Innate and Adaptive Immunity: Study Guide (Chapters 11, 12, 14)

Innate Immunity (Chapter 11)

Overview of the Immune System and Responses

The immune response is a physiological process coordinated by the immune system to eliminate foreign substances, known as antigens. The immune system is divided into two main branches: innate immunity and adaptive immunity.

• Innate Immunity: The body's first and second lines of defense, providing immediate, non-specific protection against pathogens.

• Adaptive Immunity: The third line of defense, characterized by specificity and memory, targeting particular antigens.

Comparison of Innate and Adaptive Immunity

The following table compares the main features of innate and adaptive immunity:

Feature	Innate Immunity Tools	Adaptive Immunity Tools
Response time	Immediate	~7 days
Distinguishes self from foreign	Yes	Yes
Kills invaders	Yes	Yes
Effective against diverse threats	Yes	Yes
Tailors response to specific antigen	No	Yes
Remembers antigen and amplifies response upon later exposure	No	Yes
Organism distribution	All eukaryotes	Only vertebrates

Common characteristics: Both distinguish self from foreign, kill invaders, and are effective against diverse threats.

First-Line Defenses

First-line defenses aim to prevent pathogen entry into the body. These defenses are part of innate immunity.

• Physical barriers: Skin, mucous membranes

• Chemical barriers: Lysozyme in tears, stomach acid

• Normal microbiota: Compete with pathogens, block harmful microbes, and help educate the immune system to distinguish between harmful and harmless agents.

Hygiene hypothesis: Suggests that reduced exposure to normal microbiota may increase the risk of allergies and autoimmune diseases, as the immune system may become confused without proper microbial education.

Second-Line Defenses: Cellular Components

Second-line defenses involve various leukocytes (white blood cells) that perform key immune functions:

Cell	Phagocytosis	Stimulate Inflammation	Adaptive Immunity	Initiate Allergic Responses	Defend Against Parasites
Neutrophils	✓	✓
Eosinophils					✓
Basophils		✓		✓
Mast cells		✓		✓
Monocytes	✓
Dendritic cells	✓		✓
Lymphocytes			✓

Key point: Leukocytes are central to second-line defenses due to their roles in phagocytosis, inflammation, and bridging to adaptive immunity.

Second-Line Defenses: Molecular Components

The complement system is a group of proteins that enhances immune responses. In the classical pathway, complement is activated by antibodies attached to antigens.

• Three outcomes of complement activation:

  1. Opsonization (coating pathogens to enhance phagocytosis)

  2. Inflammation (recruiting immune cells and increasing vascular permeability)

  3. Cell lysis (formation of membrane attack complex)

Inflammation

Inflammation is a key innate response with three main goals:

• Recruit immune defenses to the injured tissue

• Limit the spread of infectious agents

• Deliver oxygen, nutrients, and chemical factors essential for tissue recovery

Four cardinal signs of inflammation: Redness, pain, localized heat, swelling

Leukocytes recruited: Neutrophils and monocytes are attracted by chemical alarm signals to the site of infection, where they perform phagocytosis to limit the spread of pathogens.

Phagocytosis

Phagocytic cells engulf targets in an endocytic vesicle called a phagosome. The phagosome fuses with a lysosome (an organelle packed with hydrolytic enzymes), forming a phagolysosome where the pathogen is destroyed.

• Deficiency in hydrolytic enzymes: If these enzymes are missing due to a genetic disorder, pathogens cannot be effectively destroyed, leading to persistent infections.

Integration: Complement, inflammation, and phagocytosis work together to identify, recruit, and eliminate pathogens.

Adaptive Immunity (Chapter 12)

Third-Line Defenses: Adaptive Immunity

Adaptive immunity is characterized by specificity, memory, and the ability to tailor responses to specific antigens. It is divided into two branches:

• Humoral immunity: Mediated by B cells and antibodies

• Cell-mediated immunity: Mediated by T cells

The goal of both branches is to recognize an identified antigen and remember it for a faster response upon re-exposure.

Four Stages of the Adaptive Immune Response

1. Antigen recognition

2. Lymphocyte activation

3. Effector response

4. Memory cell formation

Antigen presentation: Antigens are presented to T cells, which are central to adaptive immunity.

T Cells: Types and Functions

• Cytotoxic T cells (TC): Express CD8 on their surface; responsible for killing abnormal cells (cell-mediated immunity).

• Helper T cells (TH): Express CD4 on their surface; regulate the activity of B cells, cytotoxic T cells, and macrophages.

• TH1 cells: Promote cell-mediated immunity.

• TH2 cells: Promote humoral immunity.

Importance of T helper cells: They coordinate and regulate the adaptive immune response, activating both B cells and cytotoxic T cells.

Effector cells: Act immediately to fight infection. Memory cells: Remain long-term and respond faster upon re-exposure to the same antigen.

Cellular Branch of Adaptive Immunity

Effector cytotoxic T cells (TC) release two key proteins:

• Perforin: Forms pores in the target cell membrane.

• Granzymes: Enter through the pores and trigger apoptosis (programmed cell death).

Humoral Branch of Adaptive Immunity

Activated B cells differentiate into:

• Plasma cells: Effector cells that produce antibodies (immunoglobulins, Ig).

• Memory B cells: Provide long-term immunity.

Three key antibody functions:

• Neutralization of pathogens

• Opsonization (enhancing phagocytosis)

• Complement activation

Antibody Classes and Functions

Class	Function
IgM	First antibody made on first exposure to antigen
IgG	Produced after IgM; longest-lasting; most abundant; crosses placenta; found in breast milk
IgA	Found in most body secretions, including breast milk
IgE	Associated with inflammation, allergies, and defense against parasitic worms
IgD	Found on the surface of B cells; may act as an antigen receptor

Immunological Memory

Primary response: The initial immune response to an antigen. Secondary response: A faster, stronger immune response upon re-exposure to the same antigen.

• Faster onset

• Greater antibody production

• Higher affinity antibodies

Memory B cells produced during the primary response are responsible for the secondary response.

Categories of Acquired (Adaptive) Immunity

Type	Description	Long-term Protection?
Naturally acquired active immunity	Contracting an infection triggers the immune system to make memory cells and antibodies	Yes
Artificially acquired active immunity	Vaccination triggers an immune response	Yes
Naturally acquired passive immunity	Receiving antibodies through nonmedical means (e.g., maternal antibodies)	No
Artificially acquired passive immunity	Receiving protective antibodies via medical treatment (e.g., antiserum)	No

• Active immunity: Provides long-lasting protection due to memory cell formation.

• Passive immunity: Provides immediate protection but is temporary (no memory cells formed).

Vaccines and Herd Immunity (Chapter 14)

Herd Immunity

When a large portion of the population is immunized, the spread of disease is reduced, protecting nonimmunized individuals (herd immunity).

Vaccine Types and Formulations

• Attenuated vaccines: Contain live, weakened pathogens; mimic natural infection and induce strong, long-lasting humoral and cell-mediated immunity.

• Inactivated vaccines: Contain killed pathogens; safer for immunocompromised individuals as there is no risk of causing disease.

• Booster doses: Necessary for inactivated vaccines to reinforce the memory response.

• Recombinant vector vaccines: Use a harmless virus or bacterium to deliver pathogen genes (e.g., Johnson & Johnson COVID-19 vaccine).

• mRNA vaccines: Deliver genetic instructions for making pathogen proteins (e.g., Pfizer and Moderna COVID-19 vaccines).

Summary Table: Vaccine Types

Vaccine Type	Example	Advantages	Disadvantages
Attenuated	MMR, Varicella	Strong, long-lasting immunity	Not suitable for immunocompromised
Inactivated	Polio (Salk), Hepatitis A	Safe for immunocompromised	Requires boosters
Subunit/conjugate	Pneumococcal, Hib	Fewer side effects	May require boosters
mRNA	Pfizer, Moderna COVID-19	Rapid development, no live pathogen	New technology, storage requirements
Recombinant vector	Johnson & Johnson COVID-19	Strong immunity, stable	Pre-existing vector immunity may reduce efficacy

Key Equations and Concepts

• Antibody structure: $\mathrm{Ig} = 2 \text{ heavy chains} + 2 \text{ light chains}$

• Complement activation (classical pathway): $\text{Antigen} + \text{Antibody} \rightarrow \text{C1 complex activation} \rightarrow \text{C3 convertase formation} \rightarrow \text{C3b opsonization, C5b-9 lysis}$

• Immunological memory: $\text{Primary response} < \text{Secondary response (speed, magnitude, affinity)}$

Additional info: For more on vaccine development and immune responses to SARS-CoV-2, see supplemental resources on mRNA vaccines and viral testing.