Introduction to Immunology

Innate Defense System

Nonspecific, response stays the same no matter what.

Innate Defenses

• Physical (skin & mucous membranes)

• Chemical (Antimicrobial substances in body fluids: saliva, lysozymes)

• Cellular (Blood cells, phagocytic cells)

• Molecular (Complement, Interferon)

Adaptive Defense System

Specific. Response is unique to whatever microbes it is fighting

Adaptive Defenses

• Antibodies (soluble proteins, humoral immunity)

• Cell mediated (T cells physically interact with pathogens)

• Antibody mediated (B cells produce antibodies and release them into your plasma)

Skin

• Physical barrier to pathogens

• Hydrophobic surface

• Routine sloughing of skin cells

• Commensal microbiota coating outer surface

• Acid mantle (thin acidic film on surface of skin)

Mucous Membrane

• Lines cavities of the respiratory tract, gastrointestinal tract, and body openings

• Cilia and microvilli in respiratory system that trap bacteria, dust, and other particles

  • Coughing and sneezing are physical responses to clear the respiratory and oropharyngeal tracts

Innate Chemical Defenses

• Secretions (mucous, gastric, sweat) with chemicals preventing pathogen growth & promote homeostasis)

• Sweat: High salt, low pH

• Low pH in gastric secretions

• Lysozyme in tears

• Saliva cleaves peptidoglycan in bacterial cell walls

• Defensins

Defensins

Small, positively charged proteins that act as natrual antibiotics and immune signals in the body’s innate immune system

• Creates pores in pathogenic cells

• Defensins attack pathogens directly

• When dealing with infected host cells, signals for help from T cells

Innate Cellular Defenses

• Blood (erythrocytes, leukocytes, plasma)

• RBCs

• Platelets (important for clotting)

• Leukocytes (2 types)

  • Granulocytes

  • Agranulocytes

Red blood cells

Enucleated cells, made from stem cells in bone marrow

• Use hemoglobin to transport O2 from lungs to tissues, and CO2 from tissues to lungs

Platelets

Formed cellular component, from megakaryocytes, important component of clotting cascade

Granulocytes

• White blood cells central to the immune system

• Contains small granules with proteins that fight infection

• Granular cytoplasm, multilobed nucleus

  • Neutrophils

  • Eosinophils

  • Basophils

Neutrophils

Most abundant leukocyte, important for phagocytosis

Eosinophils

Involved in allergy and inflammation, and target multicellular parasites

Basophils

Least abundant, release histamine and heparin into blood during inflammatory and allergic responses

Mast cells

Found in connective tissues and mucosal linings rather than free blood circulation. Shares similar functions to basophils, dealing with local inflammatory, and allergic responses.

Agranulocytes

Round nuclei and non granular cytoplasm

• Monocytes mature into macrophages that are involved in phagocytosis

• Lymphocytes: B and T cells of adaptive immunity

Phagocytosis (innate system)

• Scavengers of immune system

• Neutrophils and monocytes in blood

• Macrophages in tissues

  • Scavengers of immune system

• General activities

  • Survey tissue compartments

  • Pseudopod loops to enzymatically degrade harmful/unnecessary matter

  • Extract antigens from foreign matter

Interferon (innate molecular defenses)

Class of proteins that respond to infection or cancer

• Prevents viral replication in cells

• Aids in immune regulation of cancer cell growth

• Three types:

  • Alpha (IFN-a)

  • Beta (IFN-B)

  • Gamma (IFN-y)

Complement cascade (innate molecular defenses)

• Rapid and nonspecific cascade of 26 different proteins from blood that work together

• Enhances phagocytic activity and generates peptide fragments that result in inflammation

• Membrane Attack Complex formed on the bacterial cell surface: results in cell lysis

  • Classical and alternative pathways

Adaptive Immune responses

• Specific to an antigen or epitope

• Allows for differentiation between self and non-self antigens

• Can be humoral or cell mediated

• Can be diverse and retains memory

Antigen

Foreign substance that provokes an immune response

Epitopes

Surfaces on an antigen that are recognized by antibodies

Adaptive Humoral Immunity

Humoral immunity mediated by antibodies in blood

• B cells respond to specific antigens on bacteria, viruses, toxins, etc, using antibodies bound to their surface

• B cells differentiate into plasma cells, which synthesize and secrete antibodies

• Antibodies bind to antigens and mark it for destruction

Properties of Antibodies

• Large glycoprotein molecules on surface of B cells or secreted in blood

• Y-shaped: two heavy chains and two light chains

• Variable regions at 2 ends detect epitopes

  • Diversity of variable regions —> diversity of epitopes recognized

• 5 main classes

5 Main Classes of Antibodies

1. IgM is the first type to be released in response to infection. (Very effective in clumping bacteria together).

2. IgG is most abundant

3. IgA levels are high in secretions like saliva, tears, & mucous

4. IgE: Involved in inflammatory responses

5. IgD: Very low concentration in blood, acts as antigen receptor to help activate B cells

Primary Antibody Response

First encounter of immune system with foreign Ags

• Memory cells formed and remain in lymphoid tissue for future

Secondary Antibody response

Brings fast and efficient destruction of Ags recognized by B and T memory cells

How antibodies fight bacterial cells

• Antibodies coat bacterial cells. Can clump them to be removed, promote phagocytosis, and complement action

• Antibodies can also neutralize antigens on viruses or soluble antigens and remove them

  • Can neutralize toxins too

Opsonins

Proteins that coat pathogens and mark them so other cells of your immune system can destroy them

Adaptive Cell-mediated Immunity

Carried out by T cells, which interact with antigen presenting cells and also target viral/bacterial infected host cells.

Types of T cells

1. Helper T cells

2. Cytotoxic T cells

3. Memory T cells

T cells do not make antibodies, they have receptors on their surface that mediate binding and recognition

Lymphatic system

• Compartmentalized network of vessels, cells, and specialized accessory organs

• Transports lymph in 1 direction through vessels and nodes by contractile action of skeletal muscle

Functions of lymphatic system

• Provide an auxiliary route for the return of extracellular fluid to the circulatory system

• Acts as a drain-off system for the inflammatory response

• Surveillance, recognition, and protection against foreign materials

Origins of Lymphatic System

• Bone marrow and thymus (primary lymphoid organs)

  • Sites of B cell and T cell maturation, respectively

• Mature B cells and T cells are transported to secondary lymphoid organs (spleen and lymph nodes)

• Spleen and lymph node sites where mature T cells and B cells are activated by contact with foreign antigens