Immunology Final Exam Study Guide

Section- 1
1. What are the three lines of defense in the immune system?

The three lines of defense are:

1. Barrier immunity: Physical and chemical barriers that prevent pathogens from
entering the body.

2. Innate immunity: A rapid, non-specific response to a wide range of pathogens.

3. Adaptive immunity: A specific response to a particular pathogen, involving the

production of antibodies and the activation of T cells.

i. Compare and contrast innate and adaptive immunity.

• Innate Immunity:

o Non-specific: Responds to a wide range of pathogens.

o Natural: Present from birth.

o First line of defense: Physical barriers, chemical barriers, and innate immune
cells.

o Second line of defense: Inflammatory response, phagocytosis, and

complement system.

• Adaptive Immunity:

o Specific: Targets specific pathogens.

o Acquired: Develops after exposure to a pathogen.

o Third line of defense: Humoral immunity (antibody production) and cell-

mediated immunity (T-cell response)

Feature Innate Immunity Adaptive Immunity

Specificity Non- Specific Highly specific
Speed Immediate (mins to hour) Delayed (days)
Memory No memory Memory present
Components Physical barriers, T and B lymphocytes,
phagocytes, NK cells antibodies
Duration Short-lived Long-lasting
ii. What is innate immunity?

Innate immunity is the body's first line of defense against pathogens. It provides a rapid,
non-specific response to a wide range of threats.

iii. Why is innate immunity non-specific and natural?

Innate immunity is non-specific because it does not target specific pathogens. It responds
to general patterns associated with pathogens, such as PAMPs (Pathogen-Associated
Molecular Patterns). It is natural because it is present from birth and does not require prior
exposure to a pathogen.

iv. Why is the adaptive immune system specific?

Adaptive immunity is specific because it targets specific pathogens. It develops after

exposure to a pathogen and involves the production of antibodies and the activation of T
cells.

v. Compare and contrast primary and secondary immune responses.

Feature Primary Immune Response Secondary Immune Response
The immune response triggered The immune response triggered
when the body encounters an when the body is exposed to the
Definition antigen for the first time. same antigen for the second time
Slower; it takes several days to Faster occurs within hours to a
Speed of Response weeks to develop. few days.
Longer lag phase as naïve B and T Shorter or negligible lag phase
Lag Phase cells are activated. due to memory cells.
Lower levels of antibodies are Higher levels of antibodies are
Antibody Levels produced. produced quickly.
Mainly IgM antibodies are Predominantly IgG antibodies (or
Type of Antibodies produced initially. IgA/IgE, depending on the site).
Long-lasting and stronger
Duration Short-lived and weaker response. response.
Memory cells are generated Memory cells are activated and
Memory Cells during this response. proliferate.
Less effective in eliminating the Highly effective in eliminating the
Effectiveness pathogen. pathogen.

vi. What are PAMPs and DAMPs?

PAMPs and DAMPs are both types of molecules that can trigger an immune response.
However, they differ in their origin and function.
PAMPs (Pathogen-Associated Molecular Patterns)

• Origin: Derived from microorganisms like bacteria, viruses, and fungi.

• Function: Serve as molecular markers that distinguish pathogens from host cells.
• Examples: Lipopolysaccharide (LPS), peptidoglycan, flagellin, viral DNA and RNA

DAMPs (Damage-Associated Molecular Patterns)

• Origin: Released from damaged or dying host cells.

• Function: Signal the immune system about tissue damage or cellular stress.

• Examples: Heat shock proteins, extracellular matrix components, uric acid

crystals.
2. Lymphatic organs and their functions

Primary vs Secondary Lymphatic Organs

Type Examples Functions

Bone marrow, Site of lymphocyte development and

Primary
thymus maturation

Lymph nodes,
Secondary Site of immune response initiation
spleen

3. Why is barrier immunity called first line of defense?

• Barrier immunity prevents pathogen entry into the body, serving as the first line of
protection.

i. Components of barrier immunity.

• Physical: Skin, mucosal membranes.

• Chemical: Enzymes in saliva, stomach acid, antimicrobial peptides.

• Biological: Normal microbiota.

 ii. What are portals of entry to human body?

• Common portals of entry include the respiratory tract, gastrointestinal tract,

urogenital tract, and broken skin.

iii. Immune mechanisms at the barrier to combat invading pathogens.

• Mechanisms include mucus trapping pathogens, cilia movement, lysozyme

breaking down bacterial walls, and secretion of antimicrobial peptides.

4. What is inflammation?

• Inflammation is the body’s response to injury or infection, aimed at removing

harmful stimuli and initiating healing.

i. What triggers it?

• Inflammation is triggered by PAMPs, DAMPs, tissue damage, or infections.

ii. Cells and molecules are involved in inflammation.

• Cells: Macrophages, neutrophils, mast cells.

• Molecules: Cytokines, chemokines, prostaglandins, histamine.

iii. Briefly explain inflammation.

• It involves redness, heat, swelling, and pain, driven by vasodilation, increased

vascular permeability, and leukocyte recruitment.

iv. What is leukocyte migration from blood to tissue?

• The process where leukocytes exit the bloodstream and migrate to the site of
infection or injury, is called extravasation.

v. Players and their roles in leukocyte migration

• Selectins and integrins: Aid leukocyte rolling and adhesion.

• Chemokines: Guide leukocytes to the infection site.

vi. Benefits and detrimental effects of inflammation

• Benefits: Pathogen removal, tissue repair.

• Detriments: Chronic inflammation can cause tissue damage.

5. What is phagocytosis?

• The process by which immune cells (e.g., macrophages) engulf and destroy
pathogens.

i. The process of formation of phagolysosome

• A phagosome engulfs a pathogen, fuses with a lysosome, and forms a

phagolysosome where pathogens are degraded.

ii. Cells and receptors involved in phagocytosis.

• Cells: Macrophages, neutrophils, dendritic cells.

• Receptors: PRRs (e.g., TLRs), opsonin receptors (e.g., Fc receptors).

iii. Functions of NK cells in innate immunity

• Natural Killer (NK) cells kill virus-infected and cancerous cells by releasing cytotoxic
granules and cytokines.
 iv. How do natural killer cells avoid body cells and only act against foreign
cells?

• NK cells use inhibitory receptors that recognize self-MHC class I molecules,

preventing attacks on healthy cells.

6. What is the importance of complement pathway?

• The complement pathway enhances pathogen elimination by opsonization, cell

lysis, and inflammation.

i. How does it eliminate pathogens?

• Forms membrane attack complexes (MAC) to lyse pathogens, opsonizes them for
phagocytosis, and attracts immune cells.

ii. How does it get activated?

• Activated via three pathways:

1. Classical (antibody-dependent).

2. Alternative (pathogen surface).

3. Lectin (mannose-binding lectins).

7. What are inflammasomes?

• Inflammasomes are multi-protein complexes in innate immune cells that activate

inflammatory responses by producing IL-1β and IL-18.

i. What is their role in innate immunity?

• They detect PAMPs and DAMPs, triggering inflammation and aiding pathogen
clearance.

8. How does the innate immune system activate the adaptive immune system?
 i. Who are the main players in this process?

• Dendritic cells, macrophages, cytokines, and MHC molecules.

ii. How does this process avoid getting activated by non-pathogenic antigens?

• Tolerance mechanisms and regulatory pathways ensure that self-antigens or

harmless antigens do not activate the adaptive system.

Section 2
1. Introduction to Adaptive Immune Response

What is the Adaptive Immune Response?

The adaptive immune response provides specific, long-term immunity by recognizing and
responding to unique antigens through the activation of T and B lymphocytes.

Compare and contrast cell-mediated and humoral responses.

Feature Cell-Mediated Immunity Humoral Immunity

Primary Cells T cells (CD4+ and CD8+) B cells (plasma and memory cells)

Effector Cytokines, cytotoxic T

Antibodies produced by plasma cells
Mechanism lymphocytes (CTLs)

Intracellular pathogens like Extracellular pathogens like bacteria

Target Pathogens
viruses and toxins

Antigen Requires MHC molecules for Can recognize antigens directly (T-
Presentation activation independent antigens)
Feature Cell-Mediated Immunity Humoral Immunity

Memory
Yes (memory T cells) Yes (memory B cells)
Formation

Direct killing or activation of Neutralization, opsonization, and

Mediated by
other immune cells complement activation

Within infected or abnormal

Site of Action Blood and extracellular spaces
cells

What are the properties of the Adaptive Immune Response?

1. Specificity: Precisely targets specific antigens.

2. Memory: Provides a faster and stronger response upon re-exposure to the same
antigen.

3. Diversity: Can recognize a vast range of antigens.

4. Clonal Expansion: Rapid proliferation of antigen-specific lymphocytes.

5. Self-Regulation: Prevents excessive immune reactions.

6. Self-Tolerance: Avoids attacking self-antigens under normal conditions.

What are the cells of the adaptive immune response?

• T Cells: Helper T cells (CD4+) activate other immune cells; Cytotoxic T cells (CD8+)
destroy infected or abnormal cells.

• B Cells: Differentiate into plasma cells to produce antibodies and memory B cells
for long-term immunity.

2. Cells

What are the developmental stages of T cells?

1. Double Negative (DN): Immature T cells lacking CD4 and CD8 markers.

2. Double Positive (DP): T cells expressing both CD4 and CD8 during thymic
selection.
 3. Single Positive (SP): Mature T cells expressing either CD4+ (helper) or CD8+
(cytotoxic) markers.

What are the positive and negative selection criteria during T cell development?

• Positive Selection: T cells that can bind self-MHC molecules with low affinity are
selected to ensure MHC recognition.

• Negative Selection: T cells that bind strongly to self-antigens or self-MHC are

eliminated to prevent autoimmunity.

Compare and contrast B cell receptors (BCRs) and T cell receptors (TCRs).

Feature B Cell Receptors (BCRs) T Cell Receptors (TCRs)

Membrane-bound
Structure Heterodimer of α and β chains
immunoglobulins (IgM/IgD)

Antigen Recognizes whole, unprocessed Recognizes processed antigens

Recognition antigens presented by MHC

Binding Sites Two identical antigen-binding sites One antigen-binding site

MHC-restricted antigen
Mediated by Direct antigen binding
presentation

Signaling
Associated with Igα and Igβ Associated with CD3 complex
Molecules

Soluble Form Secreted as antibodies No soluble form

Activates T cells for cell-mediated

Function Triggers antibody production
immunity

What are monoclonal and polyclonal antibodies?

• Monoclonal Antibodies: Produced from a single clone of B cells; recognize a single

epitope.
 • Polyclonal Antibodies: Produced by multiple B cell clones; recognize multiple
epitopes on the same antigen.

What is the difference between antigens and immunogens?

• Antigens: Any molecule recognized by the immune system (may or may not trigger a
response).

• Immunogens: A subset of antigens that can elicit an immune response.

What are isotypes, and what is isotype switching?

• Isotypes: Different classes of antibodies (IgG, IgA, IgM, IgE, IgD) with specific
functions.

• Isotype Switching: A process where a B cell changes the antibody class it produces
(e.g., IgM to IgG) while retaining antigen specificity.

What is affinity maturation of B cell receptors?

• A process in germinal centers where B cells improve the binding strength of their
antibodies to a specific antigen through somatic hypermutation and selection.

What mechanisms generate diversity in variable regions of TCRs and BCRs?

• Mechanisms:

1. V(D)J Recombination: Rearrangement of variable (V), diversity (D), and

joining (J) gene segments.

2. Junctional Diversity: Addition or deletion of nucleotides at junctions of V(D)J

segments.

3. Somatic Hypermutation: Introduces point mutations in BCR genes during

an immune response.

What is the role of V(D)J recombination in lymphoma?

 • Errors in V(D)J recombination, such as chromosomal translocations, can lead to
uncontrolled lymphocyte proliferation and lymphomas.

What is co-expression of IgM and IgD?

• Naive B cells co-express IgM and IgD on their surface through alternative RNA
splicing. This co-expression helps in initial antigen recognition.

2. Cells

What are Antigen Receptors of Lymphocytes?

• Definition: Antigen receptors are highly specific proteins expressed on the surface
of lymphocytes (B and T cells) that enable the immune system to recognize and
respond to pathogens.

• B Cell Receptors (BCRs):

1. Found on B cells.

2. Can directly bind to antigens without the need for MHC molecules.

3. Are membrane-bound immunoglobulins (IgM and IgD) in naive B cells.

4. Upon activation, B cells can secrete antibodies derived from their BCRs.

• T Cell Receptors (TCRs):

1. Found on T cells.

2. Only recognize processed antigen fragments presented by MHC molecules.

3. Composed of α and β chains with variable regions for antigen binding.

4. Lack a secreted form; TCRs always remain membrane-bound.

Both receptors are essential for the adaptive immune response, with TCRs focusing on
cellular immunity and BCRs on humoral immunity.
What are Monoclonal and Polyclonal Antibodies?

Feature Monoclonal Antibodies Polyclonal Antibodies

Antibodies derived from a single B Antibodies derived from multiple

Definition
cell clone B cell clones

Recognize a single epitope of an Recognize multiple epitopes on

Specificity
antigen the same antigen

Production Produced in the laboratory using Produced naturally in response to

Method hybridoma technology an antigen

Heterogeneous in structure and

Uniformity Identical in structure and function
function

Used in diagnostics, therapy, and

Applications Used in general immune defense
research

Better at recognizing complex

Advantages High specificity, reproducibility
pathogens

Expensive, time-consuming to Less specific, may have cross-

Disadvantages
produce reactivity

Monoclonal antibodies are ideal for targeted therapies, whereas polyclonal antibodies are
more versatile in pathogen defense.

What is the Difference Between Antigens and Immunogens?

Feature Antigens Immunogens

Molecules that can bind immune Subset of antigens capable of

Definition
receptors (TCR, BCR) eliciting an immune response

Response May or may not trigger an immune Always triggers an immune

Capability response response

Vaccines, pathogens, and foreign

Examples Proteins, lipids, polysaccharides
proteins
Feature Antigens Immunogens

Size and Can be small, even non-complex Usually large and structurally
Complexity molecules complex molecules

Requires immunogenicity to Does not need external factors to

Requirement
provoke a response trigger a response

Any molecule that binds immune Molecules specifically activating

Mediated by
cells lymphocytes

Primary molecule in vaccines for

Role in Vaccines May be a component of a vaccine
immunity

Antigens need to be immunogens for vaccination, but not all antigens naturally induce
immune responses.

What are Isotypes, and What is Isotype Switching?

• Isotypes: These refer to the five classes of immunoglobulins (IgG, IgA, IgM, IgE, IgD),
each with distinct structures and functions.

1. IgM: First antibody produced; effective in agglutination and complement

activation.

2. IgG: Most abundant; provides long-term immunity and crosses the placenta.

3. IgA: Found in mucosal areas and secretions (saliva, tears).

4. IgE: Involved in allergic reactions and defense against parasitic infections.

5. IgD: Functions in B cell activation.

• Isotype Switching:

1. Isotype switching is a process during B cell maturation where the constant

region of the antibody changes, enabling a switch from IgM to other isotypes
like IgG, IgA, or IgE.

2. The specificity for the antigen remains the same.

3. Controlled by cytokines and interactions with helper T cells.

4. Allows antibodies to adapt to different roles in immune defense.

What is Affinity Maturation of B Cell Receptors?

• Affinity Maturation is a process that enhances the binding strength (affinity) of B

cell receptors (and their antibodies) to specific antigens.

1. Occurs in germinal centers of lymphoid organs.

2. Involves somatic hypermutation, introducing point mutations in the variable region

of immunoglobulin genes.

3. B cells with higher affinity receptors are selectively expanded.

4. Increases the efficacy of the immune response, particularly during prolonged or

repeated infections.

5. Critical for generating high-affinity antibodies like IgG.

What Mechanisms Generate Diversity in Variable Regions of TCRs and BCRs?

1. V(D)J Recombination:

o Rearranges variable (V), diversity (D), and joining (J) gene segments.

o Generates unique antigen-binding regions.

2. Junctional Diversity:

o Adds or deletes nucleotides at junctions of V, D, and J segments.

3. Combinatorial Diversity:

o Random pairing of heavy and light chains in BCRs or α and β chains in TCRs.

4. Somatic Hypermutation (BCRs only):

o Introduces point mutations in activated B cells for better antigen binding.

5. P-Nucleotide Addition:

o Palindromic sequences added during repair of DNA breaks in V(D)J

recombination.

6. N-Nucleotide Addition:

o Random nucleotides added by terminal deoxynucleotidyl transferase (TdT).

 7. Diversity Significance: Enables the immune system to recognize millions of
antigens crucial for adaptive immunity.

What is the Role of V(D)J Recombination in Lymphoma?

1. Errors during V(D)J recombination can lead to chromosomal translocations.

2. Such errors might activate oncogenes or deactivate tumor suppressor genes.

3. This uncontrolled proliferation of lymphocytes can result in lymphomas.

4. Example: Translocation of MYC in Burkitt’s lymphoma.

5. Highlights the dual role of V(D)J recombination in generating diversity and potential
malignancies.

What is Co-Expression of IgM and IgD?

• Naive B cells co-express IgM and IgD through alternative RNA splicing.

• Both are found on the surface of immature B cells and help in antigen recognition.

• IgM is primarily involved in the initial immune response.

• IgD's function is less defined but believed to play a role in B cell activation.

3. Molecules

What is the Capture of Protein Antigens by Antigen-Presenting Cells (APCs)?

1. Antigen Capture: Protein antigens from pathogens are captured by specialized

cells known as antigen-presenting cells (APCs), primarily dendritic cells,
macrophages, and B cells.

2. Pathways: Antigens are captured via:

o Phagocytosis (engulfment of particles).

o Pinocytosis (uptake of fluids containing antigens).

o Receptor-mediated endocytosis (specific receptors bind antigens for

internalization).
 3. Migration to Lymph Nodes: APCs process captured antigens and migrate to lymph
nodes or secondary lymphoid organs to activate T cells.

4. MHC Presentation: Processed peptides are loaded onto MHC molecules and
presented on the APC surface.

5. Signal Integration: APCs also provide co-stimulatory signals (e.g., B7-CD28

interaction) required for effective T cell activation.

6. Role of Cytokines: APCs secrete cytokines (like IL-12) to shape T cell responses.

Structure and Function of Major Histocompatibility Complex Molecules (MHC) Class I

and Class II

Feature MHC Class I MHC Class II

Single α-chain (α1, α2, α3) with Two chains: α-chain (α1, α2) and β-
Structure
β2-microglobulin chain (β1, β2)

Peptide-Binding
Formed by α1 and α2 domains Formed by α1 and β1 domains
Groove

Expressed only on professional APCs

Expression Present on all nucleated cells (e.g., dendritic cells, macrophages, B
cells)

Recognized by CD8+ cytotoxic T cells CD4+ helper T cells

Intracellular (endogenous) Extracellular (exogenous) antigens

Antigen Source
antigens (e.g., viral proteins) (e.g., bacterial toxins)

Present cytosolic antigens to

Present internalized antigens to CD4+
Function CD8+ T cells for cytotoxic
T cells for immune coordination
response

Associated Requires β2-microglobulin for

No β2-microglobulin required
Proteins stability

Both classes are critical for T cell-mediated immunity but differ in their antigen
presentation pathways and T cell interactions.
What is the Processing of Cytosolic Antigens for Display by Class I MHC Molecules?

1. Source of Antigens: Derived from proteins synthesized within the cell, such as viral
proteins or misfolded self-proteins.

2. Proteasomal Degradation: Cytosolic proteins are degraded into peptides by the

proteasome, a protein complex.

3. Transport to ER: Peptides are transported into the endoplasmic reticulum (ER) via
the TAP (Transporter Associated with Antigen Processing).

4. Peptide Loading: The peptide binds to the MHC class I molecule in the ER,
facilitated by chaperone proteins.

5. Transport to Surface: The MHC-peptide complex is transported via the Golgi

apparatus to the cell surface.

6. Presentation: Displayed peptides are recognized by CD8+ T cells, initiating a

cytotoxic response.

What is the Processing of Internalized Antigens for Display by Class II MHC

Molecules?

1. Internalization: Extracellular antigens are taken up via phagocytosis, endocytosis,

or receptor-mediated uptake by APCs.

2. Endosomal Degradation: Internalized antigens are degraded into peptides in

acidified endosomes and lysosomes.

3. MHC Class II Synthesis: Synthesized in the ER, associated with an invariant chain
(Ii) that prevents premature peptide binding.

4. Peptide Loading: The invariant chain is degraded in the endosomal pathway,

allowing peptides to bind the MHC class II molecule.

5. Transport to Surface: The MHC class II-peptide complex is transported to the cell
surface.

6. Presentation: Recognized by CD4+ T cells, which then coordinate immune

responses by activating B cells, macrophages, or other T cells.

What is the Physiologic Significance of MHC-Associated Antigen Presentation?

 1. Activation of T Cells: MHC molecules are essential for T cell recognition and
activation, a cornerstone of adaptive immunity.

2. Specificity: Class I MHC ensures that intracellular pathogens like viruses are
targeted, while Class II MHC focuses on extracellular pathogens.

3. Immune Coordination: Helps coordinate responses between cytotoxic T cells (via

MHC I) and helper T cells (via MHC II).

4. Self vs Non-Self Recognition: Prevents immune attacks on self-proteins while

targeting foreign antigens.

5. Clinical Implications: MHC mismatches in organ transplants can lead to rejection;

hence, MHC typing is critical in transplantation.

6. Autoimmunity: Dysregulation or improper MHC presentation can lead to

autoimmune diseases, such as rheumatoid arthritis.

7. Vaccine Development: Understanding MHC presentation helps in designing

effective vaccines that generate robust T cell responses.

4. Pathways

a. Cell-Mediated Pathway

Different ways that T helper cells help macrophages, eosinophils, and B cells during
adaptive immune response:

1. Activation of Macrophages:

o T helper cells (specifically Th1 cells) release IFN-γ, a cytokine that enhances
macrophage microbicidal activity.

o Direct interaction via CD40L-CD40 signaling amplifies macrophage

activation, improving their ability to destroy phagocytosed pathogens.

2. Help for Eosinophils:

o Th2 cells secrete IL-5, which stimulates eosinophil activation and

recruitment.
 o This is particularly important in combating helminths and other parasites.

3. B Cell Activation:

o Th2 cells produce IL-4 and IL-21, promoting class switching and antibody
production.

o Th cells interact with B cells via CD40-CD40L, essential for germinal center
formation and antibody affinity maturation.

4. Promotion of Granulocyte Recruitment: Th17 cells produce IL-17, which recruits

neutrophils to sites of infection for acute inflammation.

5. Cytokine Network: T helper cells coordinate immune responses by tailoring the

cytokine milieu (e.g., IL-10 for anti-inflammatory roles).

Activation of Macrophages through Contact-Mediated Signals Delivered by CD40L-

CD40 Interactions and by IFN-γ:

1. CD40L-CD40 Interaction:

o T cells express CD40 ligand (CD40L), which binds to CD40 on macrophages.

o This interaction triggers a signaling cascade in macrophages, increasing their

antigen presentation efficiency and ability to produce pro-inflammatory
cytokines like IL-12.

2. IFN-γ Release:

o Th1 cells secrete IFN-γ, which enhances macrophage killing mechanisms

such as reactive oxygen species (ROS) and nitric oxide (NO) production.

3. Combined Effect: The dual signaling of IFN-γ and CD40-CD40L boosts the
macrophages' ability to clear intracellular pathogens like Mycobacterium
tuberculosis.

Granzymes and Perforin-Mediated Killing vs FAS/FAS Ligand-Mediated Killing:

Feature Granzymes and Perforin FAS/FAS Ligand

Perforin creates pores in target cell FAS ligand on CTLs binds to FAS
Mechanism membranes, enabling granzymes to receptor on target cells, triggering
enter and induce apoptosis. the apoptotic cascade.

CTLs release granules containing CTLs express the FAS ligand

Cytotoxic T
these molecules upon recognizing during prolonged interaction with
Cell Role
antigen. target cells.

Requires physical contact between Depends on the presence of FAS

Dependency
CTL and target cell. receptors on the target cell.

Rapid and enzymatic, inducing

Slower but effective for immune
Type of Killing mitochondrial damage and DNA
regulation and apoptosis.
fragmentation.

Primarily virally infected or cancerous Often used in immune regulation

Targeted Cells
cells. or killing of autoreactive cells.

Plays a role in immune tolerance

Immune Role Key in acute responses.
and chronic regulation.

How CTLs Themselves Are Not Injured During Target Cell Killing:

1. Granule Polarization: CTLs polarize their granules (containing perforin and

granzymes) toward the immunological synapse to ensure localized delivery.

2. Protective Membrane: Perforin requires specific conditions for pore formation,

which are absent on CTL membranes.

3. Rapid Detachment: After delivering the cytotoxic payload, CTLs disengage from
target cells to avoid self-damage.

4. Serpin Proteins: CTLs produce serpin proteins that inhibit granzymes from acting
within the CTL.

5. Selective Expression: Cytolytic molecules are synthesized as inactive precursors,

activated only in target cells.

6. Regulation of FAS: CTLs regulate FAS expression to prevent self-killing.

b. Humoral Pathway

Difference Between T-Dependent and T-Independent Antibody Responses:

Feature T-Dependent T-Independent

Polysaccharides, lipids, and non-

Antigen Type Protein antigens.
protein antigens.

B Cell Requires T helper cells for

Activated without T helper cells.
Activation activation.

Class Facilitates class switching to IgG,

Limited class switching, mostly IgM.
Switching IgA, or IgE.

Affinity Undergoes affinity maturation for

Does not involve affinity maturation.
Maturation higher specificity.

Memory Produces long-lasting memory B Generates a weaker memory

Response cells. response.

Slower response due to Rapid response due to direct B cell

Speed
dependence on T cells. activation.

Response to vaccines and protein Response to bacterial capsules or

Examples
antigens. LPS.

Neutralization of Microbes and Microbial Toxins:

1. Blocking Pathogen Binding: Antibodies bind to microbial surface molecules,

preventing their attachment to host cells.

2. Neutralizing Toxins: Antibodies block the active sites of toxins, rendering them non-
functional.

3. Virus Neutralization: Prevents viruses from binding to their receptors on host cells,
stopping viral entry.
 4. IgA at Mucosal Surfaces: IgA antibodies neutralize pathogens at mucosal surfaces,
such as in the respiratory or gastrointestinal tract.

5. Opsonization Synergy: Neutralized microbes are easier targets for phagocytes

through Fc receptor-mediated uptake.

6. Enhancing Complement Activation: Neutralized antigens may initiate

complement activation for microbial lysis.

Antibody-Mediated Opsonization and Phagocytosis:

1. Opsonization: Antibodies coat pathogens, marking them for destruction by

phagocytes.

2. Fc Receptors: Phagocytes have Fc receptors that bind to the Fc region of

antibodies, facilitating uptake.

3. Enhances Phagocytosis: Makes pathogens more recognizable and digestible for

macrophages and neutrophils.

4. Key Ig Classes: IgG is the primary opsonizing antibody.

5. Complement Activation: Opsonization often works with complement proteins to

enhance pathogen elimination.

6. Pathogen Removal: Ensures efficient clearance of bacteria, viruses, and apoptotic

cells.

Antigen-Antibody Mediated Activation of Complement Pathway:

1. Classical Pathway Activation: Antigen-antibody complexes (primarily IgG or IgM)

bind to the C1q component of the complement system.

2. Complement Cascade: Activates C4 and C2, leading to the formation of the C3

convertase.

3. C3b Opsonization: C3b binds to the pathogen, enhancing phagocytosis.

4. Membrane Attack Complex (MAC): C5b-C9 form MAC, creating pores in the
pathogen membrane, causing lysis.

5. Inflammatory Response: Complement fragments (C3a, C5a) recruit and activate

immune cells.
 6. Pathogen Elimination: Facilitates direct lysis, opsonization, and immune cell
recruitment.

Section 3

1. Immunodeficiency Disorders

a. What is the difference between primary and secondary immunodeficiency?

Feature Primary Immunodeficiency Secondary Immunodeficiency

Genetic or congenital defects in the Acquired impairment of the immune

Definition
immune system. system.

It can occur at any age, depending on

Onset Usually manifests in early childhood.
the cause.

Genetic mutations affect immune External factors like infections,

Cause
components. malnutrition, or treatments.

SCID, X-linked AIDS (caused by HIV),

Examples
agammaglobulinemia, CGD. immunosuppression post-transplant.

Stem cell therapy, enzyme Address underlying cause (e.g., treat

Treatment
replacement therapy. infection).

Variable, dependent on the removal of

Progression Chronic and lifelong conditions.
the cause.

Incidence Rare. More common globally.

b. mechanisms of some diseases

I. Phagocytic Deficiencies - Chronic Granulomatous Disease (CGD)

CGD is caused by genetic defects in genes encoding components of the NADPH oxidase
complex. This complex is essential for the production of reactive oxygen species (ROS) by
phagocytes, which are crucial for killing ingested pathogens. Without functional NADPH
oxidase, phagocytes cannot effectively eliminate microbes, leading to recurrent infections,
especially with catalase-positive organisms.

II. Leukocyte Adhesion Deficiencies (LADs)

LADs result from defects in genes encoding proteins involved in leukocyte adhesion to
endothelial cells. This impairment hinders the migration of immune cells to sites of
infection, leading to recurrent bacterial and fungal infections.

III. Severe Combined Immunodeficiency (SCID)

SCID is a group of disorders characterized by severe defects in both T and B cell

development and function. This can be caused by various genetic mutations affecting
different components of the immune system. SCID patients are highly susceptible to
severe infections from a wide range of pathogens.

IV. Selective B Cell Maturation - X-linked Agammaglobulinemia (XLA)

XLA is caused by mutations in the Bruton's tyrosine kinase (BTK) gene, which is essential for
B cell development. This leads to a complete absence of B cells and immunoglobulin
production, resulting in recurrent bacterial infections.

V. Defects in T Lymphocyte Activation - Bare Lymphocyte Syndrome

Bare lymphocyte syndrome is a group of disorders characterized by a deficiency of major

histocompatibility complex (MHC) class I or II molecules on the surface of cells. This
defect impairs T cell development and function, leading to severe combined
immunodeficiency.