Immunology Flashcards
1
Q
Physical infection barriers
A
- skin + mucosal membranes
- tight junctions between cells prevent pathogen entry
- flushing action of tears, saliva + urine
- high oxygen tension in lungs
- mucus traps microorganisms + is expelled by coughing, sneezing + cilia
2
Q
Chemical infection barriers
A
- acidic pH (stomach + vagina)
- lysozyme + pepsin destroy microorganisms
3
Q
Biological infection barriers (normal flora)
A
non-pathogenic bacteria colonise on epithelial surfaces
- competes with pathogenic bacteria for nutrients + space
- produces antibacterial substances
- antibiotics can disrupt normal flora
4
Q
Phagocytes function
A
- macrophages + neutrophils
- engulf + destroy pathogens (phagocytosis)
- upon infection, macrophages release cytokines that recruit neutrophils
5
Q
Neutrophils
A
migrate from bloodstream in response to tissue damage, complement proteins + chemicals released by macrophages
- can be activated + recruited by interleukin-8 (IL-8) and tumour necrosis factor (TNF) [secreted by macrophages] or by IL-17 [secreted by T cells of adaptive immune system]
- act by phagocytosing invading organisms + presenting antigens to immune system
- segmented nuclei + cytoplasm contains pinky-purple intracellular granules
6
Q
Macrophages
A
- phagocytose + destroy pathogens + cancer cells
- tissue cells (not found on FBC)
- opsonins can increase rate of phagocytosis (eg IgG + complement protein C3b) [neutrophils + macrophages may have receptors for opsonins which may be on antigenic surface)
- stimulate response of other immune cells
- pseudopodia = processes on cell membrane which extend around pathogen
7
Q
MAMPs + PAMPs
A
microbe associated molecular patterns
pathogen associated molecular patterns
MAMPs and PAMPs recognised by toll-like receptors
toll-like receptors are found at plasma membranes and in phagosomes and they signal production of cytokines to stimulate immune cells
8
Q
What are toll-like receptors?
A
type of pattern recognition receptor (PRR) that recognises molecules shared by pathogens (but distinguishable from host molecules)
9
Q
Dendritic cells
A
present antigens on surface (trigger adaptive immunity)
present in epithelial tissue
migrate to lymph nodes on activation
numerous dendritic processes branching from cell membranes
10
Q
Which immune cells are granulocytes?
A
neutrophils
eosinophils
basophils
11
Q
Eosinophils
A
- specifically act against multicellular parasites (eg worms) by dissolving cell surfaces
- involved in IgE-mediated allergic disorders (eg asthma)
- bilobed nuclei + intracellular granules that stain brick red with eosin
12
Q
Basophils
A
- circulating counterparts of tissue mast cells
- probably involved in inflammation, parasitic infection + allergic reactions
- important for type 1 hypersensitivity reactions through binding with IgE antibodies
- bilobed nuclei + large darkly staining intracellular granules
13
Q
Monocytes
A
- produced in bone marrow, travel in blood to target tissues + become macrophages
- large cells, fine ground-glass granules + horseshoe-shaped nuclei
14
Q
Phagocytosis process
A
- phagocytes identify pathogens by recognising PAMPs using PRRs (pathogen recognition receptors eg TLRs)
- pseudopodia extend around pathogen, internalising it
- engulfed material held in phagosome
- lysosome fuses with phagosome + releases ROS/enzymes which break down phagosome contents
- phagocytes present digested protein antigens to cells of adaptive immune system via MHCs on surfaces
- when phagocyte PRRs are exposed to PAMPs, NFKB is activated (transcription factor that causes release of cytokines + initiation of inflammatory response)
15
Q
What are the 3 main lymphocyte subtypes?
A
B cells
T cells
Natural Killer cells (NK cells)
16
Q
B + T cell structure
A
- small cells
- round nuclei
- blue-ish cytoplasm
(can only be distinguished with specialist serology)
17
Q
B-cells
A
- important in humoral/antibody-mediated immunity
- plasma cells = mature B cells that secrete antibodies which recognise specific foreign antigens + bind to/destroy them
- memory cells = remember foreign antigen to allow immune system to have quicker antibody response to subsequent infections
18
Q
T-cells
A
all present CD3 + T-cell receptors (TCR) on surfaces which recognise specific antigens presented in MHC 1/2 molecule
19
Q
helper T cells (CD4)
A
- facilitate activation of immune response
- stimulate division + differentiation of effector cells
20
Q
cytotoxic T cells (CD8)
A
- provide cell-mediated immunity by targeting + killing infected cells
- contain granules filled with enzymes (eg perforins)
- kill tumour cells
21
Q
regulatory T cells (FOXP3 + CD25)
A
- AKA suppressor T cells
- limiting immune response to prevent excessive damage to tissues + organs
22
Q
memory T cells (CD62 + CCR7)
A
- remember what has happened
- allows immune system to mount faster + more effective response should offending organism return
23
Q
Natural Killer cells
A
- larger lymphocyte
- granules in cytoplasm
- express CD16 + CD56 (+some express CD8)
- part of innate + adaptive immune responses
- can destroy pathogens + infected cells without prior activation by specific antigens
- particularly important in viral immunity + tumour rejection
24
Q
Innate immune system features
A
- first line of defence against any infection
- very fast
- non-specific
- no memory
- cellular response by innate immune system, chemical response by cytokines + complement, and initiation of acute inflammatory response
25
What is MHC restriction?
MHC prevents immune system from being activated too easily
| - ensures T cells can only react to antigen if presented within an MHC complex
26
How do natural killer cells work?
- do not require activation by specific antigens so can respond immediately
- self cells protected by inhibitory effects of MHC 1 (expressed on surface of nucleated body cells)
- cells without MHC 1 likely to be non-self - NK cells release toxic granules - induce apoptosis
- MHC 1 expression often suppressed if cells infected with viruses or cancerous, therefore NK cells involved in viral immunity + tumour rejection
27
Describe the 3 pathways that activate the complement system
Classical pathway = activated by binding of antigen to IgG/IgM (formation of antigen-antibody complexes)
Alternative pathway = activated directly by microbial components + does not need antigen-antibody components for activation
Mannose-binding lectin pathway = activated by lectin binding to mannose on pathogen surface
28
What do the 3 complement pathways lead to?
Formation of C3 convertase enzyme
29
What does C3 convertase enzyme do?
bind complement component C3 + split it into C3a + C3b
30
C3a function
anaphylatoxin
| dissipates to recruit + activate leukocytes
31
C3b function
- binds to + coats pathogens - easier for phagocytes to identify + digest (opsonisation)
- can bind more C3b to form C5 convertase which binds C5 and splits into C5a (anaphylatoxin) + C5b
32
C5b function
- binds C6, C7, C8 + C9 to form membrane attack complex (MAC)
- MAC = ring-shaped - tunnels hole in bacterial cell wall allowing water to flood in causing osmotic lysis
33
Complement system functions
Formation of anaphylatoxins (C3a, C4a + C5a):
- cause release of histamine from mast cells
- C5a - chemotactic + activation agent for neutrophils, monocytes, eosinophils + basophils
Opsonisation:
- C3b coats walls of microbe
- neutrophils + macrophages have C3b receptors
```
Cell lysis (MAC):
- final stage in complement cascade = MAC formation - causes osmotic lysis of cells
```
Immunoglobulin clearance:
- removal of immune complex from circulation
34
What is a proinflammatory cytokine?
small messenger proteins released by immune cells in response to evidence of infection which interact to mediate the acute inflammatory response
(eg interleukins, tumour necrosis factors + chemokines)
35
Main phases of acute inflammation process
Vascular phase
| Cellular phase
36
Describe the vascular phase of acute inflammation
- Hageman factor activated by collagen contact or contact with microbes
- clotting system activation
- complement system activation
- kinin system activation (bradykinin produced)
- bradykinin causes vasodilation of arterioles, increased vascular permeability (endothelial cells contract, more space between cells) + pain
37
Describe the cellular phase of acute inflammation
predominant cell = neutrophil
- neutrophils attracted to injury site by chemotaxins
Migration of neutrophils:
- Margination = cells line up against endothelium
- Rolling = close contact with + roll along endothelium
- Adhesion = connecting to endothelial wall
- Transmigration/emigration = cells move through vessel wall to affected area
- Phagocytosis = once in area, neutrophils phagocytose and destroy pathogen by oxygen-dependent (using ROS), or oxygen-independent (using lysozymes) mechanisms
- Resolution = neutrophils die by apoptosis + macrophage era begins
38
What are the outcomes of acute inflammation?
Resolution + healing = anti-inflammatory cytokines (IL-10+ TGF-beta) produced by macrophages
Continued acute inflammation = IL-8 produced by macrophages recruits more neutrophils
Abscess formation = cytokines + fibrogenic growth factors produced by macrophages
Chronic inflammation = macrophages activate CD4+ helper T-cells
39
Describe the 2 main protective mechanisms preventing the immune system from being activated inappropriately
MHC restriction = ensures only antigens presented within context of MHC complexes are able to trigger immune response
Naive T helper cells need second signal from antigen-presenting cells to become fully activated by their specific antigen (dendritic cells provide this using B7 proteins which bind to CD28 receptors on T cell surfaces)
40
What is central tolerance?
removal of lymphocytes with receptors specific for self-antigens
41
How is MHC involved in immune tolerance?
Thymic medulla cells use MHC to educate T-cells by presenting self-proteins to immature T-cells
- If immature T-cells have weak binding for for MHC self-peptide they survive (positive selection)
- If immature T-cells have strong binding for MHC self-peptide they die (negative selection)
- Some self-reactive T-cells escape thymus. If they are helper T-cells they can help B-cells make antibodies against self
42
What do T helper cells differentiate into?
TH1 cells - promote cytotoxic T cells + cell-mediated immunity
TH2 cells - promote B cells + humoral immunity
43
What is humoral immunity?
Specific adaptive immune response activated by TH2 cells
Leads to production of B cells + antibodies
Fights extracellular infections
44
Describe the structure of antibodies
Y-shaped
2 large heavy chains (structure dictates whether the antibody is IgM, IgG, IgA, IgE or IgD)
2 small light chains
heavy + light chains connected by disulphide bonds
all 4 chains contain constant + variable regions (constant regions always the same, variable regions unique to each B cell + confer antigen specificity)
antigens bend to end of each arm of Y structure
base of antibody binds to complement + phagocytes
45
What are the 5 antibody isotypes?
Dictated by structure of heavy chain constant region
| IgM, IgG, IgA, IgE, IgD
46
Describe IgM
pentameric
expressed on B cell surfaces
produced early in immune response
47
Describe IgG
monomeric
provides majority of antibody-based immunity (secondary responses)
opsonisation
found mainly in circulating blood + tissues
crosses placenta to provide passive immunity to fetus
48
Describe IgA
dimeric once reaches tissue
found in mucosal areas (GI, respiratory, urinary tracts)
secreted in saliva, tears + breast milk
49
Describe IgE
monomeric
binds to allergens + mediates allergic reactions
provides immunity against multicellular organisms (eg parasitic worms)
50
Describe IgD
monomeric
| signals activation of B cells
51
What is VDJ recombination?
- antibody variable region genes are coded in three parts: V (variable), D (diversity) and J (joining) segments
- RAG proteins allow B cells to shuffle gene segments around in maturation + recombine them
52
What is isotype class switching?
mature B cells activated by specific antigen + produce IgM antibodies + undergo isotype class switching to produce different types of antibody adapted for locations within body
53
How do antibodies fight extracellular infections?
- neutralise toxins by binding to them
- bind to antigens on pathogen surfaces (agglutinates to impair mobility + opsonises to enhance phagocytosis)
- antibodies binding to antigens activates classical complement pathway
- directly activate effector cells (eg dendritic cells, NK cells + cytotoxic T cells)
54
Describe B cell activation
- naive TH0 cells activated by specific antigen = differentiate into TH2 cells
- TH2 cells locate B cell counterparts by identifying correct antigen within MHC 2 on B cell surface
- provide B cell with second signal (CD40 ligand which binds to CD40 on B cell surface)
- release cytokines which promote B cell development (eg IL-2, IL-4 + IL-5)
55
Describe B cell maturation
- B cells mature into plasma cells + begin to make antibodies
- plasma cells initially produce IgM antibodies
- isotype class switching produces different types to cover all areas of body
- clonal expansion of antigen-specific plasma cells
- antibodies released to tackle infection
56
What is affinity maturation?
antibodies with highest affinity for antigen are encouraged to proliferate
57
What happens to plasma cells after infection has been cleared?
- some plasma cells remain as dormant memory B cells
- only most highly antigen specific B cells produced by affinity maturation will be selected to become memory cells
- presence of memory cells = immediate plasma cell proliferation + antibody production can occur at time of next infection
- number of surviving memory cells increases after each reinfection
58
What is cell-mediated immunity?
specific adaptive immune response activated by TH1 cells leading to activation of antigen-presenting cells + a cytotoxic T cell response
fights intracellular infections (eg viruses)
59
Describe activation of antigen-presenting cells
- TH1 cell encounters infected antigen-presenting cell + recognises MHC 2 restricted antigen on surface
- activates APC by providing CD40 ligand second signal + secreting interferon gamma (a cytokine)
- once activated, APCs increase production of nitric oxide + superoxide radicals - can destroy ingested pathogens more effectively
60
Describe the cytotoxic T cell response
- activated APCs present antigen to specific cytotoxic T cell receptor within an MHC 1 along with a variety of 2nd signals
- process aided by secretion of IL-2 by TH1 cells + cytotoxic T cells
- once activated, cytotoxic T cells identify infected cells by recognising antigen within MHC 1 on surface + destroy these cells
61
How do cytotoxic T cells destroy infected cells?
- form immunological synapse (cells touch) + release perforin to make hole in cell wall - release granzymes + granulysin into cell to induce apoptosis + DNA fragmentation
- FAS ligand interactions between cell surface can induce apoptosis
- can release interferon gamma which can block intracellular viral replication
62
What happens to cytotoxic T cells once infection has been dealt with?
- most antigen-specific cytotoxic T-cells remain as dormant memory T-cells
- during reinfection only first signal (MHC + antigen) needed to reactivate cytotoxic T cell (no second signal needed)
- means any APC (not just dendritic cells) can activate cytotoxic T cells directly (less need for TH1 cell help)
63
Summarise the responses to intracellular + extracellular infections
```
Intracellular = TH1 = cell-mediated immune response with activated APCs + cytotoxic T cells
Extracellular = TH2 = humoral immune response with B cells + antibodies
```
64
Tissues/organs of primary immune system
(lymphocytes develop + mature)
- bone marrow
- thymus gland
65
Tissues/organs of secondary immune system
(mature lymphocytes meet pathogens)
| - spleen, adenoids, tonsils, appendix, lymph nodes, Peyer's patches, mucosa-associated lymphoid tissue (MALT)
66
Why do lymph nodes swell in infection?
- more cells than normal enter lymph node
| - dendritic cells present antigens to T-cells which help B-cells make antibody
