Chapter 9: Host Response to Infection Cells of the Immune System

Definition of Key Terms

1. Immunology: Study of the immune system and A. White Blood Cells (WBCs)
immune responses. White blood cells are critical for immune
defense and are categorized as:
2. Immunogen: Any substance capable of inducing
an immune response (humoral or cell-mediated). 1. Granulocytes (Neutrophils):
3. Antigen: Substance recognized by the immune
system (B or T cells) but may not always trigger o Comprise 50–80% of total WBCs.
a response.
4. Epitope: Specific structure on an antigen o Primary responders in acute
recognized by B or T cells. inflammation and bacterial
infections.
5. Hapten: Low molecular weight substance that
becomes immunogenic only when bound to a 2. Lymphocytes:
carrier molecule.

Properties of Antigens FCMM o Make up 20–45% of WBCs.

1. Foreignness and Genetic Composition o Predominant in viral infections and

2. Chemical Composition and Complexity chronic inflammation.

➢ Proteins – most immunogenic o Includes B cells, T cells, and natural

➢ Glycoproteins – more immunogenic than killer (NK) cells.
pure proteins
➢ Pure lipids and Nucleic acids – non- 3. Monocytes and Macrophages:
immunogenic
o Account for 3–8% of WBCs.
3. Molecular Size and Stability

➢ Molecules with molecular weight < 10,000 o Key players in chronic inflammation
daltons - weakly immunogenic or not and act as antigen-presenting cells
immunogens (APCs).
➢ Molecular weights > 10,000 daltons - potent
immunogens Neutrophils are first-line defenders in bacterial
4. Mode of Entry and Dose infections. Lymphocytes handle viral infections and
chronic inflammation, while macrophages both
➢ Proteins require lower doses than engulf pathogens and present antigens to activate
polysaccharides adaptive immunity.
➢ Some antigens work better
subcutaneously than intramuscularly B. Antigen-Presenting Cells (APCs)
Antigen-presenting cells process and present
foreign antigens to T cells, initiating adaptive
The Immune System immunity.
1. Central Lymphoid Organs (Primary): The main APCs include: MBDLKG
Bone Marrow: Site of B-cell maturation. • Macrophages: Engulf and present antigens.
• B Cells: Produce antibodies and present
Thymus: Site of T-cell maturation. antigens.
• Dendritic Cells: Most efficient APCs, bridging
2. Peripheral Lymphoid Organs (Secondary): innate and adaptive responses.
• Langerhans Cells: Specialized dendritic cells
Lymph Nodes, Spleen located in the skin.
➢ where mature B and T cells encounter • Kupffer Cells: Liver macrophages that filter
antigen blood.
• Glial Cells: Present antigens in the central
Mucosa-Associated Lymphoid Tissues (MALT) nervous system.
➢ tonsils, adenoids, Peyer’s patches in the
ileum and appendix Dendritic cells are the most important APCs.
➢ trap antigens and facilitate immune Some are found associated with lymphoid follicles
response as follicular dendritic cells. Langerhans cells
migrate from the skin to lymph nodes, becoming
interdigitating dendritic cells. Dendritic cells are the
critical link between innate and adaptive immune
systems.

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B. Other Immune Cells (Innate Immunity)
Other innate immune cells include:
IMMUNE RESPONSE
• Eosinophils: Play a role in allergic (Type I Primary Response:
hypersensitivity) reactions and defense
against parasitic infections through the • First antigen exposure activates Th1 cells
secretion of major basic proteins. → inflammation, delayed hypersensitivity,
IgM and IgG production.
• Basophils: Involved in early allergic • Antibodies appear after 7–10 days, then
responses by releasing histamine. decline.

• Platelets: Primarily involved in blood clotting Secondary Response:

but also release substances that promote
• Re-exposure activates Th2 cells → rapid,
inflammation.
strong IgG response.

• Natural Killer (NK) Cells: Large granular • Involves memory cells and class switching
lymphocytes that destroy virus-infected and (IgG → IgA/IgE).
tumor cells without the need for prior antigen
exposure. Although initially thought to be
cytotoxic T cells, NK cells do not express the IMMUNITY
T Cell Receptor (TCR) and are considered
part of innate immunity. 1. Innate Immunity:

• Non-specific, present at birth.

• First line: skin, secretions (prevent entry).

D. Major Cells in Adaptive Immunity
• Second line: phagocytes, complement
system (destroy invaders).
1. B Cells (Humoral Immunity)
• No memory.
o B cells, upon encountering an appropriate
antigen, differentiate into antibody-producing A. First line of defense – prevents
plasma cells and memory B cells. pathogen entry
o They are essential for humoral immunity, B. Second line of defense – prevents
targeting extracellular pathogens. pathogen multiplication
o B cells function as professional APCs. 2. Adaptive Immunity:

• Specific, acquired after exposure.

2. T Cells (Cell-Mediated Immunity)
• Involves B cells (antibodies) and T cells
T cells are mainly located in the paracortical and (cytotoxicity).
interfollicular zones of the lymph nodes and
• Develops memory for faster future
spleen.
response.
They mediate cellular immunity and differentiate
into: 3. Humoral Immunity:

• B cells produce antibodies.

• CD4+ Helper T Cells: Activate B cells and
cytotoxic T cells. They do not directly • Targets extracellular pathogens, toxins, and
destroy antigens but coordinate immune viruses
responses.
o Innate humoral immunity involves
• CD8+ Cytotoxic T Cells: Directly kill virus- cytokines and the complement
infected cells and tumor cells using perforin system.
and granzymes. o Adaptive humoral immunity
involves the action of antibodies.
• Regulatory T Cells (CD4+CD25+): o Antibody mediated immunity is
Maintain immune self-tolerance by directed primarily against
suppressing inappropriate immune (1) extracellular pathogens
responses. (2) toxin induced diseases
(3) certain viral infections
(4) infections caused by
CD4+ T cells are the predominant lymphocyte
encapsulated pathogens
subset in circulation and are crucial for immune
surveillance. Some T cells also become memory T
cells, providing faster responses upon re-exposure
to the same antigen.

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4. Cell-Mediated Immunity: Antibody Structure
o Defense against intracellular infections
(e.g., viruses). • A typical immunoglobulin is shaped like a "Y"
o Protection against fungi, parasites, and and composed of four polypeptide chains
bacteria. linked by disulfide bonds:
o Involved in transplant and graft rejection. o Two identical heavy chains (50–70
o Main defense against tumor cells. kDa; 440–550 amino acids each).
Key Components: o Two identical light chains (23 kDa;
• Macrophages: Present antigens and ~220 amino acids each).
phagocytose microbes. Heavy Chains
• Natural Killer (NK) Cells: Destroy infected • Each immunoglobulin class has a distinct
and tumor cells independently of antibodies. heavy chain:
• Helper T Cells (CD4+ T Cells): Coordinate o Gamma (γ) for IgG
immune responses.
o Mu (μ) for IgM
• Cytotoxic T Cells (CD8+ T Cells): Directly
kill infected or abnormal cells via perforin o Alpha (α) for IgA
and granzyme release.
o Delta (δ) for IgD
Subtypes of Helper T Cells (CD4+)
o Epsilon (ε) for IgE
• Th1 Cells:
Light Chains
o Activated on first antigen encounter.
• Two types: Kappa (κ) or Lambda (λ)
o Trigger inflammation, delayed-type
Regions of an Antibody
hypersensitivity, and production of IgM
and IgG. • Variable Region:
• Th2 Cells: o Found at the ends of both heavy and
light chains.
o Activated upon re-exposure to the same
antigen. o Contains the hypervariable region
(antigen-binding site).
o Enhance antibody production and
promote class switching (e.g., IgG → • Constant Region:
IgA/IgE).
o Uniform sequence determining the
• Th17 Cells: isotype and functional properties
(e.g., ability to activate complement,
o Recruit neutrophils.
bind Fc receptors).
o Promote further inflammation when
• Hinge Region:
needed.
o Located where the antibody arms
Cytotoxic T Cells (CD8+)
meet the stem ("Y" structure).
• Kill infected, transplanted, or tumor cells.
o Provides flexibility, allowing the
• Use perforin to create pores and arms to move and bind antigens at
granzymes to induce apoptosis. different angles.

Functions of Antibodies (Immunoglobulins) o Enzymatic digestion at the hinge

produces:
1. Neutralization of toxins and viruses.
▪ Fab fragments (antigen-
2. Opsonization to enhance phagocytosis of binding fragments).
microbes.
▪ Fc fragment (crystallizable
3. Activation of the complement system leading fragment, responsible for
to microbial destruction. effector functions like
4. Blocking microbial attachment to mucosal complement activation).
surfaces.

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ANTIBODIES (IMMUNOGLOBULINS) o Cellular infiltration (neutrophils,
eosinophils).
• IgG: Secondary response; opsonization;
most abundant. o Mediators: Leukotrienes (LTC4,
LTD4, LTE4), prostaglandins.
• IgM: First antibody in primary response;
pentamer form. o Tissue damage caused by
eosinophilic enzymes.
• IgA: Secretory antibody (mucosal
immunity). Clinical Manifestations:

• IgE: Allergy and parasite defense. • Local Anaphylaxis: Food allergy, urticaria,
eczema, allergic rhinitis, asthma.
• IgD: B cell receptor.
• Systemic Anaphylaxis: Severe, life-
threatening circulatory collapse (e.g., due to
COMPLEMENT SYSTEM food allergens).

Group of proteins (C1–C9) activated sequentially. Diagnosis:

Pathways: Alternative (innate), Classical (antibody- • History Taking: Familial patterns.

mediated), Mannose Binding • Skin Prick Test: Positive if wheal >10 mm.

• Scratch Test: Allergen applied to skin

Three main effects of activation of the scratches; positive if wheal >10 mm.
complement system
1 Lysis of cells
2 Generation of Inflammatory mediators
Type II: Antibody-Mediated (IgG/IgM)
3 Opsonization leading to enhanced
phagocytosis • Mechanisms:

Involves Four Basic Steps 1. Opsonization and Phagocytosis:

1 Initiation Antibody coating enhances
2 Formation of C3 convertase phagocytosis; activates NK cells
(ADCC).
3 Formation of C5 convertase
4 Formation of membrane attack complex 2. Complement and Fc-Mediated
(MAC) Inflammation: Antibodies deposit in
tissues → inflammation (e.g.,
rheumatic fever).

3. Antibody-Mediated Cellular
HYPERSENSITIVITY REACTIONS
Dysfunction: Autoantibodies affect
• Type I: Immediate, IgE-mediated (e.g., receptor functions (e.g., myasthenia
allergies). gravis, Grave’s disease).

• Type II: Antibody-mediated cytotoxicity

(e.g., hemolytic reactions).
Type III: Immune Complex-Mediated
• Type III: Immune complex deposition (e.g., Hypersensitivity
serum sickness).
• Mechanism: Circulating antigen-antibody
• Type IV: Delayed, T-cell mediated (e.g., TB complexes deposit in tissues →
skin test). inflammation.

• Forms:

Type I: Immediate (IgE-Mediated) o Local: Arthus reaction (complication

Hypersensitivity from repeated vaccinations).

• Immediate Phase: o Systemic: Acute serum sickness

(after exposure to foreign serum).
o Minutes after re-exposure;
vasodilation, vascular permeability.

o Mediator: Histamine. Symptoms Type IV: Cell-Mediated (Delayed)

subside but may recur within 2–24 Hypersensitivity
hours.
• Mechanism:
• Late Phase:
o CD4+ T Cells: Cytokine-mediated
inflammation (e.g., TB skin test).

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 o CD8+ T Cells: Direct cell killing via • Vaccine failure due to multiple pathogen
perforin and granzymes. serotypes.

• Vaccines do not offer 100% protection.

Vaccines and Immunization • Fever and mild side effects common after
vaccination.
Variolation vs Vaccination

• Variolation: Early method using smallpox

scabs; risky.

• Vaccination: Safer; uses killed or

attenuated organisms to stimulate immunity.

Types of Immunization

• Passive Immunization:

o Administration of pre-formed
antibodies (short-lived protection).

o Used for post-exposure prophylaxis,

symptom reduction, protection of
immunocompromised patients.

• Active Immunization:

o Vaccines stimulate the body's own

immune response (long-lasting).

Types of Vaccines

• Live Attenuated Vaccines:

o Weakened organisms (e.g., MMR,

BCG, oral polio).

o Long-term immunity but risky in

immunocompromised hosts.

• Toxoid Vaccines:

o Inactivated bacterial toxins (e.g.,

tetanus, diphtheria).

o Safe, stable; may require adjuvants

and booster doses.

• Killed/Inactivated Vaccines:

o Whole organisms killed by

heat/chemicals (e.g., typhoid
vaccine).

• Subunit Vaccines:

o Use specific antigens (e.g., H.

influenzae vaccine).

o Safer, easier to distinguish between

vaccinated and infected individuals.

Problems with Vaccines

• Risk of reversion to virulence (live

vaccines).

• Hypersensitivity and allergic reactions.

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