Exam 1 Material Flashcards
Why is the immune system so important?
- Protects animals against microbial invasion, essential for life
- Ensures freedom from invasion via innate and adaptive immunity
- Utilizes complex, interacting networks of defense mechanisms
What century was the smallpox variolation?
12th century
What year was Rinderpest inoculations?
1754
What year was Edward Jenner’s cowpox experiment; coined “vaccination”?
1798
What year was Pasteur’s fowl cholera experiment; anthrax and rabies vaccines?
1879
Who proved dead organisms can create effective vaccines? Hint: 2 names
Daniel Salmon and Theobald Smith
Who found bacterial products that also provided protection? Hint: 2 names
Von Behring and Kitasato
Define commensal
Colonize surfaces, non-invasive, and harmless
Define pathogens
Causes disease and there are primary and opportunistic pathogens
Define primary pathogens
Cause disease at any dose
What’s an example of a primary pathogen?
HIV
Define opportunistic pathogen
Cause disease in high doses
What is an example of opportunistic pathogen?
Mannheimia hemolytica
What is innate Immunity?
- Rapid, non-specific, and immediate protection
- Activated by PAMPs and DAMPs
What is adaptive Immunity?
Develops after exposure, specific, and has memory
What are the 5 components of Innate defense?
- Physical/Chemical Barriers
- Phagocytic and Sentinel Cells
- Complement System
- Cytokines
- Natural Killer (NK) Cells
What are physical/chemical barriers?
Skin, mucus membranes, microflora, stomach acid, antimicrobial peptides
What are phagocytic and sentinel cells?
Detect and eliminate pathogens
What are examples of phagocytic and sentinel cells?
Neutrophils, macrophages, dendritic cells
What is the complement system?
Enzyme cascade with antimicrobial activity
What are cytokines?
Protein messenger molecules that can act on other cells
What 3 components can cytokines act on or cell that produced it?
- Proinflammatory cytokines
- Chemokines
- Interferons
Define chemokines
- Cells migrate to sites of infection
- Some produced by sentinel cells
Define proinflammatory cytokines
- Secreted by sentinel cells (PAMPs & DAMPs)
- Cause fever, lethargy, & loss of appetite
- IL-1, IL-6, & TNF
Define interferons
- Interferes with replication of viruses
- Produced by virally infected cells
What are natural killer (NK) cells?
Kill infected/tumor cells lacking normal proteins
What is humoral immunity?
- Mediated by antibodies (IgA, IgG, IgE, IgM) from B cells
- Effective against bacterial invaders
What is Cell-Mediated Immunity (CMI)?
T cells (helper, cytotoxic) regulate responses and destroy infected cells
What are the two types of adaptive immunity?
Humoral immunity and cell-mediated immunity
What distinguishes innate from adaptive immunity?
Innate is rapid, non-specific, and lacks memory; adaptive is slower, specific, and has memory
Who coined the term “vaccination”?
Edward Jenner
What was the significance of Pasteur’s fowl cholera experiment?
It showed that aged cultures of Pasteurella multocida provided protection, launching immunology as a science
What do sentinel cells recognize to detect invasion?
Pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs)
What are antibodies also known as?
Immunoglobulins (Ig)
Which type of adaptive immunity is directed primarily against bacterial invaders?
Humoral immunity
What distinguishes commensals from pathogens
Commensals colonize surfaces without causing disease, while pathogens cause disease
What is the role of proinflammatory cytokines?
They cause fever, lethargy, and loss of appetite
What type of cells do NK cells target?
Virus-infected cells and tumor cells
How does the adaptive immune system respond to a previously encountered pathogen?
It’s faster and has a more effective response
What’s a leukocyte?
Any white blood cell (WBC)
What’s a lymphocyte?
A type of WBC (T cell, B cell, NK cell)
What’s a granulocyte?
Polymorphonuclear cells (neutrophils, eosinophils, basophils)
What’s a mononuclear cells?
Lymphocytes or monocyte
What percentage of WBCs are neutrophils?
Neutrophils make up 55-90% of WBCs
What is the primary role of neutrophils?
They are the first responders to bacterial infections
What is the lifespan of a neutrophil?
Neutrophils live 8-10 hours in the blood and up to 2 days in total
What does “neutrophilia” indicate?
Elevated neutrophil levels, or neutrophilia, indicate a bacterial infection
What does “neutropenia” indicate?
Low neutrophil levels, or neutropenia, are often seen in viral infections
What is the role of basophils?
They are important in allergies and parasitic infections due to their inflammatory mediators like histamine
What percentage of WBCs do basophils constitute?
Basophils make up <0.5% of WBCs
What is the role of eosinophils?
Eosinophils are potent mediators that target extracellular parasites
When are eosinophils levels elevated?
Elevated levels, or eosinophilia, are seen in parasitic infections and allergies
What percentage of WBCs are monocytes?
Monocytes constitute 3-7% of WBCs
What do monocytes differentiate into?
Differentiate into macrophages in tissues
What are the functions of macrophages?
Macrophages perform phagocytosis, antigen presentation on MHC II, and cytokine secretion
What percentage of WBCs are lymphocytes
Lymphocytes make up 20-35% of WBCs
What are lymphocyte types?
B cells, T cells, and NK cells
What is the lifespan of circulating lymphocytes?
Lymphocytes circulate between blood and lymphoid tissues for about 4 months
What is the function of platelets?
Platelets are crucial for blood clotting
What is the role of red blood cells (RBCs)?
RBCs transport oxygen
Where do all blood cells originate?
Pluripotent stem cells in bone marrow
What are 3 lineages of blood cells?
Erythroid (RBCs, platelets), myeloid (monocytes, granulocytes), and lymphoid (B cells, T cells, NK cells)
How do granulocytes mature?
Granulocytes are released from the bone marrow as mature cells
Where do T cells mature?
Immature pre-T cells mature in the thymus
What happens to self-reactive T cells?
Self-reactive T cells are eliminated during development
Where do B cells mature in mammals?
B cells mature in bone marrow or Peyer’s patches, depending on the species
What is the role of NK cells, and where are they released from?
NK cells, part of innate immunity, are released mature from the bone marrow
What is the role of primary lymphoid tissues?
Primary lymphoid tissues are the sites of lymphocyte maturation
What are examples of primary lymphoid tissues?
Examples include the thymus (T cells), Bursa of Fabricius (birds), and bone marrow or Peyer’s patches (mammals)
What is the role of secondary lymphoid tissues?
Secondary lymphoid tissues are where mature lymphocytes encounter antigens
What are examples of secondary lymphoid tissues?
Examples include lymph nodes, spleen, and MALT (Mucosal Associated Lymphoid Tissue)
What do endothelial cells do during infection?
Endothelial cells upregulate adhesion molecules (“addressins”) to direct leukocytes to infection sites
What is the purpose of lymphatic circulation?
Lymphatic circulation allows lymphocytes to move between tissues and blood, increasing antigen encounter and immune response
What is inflammation?
A tissue reaction that delivers mediators of host defense to sites of infection or tissue damage
Inflammation - What are the primary roles in combating infection?
- Delivering effector molecules and cells to augment microbial killing
- Providing a physical barrier to prevent infection spread
- Promoting tissue repair
What is the main purpose of inflammation?
To focus the immune response at the site of infection or injury
What are the key steps in the acute inflammatory response?
- Production of cytokines and pro-inflammatory mediators in response to microbes or damaged cells
- Increased blood vessel permeability for plasma protein and leukocyte entry into tissues
- Destruction of microbes, clearance of damaged cells, and promotion of inflammation and repair
What are the cardinal signs of inflammation?
Pain, redness, heat, swelling, and loss of function
What causes pain?
Tissue destruction and irritation of sensory nerves
What causes redness?
Increased blood flow
What causes heat?
Increased blood flow and pyrogens
What causes swelling?
Fluid leakage and phagocyte infiltration
What causes loss of function?
When an entire tissue or organ is involved
What are the stages of neutrophil adhesion and emigration from blood vessels?
Neutrophils bind to vascular endothelial cells, adhere, and exit blood vessels to reach infection sites
What is Bovine Leukocyte Adhesion Deficiency (BLAD)?
BLAD is an autosomal recessive immunodeficiency in Holstein calves characterized by recurrent infections, oral ulcerations, chronic pneumonia, stunted growth, delayed wound healing, extreme neutrophilia, and inability of neutrophils to exit blood vessels due to an integrin gene mutation
Name three major pro-inflammatory cytokines :
- Tumor Necrosis Factor-α (TNF-α)
- Interleukin-1 (IL-1)
- Interleukin-6 (IL-6)
What are the functions of Tumor Necrosis Factor-α (TNF-α)?
Promotes inflammation, adhesion molecule expression, and fever
What are the functions of Interleukin-1 (IL-1)?
Induces fever, activates endothelial adhesion molecules, and promotes cell growth and repair
What are the functions of Interleukin-6 (IL-6)?
Triggers acute-phase protein production and systemic effects
What are the effects of IL-1, TNF-α, and IL-6 on the body?
- Low levels: Local inflammation (macrophage/endothelium activation).
- Moderate levels: Fever, lethargy, acute-phase protein production, neutrophilia.
- High levels: Vasodilation, vascular injury, DIC, ARDS, and septic shock.
What are chemokines, and give examples?
Chemokines are small cytokines that guide cell migration
Examples:
-CXCL8 (IL-8): Attracts and activates neutrophils
-CXCL2: Attracts neutrophils
What are the three types of vasoactive molecules?
Vasoactive amines, vasoactive peptides, and vasoactive lipids
What’s the function of vasoactive amines (e.g., histamine, serotonin)?
Increase vascular permeability
What’s the function of vasoactive peptides (e.g., C5a, bradykinin)?
Promote histamine release, pain, and vascular permeability
What’s the function of vasoactive lipids (e.g., prostaglandins, leukotrienes)?
Induce vasodilation, smooth muscle contraction, and chemotaxis
What is the function of histamine in inflammation?
Histamine, released by mast cells, causes vasodilation, increases vascular permeability, and stimulates nitric oxide production
How does the coagulation system function in inflammation?
- Thrombin converts fibrinogen to fibrin, forming a physical barrier
- The fibrinolytic system destroys fibrin, releasing peptides that attract neutrophils
What triggers the secretion of pro-inflammatory cytokines?
Sentinel cells activated by toll-like receptors (TLRs) and pattern-recognition receptors (PRRs) in response to PAMPs and DAMPs
Why are pro-inflammatory cytokines essential in low quantities but harmful in high quantities?
-Low quantities: Promote local inflammation and immune defense
-High quantities: Lead to systemic vasodilation, vascular injury, DIC, and ARDS
What is phagocytosis?
Phagocytosis is the ability of certain cells, called phagocytes, to ingest and destroy foreign particles. It literally means “eating by cells”
What are phagocytes?
Phagocytes are cells capable of ingesting and killing microorganisms that trigger an inflammatory response. Neutrophils and macrophages are examples of professional phagocytes
Which cells initiate the phagocytic process?
Neutrophils are the first to accumulate at the site of infection, followed by macrophages that migrate to the tissue to begin phagocytosis
What are the steps involved in phagocytosis?
The process includes:
- Chemotaxis: Movement of phagocytic cells to the site of infection
- Adherence: Phagocyte binds to the target particle
- Ingestion: Engulfment of the target
- Destruction: Intracellular killing and digestion of the target
What is opsonization?
The coating of bacteria with positively charged materials (opsonins) such as IgG, IgM, and C3b
How does opsonization aid phagocytosis?
Neutralizes the negative charge on bacteria, allowing neutrophils to adhere and engulf them
What are the receptors involved in neutrophil phagocytosis?
-Fc receptors: Bind antibodies (like IgG) attached to antigens
-C3b receptors: Bind C3b-coated bacteria for enhanced engulfment
What is a phagolysosome?
A phagolysosome is formed when the phagosome (containing the ingested microbe) fuses with lysosomes. This vesicle contains enzymes and toxic molecules that digest and kill the microbe
How are bacteria destroyed inside the phagolysosome?
Destruction occurs through:
- Lytic enzymes and antimicrobial peptides
- Oxidative metabolism (respiratory burst)
- Neutrophil extracellular traps (NETs)
What are examples of lytic enzymes and peptides in neutrophil granules?
- Primary granules: Hydrolases, lysozyme, defensins, and myeloperoxidase
- Secondary granules: Lysozyme, lactoferrin, and collagenase
What is the oxygen-mediated killing mechanism?
It is the most potent neutrophil killing process, occurring in the phagolysosome and involving reactive oxygen species such as hypochlorite, hydrogen peroxide, and oxygen radicals
What is Chronic Granulomatous Disease?
It is a fatal condition caused by defective oxidative enzymes, impairing the respiratory burst pathway of neutrophils
What are neutrophils extracellular traps (NETs)?
- NETs are extracellular meshes of nuclear material (DNA, histones) and granular proteins released by stimulated neutrophils to trap and kill bacteria
- This active response is called NETosis
What happens to neutrophils after phagocytosis?
Neutrophils die and lyse after extended phagocytosis, forming pus
What is the role of macrophages after phagocytosis?
Macrophages egest debris, present microbial antigens to lymphocytes, and contribute to tissue healing by ingesting dead neutrophils
Which cells are the first responders to inflammation?
Neutrophils
What activates neutrophil migration to the infection site?
Cytokines activate vascular endothelial cells, facilitating neutrophil attachment and migration
What role do opsonins play in phagocytosis?
Opsonins like antibodies and complement enhance bacterial binding and ingestion by phagocytes
How are ingested microbes killed?
Through respiratory burst, antimicrobial peptides (e.g., defensins), and lytic enzymes
What is the lifespan of neutrophils?
Neutrophils are short-lived and cannot perform prolonged or multiple rounds of phagocytosis
What is the role of macrophages in chronic infections?
Macrophages eat surviving microbes, remove dying neutrophils, and initiate the healing process
How do macrophages support the adaptive immune system?
By presenting antigens to lymphocytes
What is the complement system?
The complement system is a group of serum and cell surface proteins activated by factors like antigen-antibody combinations. This activation leads to enzyme cascades with biological effects, including cell lysis and opsonization
What are the three pathways of complement activation?
Classical pathway, alternative pathway, and MB-Lectin pathway
What is the classical pathway?
Initiated by antibody-antigen binding (adaptive immunity)
What is the alternative pathway?
Triggered by C3b binding to pathogen surfaces (innate immunity)
What is the MB-Lectin pathway?
Activated by mannose-binding lectin binding to microbial carbohydrates (innate immunity)
What are the key features of the classical pathway?
- Initiated by antigen-antibody binding.
Requires IgM or IgG antibodies - C1 protein binds to antigen-antibody complexes, activating the cascade
-The classical pathway forms a C3 convertase (C4b2b) which cleaves C3 into C3a and C3b
How does the alternative pathway function?
- Initiated when C3 spontaneously cleaves into C3a and C3b
- C3b binds to pathogen surfaces
- Factor B binds to C3b and is cleaved by Factor D, forming C3 convertase (C3bBb)
How does the MB-Lectin pathway operate?
- Mannose-binding lectin (MBL), a pattern recognition receptor (PRR), binds to mannose on microbial surfaces
- Bound MBL activates MASP-2 (MBL-associated serine protease), which cleaves C4 and initiates the cascade
What is the terminal complement pathway?
- Common to all three pathways after C5 cleavage
- Leads to the formation of the membrane attack complex (MAC), which punches holes in the microbial membrane, causing lysis and cell death
What is the membrane attack complex (MAC)?
- Formed by the sequential binding of complement components:
- C5b binds C6, C7, C8, and multiple C9 molecules
- C9 polymerizes to form a transmembrane pore
What are the results of the membrane attack complex (MAC)?
Results in lysis of the target cell
What regulates complement activation?
- Factor H regulates the alternative pathway to prevent damage to host cells
- Regulation occurs through substrate modulation to ensure proper targeting
What are the key functions of the complement system?
- Opsonization
- Cell lysis
- Inflammation
- Immune clearance
Define opsonization
C3b coats pathogens, enhancing phagocytosis
Define cell lysis
MAC formation destroys microbial cells
Define inflammation
C5a attracts immune cells and triggers inflammationD
Define immune clearance
Removes immune complexes and dead cells
What are the biological consequences of complement activation?
- Enhanced phagocytosis through opsonization
- Direct lysis of pathogens via MAC
- Recruitment of immune cells through chemoattractants like C5a
How do the complement pathways integrate innate and adaptive immunity?
- Innate pathways (alternative and MB-lectin): Activated by microbial patterns (PAMPs)
- Adaptive pathway (classical): Activated by antibodies bound to antigens
What are cytokines?
- Low molecular weight, secreted ‘messenger’ proteins
- Regulate intensity and duration of innate and adaptive immune responses
- Their activity is receptor-mediated
What are the three main activities of cytokines?
Autocrine, paracrine, and endocrine
What’s the function of autocrine?
Act on the cell that produced it
What’s an example of autocrine?
IL-12
What’s an example of paracrine?
IL-12
What’s an example of endocrine?
IL-3, GM-CS
What are some classifications of cytokines?
- Monokines
- Lymphokines
- Interleukins
- Interferons
- Chemokines
- Colony Stimulating Factors (CSF)
- Growth Factors
What produces monokines?
Monocytes
What produces lymphokines?
Lymphocytes
Define interleukins
Communication between leukocytes (e.g., IL-1, IL-2, IL-3)
Define interferons
Inhibit viral replication
Define chemokines
Attract specific cells to locations
What do Colony Stimulating Factors (CSF) stimulate?
Stimulate stem cell differentiation in bone marrow
What do Growth Factors stimulate?
Stimulate cell growth in vitro
What are the three main categories of cytokine functions?
- Mediate and regulate innate immunity
- Mediate and regulate adaptive immunity
- Stimulate hematopoiesis
What role do cytokines play in innate immunity?
- Crucial in the first few days of infection.
- Act immediately and may influence adaptive immune responses
What are examples of cytokines that play in innate immunity?
IL-1, IL-6, TNFα, IL-12, and Type I interferons
What are Type I interferons, and what do they do?
- Includes IFNα and IFNβ
- Produced by virally infected cells
- Make other cells resistant to viral infection
What is the role of Type II interferons (IFNγ)?
- Functions in innate and adaptive immunity
- Produced by NK cells and TH1 cells
- Activates macrophages, neutrophils, and NK cells
- Promotes TH1 development and suppresses TH2
- Enhances B-cell IgG production
- Upregulates MHC expression on APCs
What are key roles of cytokines in adaptive immunity?
- Produced primarily by T lymphocytes in response to antigen recognition
- Regulate lymphocyte activation, growth, and differentiation
- Enhance innate defenses
Which cytokines regulate lymphocyte activation and growth?
- IL-2: Lymphocyte proliferation.
- IL-4 and IL-13: B-cell differentiation (IgE)
- IL-10: Inhibits TH1
- TGFβ: Treg cytokine, B-cell differentiation (IgA)
- IFNγ: B-cell differentiation (IgG)
Which cytokines enhance innate immunity?
- IFNγ: Activates macrophages, neutrophils, and NK cells
- TNF: Activates endothelial cells and neutrophils
- IL-5: Activates eosinophils
What is the role of cytokines in hematopoiesis?
- Regulate growth and differentiation of bone marrow progenitor cells
- Produced during innate and adaptive immune responses
Name key hematopoietic cytokines:
- Erythropoietin
- Thrombopoietin & IL-11
- IL-3
- IL-5
- GM-CSF
- G-CSF
- M-CSF
What’s the function of erythropoietin?
Stimulates RBC production
What’s the function of thrombopoietin & IL-11?
Stimulate platelet production
What’s the function of IL-3?
Stimulates WBC production
What’s the function of IL-5?
Eosinophil differentiation (e.g., during parasitic infection/allergy)
What’s the function of GM-CSF?
Differentiation of neutrophils and monocytes
What’s the function of G-CSF?
Differentiation of neutrophils
What’s the function of M-CSF?
Differentiation of monocytes
What mechanisms regulate cytokine activity?
- Receptor antagonists
- Soluble receptors
- Opposing cytokines
- Decoy receptors
What’s the function of receptor antagonists?
Block cytokine receptors (e.g., IL-1 receptor antagonist)
What’s the function of soluble receptors?
Neutralize cytokines (e.g., soluble TNF receptors)
What type of effect do cytokines have?
Counteract effects (e.g., IL-4 vs. IFNγ for IgE)
What’s the function of decoy receptors?
Bind cytokines without inducing signaling (e.g., decoy receptor for IL-1)
What are five key concepts in cytokine signaling?
- Immune responses involve many cell interactions
- Cells communicate via cytokines and hormones
- Cytokines bind to specific target cell receptors
- Receptor binding activates transcription factors for gene expression
- Gene expression leads to new proteins and altered cell behavior
What are some general properties of cytokines?
- Secretion is brief and self-limited
- Produced by diverse cell types
- Act locally and/or systemically
- Functions may overlap (redundancy)
- Effects are synergistic and tightly regulated
How does the innate immune system recognize pathogens?
Recognizes a limited number of conserved microbial PAMPs (Pathogen-Associated Molecular Patterns)
What triggers the adaptive immune system?
Adaptive immunity can recognize and respond to almost all foreign macromolecules in invading microbes. These foreign molecules are called antigens
What is antigenicity?
The inherent capacity of a molecule to be recognized by the immune system
What are the two main types of antigens?
Microbial antigens and non-microbial antigens
Give examples of microbial antigens:
Bacterial, viral, fungal, protozoan, arthropod, and helminth antigens
Give examples of non-microbial antigens:
Food allergens, inhaled dust (pollen), blood-group antigens, histocompatibility antigens, and autoantigens
What are autoantigens?
Antigens that induce autoimmune responses when the immune system attacks normal body components (e.g., thyroglobulin, myelin, mitochondrial proteins)
What are examples of bacterial antigens?
- Structural components: Peptidoglycans,
lipoteichoic acid, lipopolysaccharides, pili, porins, and flagellar antigens (H) - Secreted products: Exotoxins, heat-shock proteins
- Surface antigens: Capsular antigens (K)
What are the key features of viral antigens?
- A nucleic acid core surrounded by a protein capsid
- Capsid: Made of capsomeres, which are highly antigenic
- Viral proteins expressed on infected cells can provoke adaptive immunity
What types of microbial antigens can trigger adaptive immunity?
Structural components of fungi, protozoan parasites, arthropods, and helminths
Are all microbial antigens equally effective in triggering immunity?
No, their antigenicity varies, and adaptive responses may not always protect or eliminate the invader
Food allergens
Can cause allergic reactions
Pollens
Triggers immune responses when inhaled
Blood-group antigens
Glycoproteins that can lead to immune reactions during mismatched transfusion
Histocompatibility antigens
Involved in tissue graft rejection
What factors influence antigenicity?
- Size
- Foreignness
- Complexity
- Stability
Define size of antigenicity
- Larger molecules are more antigenic
- Molecules <1000 daltons are poor antigens
Define foreignness of antigenicity
Greater structural difference from self-proteins increases immune response
Define complexity of antigenicity
Complex structures (e.g., proteins) are more antigenic than simple ones (e.g., lipids)
Define stability of antigenicity
Flexible or rapidly degraded molecules are poor antigens
Why are proteins the best antigens?
They are large, complex, stable, and recognized well by the immune system
Why are lipids and nucleic acids poor antigens?
Readily degradable, but nucleoproteins can be antigenic due to their protein carrier
What are epitopes?
- Specific regions on an antigen recognized by the immune system
- A single large protein can have multiple epitopes
- The most immunogenic epitopes are called immunodominant epitopes
What is a hapten?
A small molecule (<1000 daltons) that is not antigenic alone but can become antigenic when attached to a larger carrier protein
Examples of hapten
- Penicillin allergy
- Poison ivy
Define penicillin allergy
Penicillin binds to proteins, forming an antigenic complex that triggers an allergic reaction
Define poison ivy
Urushiol binds to skin proteins, resulting in allergic contact dermatitis
What is cross-reactivity?
Identical or similar epitopes on unrelated molecules cause antibodies to react with both antigens
Examples of cross-reactivity
- Bacterial or food antigen mimics blood-group glycoproteins
- Cross-reaction between Brucella abortus and Yersinia enterocolitica
- FIP virus cross-reacting with pig transmissible gastroenteritis virus
Define recognition
The adaptive immune system is optimized to recognize microbial macromolecules
Define best antigens
Large, complex, stable, foreign proteins
Define small molecules
Poor antigens unless linked to carriers (haptens)
Define epitopes
Immune responses target specific areas of antigens
What triggers adaptive immunity?
The capturing and presenting of foreign materials to cells that recognize them, performed by Antigen-Processing Cells (APCs)
What are the three major types of Antigen-Processing Cells (APCs)?
- Dendritic cells (DCs)
- Macrophages
- B-cells
How do APCs initiate immune responses?
APCs capture foreign microbes or their products, process large proteins into peptides, and present them on their surfaces attached to Major Histocompatibility Complex (MHC) molecules
Why are dendritic cells unique among APCs?
Only dendritic cells can activate naïve T cells and trigger a primary immune response
Where are dendritic cells primarily found?
In epithelial tissues (skin, mucosa) and lymphoid organs (lymph nodes, spleen, thymus)
What are the major functions of dendritic cells?
- Serve as sentinel cells to activate innate defenses
- Process exogenous antigens to initiate adaptive immunity
- Regulate adaptive immunity
What makes dendritic cells highly efficient APCs?
They express 100 times more MHC II molecules than any other APC and can activate up to 3000 T-cells per activated dendritic cell
How do follicular dendritic cells (FDCs) differ from other dendritic cells?
- Do not migrate
- Are located in lymphoid follicles (B-cell areas)
- Lack MHC II molecules on their surface
- Carry many complement and Fc receptors
What is the primary function of follicular dendritic cells (FDCs)?
To present antigens to B-cells without processing them
What are iccosomes?
Spherical bodies on FDC dendrites formed from antigen:antibody complexes, which are ingested by activated B-cells
How do dendritic cells capture antigens in tissues?
By constantly sampling extracellular fluid through macropinocytosis
What triggers dendritic cells to migrate to lymph nodes?
The inflammatory cytokine TNF-⍺ during infection
What happens as dendritic cells migrate to lymph nodes?
They upregulate expression of MHC II molecules and co-stimulatory molecule B7, ensuring effective antigen presentation
Why are macrophages less efficient APCs than dendritic cells?
They express lower levels of MHC II and co-stimulatory molecules unless activated by cytokines like INFγ
What role do B-cells play in antigen presentation?
B-cells present antigens to T-helper cells during the secondary immune response and become efficient APCs after activation
What changes occur in B-cells after activation?
They upregulate MHC II and co-stimulatory B7 molecule expression, becoming potent activators of T-helper cells
What is required for an antigen to trigger an adaptive immune response?
Antigen molecules must be broken into fragments, bound to MHC molecules, and presented to T-cells
What are MHC molecules, and how are they encoded?
MHC molecules are glycoproteins encoded by a gene cluster called the major histocompatibility complex (MHC)
What is the function of MHC molecules in immunity?
MHC molecules control antigen presentation and influence susceptibility to infectious and autoimmune diseases
What are the three classes of MHC gene loci?
Class I, II, and III
What does class I encode?
Encodes MHC I molecules, present on all nucleated cells
What does class II encode?
Encodes MHC II molecules, restricted to professional APCs
What does class III encode?
Encodes proteins like complement proteins involved in innate immunity
How do MHC I and MHC II molecules differ in distribution and function?
- MHC I: Found on most nucleated cells; presents antigens to cytotoxic T cells, resulting in T-cell-mediated toxicity
- MHC II: Found on B cells, macrophages, and dendritic cells; presents antigens to T-helper cells, resulting in T-cell-mediated help
How are MHC molecules named in different species?
- Humans: HLA
- Dogs: DLA
- Cattle: BoLA
- Horses: ELA
- Pigs: SLA
What are the subtypes of MHC I molecules?
MHC Ia, Ib, Ic, and Id
Define MHC Ia
Polymorphic, expressed on most nucleated cells
Define MHC Ib
Reduced expression, limited ligand binding
Define MHC Ic
nvolved in NK cell signaling
Define MHC Id
Binds PAMPs (pathogen-associated molecular patterns)
What is the structure of an MHC Ia molecule?
- Composed of a heavy α chain and a β2-microglobulin chain
- The α chain forms the antigen-binding groove, while β2-microglobulin stabilizes the structure
How are peptides bound to MHC I molecules?
Peptides are 8-10 amino acids long, anchored at both ends, and fit within the binding groove
What is the endogenous pathway of MHC I?
Proteins manufactured within the cell are processed into peptides, bound to MHC I molecules, and presented on the cell surface for CD8+ T-cell recognition
Where are MHC II molecules found, and what is their structure?
Found on professional APCs, consisting of an α chain and a β chain, with their peptide-binding groove formed by the α1 and β1 domains
How do peptides bind to MHC II molecules?
Peptides are 13-20 amino acids long, with part of the peptide protruding from the groove
What is the exogenous pathway of MHC II?
Antigens are internalized, processed, and bound to MHC II molecules in vesicles. These complexes are transported to the cell surface for presentation to CD4+ T cells
What is encoded by MHC Class III genes?
Complement proteins and other molecules important for innate immunity
What is MHC restriction?
Only antigen fragments bound to MHC molecules can trigger an adaptive immune response
How does MHC expression affect disease susceptibility?
- Specific MHC alleles determine susceptibility or resistance to diseases
- Heterozygotes benefit from responding to a broader range of antigens
Give examples of MHC-associated disease resistance or susceptibility
- BoLA-Aw7: Resistance to bovine leukosis
- BoLA-A*16: Resistance to mastitis
- ELA-A9: Susceptibility to equine recurrent uveitis
What is the role of lymphocytes in the immune system?
Lymphocytes are central to the adaptive immune system and body defenses
What are the three major types of lymphocytes?
B cells, T cells, and natural killer (NK) cells
What’s the functions of B cells?
Responsible for antibody production
What’s the functions of T cells?
Regulate adaptive immunity and are responsible for cell-mediated immune responses
What’s the functions of natural killer (NK) cells?
Play a role in innate immunity
What is unique about lymphocyte subpopulations?
Within the major types, there are many subpopulations with different characteristics and functions
What are the structural characteristics of lymphocytes?
- Small, round cells, 7-15 μm in diameter
- Large, round nucleus that stains intensely with hematoxylin
- Thin rim of cytoplasm containing mitochondria, free ribosomes, and a small Golgi apparatus
How do NK cells differ structurally from T and B cells?
NK cells are usually larger and may contain obvious cytoplasmic granules
Can the structure of a lymphocyte indicate its function?
No, except for NK cells with granules, lymphocyte structure does not provide clues to their function
Identify features of B cells in the development site
Bone marrow, bursa, Peyer’s patches
Identify features of B cells in the distrubition
Lymph node cortex, splenic follicles
Identify features of B cells in the antigen receptors
BCR (immunoglobulin)
Identify features of B cells of important surface antigens
Immunoglobulin
Identify features of B cells of antigen recognized
Free foreign proteins
Identify features of B cells of progeny cells
Plasma cells, memory cells
Identify features of B cells of secreted products
Immunoglobulins
Identify features of T cells in development site
Thymus
Identify features of T cells in distribution
Lymph node paracortex, splenic periarteriolar sheathI
Identify features of T cells in antigen receptors
TCR (protein heterodimer) associated with CD3, CD4, or CD8
Identify features of T cells of important surface antigens
CD2, CD3, CD4, or CD8
Identify features of T cells in antigen recognized
Processed foreign proteins in MHC
Identify features of T cells in progeny cells
Effector T cells, memory T cells
Identify features of T cells in secreted products
Cytokines
What is the overview of lymphocyte maturation?
Lymphocytes mature through stages involving antigen receptor development and selection processes to ensure proper immune response
How are T and B cells segregated in peripheral lymphoid organs?
- T and B cells occupy distinct regions:
- T cells: Paracortex of lymph nodes and periarteriolar sheath of the spleen
- B cells: Cortex of lymph nodes and splenic follicles
What are the two main T cell receptor types, and how are they categorized?
- Alpha-beta (αβ) T cells: Includes CD4+ and CD8+ T cells
- Gamma-delta (γδ) T cells: Defined by their unique TCR, important at mucosal surfaces
What are the subtypes of CD4+ αβ T cells?
TH 1, TH2, TH17, and Treg
What’s the function of T helper 1 (TH1)?
Secretes IFNγ, IL-2; activates phagocytes, NK cells, CTLs; defends against intracellular pathogens
What’s the function of T helper 2 (TH2)?
Secretes IL-4, IL-5, IL-9, IL-13; activates mast cells, eosinophils, and B cells for IgE production
What’s the function of T helper 17 (TH17)?
Secretes IL-17, IL-21, IL-22; attracts neutrophils and monocytes, induces acute inflammation
What’s the function of T regulatory (Treg)?
Secretes IL-10, IL-35, TGFβ; suppresses T cell responses, prevents self-reactive immune reactions
What is the role of CD8+ αβ T cells?
CD8+ T cells (Cytotoxic T Lymphocytes) recognize antigens on MHC I, clonally expand, and kill cells expressing foreign antigens
How do γδ T cells differ from αβ T cells?
γδ T cells recognize unprocessed antigens, including stress proteins, and are prominent at mucosal surfaces
What are the unique features of NK cells?
- Large granular lymphocytes
- Part of innate immunity, not antigen-specific.
- Lack surface immunoglobulins, CD3, CD4, or CD8
- Activated by IFNγ, TNF, and IL-2
What is the cytotoxic role of NK cells?
NK cells target cells lacking normal MHC I or expressing stress proteins
What are the three major receptors of NK cells?
NK cells use receptors to detect abnormal surface antigens, including stress markers
What is the structure of the T cell receptor (TCR) complex?
- TCR consists of paired peptide chains (αβ or γδ) that form antigen-binding receptors
- It connects to a signal-transducing component called CD3
How can you tell if a T cell is a T helper cell by its structure?
- A T cell with TCR/CD3 associated with CD4 is a T helper cell
- CD4 binds to MHC class II molecules on antigen-presenting cells (APCs)
What is the role of CD4 and CD8 in T cells?
- CD4: Binds to MHC class II molecules on APCs, identifying T helper cells
- CD8: Binds to MHC class I molecules on all nucleated cells, identifying cytotoxic T cells
What are the key interactions in a T cell-APC dialog?
- TCR binds to antigenic peptides linked to MHC molecules
- Co-stimulation signals (e.g., cytokines) are required for full activation
What is an immunological synapse?
- It’s the interaction site between a T cell and an APC
- SMACs (Supramolecular Activation Clusters) form concentric rings:
- cSMAC: Central region for signaling
- pSMAC: Peripheral region for adhesion
What happens if co-stimulation signals are absent?
The T cell fails to activate properly, and the immune response is terminated
What are T helper cells, and how do they function?
- CD4+ T cells recognizing antigens displayed on MHC II molecules
- They are categorized by the cytokines they secrete, not surface molecules
What are the main types of T helper cells?
- TH1: Promote cell-mediated immunity
- TH2: Support antibody production
- TH17: Enhance neutrophil-mediated inflammation
- Treg: Suppress immune overactivation
How do naïve T helper cells differentiate into subsets?
- Differentiation depends on signals received from APCs and the local environment
- Stimulating cytokines determine the subset:
- TH1: IL-12
- TH2: IL-4
- TH17: IL-6, TGF-β, and IL-23
How do TH subsets regulate each other?
Each subset produces cytokines that amplify its own function while inhibiting others
What cytokines do TH1 cells secrete, and what are their functions?
- Cytokines: IFN-γ, IL-2
- Functions: Activate macrophages, NK cells, cytotoxic T cells, and B cells
What cytokines do TH2 cells secrete, and what are their functions?
- Cytokines: IL-4, IL-5, IL-13
- Functions: Stimulate IgE production, mast cell activation, and eosinophil recruitment
What cytokines do TH17 cells secrete, and what are their functions?
- Cytokines: IL-17, IL-21, IL-22
- Functions: Promote inflammation and defense against extracellular bacteria and fungi
What are the functions of T regulatory (Treg) cells?
Secrete IL-10, IL-35, and TGF-β to suppress immune responses and maintain self-tolerance
What are γδ T cells, and where are they found?
T cells with γδ receptors, often found in intestinal walls (humans) or circulating in ruminants and pigs
What is the role of γδ T cells?
- Recognize unprocessed antigens and stress proteins
- Act in innate immunity at mucosal surface
What are the key characteristics of TCR and antigen recognition?
- TCR binds peptides linked to MHC molecules on APCs
- Co-stimulation is required for activation
TH1 characteristics
Stimulating cytokines: IL-12
Secreted cytokines: IFN-γ, IL-2
Function: promotes cell-mediated immunity
TH2 characteristics
Stimulating cytokines: IL-4
Secreted cytokines: IL-4, IL-5, IL-13
Function: supports antibody production (e.g., IgE)
TH17 characteristics
Stimulating cytokines: IL-6, TGF-β, IL-23
Secreted cytokines: IL-17, IL-21, IL-22
Function: stimulates neutrophil responses
Treg characteristics
Stimulating cytokines: IL-10, TGF-β
Secreted cytokines: IL-10, IL-35, TGF-β
Function: suppresses immune overactivation
