10.18.17 Immune System & Immunosuppressants

Question 1

What are the four primary organs involved in the immune system? What happens at each?

Answer 1

• Bone marrow: source of blood cells
• Thymus: T-cell maturation
• Spleen: hematopoietic organ, site of macrophage antigen presentation, antibody response
• Lymph nodes/vessels: lymphocytes (NKC, T, B-cells)

Question 2

List three types of lymphocytes; what do they secrete?

Answer 2

B-cell (antibodies), T-cell (cytokines), NKC (cytokines)

Question 3

List three types of granulocytes; which is most abundant?

Answer 3

Neutrophil (most abundant), eosinophil, basophil

Question 4

Compare and contrast the innate vs. adaptive immunity: specificity, diversity, memory, time frame, cellular/protein components

Answer 4

INNATE: general molecular patterns (eg. wall), limited diversity, no memory, fast, cells=phagocytes, NKC, innate lymphoid cells, proteins=complement

ADAPTIVE: specific antigens, large diversity (V(J)D recombination), memory capable, slow (unless primed), cells=lymphocytes, proteins=antibodies

Question 5

Describe the three types of phagocytes and their role:

Answer 5

• Monocyte–>macrophage: kill pathogens, antigen presenting cell (APC) and cytokine release
• granulocytes: lysozyme release
• dendritic cells: degrade pathogens, APC

Question 6

During infection, list four steps/roles of a phagocyte:

Answer 6

chemotaxis, migration, ingestion and microbial killing

Question 7

Macrophages and dendritic cells express _______ which recognize ______.

Answer 7

Pattern Recognition Receptors (PRR), Pathogen Associated Molecular Patterns (PAMP)

Question 8

What are the three primary functions of the complement cascade?

Answer 8

• chemotaxis (c3a, c5a)
• opsonization (c3b coating)
• cell lysis (MAC complex c5b-9)

Question 9

Compare and contrast humoral vs. cell-mediated immune response: microbe, responding lymphocyte, effector mechanism, transferred by, and function.

Answer 9

HUMORAL: extracellular microbes, B-cell, secretion of antibodies, transferred by serum, block and eliminate extracellular microbes

CELL-MEDIATED:

• phagocytosed microbe IN macrophage, Helper T (CD4)–>(MH II), transferred by Helper T, activate macrophage to kill phagocytosed microbes
• intracellular microbe (eg. virus), Cytotoxic T (CD8)–>(MHC I), transferred by Cytotoxic T, kills infected cells and eliminate reservoir of infection.

Question 10

Which part of the antibody contributes to its variability?

Answer 10

Variable region

Question 11

Name the mechanism for diverse binding selectivity in antibodies, B-cell and T-cell receptors.

Answer 11

V(D)J Recombination

Question 12

What are the 5 immunuoglobulin types? Which is most common in allergic response? Plasma?

Answer 12

IgA, IgD, IgE, IgG, IgM (DGAME). IgE in allergic response; IgG, IgM in plasma.

Question 13

List a few actions of antibodies

Answer 13

Agglutinization, opsonization, neutralization, antibody -dependent cellular cytotoxicity (mark cells for destruction), activation of complement, therapeutic uses (Herceptin/trastuzumab to treat breast CA)

Question 14

Compare and contrast MHC I vs. MHC II: Cells present on, antigens bound, T cell associated.

Answer 14

MHC I: present on most cells, binds endogenous antigens to CD8 on Cytotoxic T cell.

MHC II: present ONLY on APC (phagocytes, NKC, etc), binds exogenous antigens to CD4 on Helper T cell.

Question 15

What is the difference between MHC and HLA?

Answer 15

MHC (Major histocompatibility complex) is a large gene family involved in immune functions in different species.

HLA (Human leukocyte antigen) is the human version of MHC genes.

Question 16

Why is HLA important in the immune response?

Answer 16

Identification of self from non-self, variable from person to person (like a barcode), responsible for tissue rejection in organ transplants

Question 17

What two signals are required to activate a T-cell?

Answer 17

1) MHC + TCR (T-cell receptor) : dendritic cell presents antigen on MHC, the T-cell engages the MHC + antigen complex.
2) Co-stimulatory molecule and receptor (without this second signal, T cell activation stops or apoptosis occurs)

Question 18

Give and example of a co-stimulatory molecule and receptor:

Answer 18

On APC: CD80/86

On T-cell: CD28

Question 19

Cell mediated immunity begins with the bacteria being ‘eaten’ by ________, which presents antigens to helper T-cell with MHC class ___. Activated helper T-cells secrete ____ and also activate ____ cells to form Ab-producing ________. Other phagocytic cells, including NK, macrophage and cytotoxic T-cells to kill invaders.

Answer 19

Cell mediated immunity begins with the bacteria being ‘eaten’ by macrophages (APC) which presents antigens to helper T-cell with MHC class II. Activated helper T-cells secrete IL-2 and also activate B cells to form Ab-producing plasma cells. Other phagocytic cells, including NK, macrophage and cytotoxic T-cells to kill invaders.

Question 20

Outline the steps T-cells take to induce apoptosis

Answer 20

1) Bind to MHC I + antigen complex on infected/diseased cell
2) Directed release of cytotoxic proteins (perforins, granzymes)
3) Recycle T-cell

Question 21

An allergic reaction to a harmless antigen is known as ____________.

Answer 21

Hypersensitivity

Question 22

Immunodeficiency is:

Answer 22

Inability to stop infection

Question 23

Define autoimmune disorder

Answer 23

Immune system targets self-antigens

Question 24

Azathioprine and mycophenolate are DNA-synthesis inhibitors. Describe their mechanism of action:

Answer 24

Azathioprine: purine analog, incorporates into replicating DNA and halts replication. It can also block the pathway for purine synthesis. Result: inhibit cell proliferation, especially fast-growing cells without method of nucleotide salvage (T, B-cells).

Mycophenolate: Inhibit inosine-5’-monophosphate dehydrogenase (IMPD). Result: control rate of de novo guanine (purine) synthesis in cell proliferation (T, B-cells).

Question 25

Describe the mechanism of action of corticosteroids (eg. prednisone, hydrocortisone, fluticasone)

Answer 25

Corticosteroid binds to glucocorticoid receptor (nuclear receptor) to change expression of genes:

• increase anti-inflammatory genes: IkBα
• Bind to NF-kB