Adaptive Immunity

Question 1

Learning Objectives

Answer 1

1. define the different cell types important for adaptive immunity and their functions
2. describe the connections between cell-mediated and humoral immunity
3. describe MHC and how antigens are processed and presented to T-cells
4. describe the major classes and functions of antibodies

Question 2

Adaptive immunity

Answer 2

two parts:
1. humoral (antibodies)
2. cell-mediated (erradicate infected cells)

matures throughout life (gains “memory”, response strengthens following initial infection)
develops highly specific responses to individual pathogens

previous exposure to a pathogen lead to an enhanced immune response upon re-exposure

Question 3

Antigen

Answer 3

substances that react with either antibodies or TCRs (T-cell receptors/T lymphocyte antigen receptors)
NOT all antigens elicit an immune response
a wide range of molecules can act as antigens (i.e. proteins, lipoproteins, many polysaccharides, some nucleic acids, and certain teichoic acids)

Question 4

Immunogen

Answer 4

antigens that elicit an immune response

Question 5

Antibodies/Immunoglobulins

Answer 5

proteins produced by plasma cells that bind to specific regions of antigens (epitopes) via a variable binding site

plasma cells - specialized B-cells

Question 6

Epitope

Answer 6

the part of the antigen recognized by the immune system
including antibodies, TCRs and BCRs

Question 7

Major histocompatibility complex (MHC)

Answer 7

a type of molecule that present antigens on cell surface for TCRs and BCRs

Question 8

MHC Class I

Answer 8

found on all nucleated cells and platelets
recognized by CD8 co-receptor
variable region: alpha 1 and 2 subunits
constant region: alpha 3 subunit
also contains a beta 2m subunit

Question 9

MHC Class II

Answer 9

found on professional antigen presenting cells (i.e. B-cells, macrophages, neutrophils, dendritic cells)
recognized by CD4 co-receptor
variable region: alpha 1 and beta 1 subunits
constant region: alpha 2 and beta 2 subunit

Question 10

The cytotoxic T-cell response

Answer 10

mediated by MHC class I
1. CD8 co-receptor binding to MHCI on infected cells
2. release of granules with perforins and granzymes from cytotoxic T-cells into infected cell
3. result in cell death by apoptosis

Question 11

How do infected cells display foreign antigens on MHCI?

Answer 11

1. internal foreign protein is processed by proteosome
2. foreign peptide molecule (antigen) is translocated through the endoplasmic reticulum via translocating antigen protein (TAP)
3. antigen is placed on MHCI receptor before the receptor is chaperoned to the cell surface
4. recognition by TLRs and CD8 co-receptor mediates apoptosis to kill infected cell

Question 12

How do professional antigen presenting cells (APCs) display foreign antigens on MHCII?

Answer 12

1. external foreign protein phagocytosed by the cell and processed by the phagolysosome (breakage into smaller peptides)
2. MHCII receptor antigen binding site is protected by a chaperone protein
3. transport of MHCII receptor into the phagolysosome from the endoplasmic reticulum
4. antigen binding to MHCII antigen binding site degrades protective chaperone protein
5. MHCII receptor is moved to cell surface and recognized by CD4 co-receptor on helper T-cells

Question 13

Helper T-cells - T(H)1

Answer 13

activates macrophages
inflammatory T-cell that activates innate immune response
release of TNF-alpha, GM-CSF, IFN-gamma cytokines

Question 14

Helper T-cells - T(H)2

Answer 14

activates B-cells
release Tfh which mediates class-switching of B-cells into antigen producing plasma cells
release of IL-4 and IL-5 (Th2 subset) by T(H)2 to mediate antibody production

Question 15

Tfh

Answer 15

class-switching (of B-cells into plasma cells) for long-term humoral immunity
cytokines: IL-21
transcription factors: Bcl-6

Question 16

Th2

Answer 16

antibody production by B-cells
cytokines: IL-4 and IL-13
transcription factors: Gata3

Question 17

Th1

Answer 17

macrophage activation
cytokines: IFN-gamma
transcription factors: T-bet

Question 18

Th17

Answer 18

neutrophil activation
cytokines: IL-17a and IL-17f
transcription factors: Ror(gamma)t

Question 19

iTreg

Answer 19

immune tolerance, lymphocyte homeostasis
cytokines: IL-10, IL-35, and TGF-beta
transcription factors: Foxp3

Question 20

Class-switching/Affinty maturation

Answer 20

long term humoral immunity is associated with immunoglobulin isotype switching (mediated by Tfh)
i.e. IgM (primary response) has less affinity than IgG (secondary response)

Question 21

Antibodies

Answer 21

Y-shaped proteins that are composed of two light and two heavy chains linked by disulfide bonds
Fab region (variable): binds to antigens
Fc region (function-conserved): binds to phagocytes to mediate phagocytosis
five major classes: IgA, IgG, IgM, IgD and IgE (varies in oligomermic state)

Question 22

IgM

Answer 22

pentamer
first antibody produced with low affinity

Question 23

IgG

Answer 23

major circulating antibodies that are found in extracellular fluid, blood and lymph
higher affinity than IgM
can cross the placenta to protect the fetus

Question 24

IgA

Answer 24

dimer
found in body secretions (i.e. saliva, tears, breast milk, colostrum, gastrointestinal secretions and mucous)

Question 25

Major functions of antibodies

Answer 25

binding of antibodies to antigens inactivate antigens by enhances phagocytosis: - **neutralization** (blocks viral binding sites, coats bacteria and/or opsonization) - **agglutination** of antigen-bearing particles such as microbes - **mediate precipitation** of soluble antigens cell lysis: - complement fixation (**activation of complement**)