to an infection?
- Infection--> effector cell recruitment e.g. neutrophils--> Recognition of PAMPs and effector cells activated, inflammation response occurs---> Removal of infectious agent
123
What is the role of lyzozymes and where are they found?
- Break down the cell walls of bacteria 'punches holes in them' (finestrates)
- In tears, saliva, phagocytes, gut
124
What is the role of defensins?
- They are like detergent
- Break down the cell wall and this forms a pore
- hole is punched so integrity of pathogen ruined
125
What are two types of cells that produce lyzozymes and defensins?
- Epithelial Cells
| - Phagocytic cells
126
Which two things can trigger innate immunity?
- PATHOGEN
| - DAMAGED CELLS
127
Are Basophils mature forms of mast cells?
- YES!!
- They induce inflammation
- Circulate and migrate to injury site
- Granules contain heparin and histamine
128
What is an example of the inflammatory response steps from a splinter penetrating the skin? (4 general steps)
1. Pathogen invasion recognised
2. Invasion responsed to
3. Mast cells send out signals that RECRUIT other cells for assistance with invasion
4. Nuetrophils and phagocytes DEAL with the invasion
129
Which forms of RNA are only found on viruses and bacteria? (PAMP)
- dsRNA (TLR-3)
| - 5'triphosphate RNA
130
Which forms of DNA are only found on viruses and bacteria? (PAMP)
- Unmethylated CpG nucleotides (microbial DNA)
| - TLR-9
131
What are PAMPs in gram positive bacteria and viruses? -
- Surface glycoproteins (GP) + Lipoproteins (LP)
| -
132
Which PAMP is present on ALL becteria?
- Peptidoglycans (PG)
133
Which PAMP is unique to gram +ve bacteria?
- Lipoteichoic Acid (LTA)
134
Which PAMP is unique to gram negative bacteria?
- LPS + Flagellin
135
What are the two classes of DAMPs (non pathogen associated)?
- NLRs (Nod Like Receptors)
| - Inflammasome
136
What are 4 important DAMPs that activate NOD-like receptors?
- ATP (extracellular)
- Uric Acid crystals (gout)--> purine degradation (nucleic material)
- Intracellular ion con. K+
- cholesterol, free FAs
137
What does Il-1 do?
- Promotes inflammation and recruits cells to infection site
138
What are 3 functions of neutrophils?
1. Phagolysosome (superoxide)
2. Degranulation (release of granules --> cytotoxic, antimicrobial molecules
3. Neutrophil Extracellular Traps (NETs)
139
What are NETs (Neutrophil Extracellular Traps) made out of and what do they do?
- Chromatin + serine proteases
| - Physically TRAP the pathogen
140
What do macrophages do in general?
- Recruit more immune cells to help (sends signals to immune system)
141
What do monocytes do during an infection?
- Migrate from blood stream --> site of infection via chemotaxis
142
Once monocytes move from blood stream to tissue, what are they known as?
- Macrophages
143
What are the names of mononuclear phagocytes in the:
| - Brain, liver , lung, spleen respectively?
- Microglia
- Kuppfer cells
- Alveolar macrophage
- Sinusoiudal macrophages
144
What are the two effector functions of macrophages?
1. Main type of cell to produce cytokine and chemokines at site of infection e.g. TNF and IL-1
2. Phagocytosis
145
What is the function of the chemokine CXCL8?
- Signals to local epithelial cells to INCREASE expression of adhesion molecules and allows for ENHANCED cell migration
146
Does the chemokine CXCR8 activate just the adaptive immune response?
NO! It activates BOTH the adaptive and innate immune responses
147
What are the 5 steps of phagocytosis? -
1. Recogntion - microbe binds to lectin receptors on phagocyte
2. Ingestion- Phagocyte membrane 'zips up' around microbe
3. Phagosome formed
4. Fusion of phagosome with lysosome = phagolysosome
5. Destruction- Phagolysosome ACTIVATED (switches on destructive enzymes)
148
Which cell types can phagocytose?
- Neutrophils
- Macrophages
- Dendritic cells
- B cells
149
What are two examples of antimicrobial products in the destruction phase of phagocytosis of neutrophils?
- Alpha and beta defensins
| - BPI (Bacerial Permeability Inducing Protein)
150
Can the activation of eosinophils cause tissue damage?
- YES! (Associated with allergic responses)
151
What do eosinophils destroy mainly?
- Parasites
152
Where are mast cells found and which receptors do they respond to?
- In skin and mucosal epithelium (lungs and gut)
| - Respond to microbe via TLRs
153
Do NK cells have antigen receptors?
- NO
154
What are the two effector functions of NK cells and what do they do?
1. DEGRANULATION: Senses STRESSED cells or VIRALLY AFFECTED CELLS and kills the cell
2. CYTOKINE PRODUCTION: NK responds to cytokine which drives them to make other cytokines to activate macohpages to kill infected cell
155
What is the process of the effector function of NK cells to activate macrophages?
- Macrophage that has phagocytosed microbe produces IL-12 cytokine which goes to NK cell
- This drives the production of another cytokine; IFN-gamma by the NK cell
- This activates the macrophage infected with intracellular pathogens and stimulates killing.
- TNF also upregulates this*
156
What is the process of extravasation?
- Activated leukocyte responds to chemokine on endothelial surface (via chemokine receptor)
- Moves from ENDOTHELIUM--> TISSUE
157
What is the effect when chemokines bind to integrin receptors in inflammation leukocyte migration? -
- Turns the integrin receptors from low--> high affintiy
158
What are the rough leukocyte migration steps in response to inflammation?
- EXPOSURE TO PATHOGEN/cell damage
- Tissue macrophage responds (releases cytokines and chemokines)
- Endothelial cell activation--> increased selectin and integrin expression
- Adhesion molecules INCREASE, leukocyte binding increases, chemokines bind to integrin receptors (low---> high affinity)
- ACTIVATED LEUKOCYTE RESPONDS TO CHEMOKINE ON ENDOTHELIAL SURFACE (CHEMOKINE RECEPTOR)
- moves from endothelium---> tissue
- LEUKOCYTES then move through tissue (following chemokine conc.) to pathogen to assist in clearing it!
159
What do leukocytes adhere to the surface of?
- Only adhere to the surface of veins (not arteries)
160
What does C3b convertase do?
- It is 'peppered' onto the microbe and phagocytosed
161
What does C5 do?
- It is the MAC (Membrane Attack Compplex)
| - Forms pore in cell wall and destroys integrity
162
What are 3 ways of phagocytosis being triggered?
1. DIRECT binding of PAMPs (via PRRs) (innate)
2. Complement mediated phagocytosis (innate)
3. Antibody mediated phagocytossi (ADAPTIVE)
163
What is the key cytokine in promoting cell proliferation?
- IL-2 (T cell activation)
