4. Immunology Flashcards
2 different immune systems
- non-specific/innate immunity
- specific/adaptive immunity
Non-specific / Innate immunity
- first line of defense
- no pathogen recognition
- same response each time
Specific / Adaptive immunity
- requires pathogen recognition
- faster response with 2nd exposure to pathogen: memory cells formed
primary lymphoid organs is the place where…
stem cells divide and immune cells develop
primary lymphoid organs (2)
- bone marrow (yolk sac and fetal liver in embryo)
- thymus
bone marrow is where
- immature B cell and T cell are produced
- B cells mature
thymus key functions
- T cell maturation site
- contains T cells, dendritic cells, epithelial cells and macrophages
- atrophies after maturity
secondary lymphoid organs is where…
most immune responses occur
secondary lymphoid organs (3)
- lymph nodes
- spleen
- lymphoid nodules
lymph nodes
- scattered throughout the body
- contain macrophages that phagocytose microbes entering lymph
spleen
- removes microbes and old erythrocytes
- largest lymphoid organ
lymphoid nodules
tonsils, appendix, Peyer’s Patches and Mucosal-Associated Lymphoid Tissues (MALT)
Immune cells are produced by…
lymphoid and myeloid stem cells
lymphoid cells: lymphocytes
- T cells
- B cells
- NK cells
myeloid cells
- neutrophils
- monocytes
- eosinophils
- basophils
- mast cells
neutrophils
phagocytes responsible for bacteria eating
monocytes
become macrophages and dendritic cells (phagocytes)
eosinophils
destroy parasites
basophils
release chemicals: i.e histamine
mast cells
release chemicals: i.e. histamine
myeloid cells filled with secretory granules
- eosinophils
- basophils
- mast cells
innate immune system (def)
ability of body to defend against microbes/foreign substances without recognition of the invading pathogen
2 lines of defense in innate immunity
- 1st line of defense = physical barriers
- 2nd line of defense = cellular and humoral factors
first line of defense
barriers to entry, creating unpleasant environment for microorganisms
physical and mechanical barriers to first line of defense
- skin: water resistant
- tight junctions in epithelia
- mucus
- hair and cilia
chemical and microbiological barriers to first line of defense
- normal flora
- secretions:
–> sebum (low pH)
–> lysosomes
–> gastric juice
second of line of defense
humoral and cellular factors
humoral response (def)
includes substances that are dissolved in tissues
humoral factors (4)
- interferons
- complement: C3b
- iron-binding proteins: transferrin
- antibodies
inflammation
non-specific response to tissue damage
4 inflammation signs
- redness
- heat
- pain
- swelling
3 stages of inflammation
- vasodilation
- Emigration of phagocytes
- tissue repair
Inflammation: vasodilation
- widening of blood vessels to increase blood flow and stretch capillary
- increased permeability of capillaries to allow substances to reach damaged site
inflammation: emigration of phagocytes
- Chemotaxis: chemically stimulated movement of phagocytes
- Margination: phagocyte sticks to endothelial cel
- Diapedesis: phagocyte crosses capillary wall to reach site of injury
what triggers vasodilation?
signals from fixed-tissue macrophages
specific role of neutrophils in inflammation
- die in the process of killing bacteria
- form NETs: Neutrophil Extracellular Traps when they lyse
- sticky pus produced: mixture of dead bacteria and neutrophils, to prevent more bacteria moving further
type I interferons
prevent viral replication by binding to uninfected cells, allowing them to produce antiviral proteins
C3b Complement
plasma protein that sticks to bacteria (opsonisation) to make it more recognisable for phagocytes
iron-binding proteins: Transferrin
binds to iron so it can’t be used by bacteria to grow/replicate
cellular factors (3)
- Natural Killer cells (NK cells)
- phagocytes
- cells with inflammatory mediators
Natural Killer cells (NK cells)
lymphocytes that target virus-infected cells and cancer cells:
- if a cell lacks MHC-I, NK cell can only bind to its activating ligand which activates NK cell for killing
- normal body cells: NK cells can bind to MHC-I and activating ligand –> stable configuration: no killing activated
cells with inflammatory mediators
- basophils
- mast cells
- eosinophils
phagocytes
non-specifically engulf microbial invaders
different types of phagocytes
- fixed-tissue macrophages: already in tissue
- neutrophils: recruited at injury site
- monocytes: become macrophages and dendritic cells
examples of fixed-tissue macrophages
PAMPs and TLRs
phagocytosis (process)
- endocytosis of microbe: phagosome formed
- lysosome fuses with phagosome to form phagolysosome
- phagolysosome releases end products into and out of cell
Pattern Recognition Receptors (PRR)
recognise Pathogen Associated Molecular Patterns (PAMPs) and send out signals
example of PRR
Toll-Like Receptors (TLRs) are transmembrane receptors with:
- extracellular domain for pathogen recognition
- intracellular signalling domain to request cytokines
Antigen Presenting Cells (APCs)
link innate and adaptive immunity
epitope
part of the antigen recognised by the antibody
how is innate immunity linked to specific immunity?
- dendritic cell kills bacteria
- dead bacteria attached to dendritic cell
- dendritic cell carrying dead bacteria travels to lymph node via lymphatic system
- lymphocytes activated in lymph node
Specific / Adaptive immunity (def)
ability of the body to defend against specific microbes and foreign substances, involves memory
what cell type does the specific immune system involve
lymphocytes: B and T cells
on which cells is MHC-I expressed?
all nucleated cells
on which cells is MHC-II expressed?
on Antigen-Presenting Cells (APCs)
antigen presentation process
T cell receptors recognise antigens only when they are associated with MHC-II
Antigen Presenting Cells (APCs) include
- dendritic cells
- macrophage
- B cell/lymphocyte
how do APCs present exogenous antigens with MHC-II?
- ingestion of antigen by APC
- digestion of antigen into peptide fragments
- synthesis + packaging of MHC-II molecules
- vesicles containing antigen peptide fragments and MHC-II molecules fuse
- antigen peptide fragments bind to MHC-II molecules
- vesicle undergoes exocytosis: antigen-MHC-II complexes inserted into plasma membrane
- complex expressed to T cells in lymph nodes
antigen characteristics (2)
- reactivity
- immunogenicity: can provoke immune response
role of helper T cells
activated B cells and cytotoxic T cells
role of B cells
transform into plasma cells and secrete antibodies
–> involved in humoral response with antibodies and complement
role of cytotoxic T cells
attack infected body/foreign/cancer cells
-> cell-mediated response
3 stages of adaptive immune response
- recognition of antigen by lymphocytes
- lymphocyte activation
- attack launched by activated lymphocytes + their secretions
How are Helper T cells activated?
- Specific recognition between MHC-II and peptide-TCR (T cell receptor)
- Co reception of CD28-B7 –> checkpoint inhibition
- cytokine release from APC which stimulates T helper cell
checkpoint inhibition
CTLA4 or PD-1 displaces CD28, inhibiting T cell activation
how to get increased T cell activation through checkpoint inhibition
antibodies generated to bind to CTLA4 so it won’t displace CD28
CD4 required in activation of…
T helper cells
antibodies produced by…
plasma cells (which come from B cells)
antibodies are part of a group of proteins called…
globulins -> immunoglobulins
heavy chains of antibody corresponds to…
Fc region
light chains of antibody corresponds to…
FAB region
Fc region
constant: same in all antibodies of a class
FAB region
variable: determines specificity of antigen
-> antigen binding site
IgG
most numerous, produced after IgM during immune response
-> 2 binding sites
IgA
found in MALT and breast milk
-> dimer: 4 binding sites
IgM
first formed during immune response: responsible for complement activating cascade
-> 10 binding sites
plasma cells function
secrete specific antibodies
memory cells purpose
allow faster response if antigen seen again
active immunity
long-lasting protection: memory cells are involved and is the person’s own immune system response to pathogen
natural, active immunity example
catching Influenza by someone coughing on the bus
artificial, active immunity example
vaccination
passive immunity
temporary protection: no memory cells involved since the person receives antibodies from someone else
natural, passive immunity example
IgG from placenta or IgA from breast milk
artificial, passive immunity example
receiving serum containing antibodies from person/animal
functions of antibodies (6)
- neutralisation
- agglutination
- precipitation
- activating complement
- opsonization
- antibody-dependent cellular cytotoxicity
neutralising antigen
antibody binds to antigen so I can’t do more damage
agglutinating antigen
makes it harder for microbe to move/divide and easier for phagocyte to recognise
precipitating antigen
prevents antigen from moving
activating complement
antibody bins to antigen, leading to C1 activation and formation of Membrane Attack Complex
opsonisation
antibody sticks to pathogen surface and prepares for eating
antibody-dependent cellular cytotoxicity
increases effectiveness of NK cells: interaction between antibody and Fc receptor activates release of granzymes and perforin
immunocompetence
development of antigen receptor
RAGs purpose
Recombination Activating Genes: splice out gene segments from V, D, J
TdT purpose
Terminal deoxynucleotidyl Transferase: adds single bases on VDJ segments to increase variation
what determines which antibody will be produced from the mRNA transcript?
the control region gene expressed
immune tolerance
clonal deletion or clonal inactivation of cells that:
- don’t recognise MHC-II
- recognise MHC-I
percentage of T cells destroyed after production
95%
activation of Cytotoxic T cells
- infected body cells synthesise MHC-I molecules
- destroyed antigen (peptide fragments) are bound to MHC-I
- antigen-MHC-I complex packaged
- antigen-MHC-I complex inserted into plasma membrane
CD8 required in activation of…
Cytotoxic T cells
factors that alter resistance to infection (5)
- protein calorie malnutrition
- pre-existing disease
- stress
- sleep deprivation
- exercise/physical conditioning
protein-calorie malnutrition
energy required for lymphocytes to divide into antibodies is insufficient
immunodeficiency disease
result from weak or impaired immune system: SCID, AIDS
Severe Combined Immunodeficiency Disease (SCID)
absence of both B and T cells (sometimes NK cells)
Acquired ImmunoDeficiency Syndrome (AIDS)
infects and kills T helper cells so the immune system can’t produce antibodies or activate T cytotoxic cells
tissue grafts and organ transplant
MHC-I proteins on graft cells and MHC-II proteins on macrophages differ from recipient so they are targeted by T cells
drug used to avoid organ transplant rejection
cyclosporine: blocks cytokine production from T helper cells so there is no more signal for proliferation of T cells
transfusion reactions
hemolysis when erythrocytes are destroyed during blood transfusion
what acts as antigens in RBCs?
membrane proteins and carbohydrates on their surfaces
universal donor
O -
universal recipient
AB
blood group A has antibody…
anti-B
blood group B has antibody…
anti-A
blood group AB has antibody…
none (has A and B antigens on surface)
blood group O has antibody…
anti-A and anti-B (has no antigen on surface)
2 types of allergic reactions
- immediate hypersensitivity
- delayed hypersensitivity
anaphylaxis
mast cells release too much histamine in response to allergen, leading to hypotension and bronchiolar constriction, causing death
autoimmune disease
inappropriate immune attack triggered by body proteins acting as antigens
examples of autoimmune disease
- type 1 diabetes
- rheumatoid arthritis
- multiple sceloris
- myasthenia gravis: ion channels in muscle cells targeted
