Lymphatic System And Immunity

Front 1

Functions of the lymphatic system

Back 1

Drain excess interstitial fluid

Transports dietary lipids and lipid-soluble vitamin

Return proteins to bloodstream

Carry out immune responses

Front 2

Four types of antimicrobial substances in innate immune system

Back 2

Interferons

Complement proteins

Iron-binding proteins

Anti-microbial proteins (AMPs)

Front 3

Four stages of phagocytosis

Back 3

Chemotaxis, adherence, ingestion, digestion, killing

Front 4

Define humoral immunity

Back 4

The aspect of immunity mediated by macromolecules (i.e. antibodies) in the blood, lymph and serum (body "humors"). Acts against soluble molecules and toxins, extracellular viruses and microbes. Key component is B lymphocytes.

Front 5

Define cell-mediated (cellular) immunity

Back 5

The aspect of immunity that is mediated by cells that respond to intracellular antigens. Acts against foreign cells, grafted tissues, cancers, intracellular viruses and microbes. Key component is T lymphocytes

Front 6

What are hematopoietic cells and what is their importance to immunity?

Back 6

Stem cells within bone marrow that produce blood cells (myeloid and lymphoid lineages). Have enormous capacity for self-renewal and proliferation. Highly sensitive to radiation but reinjection of stem cells into bone marrow can result in complete renewal of hematopoietic system. Useful in cancer research and gene therapy, and immunity to produce cells in response to infection etc.

Front 7

Define neutropenia, leukocytosis, and leukemia

Back 7

Neutropenia = too few neutrophils

Leukocytosis = too many neutrophils

Leukemia = too many neutrophils (different morphology).

Regulated by hematopoiesis

Front 8

What is the mononuclear phagocytic system?

Back 8

Monocytes (white blood cells) that differentiate into macrophages that become fixed in different tissues, e.g.

Promonocytes (bone marrow)

Alveolar macrophages (lungs)

Histiocytes (connective tissue)

Mesangial cells (kidney)

Microglial cells (brain)

Act to ingest and destroy microbes, more effectively against microbes opsonized (garnished) with antibodies. Process and present antigens to the cells of the acquired immune system

Front 9

List some examples of 1st, 2nd, and 3rd line defenses

Back 9

1st: skin, mucous membranes, antibacterial substances (sebum, mucous, sweat [contains lysozyme], other secretions)

2nd: Phagocytes, inflammation (caused by proteins), fever (increases cytokine activity), NK cells

3rd: lymphocytes, antibodies (cell-mediated and humoral immunity)

Front 10

What might be indicated by white blood cell counts?

Back 10

High: presence of bacterial infection, leukemia, autoimmune disease; also result of some medications e.g. epinephrine, corticosteroids

Low: viral infections, pneumonia, lymphoma, some autoimmune disease, lupus, radiation and cancer treatments, severe bacterial infection e.g. septicemia; result of some medications e.g. antibiotics, diuretics, anticancer drugs

Front 11

List the 8 kinds of white blood cells

Back 11

Granulocytes:

- neutrophils

- basophils

- eosinophils

Agranulocytes:

- Monocytes

- Dendritic cells

- lymphocytes (NK cells, T cells, B cells)

Front 12

Describe the function of neutrophils

Back 12

Make up 60-80% of white blood cells in the body. First at site of inflammation. Are phagocytic (microphages) and motile (i.e. can leave blood). Small cells, stain lilac. Granulocytes. Also known as polymorphonuclear (PMN) leukocytes.

Front 13

Decsribe the function of basophils

Back 13

Granulocytes, stain blue-purple. Release substances in response to inflammation (e.g. histamines). Non-phagocytic.

Front 14

Describe the function of eosinophils

Back 14

Granulocytes, stain red/orange. Main function is anti-parasitic. Bind to a parasite's outer surface and release peroxide ions to kill them. Perform some phagocytosis but are less active than neutrophils.

Front 15

Describe the function of monocytes

Back 15

Agranulocytes that are present only in low numbers in blood but move to different body tissues and differentiate into macrophages or dendritic cells (some). Collectively the macrophage system constitutes the mononuclear phagocytic (reticuloendothelial) system

Front 16

Describe the function of dendritic cells

Back 16

Agranulocytes derived either from hematopoiesis or from monocyte differentiation. Resemble dendrites of nerve cells with long extensions. Phagocytic and play a role in initiating adaptive immune response. Abundant in epidermis, mucus membranes, thymus and lymph nodes.

Front 17

Describe the function of natural killer (NK cells)

Back 17

Lymphocytes (agranulocytes) found in blood, spleen, lymph nodes, and red bone marrow. Attack and kill abnormal or foreign cells through the release of toxic substances (e.g. lytic granules containing perforin or granzymes)

Front 18

Describe the function of T and B cells

Back 18

Lymphocytes (agranulocytes) that occur in lymphoid tissues and play a role in adaptive immunity by producing antibodies (B cells) and initiating cell-mediated immune response (T cells)

Front 19

Where do T and B cells originate?

Back 19

Both originate in the bone marrow, B cells mature in bone marrow but T cells mature in thymus.

Front 20

What is involved in B and T cell maturation?

Back 20

Receptors generated (antigenic diversity) and "self-reactive" cells selected against via apoptosis - cells become immunocompetent. Maturation stimulated by cytokines and hormones (in thymus) to induce maturation.

Front 21

What is the function of lymph nodes?

Back 21

Filters lymphatic fluid, uptake of antigens and initiates immune response. Reservoirs for lymphocytes and phagocytic cells that are important in immune responses. Also contains reticular fibres which trap microbes and macrophages and dendritic cells, which destroy microbes by phagocytosis.

Front 22

Briefly describe the steps of a phagocytic immune response

Back 22

1. Release of vasoactive mediators from damaged cells (e.g. histamine, kinins, prostaglandins, complement proteins, cytokines) to initiate vasodilation, increasing permeability to blood stream

2. Chemotaxis (e.g. to microbial products, damaged tissue, cytokines)

3. Adherence of TLRs on phagocytes to PAMPs on microbes

4. Release of cytokines and extension of plasma membrane into pseudopods that engulf microbe

5. Ingestion of microbe into a phagosome sac. H+ ions pumped into phagosome to lower pH and activate hydrolytic enzymes

6. Phagosome enters cytoplasm and fuses with lysosomes containing digestive enzymes and bactericidal substances (e.g. lipases, proteases, sueproxide radicals, peroxide, nitric oxide)

7. Digested material discharged outside the cell

Front 23

What does the acronym PRISH stand for?

Back 23

Describes symptoms associated with inflammation:

Pain (release of chemicals)

Redness (blood accumulation)

Immobility (local loss of function)

Swelling (accumulation of fluids)

Heat (due to increased blood flow)

Front 24

What is the importance of inflammation?

Back 24

1. Destroy injurious agent and by-products

2. Limit effects by confining or isolating injurious agent (e.g. abcess)

3. Repair or replace damaged tissue

Front 25

Differentiate acute and chronic inflammation

Back 25

Acute inflammation develops rapidly, is usually mild and self-limiting, lasting only a few days or weeks (e.g. minor wounds, cold and flu, sore throat). Main cells are neutophils. Chronic inflammation develops more slowly and is severe, lasting months or years (e.g. ulcers, rheumatoid arthritic, mononucleosis). Principle cells are monocytes and macrophages.

Front 26

What is the main difference between innate and acquired immunity?

Back 26

How they recognize microbes: i.e. innate immune response identifies cell surface receptors or soluble molecules (e.g. mannose, lipopolysaccharides). Acquired immunity recognizes specific conformations of carbohydrates, proteins etc. by producing specific receptors on B or T lymphocyte surface (antibodies). Adaptive immunity cannot recognize dangerous vs. non-dangerous.

Front 27

What are TNF-a, IL-1, IL-6 and what do they do in an infection/inflammation?

Back 27

Tumor necrosis factor alpha, interleukin. Cytokines released by phagocytes. Induce liver to produce acute-phase proteins (e.g. c-reactive protein, mannose-binding lectin) that induce both local and systemic responses. Also activate inactive acute-phase proteins already present in the blood.

Front 28

What is margination?

Back 28

The sticking of monocytes and neutrophils to the lining of blood vessels in response to cytokine accumulation in an infection

Front 29

What is fever?

Back 29

An abnormally high body temperature induced by the hypothalamus in response to the accumulation of cytokines TNF-a and IL-1

Front 30

What is the general function of the complement system?

Back 30

A collection of over 30 plasma proteins (i.e. C1-30) produced by the liver that are activated by an immune response and cause a reaction cascade that aids in the destruction of microbes and prevention of damage to host cells. Part of the innate system but can be induced by the adaptive system.

Front 31

Describe the 3 pathways of the complement system

Back 31

See paper cards

Front 32

What are interferons?

Back 32

A group of cytokines (proteins) produced by fibroblasts, lymphocytes and other leukocytes in response to a viral infection.

Front 33

What are the functions of alpha, beta and gamma interferon?

Back 33

Alpha and beta produced by virus-infected cells. Induced to enter uninfected neighbouring cells and stimulate production of antiviral proteins. Also stimulate NK cells to produce gamma IFN. Gamma induces neutrophils and macrophages to kill bacteria, as well as produce nitric oxide to kill bacteria and tumor cells. Also increases the expression of MHC molecules and antigen presentation.

Front 34

What are disadvantages of interferons?

Back 34

Short-lasting, cannot affect already-infected cells, side effects of accumulation include nausea, fatigue, headache, vomiting, weight loss and fever. High concentrations toxic to heart, liver, kidneys and bone marrow.

Front 35

What are AMPs?

Back 35

Antimicrobial peptides. Synthesized by neutrophils when microbial chemicals attach to toll-like receptors (TLRs). Destroy microbes by lysis, inhibiting cell wall synthesis and DNA/RNA. Includes substances produced in sweat glands and platelets. Can also sequester lipopolysaccharides shed from microbes to prevent endotoxic shock. Microbes cannot develop resistance.

Front 36

What are interleukins?

Back 36

Cytokines (proteins) that serve as communicators between leukocytes to stimulate cell proliferation, maturation, migration or activation. Sometimes used to treat certain diseases and cancers.

Front 37

What are chemokines?

Back 37

Cytokines that induce leukocytes to migrate to an area of infection or tissue damage (via chemotaxis)

Front 38

What is TNF-alpha?

Back 38

A cytokine important in inflammatory reactions and autoimmune diseases.

Front 39

What are hematopoietic cytokines?

Back 39

Cytokines that help control pathways of hematopoiesis. Some are interleukins, some are colony-stimulating factors that stimulate production of leukocytes.

Front 40

What is an epitope/antigenic determinant?

Back 40

Specific regions on antigens to which antibodies bind. Antibodies have at least 2 identical antigen-binding sites that bind to identical epitopes (Y shape)

Front 41

What is clonal selection?

Back 41

The process by which mature B cells are stimulated by the presence of a specific antigen to proliferate into both antibody-producing plasma cells and long-lived memory cells that carry the antibody and can later become stimulated to become antibody-producing plasma cells.

Front 42

What are T-dependent and T-independent antigens?

Back 42

Some B cells, following ingestion and processing of an antigen for display on the MHC on the cell surface, require T helper cells to release cytokines that activate the B cell and induce clonal expansion. T-independent antigens have repeating epitopes that cross-link several antigen receptors on the same cell, and do not require the help of T helper cells but produce a weaker immune response (no memory cells produced)

Front 43

Describe 5 outcomes of an antigen-antibody reaction

Back 43

Agglutination: causes antigens to clump for easier phagocytosis

Opsonization: "coating" enhances phagocytosis

Antibody-dependent cell-mediated cytotoxicity: "coating" but microbe remains external while attacked by phagocyte

Neutralization: Inactivate pathogenicity by blocking attachment

Activation of complement system: Lysis by complement proteins + immune response

Front 44

What is thymic selection?

Back 44

The process of destroying immature T cells that do not possess the correct receptors for distinguishing foreign materials from self

Front 45

What are antigen-presenting cells (APCs)?

Back 45

Cells associated with cell-mediated immunity that have MHCs on their surfaces able to present potential antigens and antigenic fragments to T cells in lymphoid centers, leading to T cell activation. Includes B cells, dendritic cells, and activated macrophages.

Front 46

What are clusters of differentiation?

Back 46

Specific glycoproteins on T cell surfaces that differentiate function: e.g. CD4 (T helper) and CD8 (T cytotoxic lymphocytes).

Front 47

Describe the activation process of a T helper cell

Back 47

When a macrophage or other APC ingests a microbe, it presents antigens on the MHC on the cell surface, to which a T helper cell binds. This is the first signal for activation. The second signal comes from either the APC or a second T helper cell (cytokine signalling). The activated T helper cell then produces cytokines or differentiates into T helper subsets (Th1, Th2, and Th17)

Front 48

Describe the function of Th1, Th2 and Th17

Back 48

Th1: Produce cytokines to stimulate delayed hypersensitivity, stimulate macrophages, complment, production of antibodies

Th2: Produce cytokines primarily associated with production of antibodies, esp. IgE, and activation of eosinophils.

Th17: Produce IL-17 to recruit neutrophils

Front 49

What is the function of T regulatory cells?

Back 49

Combat autoimmune reactions by destroying T cells that escape deletion in the thymus as well as protect normal microbiota and fetus during pregnancy

Front 50

What is a T cytotoxic lymphocyte (CD8)?

Back 50

A specialized T cell activated by a complex process involving an APC, T helper cell and co-stimulatory signals. Recognizes and kills target altered-self cells (e.g. virus-infected)

Front 51

Describe the function and mechanism of natural killer (NK) cells

Back 51

Recognize altered self cells (tumors, virus-infected) and parasites by recognizing MHC antigens. Can kill cells by releasing perforin or granzymes (proteases that induce apoptosis)

Front 52

What is antibody-dependent cell-mediated cytotoxicity?

Back 52

The process by which humoral (antibodies) and cell-mediated immune systems interact to stimulate natural killer cells and innate leukocytes to kill targeted cells, e.g. antibodies binding to a parasite can attract cells to bind and produce substances that damage the parasite.

Front 53

What is the anamnestic response?

Back 53

A secondary immune response to exposure to the same antigen, rapid and greater in magnitude than the initial response due to the portion of activated B cells that become memory cells after the first response (higher IgG)

Front 54

Describe the stages of inflammation

Back 54

1. Microbial structures (e.g. flagellum, lipopolysaccharides) stimulate the TLRs of macrophages to release TNF-alpha

2. The liver produces acute-phase proteins (e.g. C-reactive protein, mannose-binding lectin) that induce systemic and local responses

3. All cells involved in inflammation have receptors for TNF-alpha which stimulates cells to produce more TNF-alpha, amplifying the inflammatory response

4. Blood vessels dilate (via kinins, prostaglandins, histamines, cytokines) to increase permeability to macrophages and other agents

5. Macrophages secrete cytokines to attract other cells to the site of infection. Complement system activates

6. Blood clots form to prevent spread of microbe and toxins (platelets)

7. Neutrophils and monocytes stick to blood vessels (margination)

8. Assembled immune cells squeeze between epithelial cells of blood vessel to reach damaged area (diapedesis)

9. Phagocytosis by granulocytes

10. Tissue repair via reproduction of stromal (connective tissue) or parenchymal cells (functional tissue)

Front 55

What is a hapten?

Back 55

A molecule too small to stimulate immunogenicity/antibody formation by itself. It combines with a larger carrier molecule to form a hapten-protein complex which may then trigger an immune response (e.g. the small lipid toxin in poison ivy combines with body proteins to trigger a reaction)

Front 56

What are M cells and what is their function?

Back 56

"Pocket" cells located in the Peyer's patches on the intestinal wall that facilitate passage of antigens in the digestive tract into pocket where immune cells are located

Front 57

Describe the 3 outcomes of complement system action

Back 57

1. Cytolysis: activated C3b activates C5b, C6, C7 and C8 which insert into the microbial plasma membrane and attract/split C9 to form a transmembrane channel called the membrane attack complex (MAC) which allows fluid to enter and burst the cell

2. Opsonization: C3b coats microbe and attracts phagocytes to bind to C3b receptors

3. Inflammation: C3a and C5a (activated by C3b) bind to mast cells and stimulate release of histamine

Front 58

Ways to acquire adaptive immunity

Back 58

Naturally acquired active immunity - exposure to antigens

Naturally acquired passive immunity - transfer of antibodies from mother to fetus

Artificially acquired active immunity - antigens introduced by vaccination

Artificially acquired passive immunity - IV injection of antibodies

Front 59

Effects of aging on the immune system

Back 59

- increased susceptibility to disease and infection due to lowered responsiveness of T cells

- production of more autoantibodies

- decrease in rate of antibody production following exposure to a microbe