What is Immunology?

"Exemption or protection from an obligation or penalty"

"The state or quality of being resistant to a particular infectious disease or pathogen"

"Science of Self/Non-Self Discrimination"

What is the Basic Model for Immunity?

__________ -> | __________ -> __________ ->

Pathogen -> (entrance into body) -> Recognition -> Effector Response

Do prokaryotes have an innate or adaptive immune system or both?

Innate: Restriction/modification enzymes

Adaptive: CRISPR/Cas9

Do eukaryotes have an innate or adaptive immune system or both?

Innate

Adaptive

Do invertebrates have an innate or adaptive immune system or both?

Innate

Can we generate immunity without inducting disease?

YES... through vaccination

_____________ prepares the immune system to eradicate an infectious agent before it causes disease. Widespread vaccine use has saved may lives. (ex: polio vaccine and eradication of smallpox)

Vaccination

Major Arms of the Immune System?

1.

2.

1. Innate Immunity

2. Adaptive Immunity

Comparison of Innate and Adaptive Immunity:

Response Time?

Innate: Minutes to hours

Adaptive: Days

Comparison of Innate and Adaptive Immunity:

Specificity?

Innate: Limited and fixed

Adaptive: Highly diverse; adapts to improve during the course of immune response

Comparison of Innate and Adaptive Immunity:

Response to repeat infection?

Innate: Same each time

Adaptive: More rapid and effective with each subsequent exposure

Comparison of Innate and Adaptive Immunity:

Major Components?

Innate: Barriers (e.g. skin); phagocytes; pattern recognition molecules

Adaptive: T and B lymphocytes; antigen-specific receptors; antibodies

What is the first line of defense; i,e, it's fast but non-specific and aids in activating the adaptive immune system?

The innate immune response

What is the late(r) line of defense, i.e. it's not as fast, but stronger and more specific?

The adaptive immune response

Divisions of the Adaptive Immune System:

1.

2.

1. Humoral Immunity

2. Cell-Mediated Immunity

What is the difference between Humoral Immunity and Cell-Mediated Immunity?

Humoral Immunity:

- Antibody-driven (B cells)

- Non-cellular

- Extracellular pathogens

Cell-Mediated Immunity:

- T cell-driven

- Intracellular pathogens

____________ is a hallmark of adaptive immunity.

Memory

A _______________ is initiated upon first exposure to an antigen, and some immune cells (memory) are left behind after the ___________ is cleared.

Primary Response

Antigen

A _______________ is initiated upon second exposure to the same ____________ that stimulates memory lymphocytes.

Secondary Response

Antigen

Stimulation yields faster, more significant, and better response. But, that response is specific to the ___________.

Antigen

Any substance that binds to an immune receptor.

Antigen

The immune response to a particular pathogen is tailored to the type of organism involved and depends on:

1.

2.

1. The structure of the pathogen

2. Its location, i.e. intra- or extra-cellular

______________ is a state of immunological unresponsiveness to particular antigens or sets of antigens.

Tolerance

Is the immune system correctly balanced when it always attacks foreign substances and is always tolerant of self-tissue?

No

What can result when something is wrong with one's immunity?

Autoimmunity/ Chronic Inflammation

Hypersensitivity (Allergy, Asthma)

Organ Transplants/ Pregnancy

What can result when something is wrong with one's tolerance?

Immunodeficiency (Genetic or Acquired)

Cancer

The formation and differentiation of red blood cells (erythrocytes), white blood cells (leukocytes), and platelets (thrombocytes) from hematopoietic stem cells (HSCs).

Hematopoiesis

What is meant by the term "the big picture?"

The fully functional immune system involves so many organs, molecules, cells, and pathways in such an interconnected and sometimes circular process that it is often difficult to know where to start... a focus on the details can make it difficult to see the bigger picture..."

Two Criteria for Stem Cells:

1.

2.

1. Self-Renewal

2. Differentiation into Diverse Cell Types

Can give rise to virtually any cell type (embryonic).

Pluripotency

Can give rise to cell types of a certain tissue (adult)

Multipotency

Leukocyte Lineage

Hematopoietic Stem Cell

1. ______________________ 3. ______________________

2. ______________________ 4. ______________________

1. Common Myeloid Progenitor (CMP)

2. Granulocyte; Monocyte

3. Common Lymphoid Progenitor (CLP)

4. Lymphocyte

Hematopoietic stem cell that is majorly involved in innate immunity?

CMP

Hematopoietic stem cell that is majorly involved in adaptive immunity?

CLP

4 Types of Myeloid Cells:

1.

2.

3.

4.

1. Granulocytes

2. Eosinophils

3. Erythrocytes

4. Megakaryocytes (platelets)

4 Types of Granulocytes:

1.

2.

3.

4.

1. Neutrophils

2. Eosinophils

3. Basophils

4. Mast Cells

3 Types of Lymphoid Cells:

1.

2.

3.

1. T Cells

2. B cells

3. Innate Lymphoid Cells (ILCs)/Natural Killer Cells (NK Cells)

Macrophages and Dendritic Cells are found in _________.

Tissue

Which is the most abundant cell types?

Neutrophils

Which myeloid cell has the following functions?

- Tissue Remodeling

- Direct harm to pathogens

- Regulation of proteases

- Vasodilation, inflammation

Neutrophil

Which myeloid cell has the following functions?

- Induces formation of ROS

- Vasodilation, basophil degranulation

- Antiviral activity

- Modulation of adaptive immune responses

- Attract leukocytes

Eosinophil

Which myeloid cell has the following functions?

- Modulation of adaptive immune

- Regulation of inflammation

- Vasodilation, smooth muscle activation

Basophil/Mast cell

_________________ respond quickly to infection; once they enter the tissue, they become macrophages and fight infection by phagocytosis.

Inflammatory Monocytes

_________________ tend to be much more slow-acting. They tend to "crawl" along, using amoeboid movement and may have roles in tissue repair and immune system regulation.

Patrolling Monocytes

Monocytes that migrate into tissues become _________________.

Macrophages

Macrophages have several important immune activities:

1.

2.

3.

1. Phagocytosis (pathogen clearance)

2. Antigen Presentation

3. Cytokine/Chemokine secretion

Types of Macrophages:

1.

2.

1. Tissue Resident Macrophages

2. Infiltrating Macrophages

Many _________________ don't descend from HSC, but likely are from the lineage of the organ (system) in which they find themselves.

Tissue-Specific Macrophages

Myeloid cell important in antigen capture and antigen presentation.

Dendritic Cells

Which myeloid cell has the following functions?

- A-nuclear

- Primary function in gas exchange (hemoglobin)

- Some immune activity: antibody receptors; nitric oxide production

Erythrocyte

Which myeloid cell has the following functions?

- Generate platelets, which are important in clot formation

- They contain nuclei, platelets do not

- No immune activity

Megakaryocyte

Lymphocytes (like all other cells HSCs) develop in the _____________.

Bone Marrow

What is the location of B Cell maturation?

Bursa of Fabricus

Bone Marrow

What is the location of T Cell maturation?

Thymus

Which cells have the following properties?

- principle cells involved in adaptive immunity

- small, round, with large nuclei

- distinguished by surface markers (e.g. CD4*)

Lymphoid Cells

_____ lymphoid cells in constant migration within the circulation at any given time?

- _____% of WBCs in the blood

- _____% of ALL cells in lymph

1012

20-40%

99%

Basic Nomenclature:

__________: B and T cells that are fully formed.

Mature

Basic Nomenclature:

__________: Mature B and T cells that have not yet encountered antigen.

Naive

Basic Nomenclature:

__________: Cells with specific functions to deal with pathogens.

Effector Cells

Basic Nomenclature:

__________: Cells that do not engage pathogen upon initial encounter (primary response), but persist and engage upon subsequent encounters (secondary, tertiary responses)

Memory Cells

___________: Membrane-bound antibody that makes it so each individual B cell has specificity. (~ 200,000 per cell)

B Cell Receptor (BCR)

Once the antigen binds a BCR, the cell secretes antibody (soluble BCR) and is known as a _____________.

Plasma Cell

What are the two types of T Lymphocytes?

1. T helper (Th) cell

2. T cytotoxic (Tc) cell

How can you differentiate between Th cells and Tc cells?

Th cell = CD4+

Tc cell = CD8+

Which cells are part of the lymphoid lineage, but are considered innate (Innate Lymphoid Cells (ILCs))?

Natural Killer Cells (NK Cells)

Which cells patrol looking for cells that look weird?

NK Cells

Which cells are important in tumor defense and the recycling of senescent cells?

NK Cells

Which cell employs Antibody-Dependent Cell Cytotoxicity (ADCC)?

NK Cells

What is the site of development and maturation of lymphoid cells (and all immune cells, really)?

Primary Lymphoid Tissue

The types of primary lymphoid tissue:

1.

2.

1. Bone Marrow

2. Thymus

___________ is the functional tissue of an organ as distinguished from the connective and supporting tissue. (bone marrow)

Parenchyma

__________ is everything that's not parenchyma. (bone marrowI

Stroma

Microenvironment/niche: Parenchyma

Sequestered region of stem cells lined by supporting cells that regulate:

1.

2.

3.

4.

1. Survival

2. Proliferation

3. Differentiation

4. Trafficking

Where does all immune cell development begin?

Bone Marrow

What is the site for long-lasting memory B and T cells?

Bone Marrow

Type of stromal cells:

1.

2.

3.

4.

5.

1. Endothelial cells

2. Perivascular cells

3. Sympathetic nerves

4. Macrophages

5. Osteoblasts

T cell development is not complete until the cells undergo __________ in the thymus (B cells undergo a similar process in the bone marrow)

Selection

Thymocytes (bone marrow) -> ____________________

Functional mature T cells (thymus)

_____________________ -> Functional mature T cells (thymus)

Thymocytes (bone marrow)

__________ is the protein-rich fluid that is derived from the fluid portion of the blood (plasma).

Lymph

______________________ circulate lymph (interstitial fluid); it collects in the thoracic duct and then drains into the left subclavian vein.

Lymphatic vessels

As lymph travels through lymphatic vessels, it travels through _________________.

Lymph nodes

___________ make up virtually all of the cells in the lymph - it's a quick avenue for __________ to circulate and they often travel from lymph node to lymph node.

White Blood Cells (WBCs)

The site(s) where mature, but naive lymphocytes encounter antigen.

Secondary lymphoid tissue

_____________ is where adaptive immunity begins.

Secondary lymphoid tissue

Types of secondary lymphoid tissue:

1.

2.

3.

1. Lymph Node

2. Spleen

3. Other associated lymphoid tissues (tonsils, appendix, ect.)

Entry into the Lymph Node?

Lymphocytes-High Endothelial Venules (HEVs)

Antigen/ APCs- Afferent Lymphatics

Exit from the Lymph Node?

Efferent Lymphatics

Entrance into the Spleen?

Splenic Artery

Exit from the Spleen?

Splenic Vein

Activation of adaptive immune response and generation of T and B cells in the _________ occurs in a manner similar to that of the LN.

Spleen

(Barrier) Associated Lymphoid Tissue

1.

2.

3.

4.

5.

1. Mucosal (MALT)

2. Bronchus (BALT)

3. Skin (SALT)

4. Nasal (NALT)

5. Gut (GALT)