Immune System Quiz

Complement System

• Thirty proteins produced by the liver circulate in the blood serum.
• These proteins recognize pathogens and trigger a cascade of events.
• Once activated, other components induce inflammation.
• Signals attract immune cells to the site of infection.
• Pathogens are bound to enhance phagocytic cell activity via opsonization.
• Pathogens are lysed (broken down).

Opsonization

• Complement protein C3b or antibodies bound to a bacterial surface act as opsonins.
• This promotes adherence and phagocytosis.

Complement Activation

• Complement activation requires accessory factors.
• A diagram showing the 'alternative pathway' is included.
• A membrane attack complex is formed.

Innate Immunity - Summary I

• Antimicrobial peptides (AMPs), lysozymes and lipases kill bacteria.
• Microbe-associated molecular patterns (MAMPs) are recognized by phagocytic cells.
• Examples of MAMPs are lipopolysaccharide (LPS), flagellin, and CpG motifs.
• Complement proteins are involved in the inflammatory response.

Innate Immune Components - Summary II

• Thick epithelium and tight junctions are physical barriers
• Lysozyme and AMPs (antimicrobial peptides) are chemical barriers
• Phagocytes such as neutrophils, macrophages, and dendritic cells play a vital role as cellular components of the innate immune system.
• C3, C5 complement proteins and other helper proteins are involved in complement activation.

Summary III

• Mechanical, chemical, and microbiota barriers act as the first line of defence against microbial invasion.
• Acellular responses involve the production of antimicrobial peptides and complement proteins.
• Cellular responses involve recognition of microbial associated molecular patterns (PAMPs or MAMPs) by receptor proteins on immune cells. Inflammation is triggered when invader recognition is accomplished.

Adaptive Immunity

• Adaptive immune response introduction includes B-cells, T-cells and antibodies.
• Includes: B cells and memory, T cells, cell mediated immunity.

Immune Cell Functions (Innate vs Adaptive)

• Innate immunity response is rapid (<10 hrs) and has a rapid initial response, a slow second response.
• Adaptive immunity response is slower (>72 hrs) and slower to develop; however, the response is strong and faster on subsequent exposures.

Cells of the Immune System

• Stem cells differentiate into lymphocytes, B cells, T cells and natural killer cells (NK).
• B cell progenitors mature into plasma cells.

Adaptive Immune Response - Main Players

• Lymphocytes (T cells) include cell-mediated responses.
• B lymphocytes (B cells) include humoral responses (antibodies)
• Antibodies are produced by B-cells
• Cytokines are signal molecules.

Antibody Architecture

• Antibodies recognize diverse non-host structures.
• Antibodies contain variable regions to bind to antigens.
• Each antibody recognizes a unique epitope (the part of the antigen it binds).

Antibodies and Foreign Particles

• Antigens are foreign compounds (like proteins) which trigger adaptive immune responses.
• Epitopes are the specific sites on antigens which antibodies recognize.

Humoral Response: Antibody Binding

• Humoral response neutralizes threats with antibody binding.
• Three main approaches antibodies use to clear an infective agent include opsonization, neutralization, and complement activation (ONC).

Snake Antivenom

• Antibodies are used to neutralize snake venom toxins.

B-Cells and Humoral Immune Response

• B-cells develop in bone marrow and carry B-cell receptors.
• When a B-cell receptor (BCR) binds to a specific antigen, it differentiates into plasma cells and memory cells.
• Plasma cells produce antibodies.

Antibody Antigen Recognition

• B-cells with diverse antibody structures are made in bone marrow.
• Self-reactive B cells are removed in bone marrow.
• Antigens bind to B cells, this triggers clonal propagation and somatic hypermutation - resulting in better antibodies.

Antigen Binding and B cells

• Antigen binding to B-cells triggers clonal propagation and somatic hypermutation (process refining an antibody).
• B-cells differentiate into plasma and memory cells.

Memory B-Cells

• The likely advantage of memory B-cells is the rapid response to subsequent exposures to the same pathogen.
• Existing memory cells produce refined antibodies rapidly, quickly addressing the pathogen.

T-Cells and Cell-Mediated Immune Response

• T cells develop in the bone marrow and have T-cell receptors on their surface.
• T cells bind to receptors on antigen presenting cells (APC).
• Once a T cell receptor (TCR) binds to an antigen, the T cell differentiates either to either kill infected cells or activate other cells.

T-Cell Antigen Recognition

• T cells develop specialized T cell receptors (TCR) in the thymus.
• Self-reactive T cells are eliminated during development in the thymus.

Antigen Presenting Cells (APCs)

• T cells encounter their antigens by interacting with APCs like dendritic cells, which display antigens on MHC molecules.
• MHC molecules present antigens to T cells.

APC Antigen Presentation

• APCs present antigens on MHC molecules to T cells.
• MHC II is a major histocompatibility complex molecule.

T-Cell Activation

• Antigen presenting cells display antigens on the MHC II receptor.
• T cells with the right receptor are activated to divide and become effector T-cells (some becoming memory).

T-Helper Cells (B-cell Activation)

• T-helper cells activate B cells to differentiate into plasma and memory cells.
• This process requires the presentation of antigen fragments by MHC II molecules to T helper cells.

Why Two Events for Immune Response

• The two events (B and T-cell recognition) are necessary for a robust and effective immune response.

Cell-Mediated Immunity

• Cytotoxic T cells kill infected cells by producing cytokines and perforins/granzymes that destroy the target cell.
• Activated effector cytotoxic T cells release cytokines to activate other cytotoxic T cells.

T-Cell Receptor Antigen Recognition

• T-cell receptors develop in the thymus, a specialized site for T-cell maturation.
• Self-reactive T cells are eliminated in the thymus.

T-Cells and APC Meeting Locations

• T-cells and APCs meet in lymphoid tissues and lymph nodes.
• Specific maturation sites for B and T cells are in the bone marrow and thymus, respectively.
• Mature T cells and APCs migrate to lymphoid tissues where they can interact.

Dendritic Cell Migration

• Immature dendritic cells reside in peripheral tissues.
• As infection progresses, dendritic cells migrate to lymph nodes for activation of T cells.

Cytotoxic T Cells

• Cytotoxic T cells search for target cells.
• Cytotoxic T cells release perforin and granzymes to kill target cells.

Transplant Patient Medications

• Transplant patients often take medications to suppress cytotoxic T cells to prevent rejection of the transplanted organ.
• Cytotoxic T-cells often recognize a transplanted organ as foreign and thus destroy it, requiring immunosuppression.

Putting it Together: Humoral Response

• The humoral response involves B cells, memory B cells, and T helper cells.
• The ONC activity (opsonization, neutralization, complement activation) is the central strategy of the humoral response.

Putting it Together: Cell-Mediated Response

• The cell-mediated response is led by cytotoxic T-cells (CD8+).
• Cytotoxic T-cells are activated when helper T-cells (CD4+) detect an infection's presence, triggering the activation of cytotoxic cells.
• Helper T cells are needed for cytotoxic T cell activation.

Summary

• The humoral response, mediated by B-cells and antibodies, neutralizes toxins and pathogens.
• The cell-mediated response, performed by T-cells (cytotoxic and helper), directly attacks infected cells.
• The immune system has memory, improving responses to subsequent pathogen encounters.