EXAM 4-INNATE IMMUNITY

Immunity

ability to resist a disease

Susceptibility

lack of resistance to a disease

Innate immunity

Immunity that is present before exposure and effective from birth. Responds to a broad range of pathogens.

Adaptive Immunity

immunity or resistance to a specific pathogen; slower to respond, has memory component

Components of Innate Immunity

• Physical, mechanical barriers(skin, mucous membranes)

• Chemical mediators (enzymes,peptides, cytokines, complementproteins)

• Innate immune cells, lymphoidtissues, organs

• Pattern recognition receptors (C-type lectins, TLRs, NOD-like,RIG-1-like; STING)

• pathogen-associated molecular patterns (PAMPs) on microbe surface

Physical Factors - 1st Line of Defense

• Skin (Mechanical): Dermis, Epidermis (with keratin), Shedding and dryness (inhibits microbial growth)

• Mucous membranes: Mucus: viscous glycoproteins (trap), prevent tracts from drying out, Lacrimal apparatus: drains tears; washes eye

• Ciliary escalator: transports microbes trapped in mucus away from the lungs

• Earwax

• Urine

• Vaginal secretions

• Peristalsis, defecation,vomiting, diarrhea

Where are mucous membranes located? What areas of the body are lined with mucous membranes to protect from external environment?

respiratory tract, ears, eyes, mouth, nose

Chemical Factors - 1st Line of Defense

• Sebum

• Lysozyme in perspiration, tears, saliva, and urine destroys bacterial cell walls

• gastric juice

• vaginal secretions

• perspiration

Normal Microbiota-1st line of defense

• Normal microbiota compete with pathogens via microbial antagonism (competitive exclusion)

Formed Elements in Blood -2nd and 3rd Defenses

• Cells and cell fragments suspended in plasma

• Erythrocytes (RBCs)

• Leukocytes (WBCs): Agranulocytes, Granulocytes

• Thrombocytes (platelets)

• hematopoiesis: blood cell production

Discriminate between self and non-self

• Pattern recognition receptors (PRRs): simple molecules,patterns of molecular structures

• Bind to pathogen-associated molecular patterns (PAMPs)

Granulocytes - 2nd Line of Defense

• Granulocytes have granules in cytoplasm

• Neutrophils: phagocytic; first responders

• Basophils: release histamine; allergic responses

• Eosinophils: phagocytic; toxic against parasites and helminths

• Mast cells: vasoactive mediators, affinity for IgE, allergy,anaphylaxis

Agranulocytes- 2nd and 3rd Defenses

• Monocytes: mature into phagocytes (macrophages, dendritic cells) in tissues

• Lymphocytes: T cells, B cells; play a role inadaptive immunity

Innate lymphoid cells - ILCs and NKs

• No antigen-specific receptors

• No memory

• Stimulated by opsonized microbes, antigens, cytokines

1. ILC-1: activate macrophages

2. ILC-2: vasodilation, mucusrelease, activate macrophages

3. ILC-3: immune homeostasis

4. Natural killer cells: granular;destroy stressed/malignant,viral-infected cells

Innate lymphoid cells - NKs

• No antigen-specific receptors

• No memory

• Stimulated by opsonized microbes, antigens, cytokines

4. Natural killer cells: granular; destroy stressed/malignant ,viral-infected cells, Release perforin, granzymes

Lymphoid organs, tissues

• Primary: bone marrow, thymus

• Secondary: spleen, lymph nodes

• Lymphoid tissue: SALT, MALT (GALT and BALT)

Phagocytes - 2nd line of Defense

• "Cell eating"

• Fixed (residents) vs free (patrolling)

• Neutrophils, macrophages, dendritic cells, B-cells

Phagocytosis Mechanism

1. Chemotaxis attraction of phagocyte to microbe

2. Adherence phagocyte attaches to microbe surface

3. Ingestion, opsonization, microbe coated with proteins

4. Digestion microbe digested by phagolysosome

What are some potential PAMPs?: peptidoglycan, LPS, something fungi specific

Inflammation - 2nd line of Defense

• Signs/symptoms: pain, redness, immobility, edema, heat

• Destroys/limits effects on the body

• Repairs/replaces damaged tissues

Phagocyte Migration and Phagocytosis

• Margination : phagocytes stick to blood vessels

• Diapedesis: squeeze through blood vessels to infection site

Tissue Repair

• all harmful substances are removed or neutralized

• Stroma: supporting CT that is repaired

• Parenchyma: functioning part of the tissue that is repaired

Fever - 2nd line of defense

• Abnormally high body temperature

• Hypothalamus: set at 37°C

• Cytokines induce hypothalamus to release prostaglandins = higher temperature

• higher temperature maintained until the cytokines removed

• Crisis: vasodilation and sweating occurs

The Complement System

• Serum proteins, enhances the immune system in destroying microbes

• complement activation

• inflammation, phagocytosis, cell lysis and activation

Complement Activation

1. Cytolysis: form membrane attack complex (MAC)

2. Opsonization: attachment of a phagocyte to a microbe

3. Inflammation: activated complement proteins bind to mast cells, releasing histamine

Cytokines: Chemical Messengers

• Cytokines are chemical messengers produced in response to a stimulus

• Interleukins (ILs): between leukocytes

• Chemokines: migration of leukocytes

• Interferons (IFNs): interfere with viral infections

• Tumor necrosis factors (TNF): stimulate inflammation;example TNF alpha(TNF-α): pro-inflammatory

• Hematopoietic cytokines: formation new red and white blood cells; subgroup includes colony-stimulating factors(CSF) for growth/differentiation

• Overproduction of cytokines leads to a cytokine storm

Interferons

• Cytokines produced by cells; have antiviral activity

• IFN-α and IFN-β: produced by cells in response to viral infections

• IFN-γ: activates neutrophils and macrophages to kill bacteria

Antimicrobial enzymes

• Lysozyme: lyses bond between NAM and NAG in peptidoglycan

• Lactoperoxidase: produces superoxide radicals

Iron-Binding Proteins

• Bacteria produce siderophores to compete with iron-binding proteins

• Host uses transferrin, lactoferrin, ferritin,hemoglobin to bind, transport iron

Antimicrobial Peptides - 2nd line of defense

• Host defense peptides

• Made in response to protein, sugar molecule son microbes

• Inhibit cell wall synthesis

• Form pores in the plasma membrane

• Broad spectrum of activity

• Positively charged(cationic peptides) from host cells

• Defensins,cathelicidins, histatins

• bacteriocins from host microbiota