Chapter 21 - adaptive immune system

The adaptive immune response

• antigen specific

• systemic

• memory

Humoral (antibody-mediated) immunity

B cells may bind directly with antigens

• produces antibodies that bind with the antigen of pathogens and toxins in blood and lymph

Cellular (cell-mediated) immunity

T cells recognize only processed antigens

• attack cellular targets (infected self or foreign cells)

What qualities does a molecule need to possess, to be a complete antigen?

1. immunogenicity → ability to stimulate proliferation of specific lymphocytes and antibody production

2. Reactivity → ability to react with antibodies and activated lymphocytes

Class I MHC proteins

Virtually all body cells

Class II MHC proteins

On particular cells in the immune system

B lymphocytes

antibody producing cells which oversee humoral immunity

T lymphocytes (T cells)

non-antibody producing cells which oversee cellular immunity

Antigen presenting cells (APCs)

Process and display foreign antigens to T cells

• macrophages, B cells and dendritic cells

Lymphocytes

• lymphocytes undergo a selection process, ensuring:

immunocompetence → recognize and bind to a specific foreign antigen through cell surface receptors

self-tolerance → unresponsiveness to self antigens so it does not attack your own body cells

What does it mean when B and T cells are Naive?

immunocompetent B and T cells not yet exposed to antigen are called naive

• exported from primary lymphoid organs (bone marrow and thymus) to “seed” secondary lymphoid

  • increases chance of encounter with antigen

Antigen challenge

• first encounter between an antigen and a naive lymphocyte is usually in a lymphoid organ

  • lymphocyte has a receptor on its surface which recognize a specific antigen upon binding

clonal selection

naive lymphocyte’s first encounter with antigen leads to activation of the lymphocyte

• selected for further development and completion of differentation

antigen receptor diversity

• The genome, not antigens, determine which foreign substances immune system will recognize

B lymphocyte maturation

• B cells mature in red bone marrow

• positively selected if they successfully make antigen receptors (which are basically antibodies embedded on their surface)

• Those that are self-reactive are eliminated by apoptosis (clonal deletion)

B lymphocyte selection

• antigen “selects” antigen specific lymphocytes with complementary receptors (tethered to the outside of B cell)

antigen binds to B cell surface receptors → Receptor-mediated endocytosis occurs → B cell proliferates to form a clone

B lymphocyte proliferation and differentation

Most clone become plasma cell

• secretes antibodies

Some clone cells become memory cells

• mount a rapid response to subsequent exposure of the same antigen

  • provide immunological memory

What are the 2 types of active humoral immunity?

1. naturally acquired → response to real bacterial or viral infection

2. artificially acquired response to vaccine of attenuated pathogens (or antigens)

   • provide antigenic determinants that are immunogenic and reactive

   • spare us symptoms of primary response

   • weaker memory established than with naturally acquired

What are the 2 types of passive humoral immunity?

1. Naturally acquired → from mother’s blood to fetus through the placental barrier or to infant through breast feeding

2. Artificially acquired → from injection of serum containing antibodies

Antibodies

Antibodies = immunoglobulins

Antigen-binding sites:

→ two variable (V) regions at the top of the “Y”

→ constant (C) regions in the stem determine the functions of antibodies of that class

• contain binding sites for cells and chemicals

• allows for complement fixation, crossing of the placental barrier

Antibody functions

• Bind to antigens to form antigen-antibody immune complex

  1. Neutralization

  2. Agglutination

  3. Precipitation

  4. Complement fixation

(neutralization, agglutination, precipitation are susceptible to phagocytosis)

Neutralization

Antibody binds to specific site on virus or bacterial toxins, preventing them from binding to receptors on tissue cells

Agglutination

Antibody cross-links cell surface antigen of several different cell, causing clumping (agglutination)

Precipitation

Water soluble molecules are cross-linked into large insoluble complexes that precipitate

Complement fixation

• main antibody mechanism against cellular antigens (bacteria, mismatched RBCs)

• antibodies bound to cells expose the complement binding sites on their stems and change shape

  • complement fixation and activation leads to:

    → cell lysis

    → enhancement of the inflammatiory response and phagocytosis

Cell-Mediated immune response

Two major populations of T cells based upon additional cell surface receports: CD4 and CD8

• CD4 → Helper T cells

• CD8 → Cytotoxic (killer) T cells

T cell receptors (TCRs)

antigen-specific receptors

CD receptors

assist in cell-to-cell interactions

• Must simultaneously recognize:

  → Nonself

  → Self (MHC protein of a body cell)

1. CD4 cells (T4 cells) become helper TTcells or regulatory T cells

2. CD8 cells become cytotoxic T cells

3. either become memory T cell

T lymphocyte Maturation

T cells mature in thymus under postive and negative selection pressure

1. Positive selection

   • Ensure recognize of “self” MHC

2. Negative selection

   • Ensure recognition of “foreign” MHC proteins

What are the two types of MHC proteins are important to T cell activation?

1. Class I MHC proteins

   • On all cells (including APCs)

   • Display endogenous (self) antigens

   • in infected cells, may display portions of foreign antigens

   • Present foreign antigens to CD8 cells

2. Class II MHC proteins - only on APCs

   • Only on APCs

   • present foreign antigens to CD4 cells

MHC class I proteins

• present on all cell surfaces

• Normally display endogenous antigens:

  • self peptides in a normal cell

• Infected or abnormal cells display foreign antigens (non self)

  • Antigenic peptides displayed by class I MHC on infected or cancerous cell are recognized by cytotoxic T (CD8) cells

MHC class II proteins

MHC II are present on APCs (dendritic cells, macrophages and B cells)

• display only on foreign antigens that have been phagocytized by the APC

• Anti-genetic peptides displayed by class II MHC are recognized by helper T (CD4) cells

Positive selection

T cells “in training” must recognize self MHC proteins during early maturation process

Negative selection

T cells “in training” must NOT recognize self antigen during the late maturation process

• otherwise, premature activation of T cells against a self antigen may result in auto-immunity

Dendritic cells

Connective tissue and epidermis

• after exposure to antigen in tissue, they migrate via lymphatics to lymphoid organs and present antigens to T cells

  • Most important type of APC

Macrophages

• fixed in lymphoid organs and in connective tissue

• present antigens to T cells

  • interaction can activate macrophages to become more phagocytic

B cells

can also present antigens to helper T cells

Helper T cells

• once activated by an APC, T helper cells help activate B and cytotoxic T cells and induce clone formation

• Release cytokines to act upon B and T cytokines cells

Helper T cells → Activation of B cells

• T helper cells displaying antigen fragments bound to MHC II receptors

• TH release interleukins stimulating B cells to divide more rapidly and antibody formation

• Most antigens require TH stimulation to activation B cells: T cell-dependent antigens

Helper cells → Activation of CD8 cells

CD8 cells require TH cell activation to develop into destructive cytotoxic (killer) T cells

• TH cause denritic cells to express interleukins required for CD8 cell activation into TC

Cytotoxic T cells

circulate throughout the body (immune surveillance)

• these are the only T cells that can directly attack and kill other cells

Targets include:

• virus-infected cells (primary targets)

• cells with intracellular bacteria or parasites

• cancer cells

• foreign cells from blood transfusions or transplants

induces a ‘lethal hit’ on the target cell

TC cells releases perforins by exocytosis

Perforins

create pores through which apoptosis-stimulating chemicals (granzymes) enter target cell