Immunology: Immune Cells Powerpoint study material

What are hematopoietic stem cells?

They are pluripotent stem cells that can become many different types of blood cell types through a process called hematopoiesis

What are the two primary lineages that give rise to most immune cells?

The myeloid lineage and the lymphoid lineage

What are primary lymphoid organs?

Organs where immune cells are grown and mature. Primary lymphoid organs consist of the bone marrow and the thymus.

What are secondary lymphoid organs?

These are organs where the immune cells meet pathogens and become activated. Secondary lymphoid organs consist of the spleen, lymph nodes, tonsils, Peter’s patch, and the appendix.

What are the three lineages of the blood cells?

Erythroid, myeloid, and lymphoid

What are the purpose of erythrocytes?

. They produce red blood cells and platelets

. Their primary job is transporting oxygen and blood clotting

What are the purpose of myeloid cells?

. Produce neutrophils, basophils, eosinophils, monocytes, macrophages, mast cells, and some dendritic cells

. These are the cells that dominate the innate immune response

What are the purpose of lymphoid cells?

. Produces B cells, T cells, NK cells, and innate lymphoid cells

. These cells are responsible for adaptive immunity (except for NK cells which belong to the innate immune response)

What are granulocytes?

A type of blood cell that contains granules filled with proteins and toxic chemicals that can be released rapidly by a process called degranulation

What are the three types of granulocytes?

. Neutrophils

. Basophils

. Eosinophils

What are some characteristics of Neutrophils?

. They are the first responders of the immune system; the first ones to the sight (also called PMNs)

. They phagocytose bacteria, kill bacteria with toxic granules, and for NETs (neutrophil extracellular traps)

. They do not express MHC class II and are thus not antigen presenting cells

. They are found in high levels during bacterial infections (leukocytosis)

. Mature PMNs are called Sags and immature PMNs are called Bands (PMNs are acted on by C5a)

. They have a short life span and will migrate to tissues

Why are neutrophils involved in both innate and adaptive immunity?

. Neutrophils are innate immune cells but once antibodies are produced during adaptive immunity response, neutrophils can recognize antibody-coated pathogens and use those to kill pathogens more effectively.

. They also participate in antibody-dependent cell toxicity (ADCC)

What are some characteristics of Basophils?

. They are allergy specialists and are considered the mast cells of the blood stream

. They bind IgE (a type of anti-body protein produced by the immune system to fight parasites and respond to allergens)

. They promote TH2 immune responses (a branch of adaptive immune response that fights extracellular parasites and triggers antibody production)

. Majority of basophils reside in the mucosal tissues (?)

. They are granulocytic and phagocytic

. antiworm, antiallergy, and antitick

. They are especially present in epithelial barriers

How do basophils coincide with both innate and adaptive immunity?

. For innate immunity: They comes to the sight of the worm infection and are more present in the spleen and liver than in the lymph nodes. They are activated by worms, bacteria, and viral signals and drive immune responses towards TH2

. For adaptive immunity: They express receptors for IgE and IgG and induce strong TH2 responses upon activation. They induce systemic responses sometimes leading to anaphylaxis. They will go to the lymph nodes and promote antibody production and can express MHC class II under certain conditions.

What are some characteristics of Eosinophils?

. They are parasite fighters and specialize in large parasites that are too big to be swallowed by phagocytosis

. They bind to IgE and IgG (in adaptive immunity) and release toxic molecules to help eliminate worms.

. They contribute to allergy inflammation

how do Eosinophils coincide with both innate and adaptive immunity?

. For innate immunity: They are still not fully understood but they reside in mucosal tissues mostly and secrete toxic compounds that increase inflammation and stimulate basophils and mast cells

. For adaptive immunity: They bind to IgE and IgG and assist with the killing of anti-body coated parasites.They have been shown to express MHC class II under certain conditions and go to lymph nodes as antigen presenting cells. They also stimulate T cell activation and TH2 response

What is a Monocyte?

A monocyte is the immature form of a macrophage that resides in the blood. They will enter into the tissues of the body and mature into many different kinds of macrophages.

What is a macrophage and what are its characterisitcs?

. They are mature monocytes (“large eaters”)

. They are involved in many different responses and are very important in the innate immune response leading to the adaptive immune response

. They have both MHC class I and II

. They will phagocytose any anti-body-coated pathogens

. will activate bactericidal functions if they detect a pathogen

. They have granules for extracellular killing

What are resident macrophages?

Macrophages that are long-living and are distributed throughout the tissues. (They take on special roles)

What are Kupffer cells?

Kupffer cells clear bacterial blood infections

What are the four different jobs of Macrophages?

1. Janitorial response: Clean up debris from cells, tissues and pathogens, They help to maintain healthy tissue

2. Inflammatory response: Recognize foreign material and release cytokines that stimulate inflammation and dendritic cell activation

3. Antigen presentation: Presents antigens to help activate adaptive immunity. They play a minor role in naive T cell and B cell activation in lymph nodes; however, they can activate memory T cells and B cells in the tissues

4. Cell killing: Destroys pathogens and kills infected cells

What is one major characteristic of Macrophages?

Because they connect the innate and adaptive immune responses?

What are some characteristics of Mast cells?

. They originate in the bone marrow and then travel to tissues when they are mature

. They cause prolonged inflammation and release histamines

. Mast cells are essential intermediants in most inflammatory reactions

What do Mast cells release when activated?

. Histamines

. Prostaglandins

. Leukotrienes

. Cytokines

These substances increase blood vessel permeability (Connective tissue mast cells) and also bind to IgE and are essentially in response to parasites and allergens (Mucosal mast cells).

What are the two major players of the adaptive immune response?

T cells and B cells

What do T cells do?

T cells coordinate the immune response or directly kill infected cells

What do B cells do?

B cells produce antibodies that help eliminate pathogens

What are some characteristics of adaptive immunity?

• Highly specific

• Has memory

• Responds more strongly after repeated exposures

Where do T cells and B cells come from and mature?

B cells: they originate in the bone marrow and mature in the bone marrow

T cells: they originate in the bone marrow but mature in the thymus

What are the three functional stages of T cells and B cells?

. Naive cells

. Effector cells

. Memory cells

What is a naive cell?

A cell that has never encountered its specific antigen; it is resting and inactive

What happens after a naive cell is activated?

The naive cell will turn into either an effector cell or a memory cell

What are effector cells?

Effector cells perform immediate immune responses. They are short-lived

What are some examples of Effector cells?

• Plasma B cells

• Cytotoxic T cells

• Helper T cells

What are memory cells?

memory cells are dormant resting cells waiting for specific reactivation. They respond to the infection much faster the second time the host is exposed. (this is the principle behind vaccinations). They survive for years.

Why are each T and B cell unique to one another?

Because each one recognizes one specific antigen or self-antigen

What is tolerance?

Tolerance is when a T or B cell recognizes its self-antigen and is deleted. This process is called tolerance.

What are the three major types of T- cells?

1. Helper T cells

2. Cytotoxic T cells

3. Regulatory T cells

What are Helper T cells?

• CD4 cells (basically the generals)

• They don’t kill pathogens directly, but instead, tell everyone else what to do

• Helper T cells recognize antigens presented on MHC class II

What are the Helper T cell subtypes?

• TH1

• TH2

• TH17

• THF

• Treg

Explain TH1 cells

• They are inside the cell

• They activate macrophages and other T and B cells

• They contribute to intracellular immunity - promote inflammation

• They are best for intracellular bacteria and some viruses

Explain TH2 cells

• Specific for parasites and allergies

• They contribute to mucosal and barrier immunity

• They activate basophils, eosinophils, and alternatively activated macrophages

• They stimulate B cells to make IgE and IgA

• They are best for worms and allergic responses

Explain TH17 cells

• They are outside the cells

• Contribute to extracellular immunity

• They activate neutrophils

• They work best for extracellular infections (specifically bacteria and fungi)

Explain THF cells

• These are follicular helper cells

• They promote activation in lymphoid follicles

• They stimulate production of IgG through induced B cells

• *THF = friend of B cells

Explain Treg cells

• They are regulatory cells (basically the breaks)

• They turn the immune system off

• Help to prevent excessive inflammation and autoimmunity

• Also are sometimes called TH3 or TR cells

What are cytotoxic T cells?

• CD8

• Unlike helper T cells, these actually kill infected cells

• They recognize and kill altered self-cells as well

• They bind to MHC class I

• Their main job is to destroy virus-infected cells and abnormal self-cells

• *CD8 = Killer

What are the differences between CD4 cells and CD8 cells?

CD4 cells: CD8 cells:

. Helper T cells . Cytotoxic T cells

. bind to MHC class II . bind to MHC class I

. coordinate response . Kill infected cells

What are B cells?

• Their main function is to produce antibodies

• They express both MHC class I and II

• They can also function as antigen presenting cells

• When activated, B cells become plasma cells, which produce enormous amounts of antibody

What are the different types of B cells?

• Naive B cells

• Plasma B cells

• Memory B cells

What are memory B cells?

• They are reactivated later to produce more plasma B cells. They are phagocytic and can function as antigen presenting cells

What are the subtypes of B cells?

• B-1 cells

• Marginal B-zone cells

• B-2 cells

Explain B-1 cells

• Innate immune cells (make up about 5% of B cells)

• express unmutated/minimally mutated immunoglobulins mainly found in peritoneal and pleural cavities

• They respond mostly to polysaccharide antigens

• Produce IgM

• No memory cells

• Protects the body cavities

• Are T- cell independent

Explain marginal B-zone cells

• Similar to B-1 cells, but are found in marginal zone of spleen and are more activatable than B-1 cells. They appear after birth

• They respond to polysaccharides

• Produce mostly IgM; some produce IgG

• Are T-cell independent; produce natural antibodies

• Are specific but innate antibody production

Explain B-2 cells

• “traditional B cell”

• Are used to make most mucosal and systemic antibodies

• Are activated by helper T cells

• Produce most antibodies during adaptive immune responses

What are the two different regions on an antibody?

• The variable region (arms): binds to the antigen; unique for every antibody

• Constant region (stem): signals the rest of the immune system to destroy the target. Basically a big reg flag that marks the antigen/pathogen as foreign, marking it for destruction

What are the six antibody functions?

1. Neutralization

2. Agglutination

3. Opsonization

4. Complement activation

Explain Neutralization

• Some antibodies function not only as markers, but by binding to the antigen/pathogen to block its activity, rendering it non-functional

Explain Agglutination

• Clumping; the antibodies bind to the antigens/pathogens, causing them to clump together

Explain Opsonization

• Antibody-mediated phagocytosis; phagocytic cellsbind to antibodies and eat whatever they are stuck to

Explain Complement activation

• Complement is a set of proteins that can make holes in the membrane, causing cells to become leaky and die

Explain ADCC

• An immune defense mechanism where an effector cell lyses a target cell that has been coated with antibodies

Explain Intracytoplasmic antibody detection

• a crucial intracellular immune defense mechanism that protects the host by intercepting antibody-coated pathogens after they have penetrated the cell membrane

How are antibodies made? (produced)

1. Helper T cell activates naive B cells

2. Naive B cells become lymphoblasts and then mature into effector B cells. AKA: Plasma B cells or “plasmoblast’ B cells

3. The plasma B cells secrete antibodies

4. Some of the plasma B cells migrate to the germinal center of the lymphoid tissue

5. B cells in the germinal center proliferate and mutate the antibody variable region- this is known as affinity maturation. A higher affinity antibody is then produced

6. Higher affinity b cells leave the germinal center and some of the them become long-living plasma B cells, producing more antibody and memory B cells

7. SOme signals from TFH result in class switching, which causes the B cells to change from making IgM to making IgG, IgA or IgE

* Memory B cells can be easily activated to again proliferate and make more plasma B cells and memory B cells

* The B cells are also phagocytic and antigen presenting cells

What are NK (Natural killer) cells?

• They belong to the lymphoid lineage BUT function in innate immunity

• Unlike cytotoxic T cells, they do not require prior activation by a specific antigen

What ate two types of large granular lymphocytes?

1. Natural Killer cells

2. Cytotoxic T cells

What all are considered lymphocytes?

• T cells

• B cells

• NK cells

What do granular lymphocytes do?

• They recognize antibodies bound to the host cell or abnormalities in the host cells (ex: reduced MHC class I)

• They then release cytotoxic granules that kill the infected host cell

What are some characteristics of NK cells?

• They are important for innate immunity

• They express receptors to detect host cell membrane abnormalities (like reduced MHC class I)

• Will kill some tumor cells

• Will kill some infected cells through the innate defense pathway; this is important for early phases of infections (ex: herpes)

How are NK cells used in adaptive immunity?

• binds IgG

• Kills antibody-coated target cells

• They also participate in ADCC by binding IgG

• They are known as innate lymphocytes

• Deficits in NKT cells are associated with autoimmune diseases like Diabetes

• They are thymus-derived

• Express invariant TCR and recognize glycolipid antigen

• recognizes MHC class 1B - expressed on Thymocytes and intestinal epithelium

What are innate lymphoid cells? (ILCs)

• develop on the same lineage as NK cells

• Use the same genetic program as helper T cells

• (Ex: TH1 and ILC 1 have the same genetic switches)

What are the 3 different groups of innate lymphoid cells?

• ILC 1

• ILC 2

• ILC 3

Explain ILC 1

• Intracellular immunity - (acts like TH1)

• Releases IFN-Y

• Promotes inflammation and activation of intracellular responses; viruses and bacteria

Explain ILC 2

• Mucosal and barrier immunity - (acts like TH2)

• Releases IL-5 and IL-13

• Activates basophils and eosinophils

• Supports IgE and IgA responses

Explain ILC 3

• Extracellular immunity - (Acts like TH17)

• Releases IL-22 and IL-17

• Recruits neutrophils

• Protects against extracellular bacteria and fungi

What are conventional dendritic cells?

• They migrate to the lymph nodes

• They are derived from both the myeloid lineage and the lymphoid lineage

• They are phagocytic cells and antigen-presenting cells vis MHC class II

• After activation, they search out Naive T cells to activate them

CDC1 VS CDC2

cDC1 cells specialize in cross-presenting antigens on MHC class I molecules to activate CD8+ cytotoxic T cells. cDC2 cells present antigens on MHC class II molecules to activate CD4+ helper T cells (Th1, Th2, and Th17

What are plasmocytoid dendritic cells?

They circulate in the plasma (blood) and are reactive to virus and stimulate strong anti-viral responses

What are the two functions of conventional dendritic cells?

1. Inducing tolerance: when “naive”, they phagocytose host debris, presenting antigens and inducing tolerance

2. Stimulate specific B and T cells: when activated, they present antigen and begin to stimulate an immune response. When mature, they are no longer phagocytic, but migrate to the lymphoid tissue to begin activating T cells and stimulating (not activating) B-cells

What are Thymic dendritic cells?

• May come from the bone marrow or thymocytes in the thymus

• Are important for negative selection

What are plasmocytoid dendritic cells?

• They are important for antiviral responses; they eat mostly small particles

What are follicular dendritic cells?

• They are only found in the lymph nodes and other lymphoid tissues

• They are NOT bone marrow derived; NOT related to dendritic cells

• They are NOT phagocytic

• They bind antibody and complement on their surface to help stimulate B cells

• They do NOT express MHC class I (very unsual)