Innate Immunity and Host Defenses: Microbiology Study Notes

Innate Immunity and Host Defenses

Definitions and Key Concepts

Innate immunity refers to the non-specific defense mechanisms that come into play immediately or within hours of an antigen's appearance in the body. These mechanisms include physical barriers, chemical factors, and cellular responses that protect against pathogens.

• Susceptibility: Lack of resistance to a disease.

• Immunity: Ability to ward off disease.

• Innate immunity: Defends against any pathogen; non-specific.

• Adaptive immunity: Immunity or resistance to a specific pathogen; acquired and specific.

Physical Factors

Physical barriers are the first line of defense against microbial invasion.

• Skin: Epidermis consists of tightly packed cells with keratin, a protective protein.

• Mucous membranes:

  • Mucus traps microbes.

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

  • Lacrimal apparatus: Washes eyes.

  • Saliva: Washes microbes off.

  • Urine: Flows out.

  • Vaginal secretions: Flow out.

Chemical Factors

Chemical barriers help inhibit microbial growth and survival.

• Fungistatic fatty acid in sebum.

• Low pH (3-5) of skin.

• Lysozyme in perspiration, tears, saliva, and urine.

• Low pH (1.2-3.0) of gastric juice.

• Low pH (3-5) of vaginal secretions.

Normal Microbiota and Innate Immunity

Normal microbiota play a role in protecting the host by competing with pathogens and modulating immune responses.

• Microbial antagonism/competitive exclusion: Normal microbiome competes with pathogens or alters the environment.

• Commensal microbiota: One organism (microbe) benefits, and the other (host) is unharmed.

Hematopoiesis

Hematopoiesis is the formation of blood cells by differentiation of hematopoietic stem cells in the bone marrow.

Differential White Cell Count

The differential white cell count is the percentage of each type of white cell in a sample of 100 white blood cells.

Phagocytosis

Phagocytosis is the ingestion of microbes or particles by a cell, performed by phagocytes.

• Neutrophils

• Fixed macrophages

• Wandering macrophages

Phago- from Greek, meaning 'eat'; -cyte from Greek, meaning 'cell'.

Mechanisms of Phagocytosis and Inflammation

Toll-like Receptors (TLRs)

TLRs are proteins that recognize pathogen-associated molecular patterns (PAMPs) and activate immune cell responses.

• TLRs induce cytokines that regulate the intensity and duration of immune responses.

Oxygen-Dependent and Oxygen-Independent Killing

Phagocytes kill microbes using oxygen-dependent and oxygen-independent mechanisms.

• O2-dependent: $O_2 \rightarrow O_2^- \rightarrow H_2O_2$

• O2-independent: Lysozyme, lactoferrin, hydrolytic enzymes.

• Myeloperoxidase: $H_2O_2 + Cl^- \rightarrow$ hypochlorite (OCl-).

Inflammation

Inflammation is a complex biological response to harmful stimuli, such as pathogens or damaged cells.

• Activation of acute-phase proteins (complement, cytokine, and kinins).

• Vasodilation (histamine, kinins, prostaglandins, and leukotrienes).

• Redness

• Swelling (edema)

• Pain

Chemical Release by Damaged Cells

Damaged cells release chemicals that mediate inflammation and immune responses.

• Histamine: Vasodilation, increased permeability of blood vessels.

• Kinins: Vasodilation, increased permeability of blood vessels.

• Prostaglandins: Intensify histamine and kinin effect.

• Leukotrienes: Increased permeability of blood vessels, phagocytic attachment.

Fever

Fever is an increase in body temperature that can enhance immune function but may also have disadvantages.

• Advantages:

  • Increases transferrins

  • Increases IL-1 activity

  • Produces interferon

  • Inhibits pathogen growth

• Disadvantages:

  • Tachycardia

  • Acidosis

  • Dehydration

  • 44-46°C can be fatal

Fever mechanism:

• Hypothalamus normally set at 37°C

• Gram-negative endotoxins cause phagocytes to release interleukin-1 (IL-1)

• Hypothalamus releases prostaglandins that reset the hypothalamus to a higher temperature

• Body increases rate of metabolism and shivering occurs, raising temperature

• Vasodilation and sweating: body temperature falls (crisis)

The Complement System

Overview

The complement system is a group of serum proteins that act in a cascade to help eliminate pathogens.

• Activated by:

  • Antibody reaction

  • Pathogen

• Proteins: C3, B, D, P and a pathogen

Effects of Complement Activation

• Opsonization: Enhanced phagocytosis due to immune adherence.

• Membrane attack complex: Cytolysis.

• Attracts phagocytes and inflammation.

Bacterial Evasion of Complement

• Capsules prevent C activation.

• Surface lipid-carbohydrate complexes prevent formation of membrane attack complex (MAC).

• Enzymatic digestion of C5a.

Interferons (IFNs)

Interferons are proteins produced by host cells in response to pathogens, especially viruses.

• IFN-alpha and IFN-beta: Cause cells to produce antiviral proteins that inhibit viral replication.

• IFN-gamma: Causes neutrophils and macrophages to phagocytize bacteria.

Innate Immunity: Iron-Binding Proteins and Antimicrobial Peptides

• Transferrins: Bind serum iron.

• Antimicrobial peptides: Lyse bacterial cells.

Table: Physical and Chemical Barriers of Innate Immunity

Barrier Type	Examples	Function
Physical	Skin, mucous membranes, ciliary escalator	Prevent entry of pathogens
Chemical	Lysozyme, low pH, fatty acids	Destroy or inhibit microbes
Cellular	Phagocytes (neutrophils, macrophages)	Engulf and destroy pathogens

Table: Effects of Complement Activation

Effect	Description
Opsonization	Enhanced phagocytosis
Cytolysis	Membrane attack complex formation
Inflammation	Attracts phagocytes

Additional info: Academic context and expanded explanations have been added to ensure completeness and clarity for exam preparation.