Lecture 2: Intro to Immunology Flashcards
What is the most common manifestation of an infection?
Fever.
It inhibits the proliferation of an infection
What are extracellular and intracellular microbes?
Extracellular microbes can survive in animals by growing extracellularly, as long as they have nutrients.
Intracellular microbes invade, live and replicate intracellularly and use the hosts energy sources.
Characteristic of all microbes
They can
- Grow
- Reproduce
- Infect humans
What are self-particles?
Those that are made by your body. Something that is self should NOT be targeted or destroyed by the immune system.
What are non-self particles?
Sometimes called foreign bodies.
Particles NOT made by your body that can be recognized as potentially harmful by making antigens.
What are antigens?
Antigens are made by non-self particles and let the body know that they want to damage.
What is a cytokine?
Molecules that are used in cell-signaling to communicate with neighboring cells about initiating a immune response.
They also trigger movement to a specific part of the body.
What are chemokines?
Chemokines are release by an infected cell and initiate an immune response by warning neighboring cells.
Immunity is a set of _________________, which can protect us against diseases.
cooperative defense mechanisms
Immune responses against microbes (pathogens) can cause what?
Damage to tissue: aka; collateral damage.
_______ can elicit an autoimmune response.
Self-antigens.
If self-antigens are attacked; autoimmune response.
The immune system is made up of what 2 elements?
- Fixed elements, which are lymphoid organs that can be primary or secondary.
- Mobile elements, which are immune cells or soluble (humoral) components, such as antibodies, complement and acute phase proteins.
Primary fixed elements
- Bone marrow
2. Thymus
Secondary fixed elements
- Spleen and lymph nodes
2. Mucosal immune tissues
Roles of immune system
- Defend against infections and tumors
- Can injure cells and cause inflammation
- Recognize and responds to tissue grafts and new proteins, which is often a barrier to transplants.
What is the most effective method of protection against infections?
Vaccinations, which stimulate a immune response against pathogens.
What is herd immunity?
As more people are vaccinated, the spread of disease decreases
What is the difference between active and specific immunity?
Active immunity is the immunity to a dz acquired by making your own antibodies when you are exposed to the dz through infection or vaccination.
Passive immunity occurs when you are given antibodies or t-lymphocytes to a disease rather than making them yourself.
Both help to resist infection and are specific. However, only active immunity generates memory.
What are the 2 types of immunity?
- Innate immunity
2. Adaptive (acquired) immunity
What is innate immunity?
Innate immunity is our first line of defense that as soon as something attacks.
It has SOME specificity for antigens but has no memory.
It creates acute inflammation.
What is adaptive immunity?
Adaptive immunity develops more slowly and occurs only after the body has experienced an initial attack. Thus, it has memory for SPECIFIC antigens.
Compare and contrast the diversity of innate immunity and adaptive immunity
Innate immunity does not have much diversity; it provides generalized protextion
Adaptive immunity, on the other hand, is very diverse. Different receptors are made by somatic recombination.
Which react to self:
Innate immunity or adaptive immunity?
Neither.
Innate immune system first line of defense and second line of defense
Induced?
Specific?
1st line of defense is NON-induced and NON-specific: skin, saliva, pH of stomach.
2nd line of defense is INDUCED and BROADLY-SPECIFIC. Inflammatory response try to fight off infection: phagocytosis, compliment activation and secretion of cytokines. It occurs 4-96 hours after infection
What is phase 3 of defense?
Adaptive immunity- a HIGHLY SPECIFIC response to an antigen initiated by
- B cells (Ab)
- helper T-cells
- Cytolytic t-cells
Examples of cells of innate immunity
- Skin
- Mast cells
- Phagocytes
- Dendritic cells
- Compliment
- NK and ILCs
How do our cells of innate immunity act so quickly?
They circulate in our blood and delivered to tissue on demand.
Which immune cells live in our blood?
- Neutrophil
- Eosinophil
- Basophil
- Monocyte
- T-cell
- B- cell
- NK cell
- Platelets
- RBC
Which immune cells are located in our tissues?
- Tissue eosinophil
- Mast cells
- Macrophages
- T-lymphocyte
- Plasma cell
- NK cell
Phagocytes?
- Neutrophil
- Monocytes
- Macrophages
What are the 4 polymorph granulocytes of innate immunity?
- Basophil
- Eosinophil
- Basophil
- Mast cells
Granules are released on-demand of infection
Infection and tissue damage can lead to what?
- Heat
- Redness
- Swelling
- Pain
- Loss of function
What do innate immune cells originate from?
Pluripotent HCS, which the differentiate to become CMD (common myeloid progenitors)
Our innate immune cells will be derived from the common myeloid progenitors + NK cells.
What is CD?
Stands for [cluster of differentiation], which allows cells to be identified by the receptor on their surface.
What are the 4 mononuclear cells of innate immunity?
- Monocyte
- Macrophage
- Dendritic cells
- NK cells
NK cells are raised as ____________, but assist in _______________.
Lymphocyte
Innate immunity
Primary fx of phagocytes?
Phagocytes are long living because they require little maintenance.
Ingest, destroy pathogens and get rid of damaged tissues (scavenger cells)
Steps in the response of phagocytes?
RRID
- Recruitment to the site of infection
- Recognize pathogen and get activated
- Ingest via phagocytosis
- Destruct
Once activated, they secrete cytokines
Do cytokines act on every cell?
No. that cell must have a [R] for it.
Neutrophils are also called what?
What is something crazy about neutrophils?
Neutrophils are called polymorphonuclear leukocytes because their nucleus has 3-5 lobes.
Most abundant population of circulating spherical WBC, which help in the earliest phase of inflammatory reactions.
What is the most abundant population of circulating WBCs?
Neutrophils
Where are neutrophils made and what do they arise from?
Bone marrow and arise from precursors that ALSO make mononuclear phagocytes.
Production of neutrophils is stimulated by cytokine called what?
granulocyte colony‐stimulating factor (G‐CSF)
Life of a neutrophile
we make 10^11 in a day and each circulated in blood for hours or a few days.
After they enter tissues, they only fx for 1-2 days then DIE.
Mast cells, basophils and eosinophils
- All involved in innate and adaptive immunity
- Protect against helminthes and allergic reactions
- All have cytoplasmic granules
Mast cells are located STRATEGICALLY. Why is that?
Masts cells are located in tissue that are exposed to the EXTERNAL environment, near blood vessels.
This allows them to regulate permeability and recruit effector cells by releasing mediators. .
What cells does the mono-nuclear phagocytes system include?
- Monocytes (which live in the blood)
2. Macrophages (live in tissue), which play role in adaptive and innate immunity.
Monocytes–> Macrophages
Mature monocytes–>blood circulation–> tissues, where they mature into macrophages, especially during inflammation.
Creation of cells in the macrophage lineage
MoP/CFU-M (monocyte progenitor) in the bone marrow will become monocytes –> macrophages
via M-CSF (monocyte/macrophage colony stimulating factor)
Vascular Route for Monocyte/Macrophage Recruitment
When there is inflammation, circulating monocytes will go into the tissue and become macrophages after a few days.
They will cause inflammation and then REPAIR the inflammation.
Characteristics of macrophages
Perform tissue specific and niche-specific fx such as
- Homeostasis
- Immune surveillance
- Respond to infection
- Repair inflammation
Dendritic cells
- Involved with innate immunity
- Antigen-presenting cell (APC)
- Stimulate T-cells to cause adaptive immunity
- 2 kinds: myeloid (mDCs) and plasmacytoid(pDCs) dendritic cells
- include langerhan cells
mDCs
Myeloid dendritic cells that are derived from monocytes and differentiated from plasma blood mononuclear cells (PBMC)
What type of cell is a langerhan cell?
Dendritic cells
What are the two types of adaptive immunity?
- Cellular immunity- accomplished by T cells
2. Humoral immunity- accomplished by B cells
Adaptive immunity is geared to specific pathogens by having memory for them; allowing them to respond quicker and faster. What causes this?
The interaction between (T-cells), (B-cells) and (APCs).
Cellular immunity
Accomplished by T-Cells, which develop and mature in the thymus.
[T helper cells] will activate macrophages to kill pathogens that have been phagocytosized or
cytoxic t lymphocytes (CTLS) to directly destroy infected cells. Because they do not secrete antibodies, they kill pathogens located INTRACELLULRLY (presented by APC)
They will then kill the infected host cell
Humoral Adaptive Immunity
B cells(which mature in bone marrow) secrete antibodies in the blood and mucous and target EXTRACELLULAR pathogens and their toxins.
The antibodies will recognize the Ag, neutralize the infectivity and target them for elimination.
Humoral immunity involves the production of immunogolbins (antibodies)
Adaptive immunity specificity
Ensures that our immune system responds to a specific pathogen or antigen.
Adaptive immunity diversity
Allows our immune system to respond to a large variety of antigens
Adaptive immunity memory
Memory allows us to fight infections to the same pathogen quicker.
Adaptive immunity clonal expansion
Clonal expansion will increase the number of antigen-specific lymphocytes.
Adaptive immunity specialization
The responses that are made are optimal for defense against pathogens.
Adaptive immunity contraction and homeostasis
Adapative immunity allows the immune system to recover from 1 response, so that we can better respond to new antigens
MEMORY
Adaptive immunity non-reactivity to self
Prevents the injury of hosts when killing foreign antigens.
What are naive B cells?
Those that have not been exposed to an antigen
Differentiation into B cells occurs where?
- fetal liver
2. bone marrow, after birth
Development of B cells requires what?
- Stromal cells
- IL-1
- IL-6
- IL-7
Receptors on B-cells
The receptors on B-cells are specific for only 1 type of antigen.
Common lymphoid progenitor cells make T-cell via what cytokines?
IL-1
IL-2
IL-6
IL-7
Receptors on T-cells
Like B cells, T-cells have receptors for only 1 type of antigen made by gene rearrangement
What happens when T-cells and B-cells react with self-antigens?
Undergo apoptosis.
What are the 2 types of T-cells?
- T-helper cells- express CD4 and help B cells grow and differentiate.
- Cytotoxic T-lymphocytes- express CD8 and kills virus-infected cells.
What do mature T-cells do?
Migrate to secondary lymphoid tissue to help protection
How does the immune system respond to a large number of different antigens?
This is called the clonal selection hypothesis.
The clonal selection hypothesis says that before and independent of an antigen, a B-cells and T- cells will give rise to a variety of specific daughter cells (clones) with different receptors in the bone marrow and thymus.
Upon infection, mature B and T cells will then migrate to the lymph nodes. When they are activated by an antigen, B and T cells will then differentiate and proliferate into clones for that specific antigen (Clonal expansion).
The clones will SPECIFICALLY react with that antigen to neutralize it or eliminate. This is how we develop memory for cells.
B lymphocytes recognize what kind of antigens? How do they respond
Recognize soluble antigens and secrete antibodies to combat
T-helper lymphocytes recognize what kind of antigens? What do they do after?
Recognize antigens on APCs and secrete cytokines, which then activate
- Macrophages
- B-lymphocytes
- T-lymphocytes
Cytotoxic T lymphocytes (CTL)
Recognize antigens on infected cells and kills them.
Regulatory T cells
Suppress the immune response.
______ can cause septic shock.
Cytokines.
Thus, they must be contained. Young people secrete more so they are more at risk
Where do naive, activated and memory T cells migrate to?
Naive- Peripheral lymph nodes
Activated- Inflamed tissue
Memory- one subset to [lymph node, mucosa and inflamed tissue]
What are the type of immunoglobulins found in naive, activated and memory B cells?
IgM & IgD
IgG,IgA,IgE
IgG,IgA,IgE
Which have effector function: naive, activated or memory T cells?
Activated: secrete cytokines (CD4 T-helper cells) or have cytoxic activity (CD8 T cells)
Naive and memory have none.
Which have effector function: naive, activated or memory B cells?
Activated B cells: secrete antibodies
What is the cutaneous immune system?
The skin has 20 billion T-cells.
The primary APC in the skin are langerhan cells. When a cell is damaged or a pathogen is present, they will pick up the antigen, present it on its surface and go to the lymph node.
When at the lymph node, the DC cells activates and calls on naive T-cells to secrete cytokines (CD4+ helper cells) and kill pathogens (CD8+)
The skin has both (CD4+) T-helper cells and CTLs (CD8+) are both present and release cytokines to care for the skin.
In the cutaneous immune system, where do CD8+ cells live?
Cytotoxic T-cells- epidermis, allowing them to respond rapidly to damage.
In the cutaneous immune system, where do CD4+ cells live?
T-helper cells- dermis, allowing them to carry out effector functions
What is the mucosal immune system?
The epithelium of mucosal membranes secrete mucous, forming a barrier to microbial invasion. Cells such as [dendritic cells, T-cells and macrophages ARE LOCATED IN LAMINA PROPRIA] provide innate and adaptive protection against pathogens.
In the small intestine, they can form patches called Peyer’s patches.
Antigens enter our tissues from the lumen via M-cells, and are taken to lymph nodes.
The dominant antibody found in this system is immunoglobin A (IgA).
In the mucosal immune system, how do antigens pass through lumen?
M-cells
What is the dominant antibody found in the mucosal immune system?
IgA
Fluid that leaks out of the walls of the blood vessels (lymph) goes to lymphatic vessels–> lymph nodes–> and back into circulation. Thus, what does lymph contain?
A mixture of antigens that are absorbed from our tissues and blood and takes them to our lymph nodes.
What happens when an antigen enters lymph nodes?
Naive B cells aggregate in [B cell zone] and sample the antigen.
Dendritic cells take the antigen to the [T-cell zone] so that naive T-cells can sample the antigen.
Thus, antigens become concentrated in the lymph nodes.
How are T and B cells dispersed in the lymph nodes?
T cells are in the central part of LN
B cells are in periphery.
What happens to antigens present in blood?
Local APC (dendritic cells and macrophages) take them to the spleen via sinusoids.
In the SPLEEN, how are naive T cells and naive B cells arranged?
Naive T-cells are located in PALS (periarterioral lymphoid sheath) located around central arterioles of the spleen.
Naive B cells are located in FOLLICLES at the periphery of PALS.
T-cell zone in spleen and B-cell zone in spleen are called what?
Together, they are called?
T-cell zone: PALS
B-cell zone: Follicles
Together, these zones are called WHITE PULP.
WHITE PULP= PALS and FOLLICLES
Lymphocytes develop from what kind of cells?
Where do they mature
- Bone marrow stem cells (HSC)
2. Mature in lymphoid organs (bone marrow and thymus)
Where do mature lymphocytes circulate through the blood to?
Secondary lymphoid organs such as
- LNs
- Spleen
- Regional lymphoid tissues (mucosa associated lymphoid tissues (MALT))
Where are antigens captured and where do they then, go?
Captured at site of infection
Taken to the lymph node, where the immune response is begins.
Migration of T-cells
Naive T cells enter LN through HEVs (high endothelial venules) into the T-cell zone. Chemokines made in T cell zones presented on the surface of HEV, bind to [chemokine receptor CCR7] on T cell, which causes T cells bind tightly and go to the T-cell zone.
In the T-zone, antigens are then presented to them via DCs and they are activated.
Migration of B-cells
B-cells enter LN similarly to T-cells.
However, they are guided to LN follicles by chemokines t that bind to CXCR5 receptors presented on B cells.
What are the 5 phases of adaptive immune responses?
- Antigen recognition
- Lymphocyte activation
- Antigen elimination
- Contraction/Homeostasis- antigen stimulated lymphocyte dies, causing the response to decline and restoring homeostasis.
- Memory- the few antigen-specific cells that survive are responsible for memorty
The secondary adaptive immune response to an antigen is more rapid and larger than the primary response due to?
Memory cells!
Memory cells are more effective in combating pathogens than naive cells , as well as more numerous and respond faster.
Antibody levels decline with time after each immunization… why?
Contraction of immune response
What is the important goal of vaccinations?
Creating an immune response
Where are basophils located?
Blood
Where are mast cells located?
Tissue.
Where are monocytes located?
Blood.
Once in the tissue; they become macrophages.
Where are B cells located?
Blood
Where are plasma cells located?
tissue
Where are NK cells located?
Blood and tissue
Where are T cells located?
Blood and tissue
The majority of effector lymphocytes induced by a pathogen die by apoptosis after the microbe is eliminated. What does this cause?
Homeostasis.
This occuurs because pathogens provide important stimuli to keep lymphocytes alive and to activate them. Effector cells are short-lived.
As the stimuli are eliminated, the activated lymphocytes die.
What is an imporant goal of vaccination?
Generation of a memory response.
