Innate Immunity

Innate Immunity

Non-specific control of infection

Host Defenses:

Innate, nonspecific
First line of defense

  • Physical barriers

  • Chemical barriers

  • Genetic components

Second line of defense

  • Phagocytes

  • Inflammation

  • Fever

  • Antimicrobial proteins

Acquired, specific
Third line of defense

Active

  • Maternal antibodies

Passive

  • Infection

Barriers: A First Line of Defense

  • Skin

    • Keratinized, impervious, and waterproof

  • Sweat glands

    • Flush away microbes; high salt impedes growth

  • Mucous membranes

    • Mucous impedes entry and attachment

  • Respiratory tract

Physical or Anatomical Barriers at the Body’s Surface

  • Nasal hairs and mucus trap large particles

  • Mucous and fluids flush microbes and allergens

    • Response to allergens or URT infection

  • Cilia in LRT push particles up to trachea

  • Cough/sneeze to expel

Nonspecific Chemical Defenses

  • Skin and mucous membranes:

    • Sebaceous secretions exert an antimicrobial effect

    • Lysozyme:

      • Found in tears and saliva

      • Hydrolyzes peptidoglycan in the cell walls of bacteria

    • Lactic acid and electrolyte concentrations in sweat

    • Skin’s acidic pH

    • Fatty acid content

  • Stomach:

    • Hydrochloric acid

  • Intestines:

    • Digestive juices

    • Bile

  • Urogenital:

    • Urine is low pH

    • Semen has antimicrobial chemicals

    • Vagina has a protective acidic pH maintained by normal biota

Active but non-specific protection - Second line of defense

  • Innate immunity

    • Nonspecific

    • Internalized system of protective cells

    • Inflammation and phagocytosis

  • Kill or destroy anything foreign that enters the body

  • Not harm self

Body Compartments Involved in Immune Defenses

  • The mononuclear phagocyte system

  • Spaces surrounding tissue cells that contain extracellular fluid (ECF)

  • The bloodstream

  • The lymphatic system

Lymphatics - your body’s sump pump

  • Lymphatics

    • Return of extracellular fluid to the circulatory system

    • Act as a “drain-off” system for the inflammatory response

    • Render surveillance, recognition and protection against foreign materials

  • Lymph nodes

    • Filter for lymph

    • Location of antigen presentation to B and T cells

Phagocytes - eating the enemy

  • Monocytes

    • Clear invaders

    • Present antigens to lymphocytes

  • Dendritic cells

    • Surveillance system in tissues

  • Macrophages

    • Resident and patrolling “big eaters”

    • Monocytes that have left circulation to enter tissues

Determining self from invader

Pathogen-associated molecular patterns (PAMPs):

  • Recognized by phagocytes and other defensive cells

  • Serve as signal molecules on the surfaces of microbes

  • Not present in mammals

  • Bind to Pattern Recognition Receptors (PRRs) on immune cells

  • Examples of PAMPs:

    • Peptidoglycan

    • Lipopolysaccharide

    • Double-stranded RNA found in viruses

Immunity requires specificity

  • Innate immunity targets anything deemed foreign

  • Must not target self

Granulocytes - Chemical warfare

  • Neutrophils (a.k.a PMNs)

    • Produce toxic chemicals

    • Attack in large numbers

  • Eosinophils

    • Attack eukaryotic invaders (helminths)

  • Basophils

    • Similar to mast cells

    • Contrbiute to histamine (i.e. allergies)

Neutrophils-total destruction when Macs are not sufficient

  • 40-70% of circulating WBC

  • Only cell capable of unchecked tissues destruction

  • Active in very large numbers

  • Phagocytic

  • Release of chemical mediators to destroy invaders and infected tissues

    • Bleach, other oxygen halides

    • Reactive oxygen and nitrogen species

    • Proteases, lipases, coliagenase

  • NETs- Neutrophil Extracellular Traps

    • Release chromosomes to entangle invading organisms

Bringing in reinforcements

  • If local cells can’t control infection, signal for help

  • Releases of cytokines and chemokines

  • Additional cells use chemotaxis towards chemokines to find site of infection

Cytokines allow cells to talk with one another

  • Autocrine - Same cell secretes and receives cytokine signal

  • Paracrine - Cytokine signal secreted to a nearby cell

  • Endocrine - Cytokine signal secreted to circulatory system; travels to distant cells

The Inflammatory response

  • Serves multiple functions

    • To mobilize and attract immune components to the site of injury

    • Initiates tissue repair and removal of harmful substances

    • Destroy microbes and block their further invasion

  • Classic signs and symptoms:

    • Rubor: redness caused by increased circulation and vasodilation in injured tissues

    • Calor: warmth from the increased flow of blood

    • Tumor: swelling from increased fluid escaping from tissues

    • Dolor: pain caused by the stimulation of nerve endings

Controlling microbes in the bloodstream

  • Complement

    • Protein cascade that targets bacterial membranes

    • Causes

    • bacterial lysis

    • Complement also signals macrophage chemotaxis and activation

Blocking Viral Replication

  • Interferon

    • Released by cells infected w/ a virus

    • Tells neighboring cells of infection

    • Those cells turn on anti-viral systems

    • Does not have initially infected cells

    • Reason you feel horrible when you have a viral infection

Nutritional immunity - Preventing bacterial growth

  • Host Iron-binding proteins

    • Hemoglobin:

      • Located within red blood cells

    • Transferrin:

      • Found in blood and tissue fluids

    • Lactoferrin:

      • Found in milk, blood, tears, and saliva

    • Ferritin:

      • Found in every cell type

    • Host Zinc binding proteins

      • Calprotectin

        • Found in most cell types and compartments

    • Bacteria counter with siderophores and iron carrier receptors


Adaptive Immunity

  • Specific targeting of pathogens by the immune system.

Components of Adaptive Immunity

  • Immunocompetence: Ability of the immune system to react to countless foreign substances.

  • Antigen: A molecule that elicits an adaptive immune response.

  • Immunologic Memory: Rapid activation of lymphocyte clones programmed against previously encountered invaders.

Characteristics of Antigens

  • Definition: A substance that provokes an immune response in specific lymphocytes.

  • Epitope: The portion of an antigen that the immune system recognizes.

  • Characteristics:

    • Molecules of complex composition.

    • Typically proteins or protein-containing complexes.

    • Polysaccharides are generally poor antigens.

Origin of Immunologic Diversity

  • Adaptive Response: Dependent on B and T cells.

  • Cells activate in response to immunological challenges.

  • Make clones to combat infections, which persist and provide memory against future infections with the same pathogen.

Lymphocyte Development

  • B Cells: Produce antibodies.

  • T Cells:

    • Activate B cells.

    • Target virus-infected and cancerous cells.

    • Stimulate inflammation.

    • Regulate the immune response.

Lymphocyte Receptors and Specificity to Antigen

  • Coreceptors:

    • CD4 on T helper cells; recognizes MHC-II.

    • CD8 on Cytotoxic T cells; recognizes MHC-I.

Major Histocompatibility Complex (MHC)

  • MHC presents antigens to the immune system:

    • MHC-I: Found on all nucleated cells; shows the immune system what proteins are being made inside the cell.

    • MHC-II: Found only on antigen-presenting cells (APCs) such as

    • dendritic cells

    • macrophages

    • and B cells

    • presents to TH cells for immune surveillance and destruction of foreign matter.

Phagocytes and Antigen Presentation

  • Phagocytes display antigens on MHC-II, enabling T cells to respond.

TH Cell Development

  • TH Cell Types:

    • TH17: Promotes inflammation.

    • TREG: Damps immune response.

    • Activates CD8+ Cytotoxic T Lymphocytes (CTLs) and helps in B cell activation, forming long-term memory.

Activation of Cytotoxic T Lymphocytes

  • CD8+ CTLs activated by APCs and TH1 cells to target infected cells.

Natural Killers (NK) Cells

  • CTLs target cells expressing foreign antigens while NK cells target those that lack MHC-I expression or show stress.

B Cell Activation and Expansion

  • Impact of Losing T Cells: Can severely impede B cell activation and the overall immune response.

Classes of Immunoglobulins

Monitoring Antibody Production Over Time

  • Antibody responses typically take approximately 3 days to develop at first encounter.

Antigen-Antibody Interactions

  • Key mechanisms by which antibodies neutralize pathogens and mediate immune responses.

Types of Vaccines

  • Whole Cell Vaccines:

    • Advantages: Can provide strong immune responses.

    • Disadvantages: Risk of strong side effects.

  • Component Vaccines:

    • Advantages: Target specific parts and often have fewer side effects.

    • Disadvantages: May require multiple doses for effectiveness.

  • mRNA Vaccines: New class of vaccines that instruct cells to produce an antigen.

Acquired Immunity

  • Active

  • Passive