Infection and Immunity- Pathophysiology

What is the First Line of Defense?

Innate Immunity

What is the First Line of Defense:1. Physical & mechanical barriers?

Skin

Linings of the gastrointestinal, genitourinary, & respiratory tracts

• Sloughing off the cells (barrier maintenance)

• Mucus & cilia (separation)

• Coughing & sneezing (protective reflexes)

What is the First Line of Defense: 2. Biochemical Barriers?

Synthesized & secreted → saliva, tears, earwax, sweat, & sebum

• Antimicrobial peptides: defensins & collectins

• Normal bacterial flora

What is the First Line of Defense: 3.

Molecular & Cellular defense

What is the Second Line of Defense?

Inflammation!

What is the Second line of defense- Inflammatory Response?

Caused by a variety of agents: infection, ischemia, mechanical damage, etc.

Local manifestations: 5 cardinal signs of inflammation

Vascular response: Blood vessel dilation, increased vascular permeability & leakage, WBC extravasation

Cells of Innate Immunity: Phagocytic Leukocytes:

Neutrophils, monocytes/macrophages, Dendritic cells

Cells of Innate Immunity: Natural Killer (NK) Cells:

Recognize altered host molecules

Cells of Innate Immunity: Mast Cells:

Secrete histamine (enhance inflammatory response)

Cells of Innate Immunity: Mucosa-associated invariant T cells:

Prime & recruit the other immune cells

• Lyse the infected cells

Cells of Adaptive Immunity: T Cells

T Helper cells (CD4+)

• Recognize foreign antigens

• Start immune response

  • Activate other T cells

  • Activate B cells

T Cytotoxic Cells (CD8+): Kill infected cells

Cells of Adaptive Immunity: B Cells

Plasma Cells: Secrete antibodies (immunoglobulins)

Memory B Cells: Remain in the body for subsequent, quicker reactions

What is a Host?

Any organism capable of supporting the growth of another organisms

What is Colonization?

The act of establishing a presence, a step required for infection

What is Infection?

The presence & multiplication within a host of another organism, with subsequent injury to the host

What is Virulence?

Disease-producing potential of the microorganism

What are Microorganisms?

Bacteria, fungi, archaea, & protists

• Cell count is similar to the host

• Beneficial and opportunistic microorganism

• Genome is 2-10 fold of the host genome

What is the Mutual Relationship of Microbiota?

Commensalism: Normal microflora

Mutualism: Vitamin K-secreting bacteria in the GI tract

Relationship can be breached by injury

• Leave their normal sites & cause infection elsewhere

What are Infectious Disease?

The host sustains injury or pathological damage in response to the infecting organism

What are Opportunistic Pathogens?

Capable of producing an infectious disease when the health & immunity of the host is compromised by illness, malnutrition, or medical therapy

• Staphylococcus aureus: normal flora on human skin by may cause infection

• HSV: In most people with healthy immune system, HSV is in an inactive state

Stages of Infection: Colonization?

Begins when organism enters body (before infection)

Stages of Infection: Incubation?

Period of growth & invasion & no symptoms

Stages of Infection: Clinical Threshold?

Stage at which symptoms appear

What are Virulence Factors?

Substances or products generated by infectious agents that enhance their ability to cause disease

What are Toxins?

Exotoxins (tetanus, botulinum) & endotoxins (LPS, lipopolysaccharide found in the cell wall of gram negative bacteria)

What are Adhesion factors?

Help attach to the cells (influenza virus)

What are Evasive Factors?

Help keep immune system from killing infective agent (IgA protease, capsule)

What are Invasive Factors?

Surface components allow the infectious agent to inavade the host cells (protease, collagenase, phospholipase)

What are Virus Particles?

A small collection of genetic code, either DNA or RNA, coated by protein

• Smallpox viruses, HSV, HIV, Coronavirus, HPV, Hepatitis

What can Viruses do?

Can only replicate insife living cells

What is the Mutation Rate?

RNA >DNA

• SARS-CoV2: Aplha, Beta, Gamma, Detla

What are the Viruses Mechanism/Pathology Consequences?

Cell Lysis: Poliovirus

Latency: Herpesviruses

Oncogenesis: HPV and Hepatitis B & C

What is Human Immunodeficiency Virus (HIV)?

Targeting the immune system (CD4+ T cells), compromising host immunity

Treatment & Prevention: Antiretroviral therapy (ART)

• Pre-exposure prophylaxis (highly efficiency)

• Post-exposure prophylaxis (take within 3 days)

What is Bacteria Mechanism/Pathology

Lack a distinct nucleus & membrane-bound organelles (prokaryotes)

• Cytoplasmic membrane is surrounded by a rigid cell wall (peptidoglycan)

• Live independently

• Can produce toxins (virulence factors)

  • Endoxtins and Exotoxins

What are Exotoxins?

Proteins released by bacteria specifically produced to damage or kill host cells

What are Endotoxins?

Parts of the bacteria (usually cell wall); cause host immune reactions (side effect)

What is Mycobacterium Tuberculosis?

Bacterium that infects the lung epithelial

• Lives in macrophages!

• Prevents phagosome formation

Primary cause of Tuberculosis

What are the Virulence Factors in Myobacterium Tuberculosis?

Capsule- prevents immune attack

Tuberculosis necrotizing toxin (TNT)

• Exotoxin- causes macrophage death

What are Granulomas?

Dynamic “battlefield” Structure

• Consists of macrophages, T cells, Fibroblasts

• Dead tissue

What us Adaptive Immunity- Hypersensitivity Disorders?

Excessive or inappropriate activation of the immune system

• The body is damaged by the immune response, rather than by the antigen (often called allergen)

4 Types

What is Type I: Immediate Hypersensitivity Disorder?

Mediated by IgE

Asthma, allergic rhinitis, food allergy

What us Type II Antibody-Mediated Hypersensitivity?

Mediated by IgG or IgM Abs

• Endogenous or exogenous antigens

• Can involve antibody-complement interactions

• Mismatch blood transfusions, Myasthenia gravis, glomerulonephritis

What is Type III Immune Complex-Mediated Disorder?

Mediated by antigen-antibody complexes

• Systemic lupus erythematosus, Serum Sickness

What is Type IV cell-Mediated Hypersensitivity?

Direct cell cytotoxicty (CD 8+)

• Hepatitis B

Delayed hypersensitivity response (CD4+)

• Tuberculin test, allergic contact dermatitis