Immunology part 1 (trans 1) Flashcards
What are the central lymphoid organs?
Thymus:
- histologic hallmark are hassal’s corpuscles
Bone marrow
- site of hematopoiesis shortly before birth
What are the peripheral lymphoid organs
- tonsils
- adenoids
3 Lymph nodes - Spleen
- Ileum
REMEMBER
Lymphocytes: B lymphocytes, T lymphocytes, natural killer cells
Antigen-presenting cells: Dendritic cells, macrophagrs, follicular dendritic cells
Effector cells: T lymphocytes, macrophages, granulocytes
Lymphocytes: Specific recognition of antigens
Antigen-presenting cells: capture of antigens for display to lymphocytes
Effector cells: Elimination of antigen
FUNCTION Lymphocytes B lymphocytes: T lymphocytes: Natural killer cells:
LYMPHOCYTES
B lymphocytes: Humoral immunity
T lymphocytes: cell-mediated immunity
Natural killer cells: innate immunity
FUNCTION Antigen-presenting cells Dendritic cells: macrophages: follicular dendritic cells:
Antigen-presenting cells
Dendritic cells: Initiation of T cell responses
macrophages: Initiation and effector phase of cell-mediated immunity
follicular dendritic cells: Display of antigens to B lymphocytes in humoral immune responses
FUNCTION Effector cells T lymphocytes: Macrophages and monocytes: Granulocytes:
Effector cells
T lymphocytes: Helper T cells and cytolytic T lymphocytes
Macrophages and monocytes: cells of the mononuclear phagocyte system
Granulocytes: neutrophils, eosinophils
Critical cells that engulf and kill pathogens, process and present antigen, and regulate immune reactivity by producing cytokines and chemokines; these are monocytes that have migrated into the tissues
Macrophages
leukocytes that contain densely staining granules
Granulocytes
Innate (nonspecific) immunity is responsible for the first and second line of defense:
- First line of defense - surface protection composed of anatomical and physiological barriers that keep microbes from penetrating sterile body compartments
- Second line of defense
- cellular and chemical system that comes immediately into play if infectious agents make it past the surface (first line) defenses
First line of defense (innate immunity)
EYES:
- Washing by tears and Lysozymes
RESPIRATORY TRACT:
- Mucus, Ciliated epith, Antibody and Phagocytosis
DIGESTIVE TRACT:
- Stocmach acidity, normal flora, alkaline pH in intestine, mechanical flushing, enzymes and bacteriocins
SKIN:
- Anatomical barrier, antimicrobial secretions, low pH and commensal microbes
GENITOURINARY TRACT:
- Flushing action of urine, acidity of urine, lysozyme and vaginal lactid acid
Second line of defense (innate immunity)
Inflammatory response - a protective response which aims to digest, dilute or wall off the offending agent so it will not spread
1. interferons - against virally infected cells and tumors
2. Phagocytosis
3. Complement system
Adaptive immunity (third line of defense)
- long term immunity with memory
- includes specific host defenses that must be developed uniquely for each microbe through the action of specialized white blood cells:
1. B-cells: humoral
2. T-cells: cell mediated
3 accessory cells
4. cytokines
NATURALLY ACQUIRED IMMUNITY 1. active - the host plays a role in the manufacturing of antibodies 2. passive - maternal antibodies ARTIFICIALLY ACQUIRED 1. active - live attenuated vaccines 2. passive - preformed antibodies
Differences in terms of TYPE OF CELLS INNATE IMMUNITY - greater diversity than adaptive immunity - epith barrier - phagocytes (neutrophils, macrophages) - complement - natural killer cells
ADAPTIVE IMMUNITY
- B lymphocytes/B-cells (Humoral Immunity) - produce plasma cells that has eccentrically located nuclei with small, dark, and round nucleus; produces the antibodies
- T lymphocytes/T-cells (Cellular-mediated Immunity) - have effector T-cells few days after infection and mediates cellular immunity; derived from the thymus
Differences in terms of SPECIFICITY and RECEPTORS
INNATE IMMUNITY
specificity: for structures shared by classes of microbes (molecular patterns)
receptors: encoded in germline; limited diversity
distribution: non-clonal - identical receptors on all cells of the same lineage
Discrimination of self and non-self: yes
ADAPTIVE IMMUNITY
specificity: for structural detail of microbial molecules (antigens)
receptors: greater diversity; encoded by genes produced by somatic recombination of gene segments
distribution: Clonal - clones of lymphocytes with distinct specificities express different receptors
Discrimination of self and non-self: yes’ imperfect
What are the 3 types of cytokines?
1 Interferons (glycoproteins that has virus-nonspecific antiviral activity)
- Tumor Necrosis Factor
- Produced mainly by macrophages
- Mediator of host response to gram-negative bacteria - Interleukins (Means of communication between leukocytes)
3 groups of interferons (IFN)
- alpha-IFN: aka leukocyte IFN
- beta-IFN: aka epith IFN, fibroblast IFN, fibroepithelial IFN, B-cell stimulating Factor 2
- Gamma IFN: produced by immunologically stimulated lymphocytes, primarily T lymphocytes; aka Immune IFN; a lymphokine
Types of interleukins
IL-1 (Lymphocyte-Activating Factor)
IL-2 (T-cell growth factor): Activates cytotoxic cells, NK cells, LAK cells
IL-3 (Multi-colony Stimulating Factor): Stimulates hematopoietic cells
IL-4: stimulate proliferation of B-cells
IL-5 (B-cell Growth Factor 2): Shares functions with IL-4
IL-6 (IFN beta 2): Induces secretion of Ig and other plasma proteins
IL-7 (Lymphopoietin 1): Stimulates maturation of early B and T-cells
IL-8 (Monocyte-derived Neutrophil Chemotactic Factor): Principal inflammatory cytokine
IL-9: stimulates proliferation of T-cell and Mast cells
IL-10: inhibits cytokine synthesis
IL-11: regulates hematopoiesis
IL-12 (NK Cell Stimulating Factor): Enhances activity of cytotoxic effector T-cells
Tumor necrosis factor
Principal cell source:
Principal cellular targets and biologic effects:
Tumor necrosis factor Principal cell source: Macrophages, T cells Principal cellular targets and biologic effects: Endothelial cells - activation Neutrophils - activation Hypothalamus - fever Liver - acute phase proteins Muscle, fat - catabolism (cachexia)
IL-1
Principal cell source:
Principal cellular targets and biologic effects:
IL-1
Principal cell source: Macrophages, endothelial cells
Principal cellular targets and biologic effects:
Endothelial cells - activation
hypothalamus - fever
liver - acute phase proteins
Chemokines
Principal cell source:
Principal cellular targets and biologic effects:
Chemokines
Principal cell source: macrophages, endothelial cells, T cells, fibroblasts, platelets
Principal cellular targets and biologic effects:
leukocytes - chemotaxis, activation
IL-12
Principal cell source:
Principal cellular targets and biologic effects:
IL-12
Principal cell source: macrophages, dendritic cells
Principal cellular targets and biologic effects:
NK cells and T cells - IFN-y synthesis, increased cytolytic activity
- T cells - TH1 differentiation
IFN-y
Principal cell source:
Principal cellular targets and biologic effects:
IFN-y
Principal cell source: NK cells, T lymphocytes
Principal cellular targets and biologic effects: activation of macrophages, stimulation of some antibody response
Type I IFNs (IFN-a, IFN-b)
Principal cell source:
Principal cellular targets and biologic effects:
Type I IFNs (IFN-a, IFN-b)
Principal cell source: IFN-a - macrophages; IFN-b - fibroblasts
Principal cellular targets and biologic effects: increased class I MHC expression, NK cells activation
IL-10
Principal cell source:
Principal cellular targets and biologic effects:
IL-10
Principal cell source: macrophages, T cells (mainly TH2)
Principal cellular targets and biologic effects:
macrophages - inhibition of IL-12 production, reduced expression of costimulators and class II MHC molecules
IL-6
Principal cell source:
Principal cellular targets and biologic effects:
IL-6
Principal cell source: macrophages, macrophages, endothelial cells, T cells
Principal cellular targets and biologic effects:
liver - acute phase proteins
B cells - proliferation of antibody producing cells
IL-15
Principal cell source:
Principal cellular targets and biologic effects:
IL-15
Principal cell source: macrophages
Principal cellular targets and biologic effects: nk and T cells proliferation
IL-18
Principal cell source:
Principal cellular targets and biologic effects:
IL-18
Principal cell source: macrophages
Principal cellular targets and biologic effects:
NK and T cells: IFN-y synthesis
a substance that can provoke the production of an antibody
antigen
TYPES of ANTIGEN
- Autologous or autoAg - triggers auto-antibodies
- Homologous - antigen used in antibody production
- Heterologous - different antigen from that used in the immunization
- Heterophil/Heterogenetic - antigens that exist in unrelated plants or animals producing cross reaction
Bind to MHC molecules outside the peptide-binding cleft that cause great amount of T-cells to be nonspecifically activated leading to release of large amounts of cytokines.
Superantigens
**compared to normal antigens that bind inside the cleft and cause activation of less amount of T-cells
Major histocompatibility complex (MHC)
- In humans, located in the short arm (p) of chromosome 6
- bind peptide antigens and present them to T-cells (T-cell receptors only recognize antigens presented by the MHC molecules on another cell, the antigen presenting cell)
MHC class I
- composed of alpha 1, 2 and 3 subunit and beta 2 micro globulin subunit
- Peptide antigens associated with class I MHC molecules are recognized by CD8+ cytotoxic T lymphocytes
MHC class II
- alpha 1 and 2, and beta 1 and 2 subunit
- recognized by CD4+ helper T-cells
REMEMBER Among the many important genes in the human MHC, also known as HLA (or Human Leukocyte Antigens), are those that encode the class I, II, and III MHC proteins
clinical correlation
People with HLA B27 - 90% found associated with AN INCREASED RISK OF DEVELOPING Ankylosing Spondylitis which is a disease affecting the sacroiliac joint.
REMEMBER
Cell-mediated immunity
- Important in toxin-induced disorders, microbial infections and viral infections
- Each class of T-cells produces cytokines, becomes activated, and expands by clonal proliferation
T-cells can differentiate into effector cells:
- CD4+ Effector Cells
- CD8+ Effector Cells
CD4+ Effector Cells
- Th1 cells (stimulate phagocyte mediated defense against infections, especially with intracellular microbes)
- Th2 cells (stimulate IgE and eosinophil/masT-cell-mediated immune reactions; downregulates Th1 response)
- Th17 cells (chemokine responsible for recruitment of neutrophils and macrophages)
- Regulatory (Treg) cells/T-suppressor cells (suppress T-cell responses to prevent overactivity that may develop autoimmunity)
- TDH (T-delayed hypersensitivity)
CD8+ Effector Cells
- T Cytotoxic/killer cells (destruction of cells in tissue grafts, tumor cells, or cells infected by viruses)
REMEMBER Humoral Immunity (B-cell) - Helper (CD4+) T lymphocytes recognize the pathogen's antigens complexed with class II MHC molecules on the surface of an APC (eg, macrophage, B-cell) and produce cytokines that activate B-cells expressing antibodies that specifically match the antigen - The B-cells undergo clonal proliferation and differentiate into plasma cells, which then produce specific immunoglobulins (antibodies).
ANTIBODY
- Immunoglobulins produced by plasma cells
- Can be separated using electrophoresis
- Nomenclature depends on the heavy chain
Domains of Immunoglobulin:
- Variable region - responsible for specificity; the antigen binding site
- CH2 (Constant heavy chain 2) - binds complement, specifically C1q, and initiates complement pathway
- CH3 (Constant heavy chain 3) - responsible for cytotropic reactions involving macrophages and monocytes, mast cells, cytotoxic killer cells and B-cells
- CL (Constant light chain) - responsible for the light chain type; either kappa or lambda
Classification of Antibody
- Isotype – variants in normal persons (ex IgG1, IgG2, IgG3, IgG4)
- Allotype – genetically controlled alternate forms, not in all persons
- Idiotype – variable regions
ANTIBODY RESPONSE
Primary:
- an individual encounters an antigen for the first time
- antibody produced against that antigen will be detectable in serum within days or weeks
- serum antibody concentration continues to rise for several weeks and then declines
- first antibodies formed are IgM, followed by IgG, IgA or both (IgM levels then decline sooner than IgG levels)
Secondary:
- shorter lag phase, longer plateau, more gradual decline
- . second encounter with the same antigen or a closely related “cross-reacting” antigen months or years after the primary response
- produce qualitatively similar IgM; much more IgG is produced; persists longer than the primary response
- antibody produced tends to bind antigen more firmly, have higher affinity and dissociate less easily
IgG
Activate complement:
Other name:
Features:
IgG Activate complement: Yes, except IgG4 Other name: Serum Ig; Monomer Features: - Can cross the placenta excpt IgG2 - Major Ig in secondary immune response - Anamnestic response (never forgetting) - Longer half life than the rest
IgA
Activate complement:
Other name:
Features:
IgA
Activate complement: Alternative pathway only
Other name: Secretory Ig; Dimer
Features:
- Predominant Ig in secretion; with 2 types (serum IgA and secretory IgA - more active, found in mucous membrane)
- with J chain
- exist as a monomer in serum and dimer in secretion
IgM
Activate complement:
Other name:
Features:
IgM
Activate complement: yes, most efficient
Other name: pentameric Ig
Features:
- predominant Ig in primary immune response
- Has J chain
- first to be produced in life and last to disappear in senesence
IgD
Activate complement:
Other name:
Features:
IgD Activate complement: no Other name: - Features: - involved in B cell activation - susceptible to enzyme degradation - heat and acid labile
IgE
Activate complement:
Other name:
Features:
IgE Activate complement: no Other name: reagenic Ig Features: - Asso. w/ immediate hypersensitivity - Binds basophils and mast cells - Elevated during parasitic infections
In chediak-higashi, there is a defect in?
intracellular killing.
Coating of an antigen by a substance that facilitates uptake of a foreign particle is?
opsonization
To become active, a hapten must combine with?
carrier
