Host Response to Infection and Immunology

• Presents a review of host response to infection, immunology terminology
• Covers properties of antigens, immune system, immune responses (innate and adaptive)
• Presents humoral and cell-mediated immunity, the complement system, hypersensitivity, and vaccines.

Learning Objectives

• The goals are to differentiate antigens and immunogens
• Explain antigen properties determining immunogenicity
• Describe the body's defense lines
• Detail the roles of T and B cells in host defense
• Distinguish adaptive from innate immunity
• Discuss hypersensitivity reaction mechanisms
• Outline the role of vaccines in preventing infectious diseases

Terminology

• Immunology studies the immune system
• An immunogen provokes an immune response
• An antigen binds to immune system components
• An epitope is the part of an antigen that an antibody binds
• A paratope is the part of an antibody that binds an antigen
• A hapten is a small molecule that can elicit an immune response only when attached to a larger carrier

Properties of Antigens

• Foreignness and genetic composition affects antigen behavior
• Chemical composition and complexity affects antigen behavior
• Molecular size and stability affects antigen behavior
• The mode of entry of the antigen affects its behavior

Immune System Organization

• Central lymphoid organs include primary sites for T and B cell differentiation and maturation and play a vital role in adaptive immunity
• B cells differentiate and mature in bone marrow
• T cells differentiate in the bone marrow
• Peripheral lymphoid organs are sites of reactivity or "waiting areas"
• Lymph nodes, spleen, and MALT are peripheral lymphoid organs
• Both T and B cells reside in peripheral lymphoid organs

Innate Immunity

• Innate immunity is active from birth
• Key functions involve destroying invading organisms and activating immune responses
• Innate immunity doesn't improve after exposure, has no memory, and provides short-term protection
• The first line of defense involves host barriers
• The second line of defense is phagocytosis
• Pathogen-associated molecular patterns (PAMPs) affect MAC and phagocytosis

Adaptive Immunity

• Adaptive immunity uses a final defense when microbes escape initial defenses.
• T and B cells recognize foreign invaders' epitopes.
• B cells produce antibodies; T cells become cytotoxic T cells
• Takes 7-10 days to produce antibodies, offers longer protection
• Positive memory produces a stronger response upon antigen re-exposure

Immune Response Details

• First antigen exposure activates Th1 cells, triggering inflammatory cells and delayed hypersensitivity, with B cells producing IgM and IgG
• Secondary response: re-exposure activates Th2 cells for Ig production (except IgM), prompting rapid, high-intensity Ab response, mostly IgG antibody switching

Humoral Immunity

• Innate immunity's humoral response involves cytokines and the complement system
• Adaptive immunity's humoral response involves antibodies
• Effective against extracellular pathogens, toxin-induced diseases, certain viral infections, and infections caused by encapsulated pathogens

About Antibodies

• Globulin proteins/Immunoglobulins react to the antigen that stimulates their production
• Functions:
  • Neutralize toxins and viruses
  • Promote opsonization
  • Activate the complement system
  • Prevent microbe attachment to mucosal surfaces

Antibody Structure

• Y-shaped structure linked by disulfide bonds composed of polypeptide chain
• Includes 2 identical light chains (Kappa or Lambda) and 2 identical heavy chains (Gamma, Mu, Alpha, Delta, Epsilon)
• Variable region contains hypervariable region as antigen binding site
• Contains antigen binding site composed of variable regions of both heavy and light chains
• Flexible hinge region of the arms.
• Digestion yields antigen binding fragment (2 Fab) and crystallizable fragment (1 Fc)

Cell-Mediated Immunity (CMI)

• Provides resistance and recovery from intracellular organisms (viruses)
• Defends against fungi, parasites, and bacteria
• Is involved in transplant and graft rejection
• Is a main defense against tumor cells
• Involves macrophages, NK cells, Th1, Th2 cells
• Macrophages, B, and dendritic cells present antigens to T cells, ingesting and destroying microbes

Helper T Cells

• CD4 T cells
• Key cells: Th1, Th2, Th17
• Stimulates B cell differentiation into plasma cells and activates cytotoxic T cells
• Th1 cells: first encounter triggers inflammation and delayed-type hypersensitivity, synthesizing IgM and IgG
• Th2 cells: next encounter activated for rapid Ab production and class switching
• Th17 cells: chemotactic to neutrophils and promote inflammation

Cytotoxic T Cells

• CD8 T cells
• Destroy antigens through the perforin-granzyme mechanism
• Antigen activates CTL, releasing granzyme, activating caspases, and program cell death/apoptosis

Complement System

• Group of proteases (C1-C9) that sequentially cleave and activate each other
• Secreted as inactive enzymes
• Stimulated by one IgM or two IgG molecules
• Effects include cell lysis, inflammatory mediator generation, and enhanced phagocytosis through opsonization

Basic Steps of Complement System

• Initiation
• C3 convertase formation
• C5 convertase formation
• Membrane Attack Complex formation

Three Complement Pathways

• Classical pathway
• Alternative or Properdin pathway
• MBL pathway

Alternative or Properdin Pathway

• Stimuli: bacterial products (e.g., endotoxin) or immunoglobulin complexes
• Part of innate immunity, first activated on initial antigen exposure
• Bypasses C3 convertase
• C3 component (hydrolysis) activates Factor B to form C3bBb (C3 convertase)
• C3 convertase cleaves C3 to form C3bBb3b (C5 convertase)
• C5 convertase forms C5b6789 (MAC)
• C3 convertase is stabilized by properdin P and utilized through an amplification loop

Classical Pathway

• Stimulus: Ag-Ab complexes
• Ag-Ab complexes + C1qrs (recognition unit)
• Activation and cleavage of C4 and C2 C4b and C2b combine to form C4b2b (C3 convertase)
• Cleaves C3 to form C4b2b3b (C5 convertase)
• Activates MAC
• Can occur in both innate and active immunity
• Activated last because it requires specific antibodies

Mannose Binding Lectin Pathway

• Stimulus: Mannose-containing sugar
• Sugar presented to Mannose/Ficolin receptor activates C4 and C2 (same as classical pathway)
• Does not utilize C1
• C3 convertase (C4b2a) and C5 convertase (C4b2a3b) are formed

Actions of the Complement System

• C3b is the central molecule
• C3b and C1q are opsonins
• C3a and C5a are chemotactic for neutrophils and chemical mediators in inflammation
• C3a, C4a, and C5a are anaphylatoxins, causing degranulation of mast cells and histamine release
• MAC causes lysis of the bacterial cell wall

Hypersensitivity Reactions

• Immune response causes harmful exaggeration or inappropriate reactions
• Classification:
  • Type I - Anaphylactic, immediate hypersensitivity to allergen, mediated by IgE, histamine is key, e.g., asthma
  • Type II - Cytotoxic, antibody dependent, mainly involves IgG, e.g., AIHA, HDN, BT
  • Type III - Immune complex-mediated, IgG and IgM combine with Ag, activating complement, causing inflammation, e.g., glomerulonephritis, SLE
  • Type IV - Cell-mediated, delayed hypersensitivity, no antibody involved, e.g., tissue transplantation, viral diseases, contact dermatitis

Essential Characteristics of Active Immunity

• Recognition: Ability to identify antigens
• Specificity: Specific Ag-Ab reactions
• Memory: Recognize the same antigen upon re-exposure

Vaccines

• Suspensions of killed, living, or attenuated microorganisms
• Used as antigens to produce immunity against specific microorganisms

Toxoids

• Made from exotoxins
• The poisonous component is destroyed using heat, UV light, or chemicals without altering the antigenic specificity

Routes of Vaccine Administration

• Intramuscular and subcutaneous: rabies, DPT
• Intradermal/intracutaneous: BCG
• Oral: OPV, Sabin vaccine
• Intranasal: influenza vaccine

Bacterial Vaccines

• Killed bacteria (e.g., Pertussis): prepared using heat or chemical agents
• Live attenuated (e.g., BCG): frequent sub-culture on artificial media
• Bacterial material (e.g., Toxoids): Component of bacterial structure (e.g., capsule, pili)