Lecture 38 - Immune System: Adaptive Immunity

Question 1

When does adaptive immunity come into play?

Answer 1

When innate immunity is unable to remove the pathogen

Question 2

What makes the adaptive immune system different than innate?

Answer 2

Innate immunity is non-specific and genetically determined, whereas adaptive immunity is acquired following antigen exposure

Question 3

What are the 4 characteristics that are unique to the adaptive immune system?

Answer 3

1. Specificity - T cells and B cells equipped with receptors that recognize a specific antigen. Activated lymphocytes direct their attack specifically at their cognate antigen and ignore other antigens
2. Memory - activated lymphocytes divide into effector or inactive memory cells. Memory cells mount a faster, stronger, and more efficient attack during subsequent antigen exposures
3. Versatility - each lymphocyte recognizes a specific antigen. Since people have millions of lymphocytes, a massive diversity of antigens can be recognized by lymphocytes
4. Tolerance - ensures “self” tissues are ignored while “non-self” tissues are considered a threat. Usually genetically established but can be induced by repeated antigen exposure

Question 4

What are antigens?

Answer 4

They are molecules that stimulate an immune response

Question 5

What are antigen-presenting cells?

Answer 5

They prepare and present antigens to lymphocytes

Question 6

What do T cells do?

Answer 6

Execute cell-mediated immunity to physically or chemically destroy pathogens and infected cells

Question 7

What do B cells do?

Answer 7

Facilitate humoral immunity and produce antibodies that target antigens for destruction

Question 8

Describe the lymphocyte lifecycle

Answer 8

1. Lymphocyte precursors are produced at the red bone marrow
2. T cell selection, differentiation, or death is located at the thymus
3. They then go to peripheral lymphoid organs and tissues for immune cell surveillance, activation, and proliferation (ex. tonsils, spleen, lymph nodes, lymphoid nodules)
4. They then undergo apoptosis weeks - years after production

Question 9

Primary lymphoid structures

Answer 9

Sites where lymphocytes are produced and mature

Question 10

Secondary lymphoid structures

Answer 10

Sites where lymphocytes are activated

Question 11

How do lymphocytes determine their target?

Answer 11

Antigen presentation:

They only recognize antigens when they are bound to MHC (major histocompatibility complex) molecules. There are MHC class 1 and MHC class II

When antigen is presented by an MHC molecule, lymphocytes learn to direct their attack against that specific antigen and nothing else

Question 12

Which class are intracellular antigen presented to?

Answer 12

MHC Class I - intracellular antigens (from viral or bacterial infection) undergo processing and presentation through the MHC class I pathway. MHC class I molecules are located on the surface of all nucleated cells

Note: since RBCs don’t have a nucleus, they don’t have MHC class I!

Question 13

Which class are extracellular antigen presented to?

Answer 13

MHC Class II - extracellular antigens are phagocytosed, broken down into smaller peptides, then loaded onto MHC class II molecules for cell presentation. MHC class II molecules are exclusively located on the surface of antigen presenting cells and lymphocytes

Question 14

What does T cell activation rely on?

Answer 14

Antigen recognition (which relies on antigen presentation) through their receptors, which are unique to each lymphocytes. Different lymphocytes recognize different antigens

MHC class I and class II molecules are recognized by different types of T cells which generates different immune responses against the presented antigen

Question 15

How do different types of T cells recognize different MHC molecules?

Answer 15

Through the cluster of differentiation (CD) markers that exist on the surface of leukocytes. CD markers play a role in antigen recognition, intercellular communication, and environment sensing

Question 16

Name 2 examples of CD markers

Answer 16

CD4 in MHC class II (respond to antigen presenting cell)
CD8 in MHC class I (respond to nucleated cell)

Question 17

What does antigen recognition lead to?

Answer 17

CD8+ T cell activation - CD8+ T cells only recognize antigens when they are presented on MHC class I molecules. When an inactive (naive) CD8+ T cell interacts with an MHC class I molecule and recognizes the bound antigen, the T cell becomes primed

Question 18

What would require a full CD8+ T cell activation?

Answer 18

It must receive a co-stimulation signal either from the infected cell or from its surrounding. Activation stimulates T cell division and differentiation

Question 19

What occurs when CD8+ T cells are activated?

Answer 19

They differentiate into cytotoxic T cells (T_c) or memory T_c cells.

Tc cells - directly attack and destroy infected cells by releasing cytotoxins that enter the infected cell and induce cell death

Memory Tc cells - inactive Tc cells that remain in secondary lymphoid organs until a later antigen exposure

Question 20

What do CD4+ T cells differentiate to? How?

Answer 20

Into active helper T cells, memory helper T cells, or regulatory T cells

1. inactive CD4+ T cells become primed after binding and recognizing antigen presented by MHC-II
2. CD4+ T cell activation requires co-stimulation
3. activated CD4+ T cells divide and differentiate into helper T cells, memory T cells, or regulatory T cells

NOTE: regulatory T cells suppress immune activation by releasing inhibitory cytokines

Question 21

What is sensitization and when does it occur? How does it occur?

Answer 21

Sensitization achieves to coat B cell surface with target antigen. This precedes B cell activation

B cell receptors (antibodies) bind antigen and initiate sensitization. B cells endocytose antigens, load them onto MHC-II molecules and present them on cell surface

B cell is sensitized and awaits helper T cell interaction for activation

Question 22

How do B cells become activated?

Answer 22

They require helper T cells:

1. Sensitized B cells search for a helper T cell that has encountered the same antigen
2. Many circulating helper T cells will attempt to bind the antigen-MHC-II complex on the sensitized B cell
3. Upon antigen recognition by the helper T cell receptor, the helper T cell releases cytokines to induce B cell activation

Question 23

What do B cells do after they activate? (review on slides)

Answer 23

They divide and differentiation

Active helper T cells help activate B cells. This activated B cell can become:

• Inactivate memory B cells: located at secondary lymphoid organs until subsequent antigen exposure when they will differentiate into plasma cells and secrete antibodies specific to antigen
• Active B cells: cytokines stimulate differentiation to antibody-secreting plasma cells

Question 24

Describe the structure of antibodies. What happens when they bind to their target antigen?

Answer 24

They consist of 2 parallel polypeptide chains - a heavy chain and a light chain. Each chain contains a variable segment and a constant segment. The tips of the variable segments form a unique antigen-binding site

When the variable segment bind their target antigen, binding sites on the constant segments are accessible and bind complement proteins or innate immune cells

Question 25

What are the 3 mechanisms antibodies use to defend the body from pathogens?

Answer 25

1. Neutralization and Preventing Adhesion - antibodies physically block the pathogen from binding to healthy cells
2. Complement - binding sites on antibodies bind complement proteins which tags the antigen for degradation
3. Opsonization, Phagocytes, and Inflammation - antibodies attract phagocytic cells that engulf the pathogen and stimulation release of pro-inflammatory cytokines

Question 26

What are the 5 different classes of antibodies (ie. immunoglobulins, Igs)? Where can they be found/what are they associated with?

Answer 26

1. IgG - most common. Protects against bacteria, bacterial toxins, and viruses
2. IgA - found in glandular secretions and mucus membranes and prevent pathogens from accessing internal tissues
3. IgM - the first Ig type to be released during infection and circulates through blood and lymph
4. IgE - associated with allergic reactions and binds mast cells, eosinophils, and basophils
5. IgD - located on B cells and binds extracellular antigen during sensitization

Note: These differ through their heavy-chain constant segments

Question 27

Explain Primary Response: first antigen exposure

Answer 27

Antibodies can’t be released until B cells become activated and differentiate into plasma cells. Antibody titre peaks around 1-2 weeks after initial antigen exposure

Question 28

Explain Secondary Response: subsequent antigen exposure

Answer 28

The infected host already has the necessary tools, so memory plasma cells quickly generate antibody titres that far surpass the primary response in both level and time

Since memory plasma can survive for 20+ years, this secondary response will appear even if years pass before the subsequent antigen exposure