Lecture 1 - Cells & Structure Function of Immune System Flashcards

1
Q

What is innate immunity?

A

Google: Body’s first line of defense against germs entering the body

Involve: Epithelial barriers, phagocytes, dendritic cells, complement, NK cells

Time of activation: 0-12 hours after infection

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2
Q

What is adaptive immunity?

A

Google: Acquired immunity or specific immunity, only found in vertebrates. The adaptive immune response is specific to the pathogen presented.

Involve: B-lymphocytes, T-lymphocytes (1-3 days)** / Proliferation (3-4 days)** / Antibodies & T-cells respectively (4-7days)**
**Number of days after infection

2 types: Humoral & Cell-mediated (aka cellular)

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3
Q

What is humoral immunity?

B-CELLS!!!!

A

Microbe (i.e Extracellular microbe) → Responding lymphocytes (i.e. B-cells) → Effector mechanism (Secreted antibodies) → Transfer medium (i.e. Serum)

Function: Block infections & eliminate extracellular microbes.

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4
Q

What is cell-mediated immunity?

T-CELLS!!!!

A

2 types (CD4/CD8 T-cells)

Phagocytosed microbes in phagocytes → CD4/T-helper → binding → T-cells macrophages
Function: Activate macrophages to kill phagocytosed microbes.

Viruses → CD8/cytotoxic T-cell → binding → T-cells
Function: Kill infected cells and eliminte reservoirs of infection

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5
Q

Briefly describe the phases of adaptive immunity.

A
  1. Antigen recognition (0-4 days):
    Still feel sick
    Antigen presenting cell binds to naive T-cells
    Pathogen / virus binds to naive B-cells
  2. Lymphocyte activation (4-12 days):
    Clonal expansion
    Differentiation
    Antibody producing cell and effector T-cells count are at their peak on the 12th day/
  3. Antigen elimination (12-16 days):
    Elimination of antigens first through humoral immunity
    Cell-mediated immunity comes next?!
    Starts to feel better already.
  4. Contraction (homeostasis) (16 days onwards):
    Apoptosis of lymphocytes
  5. Memory generation
    Surviving memory cells
    Back to basal level
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6
Q

Memory T-cells increase with age. How?

A

As we grow older, thymus output decreases (fewer naive T-cells made as rate of production drops)
We also encounter more variety of pathogens leading to the conversion of naive T-cells to Memory T-cells
So, we are just using up our naive T-cells reserve.

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7
Q

What are the features of adaptive immunity?

A
  1. Specificity
    Ensures that distinct antigens elicit specific responses (imprt for vaccine development)
  2. Diversity
    Enables immune system to respond to a large variety of antigens
  3. Memory
    Leads to enhanced responses to repeated exposures to the same antigens (special1)
  4. Clonal selection & expansion**
    Increases number of antigen-specific lymphocytes from a small number of naive lymphocytes (allow for faster release of immune cells)
  5. Specialisation
    Generates responses that are optimal for defense against different types of microbes.
  6. Contraction and homeostasis
    Allows immune system to respond to newly encountered antigens
    Avoid tissue damage (side effect of constant expression) + save energy
  7. Non Reactivity to self
    Prevents injury to the host during responses to foreign antigens (tolerant to host cells)
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8
Q

What is clonal selection?

A

+ Lymphocyte clones mature in generative lymphoid organs, in the absence of antigens

+ Clones of mature lymphocytes specific for diverse antigens enter lymphoid tissues

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9
Q

What is clonal expansion?

A

+ Antigen-specific clones are activated (“selected”) by antigens

+ Antigen-specific immune responses occur

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10
Q

What are the differences between innate immunity & adaptive immunity?

A
  1. Response Time
    Innate: Mins / hours
    Adaptive: Days
  2. Specificity
    Innate: Not that specific to strain but specific for molecules and molecular patterns associated with pathogens
    Adaptive: Highly specific discrimination even minor difference in molecular structure, details of microbial or nonmicrobial structure recognised with high specificity
  3. Diversity
    Innate: Limited number of germ-line encoded receptors
    Adaptive: Highly diverse, very large number of receptors arising from generic recombination of receptor genes (diff. B & T-cell receptors to tackle more variety of pathogens)
  4. Memory responses
    Innate: none
    Adaptive: Persistent memory, with faster response of greeted magnitude on subsequent infection
  5. Self/non-self discrimination
    Innate: Perfect; no microbe-specific patterns in host (will not attack self)
    Adaptive: Very good; occasional failures of self/nonself discrimination result in autoimmune disease
  6. Soluble components of blood or tissue fluids
    Innate: Many antimicrobial peptides and proteins
    Adaptive: Antibodies
  7. Major cell types
    Innate: Phagocytes (monocytes, macrophages, neutrophils), natural killer cells and dendritic cells, antigen-presenting cells
    Adaptive: T cells, B cells, antigen-presenting cells
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11
Q

List the different types of cells in the immune system. + Their localisation

A

All cells in the immune system arise from pluripotent hematopoietic stem cells in the bone marrow.
3 types of cells differentiation: Common lymphoid progenitor & Common myeloid progenitor & dendritic cells

a. Common myeloid progenitor →
Granulocyte / macrophage progenitor (Bone marrow)
Neutrophil (Blood)
Eosinophil (Blood)
Basophil (Blood)
Unknown precursor of mast cell (Blood) → Mast cell (Tissue)
Monocyte (Blood) → Macrophage (Tissue)

b. Megakaryocyte / erythrocyte progenitor (Bone marrow)
Megakaryocyte (Bone Marrow) → Platelets (Blood)
Erythroblast (Bone marrow) → Erythrocyte (Blood)

c. Common lymphoid progenitor → 
Blood → Lymph nodes → Effector cells 
B-cell 
T-cell
NK cell 

d. Immature dendritic cells →
Blood → Tissues → Lymph nodes

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12
Q

What is neutrophil?

A
  • Mediate the earliest phases of inflammation (fastest!)
  • Short-lived, function only for 1-2 days and then die
  • 1st line of defense
  • Activated function: Phagocytosis and activation of bactericidal mechanisms downstream.
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13
Q

What is eosinophil?

A
  • Present in mucosal linings of the respiratory, gastrointestinal, and genitourinary tracts, and numbers can increase during inflammation
  • Activated function: Killing of antibody-coated parasites
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14
Q

What is basophil?

A
  • Low numbers in tissues, may be recruited to some inflammatory sites
  • Activated function: Promotion of allergic responses and augmentation of anti-parasitic immunity
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15
Q

What is mast cell?

A
  • Defense against helminths and other microbes
  • Responsible for allergic reactions
  • Hypersensitivity (to be elaborated)
  • Activated function: Release of granules containing histamine and active agents.
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16
Q

What is macrophage?

A

+ Macrophages have two forms depending on the site of localisation (blood monocytes or activated tissue macrophage)
+ Major function of macrophages in host defense is to ingest and kill microbes via phagocytosis
Ingest dead cells – clean up process
+ Secrete cytokines to recruit more monocytes and leukocytes
+ Serve as antigen presenting cells to stimulate T-cells
+ Tissue repair by stimulating new blood vessel growth / activation of fibroblast formation

17
Q

What are the functions of B-lymphocytes?

A

+ Neutralisation of microbe
+ Phagocytosis
+ Complement activation

18
Q

What are the functions of Helper T-lymphocytes?

A

+ When microbial antigen presented by APC, release of cytokines
+ Lead to activation of macrophages, Inflammation, Activation of T & B-cells

19
Q

What is the function of cytotoxic T-lymphocytes (CTL)?

A

Killing of infected cells.

20
Q

What is a regulatory T-cell?

A

+ CD4 / cytotoxic T-cell
+ Involved in the contraction / natural process.
+ Suppression of T-cells to maintain homeostasis.

21
Q

What are NK cells?

A

+ Killing of viral infected cells
+ Antibody-dependent cell-mediated cytotoxicity (ADCC)
+ Releases lytic granules that kill some virus-infected cells

22
Q

What are dendritic cells?

A

+ Most important Antigen-presenting cells (APCs) for activating naive T-cells
+ Major roles in linking innate and adaptive immune responses.

23
Q

What are the uses of antibodies?

A

+ Complement activation
+ Neutralise microbes
+ Facilitate in phagocytosis

24
Q

What is the difference between small lymphocytes and lymphoblast?

A

+ Lymphoblast are activated small lymphocytes.

+ The nucleus becomes smaller, more cytoplasm since more proteins are made.

25
Q

What are the processes involved in the maturation & activation of lymphocytes?

A

a. Maturation of lymphocytes
Develop from bone marrow stem cells (common lymphoid precursor)
Mature in the generative lymphoid organs (bone marrow → B cells / Thymus → T-cells)
Circulate through the blood to secondary lymphoid organs (lymph nodes, spleen)

b. Activation of lymphocytes
Naive T-cells & immature B-cells migrate into secondary lymphoid organs (lymph nodes, spleen)
B cells complete maturation
Naive B & T cells activated by antigens differentiate into effector and memory lymphocytes.
Some of the effector and memory lymphocytes migrate into peripheral tissue sites of infection.
Antibodies secreted by B cells enter blood and are delivered to sites of infection. (B cells do not need to be at the site of infection)

26
Q

What are the features of bone marrow?

A
  • Primary lymphoid organ
  • Site of generation of most mature circulating blood cells
  • Site of early events in B cell maturation.

**B-cells require further maturation in secondary lymphoid organs.

*** T-cells do not mature in bone marrow. They mature only in Thymus after being made in bone marrow.

27
Q

What is the purpose of Thymus?

A
  • Site for T-cell Maturation

Parts: Medulla, Cortex, Blood vessels, Thymocytes, Hassall’s corpusle

28
Q

Describe the lymphatic system.

A

Function: Links the lymphoid organs (tonsils, thymus glands, lymph nodes, spleen, bone marrow)

+ Antigens from sites of infection reach lymph nodes via lymphatics
+ Naive lymphocytes enter lymph nodes from blood
+ Lymphocytes and lymph return to blood via the thoracic duct.

29
Q

What are lymph nodes?

A

+ Encapsulated, vascularised secondary lymphoid organs with anatomic features that favour the initiation of adaptive immune responses to antigens carried from tissues by lymphatics.
+ B-cells complete their maturation here.
+ Spaces in between the T-cell zone and the B-cell zone make interactions possible.
+ B & T cells are sequestered in distinct regions of the cortex of lymph nodes, each region with its own architecture of reticular fibers and stromal cells.

30
Q

Describe the features of the spleen.

A

Highly vascularised organ whose major function are to remove aging and damaged blood cells and particles (i.e. immune complex) from the circulation and to initiate adaptive immune responses to blood-borne antigens.

  • White pulp (B & T-cells) contains the cells that mediate adaptive immune responses to blood-borne antigens.
  • Red pulp → Blood vessels
31
Q

Regional Immune System

A

+ All major epithelial barriers of the body, including skin, gastrointestinal mucosa, and bronchial mucosa, have their own system of lymph nodes, nonencapsulated lymphoid structure, and diffusely distributed immune cells (Considered secondary lymphoids)
+ Work in coordinated ways to provide specialised immune responses against pathogens that enter at those barriers.

32
Q

What is the distribution of lymphocytes in lymphoid organs and other tissues like?

A
  1. Lymph nodes: 190 X 10^9
  2. Spleen: 70 X 10^9
  3. Bone Marrow / Intestines: 50 X 10^9
  4. Lungs: 30 X 10^9
  5. Skin: 20 X 10^9
  6. Blood / Liver: 10 X 10^9