M7 - Immunology Flashcards
phagosome
吞噬體
phagocytosed
被吞噬
induce
誘發
evade
逃避
engulf
吞噬
fetus
胎兒
atherosclerosis
動脈粥狀硬化
asbestosis
石棉肺
deficiency
缺陷
hypersensitivity
超敏反應
Allergy
過敏
Immunodeficiency
免疫缺陷
Rheumatoid arthritis
類風濕關節炎
necrosis
壞死
incapacitated
喪失行為能力
ankylosing spondylitis
僵直性脊椎炎
cytokine
a protein that is released from a cell that acts on receptors on other cells
細胞激素
sanitation
衛生設施
vaccination
疫苗接種
smallpox
天花
rivalry
競爭
tetanus
破傷風
Cellular immunity
immune mechanisms involving direct action of a cell to eliminate a pathogen
Humoral immunity
any immune mechanism using secreted factors, but usually refers to antibodies produced by B cells
innate
天生的
Mechanisms of Prevention of Infection
- Physical and chemical barriers to pathogen invasion
- Active defence by innate immune cells天生
- Active defence by cells of the acquired immune system後天
Mucus
黏液
Gut
腸道
entrap
捕獲
shed
脫落
Physical barriers
- Skin: tight junctions between epithelial cells
- Gut: mucus + thick layer that prevents association between bugs and the epithelium.
- Lung: Mucus entraps organisms
- Physical removal of bacteria – flow of urine, shedding of mucus in gut, ciliated epithelium moving mucus up and out of the lung.
peptide
胜肽
Commensal
共生體
Lysozyme
溶菌酶
degrade
降解
Chemical barriers
- Acid pH: in stomach and skin
- Antimicrobial peptides secreted onto epithelial surfaces: disrupt bacterial membranes.
- Enzyme: degrades the bacterial cell wall. ex. lysozyme in tear & saliva
Biological competition example
Commensals in gut and skin compete with pathogens – if the niche生態位 is already occupied, pathogens cannot move in.
Monocytes
單核細胞
macrophages
巨噬細胞
natural killer cells
自然殺手細胞
dendritic cells (DC)
樹突狀細胞 (DC)
neutrophils
嗜中性球
basophils
嗜鹼性球
eosinophils
嗜酸性球
mast cells
肥大細胞
complement system
補體系統
Lysis of pathogens through the attack of several dozen secreted proteins
influx
湧入
Feature of Innate Immunity
- Rapidly acting
- Same response for same pathogen
Lysis
裂解
Phagocytosis and destruction of pathogens by…
neutrophils, monocytes, macrophages, DC
antigen
抗原
Feature of Acquired Immunity
- slower to develop for the first-time infection
- specific customized
- has “memory”: when facing the next same infection, the response is more rapid and effective.
the work of B cell
antibody production
the work of T cell
killing of infected cells
Peripheral
周圍
phagocytosis
吞噬作用
bone marrow
骨髓
thymus
胸腺
Immunity is mediated by cells which develop in…
the primary lymphoid organs (bone marrow and thymus)
spleen
脾臟
Immune cells circulate through…
blood and lymph and secondary lymphoid tissues (spleen, lymph nodes and mucosa- associated lymphoid tissue –MALT)
The acquired immune response is initiated in…
secondary lymphoid tissues.
Tonsil
扁桃體
anticoagulant
抗凝血劑
centrifugation
離心
Serum
血清
clot
凝塊
Lymphocytes
淋巴球
Granulocytes
粒細胞
polymorphonuclear leukocytes
多形核白血球
3 types of leukocytes
•Lymphocytes (T cells, B cells and NK cells)
•Monocytes
•Granulocytes (also called polymorphonuclear leukocytes) - Neutrophils, Eosinophils, Basophils
haematopoiesis
造血作用Differentiation of blood cells
haematopoietic stem cells
造血幹細胞
proliferate
增生
precursor
前驅物
T Cell Differentiation in
thymus
Lymph fluid returns to the blood stream via…
thoracic duct.
Lymph is not pumped, but moved via
skeletal muscle contractions
debris
碎片
Lymph contains:
•Leukocytes
•Proteins similar to plasma
•Cell debris
•Pathogens
•(Cancer cells)
the secondary lymphoid organs:
– Lymph nodes
– Spleen
– Mucosa-associated Lymphoid Tissues (MALT)
MALT acquires antigen from…
gut and airways
Red pulp of Spleen
site of RBC disposal處置
Pulp 髓
pulp
髓
White pulp of spleen
sites of T and B cell activation similar to lymph nodes
“naïve” lymphocytes
Lymphocytes that have not previously been activated by recognition of a foreign antigen molecule.
lysosome
溶小體
carries proteases actived at acid pH
acidification
酸化
Stages of Phagocytosis
• Recognition
• Extension of membrane
• Fusion of membrane to form phagosome
• Fusion of phagosome with a lysosome and then acidification of the phagolysosome
• Killing and degradation of bacterium
Opsonisation
調理作用
Free radicals
自由基
molecules with a lone unpaired electron
proteoglycan
蛋白質多醣
sequester
isolate
Main Microbial Killing by Phagocytes
Utility of Reactive Oxygen and Nitrogen Species:
[Backgroung: Free radicals are highly reactive.]
1. NADPH oxidase enzyme makes O(2-) (superoxide) targeted into the phagosome or into extracellular space. Then, non-enzymatic reactions of O(2-) generate: H2O2 (hydrogen peroxide), HO (hydroxyl radical)
2. NO- is made by inducible誘導型 nitric oxide synthase一氧化氮合成酶.
Other means of attack to kill microbial by phagocytes
- Degradative enzymes: lysozyme attacks proteoglycan in the cell wall & acid proteases degrade proteins
- Antimicrobial Peptides (positively charged peptides that attack bacterial cell wall)
- Other proteins bind and sequester iron, that is essential to bacteria
Granules
顆粒
Features of Neutrophils
- strucuture: Multi-lobed nucleus + cytoplasmic granules (with antimicrobial peptides, lysozyme, degradative enzymes)
- Short-lived, and many die at the site of infection, contributing to pus formation. In the process of dying they can release DNA and anti-bacterial proteins which together trap and kill organisms.
macropinocytosis
巨胞飲作用
taking in fluid from the surroundings into large vesicles
endocytosis
內吞作用
Location of Mast cells
in the tissues near blood vessel
histamine
組織胺
The function of Mast cells
- Release histamine which causes inflammation, increases vessel permeability and attracts leukocytes.
- Related to allergy
serum proteins
血清蛋白
cascade
serum proteins of Complement are activated one by one
Three classical pathway of complement activation
- Classical pathway : antibody bound to the pathogen surface
- Mannose-binding lectin pathway: Binds to sugar molecules on the surface of pathogens
- Alternative pathway: Direct recognition of bacterial surface by complement proteins
Function of inflammation
- attract and activate immune cells
- prevent the spread of infection
- initiate tissue repair
Inflammation can be initiated by:
(i) Cell damage - release of molecules from damaged cells – “danger signals”
(ii) Recognition of pathogen molecules
Extravasation
免疫反应过程，白血球能够离开血管，进入受损或感染的组织，以进行免疫防御和修复
- Receive message
- Rolling on the inner wall of blood vessels
- Adhesion附著 to the vessel wall.
- Transendothelial跨內皮 migration
- Chemotaxis towards source of infection
- Phagocytosis of invading organisms
Pathogen Recognition Receptors(PAMPs)
• PAMPs include many bacterial and yeast cell wall products, bacterial and viral DNA, and viral RNA
• These are recognised by Pathogen Recognition Receptors (PRR) on innate immune cells.
Toll-like Receptors (TLRs)
• Key receptors for Pathogen Recognition Receptors(PAMPs) expressed by innate immune cells
• Some are expressed on the cell surface, and some within the endosomal/phagosomal system
Function of cytotoxic T lymphocytes (CTL)
kill infected cells
The function of helper T cells (Th)
- help B cells make antibody
- help macrophages kill phagocytosed organisms
The function of B cell
make antibodies
antigen
抗原a molecule against which B and T cells generate a response.
B cell receptor
Just antibody
B cells recognise antigens through B cell receptor (BCR). The BCR is later produced as a secreted form, which is antibody (also known as immunoglobulin - Ig).
immunoglobulin (Ig)
免疫球蛋白(Ig)
Activated B cells secrete “antibodies”
Two parts for antibody
“Fc”: constant
“Fab”: variable
Consequences of Antigen Recognition by T and B cells
- Proliferation: clonal selection or clonal expansion.
- Differentiation
• B and T cells develop mature“effector” cell function.
• B cells become antibody-secreting “plasma cells”
• T cells become CTL or T helper cells
• Some T and B cells become long-lived memory cells
Progenitor cell
祖細胞
Clonal Expansion
1st generation: Progenitor cell - Receptor variability generated during development
2nd generation:
- Lymphocyte pool with different Ag specificity
- Removal of self-reactive lymphocytes leads to self tolerance
3nd generation: Recognition of foreign antigen by mature naïve lymphocytes and clonal expansion
Receptor variability generated during development
How do B and T Cells make so many different Antigen Receptors?
B and T cell genes rearrange during development, randomly combining different gene segments to generate variable receptors.
Neutralisation
中和作用
antibody binding to virus can block entry into cells. Antibody can also neutralise bacterial toxins (e.g. tetanus toxin) and prevent effects on cells
Some Ways in Which Antibodies Act:
- Neutralisation
- Opsonisation
- Antibody-dependent cellular cytotoxicity.
- Activation of classical pathway of complement system –lysis, opsonisation, inflammation
- Triggering of mast cells to release histamine
Antibody 5 Classes
vary by the use of different heavy chain constant regions – IgM, IgD, IgG, IgA, IgE
class switching of antibody
B cells can switch from making one class of antibody to another, but it does not change the antigen specificity of the antibody
IgM
First class produced in response to a new Ag. Activates complement well. Can be pentameric.
IgG
Major Ig in blood, crosses placenta胎盤 into fetus胎兒.
IgA
Present in tears, saliva, mucus, milk as well as blood. Protects mucous membranes and infants. Can be dimeric二聚體.
IgE
Activation of Mast cells, basophils - allergy and anti-helminth (worm parasite) responses
IgD
Primarily B cell surface bound – function not well understood
affinity
親和力
fluorescently-labelled
螢光標記
CD4 marker
a surface protein
T helper (Th) cells have
(i) help B cells make antibody – Th2 subset are good at this
(ii) activate macrophages to kill ingested organisms – Th1 subset are good at this
Th2 subset of CD4 maker
help B cells make antibody
help B cells make antibody
activate macrophages to kill ingested organisms
CD8 marker
Cytotoxic T lymphocytes (CTL) have to directly kill infected cells or tumour cells
T Cell Antigen Recognition
• TCR does not recognise free antigen
• TCR recognises peptides from antigens which are “processed” by antigen presenting cells (APC) and presented on a molecule called MHC (major histocompatibility complex).
Antigen “processing”
proteins are broken down by proteases to give short peptides.
The major APC (Antigen-Presenting Cell) involved in activation of naïve T cells
Dendritic Cells
HLA (human leukocyte antigen)
MHC proteins
major cause for incompatibility in transplantation
MHC proteins are highly variable between individuals
MHC Class I
-displays peptides derived from cytoplasmic proteins (inside)
-activates CD8 T cells to become CTL
MHC Class II
-displays peptides derived from proteins from outside cell and within phagosomes/endosomes (outside)
-activates CD4 T cells to become T helper cells
MHC I or MHC II provides information on the location of the pathogen, and directs an appropriate immune response:
• MHC II: An extracellular infection needs T helper cell activation
• MHC I: An intracytoplasmic infection needs CTL activation
Naïve T cell activation by activated DCs requires 2 signals
Signal 1 = T cell receptor binding MHC- Ag peptide
Signal 2 = Costimulatory signal (e.g. CD28 on T cell binds B7 on dendritic cell)
why the dendritic cell only expresses B7 if it is activated
This helps to restrict T cell activation to infectious situations.
The difference between PAMPs AND Antigens
1) The antigen (usually a protein) which is taken up and processed for presentation on MHC.
2) the PAMP (e.g. LPS, bacterial DNA) which alerts the APC to the fact there is an infection – the PAMP is not an antigen. PAMP signaling induces expression of B7 on the surface of the DC, to provide the essential signal 2.
apoptosis
細胞凋亡
Function of Cytotoxic T Cells
•Kill virally infected cells or tumour cells.
•Release granules which induce apoptosis.
The function of T helper (“Th”) cells
Th1 and Th2 cells secrete different types of cytokines and are particularly good at helping macrophages and B cells, respectively
Activated T cells can be:
(i)Cytotoxic T lymphocytes
(ii) T helper (“Th”) cells
Summary of T cell Life
- T cell progenitors [Bone marrow]
- Develop & rearrange TCR gene [thymus]
- Central tolerance: T cells with a TCR strongly recognising self proteins are deleted
- Mature naïve T cells leave thymus and circulate [blood and secondary lymphoid organs]
- Stimulate to be Effector T cell (CTL or Th cell) through the recognition of antigen epitope by TCR
- Do the work of Effector T cells
- After antigen disappeared, Responsive T cell ↓, but memory T cells remain
susceptibility
易感性
“Severe Combined Immunodeficiency” (SCID)
T cell deficiency 缺陷
Acquired Immunodeficiency Syndrome (AIDS)
後天免疫缺乏症候群（愛滋病: AIDS就是因為其攜帶的HIV-1反转录病毒取代CD4使具有CD4分子的细胞（例如：Th细胞细胞）死亡，甚至导致未感染的免疫细胞死亡，導致免疫系統受損。
Autoimmunity
自體免疫The Immune System Sometimes Attacks The Body
Peripheral tolerance
some cells escape central tolerance and a range of processes in the periphery control self-reactive T cells
一些細胞逃避中樞耐受性，週邊的一系列過程控制自身反應性 T 細胞
Two types of Mechanisms of tolerance
Central tolerance
Peripheral tolerance
Failure of tolerance leads to…
autoimmunity
Example of Autoimmunity – Type I Diabetes (Insulin-dependent diabetes mellitus- IDDM)
負責產生胰島素的胰島 b 細胞會被 CTL 特異性破壞導致胰島素分泌減少=血糖值失控
Example of Autoimmunity - Multiple sclerosis
多發性硬化症
中樞神經系統的神經 - 感覺、運動、視力問題被影響。每個患者都有Epstein Barr virus (EBV)感染，但不清楚具體機制。B 細胞療法是有效的。
Example of Autoimmunity - Narcolepsy
嗜睡症
症狀是白天嗜睡，因為無法調節睡眠-覺醒週期。被認為是由於下視丘神經元受到自體免疫攻擊導致無法生產下視丘分泌素神經肽激素。
anaphylactic shock
過敏性休克
Process of Allergy
- Prior sensitisation to allergen: T cell and B cell activation to produce IgE
- Allergen-IgE binding to Mast Cells leading to “degranulation”- release of histamine to show the symptom of allergy
- Severe response causes anaphylactic shock: many mast cells degranulation causing a dangerous drop in blood pressure
- 事先對過敏原致敏：T細胞和B細胞活化產生IgE
- 過敏原-IgE與肥大細胞結合導致「脫粒」－釋放組織胺以顯示過敏症狀
- 嚴重反應導致過敏性休克：許多肥大細胞脫顆粒導致血壓危險下降
