Immunology 2 Flashcards
Involves a third line of defense
Slower response but has a memory component
Involves Lymphocytes and Antibodies
Adaptive Immmunity
Different types of adaptive immunity
Naturally Acquired Active Immunity
Naturally Acquired Passive Immunity
Artificially Acquired Active Immunity
Artificially Acquired Passive Immunity
Type of adaptive immunity where antigens enter the body and produces Ab and specialized lymphocytes (Infections)
Naturally Acquired Active Immunity
Type of adaptive immunity where vaccination or immunization are administered
Artificially Acquired Active Immunity
Type of adaptive immunity where preformed Ab are given
Artificially Acquired Passive Immunity
Type of immunity carried out by antibodies circulating in the blood in response against a specific epitope and provide defense against extracellular microbes
Humoral immunity
In every 10 trillion B cells, there are
100M distinct Ab
Any molecule (either proteins or polysaccharides) that can bind specifically to generate antibodies
Antigen
Antigen that can elicit Ab production
Immunogens
Usually antigenic when combined with proteins and polysaccharides
Lipids and nucleic acids
Chemical basis of Ag resides in their macromolecular composition
Carbohydrates Glycoproteins Proteins Lipids Lipoproteins Nucleic acid Nucleoproteins
Most antigenic composition of antigens
Proteins
Least antigenic composition of antigens
Nucleic acids
Antigenic determinant and regions on Ag which an Ab recognize
Epitopes
Site on Ab that binds to the epitope
Paratopes
Unique set of antigenic determinants on the variable portion of an Ab
Idiotypes
Antigens that do not elicit elicit antibody production by themselves
Haptens
Chracteristics of haptens
Small molecules (with low MW: < 10,000) Act as Ag if bind to bigger molecules
Example of a hapten
Penicillin (hapten) when bound to host serum proteins, it can initiate an immune response
True or False.
Antigenicity is related to MOLECULAR WEIGHT.
True.
Very large molecules (10,000 Dalton to 600,000 Da) = highly antigenic
Low molecular weight molecules (< 5000 Da) - non-antigenic
“anti-antigens”
Class of proteins called immunoglobulins (Ig) found in blood serum, body fluids, tissues
Antibodies
Produced in response to a particular epitope on the surface of pathogen
Helps other cells or molecule inactivate or destroy the infectious agent or their products
Antibodies
Characteristics of antibodies
Highly specific
Soluble
Antibody structure
4 polypeptide chains (2 light chains and 2 heavy chains) Disulfide bond Variable region (antigen-binding site) Constant region Fab (Fragment antigen binding) Fc (Fragment crystallizable)
Antigen binding fragment
Recognizes antigen
Attaches to disease agent’s epitopes
Fab
Mediates binding of Ig to host tissues, thus mediating biologic activity of the Ig molecule → constant regions heavy chains: alpha (IgA), gamma (IgG), mu (IgM), delta (IgD), and epsilon (IgE)
Fc
Classes of Ab
IgG IgM IgA IgD IgE
Characteristics of IgG
80% of serum Ig; 20% of all plasma protein
Only Fc region recognized by phagocytes and NK cells
Characteristics of IgM
5-10% of Ig in normal human serum
Located in serum and B cell membrane
Predominant Ab involved in response to the ABO blood group Ag on the surface of RBCs
Aids in phagocytosis
With minor role in inhibiting microbial adhesion
Characteristics of IgA
Accounts for 10-15% of total Ig
Small amounts in blood serum
Usually secreted across mucosal surfaces (respiratory, GIT, gut)
Characteristics of IgD
Found in serum
< 0.2% of the total serum Ab
Less than 10% of fetal Ig
Found in blood, lymph, and surface of B cells
Act as Ag receptors on surfaces of B cells
No well defined function in serum
Characteristics of IgE
Very low concentration in serum (0.002%)
Monomer
Found mainly in body fluids, beneath the skin and mucosa
Fc has special affinity for receptors on plasma membrane of basophils in blood and mast cells in tissues (specialized cells that participate in allergic reactions)
Main class of Ab
IgG
Monomer-shaped Ab
IgG, IgD, IgE
Ab that can cross the placenta
IgG
Ab that can activate the complement
IgG
First Ig produced in an immune response, but short-lived
IgM
Shape of IgM in secretion
Pentamer: 5Y shaped units connected by Fc region to J chain
Shape of IgM in plasma
Monomer: Single Y shape IgM forms part of B cell plasma membrane
First Ig formed in fetus
IgM
Most abundant Ab in the body
Secretory Ab: main Ig in external body secretions (mucus, tears, saliva, breast milk - colostrum, urine)
IgA
Function of IgA
Prevent attachment of microbial pathogen to mucosal surface
IgA immunity is relatively shorter-lived
Shape of IgA in serum
Monomer
Shape of IgA in mucous membrane
Dimer
Concentrated along with IgM on plasma membrane of human B lymphocyte
IgD
Called reagin
IgE
Functions of IgE
Antigen → cross links with IgE + basophil/mast cell → release of Histamine or chemical mediators → allergic response
Attract complement and phagocytic cells
Key role in combating helminths
With damaging role in development of allergies such as drugs, pollens, and certain food
These are B cells in the resting stage
Produce IgM and IgD on their surface
If binds to antigen: activation is initiated
Naive B cells
When infection is over plasma cells die and memory cells continue to circulate
Immunological memory
Ability of the immune system to quickly and recognize an Ag that the body has previously encountered and initiate a corresponding immune response
Immunological memory
Primary or Secondary immune response.
First time to encounter Ag
Primary
Primary or Secondary immune response.
Anamnestic response
Secondary
Primary or Secondary immune response.
Initiated by virgin B cells
Primary
Primary or Secondary immune response.
Initiated by memory B cells
Secondary
Primary or Secondary immune response.
Takes 1-2 weeks to develop fully
Primary
Primary or Secondary immune response.
Produce Ab more rapidly in a few days because it recognizes the microbe already
Secondary
Primary or Secondary immune response.
Generate more Ab due to memory cells`
Secondary
Primary or Secondary immune response.
IgM is the first Ig produced
Primary
Functions of antibodies in host defense
Neutralization Opsonization Agglutination Inflammation Antibody-dependent cell cytotoxicity (ADCC) Complement system activation
Inactivate toxins or vital compounds on surface of pathogens by binding on them
Neutralization
Mechanisms of neutralization
- Some Ab (antitoxins) → binds to toxins (Ag) → Inactivates toxins
- Ab → bind to Ag (responsible for attachment to host cell) → Virus can’t attach to host cell → Infection prevented
Ab bind to Ag on surface of pathogens facilitating destruction by phagocytes
Opsonization
Ab cause Ag to agglutinate
Binds microbes together and then eliminate it through phagocytosis
Agglutination
When cells/microorganisms are destroyed this attracts phagocytes to the area therefore increasing neutrophils leading to inflammation
Inflammation
Mechanism of inflammation
Cells/Microbes are destroyed → Attracts phagocytes → Increase Neutrophils → Inflammation
Leads to cytolysis, inflammation, and phagocytosis
Complement system activation
Major biologic effects of complement system
- Opsonization
- Chemotaxis
- Anaphylatoxins
- Cytolysis
Ab-Ag complexes easily phagocytosed in the presence of C3b (many C3b Rc on phagocytes)
C3b enhances phagocytosis
Opsonization
Movement of leukocytes to site of infection
Neutrophil and monocyte movement stimulated by C5a
Chemotaxis
C3a and C5a (potent anaphylatoxins) binds to mast cells causing degranulation of mast cells
Releases histamine causing vasodilation, increased vascular permeability and muscle contraction.
Anaphylatoxins
Lysis of cells (RBC, bacteria, tumor cells) due to the development of membrane attack complex (C5b6789)
Cytolysis
Type of immunity that provide defense against intracellular microbes and can control intracellular infections that Ab cannot reach
Cell-medicated immunity
Immunity that is mediated by T lymphocytes
Cell-mediated immunity
Recognize antigens produced by intracellular microbes
Usually occurs when the antigens are embedded in the cell membrane or inside the host cells
Therefore, inaccessible to antibodies
Cell-mediated immunity
True or False.
T cells with membrane receptors for antigens provide defense against intracellular microbes.
True
Cell-mediated immunity is effective in:
Clearing the body of virus-infected cells
Defending the body against fungi, helminths, cancer, and foreign tissue (transplanted organs)
Phenomenon when T cells in the resting state bind the antigen fragment on MHC or on APC to stimulate T cell to divide & secrete lymphokines. This sets the immune response into motion.
T-cell activation
True or False.
T-cell activation stimulates itself by producing IL-2 which combines with Ag causing it to multiply.
True
recognition molecule for T cells
TCR complex
2 classes of TCR
a-B (more common)
y-D
True or False.
Similar to Fab regions of Ig, it has variable and constant regions. Variable region binds the peptide-MHC complex.
True
True or False.
T cell signal is also enhanced by coreceptors, CD4 and CD8 molecules CD4 binds to MCH II and CD8 binds to MHC I.
True.
Mechanism of cell-mediated immunity
- A macrophage inserts an antigen or a peptide fragment on the MHC of the macrophage.
- The T helper cell recognizes the peptide on the MHC of the macrophage.
- Activation of the T helper cell and production of interleukins
- Interleukins initiate cell division into memory T cells, T helper 1 cell (TH1) and T helper 2 cell (TH2).
- T helper 1 cell recognizes peptide on the MHC of an infected macrophage and activate the infected macrophage to destroy the bacterial infections.
- T helper 2 cell attaches to the B cell to produce a humoral response.
Mechanism of cell-mediated immunity in virally infected cells
The fragmented viral proteins bind to the class I MHC proteins.
They are transported to the surface of the cell so that the T cell can recognize them.
If they are recognized, the T cell can secrete perforins to destroy and lyse the infected cells.
Large cluster of genes associated with Chromosome 6
Give rise to MHC protein molecules class I, II, III
Set genes that code for human cell receptors
Responsible for T-cell antigen recognition
Human Leukocyte Antigen (HLA) Complex
Play a vital role in recognition of self and rejection of foreign tissue
HLA complex
True or False.
MHC proteins have broad specificity to peptide antigens.
True
True or False.
MHC polymorphism allow for binding of many specific and different peptides. Different alleles can bind and present different peptide antigens.
True
Membrane proteins on APCs that display peptide antigens for recognition by T lymphocytes
Major Histocompatibility Complex (MHC)
Act as “signpost” that alert immune system if foreign material is inside the cell
MHC
Presentation of peptide on cell surface allows for pathogen surveillance and development of immune response
MHC
True or False.
In polygenic and polymorphic MHCs, MHC genes codominantly expressed.
True.
Classes of MHC
Class I MHC genes
Class II MHC genes
Class III MHC genes
Genes that encode Class 1 MHC genes
HLA-A, B and C
Characteristics of Class I MHC genes
Made up of transmembrane glycoprotein and β2-microglobulin
Expressed on nearly all nucleated cells
Function of Class I MHC gene
Code for markers that display unique characteristics of self
Each human inherits a particular combination of Class I MHC (HLA)
Acquire peptide from cytosolic proteins
Present peptides to cytotoxic T cells (CD8 T cells)
True or False. MHC class I locus contains genes that encode proteins required in antigen processing.
True
Genes that encode Class II MHC genes
HLA-D region
APCs where Class II MHC genes are found
Macrophages
B cells
Dendritic cells
*restricted distribution
Function of Class II MHC genes
Involved in presenting antigens to T cells during cooperative immune reaction
Mechanism of Class II MHC genes
- APCs take up pathogens & process within phagosomes
- Acquire peptides from intracellular vesicles
- Class II MHC on APCs present these fragments to helper T cells (CD4 T cells) to stimulate immune reaction
Requires IFN-Y to be expressed in other cells.
Class II MHC genes
This locus controls immune responsiveness and different allelic forms of these genes confer differences in the ability of an individual to mount an immune response
Class II MHC genes
Encode proteins involved with the complement system
Class III MHC genes
Mechanism of MHC
Macrophage → engulfment of microbe → fragmentation → → short peptides bound to MHC → goes to surface of the APC → → present antigen to helper t cell → binding these two would cause the macrophage to release IL-1 which acts on helper t cells → helper t cells release IL-2 which acts on itself and produces clones of helper t cells → participate in cell-mediated and humoral immunity → have the ability to attack the infected cells and secrete antibodies by the B cells
True or False.
T cell cannot recognize the antigen if it is not bound to the MHC. T cells needs the MHC to present the antigen.
True
Mechanism of MHC in viruses
Viral infected cell → binds with MHC proteins → brought to surface → binds with the T cells (for some time) → until it lyses the viral infected cell
Occurs when T cells recognize Ag which is processed by APCs (antigen presenting cells) - macrophages & dendritic cells
Antigen recognition
Hallmark of adaptive immune response
Antigen processing and presentation
Major functions of Receptors
- To perceive and attach to antigens
- To promote recognition of self molecules
- To receive and transmit chemical messages among other cells of the system
- To aid in cellular development
Some bacterial and viral antigens cause T cell activation through a special pathway, they are called
Superantigens
Mechanism of superantigens
Do not require processing and can bind readily to MHC outside the binding cleft. As a result they can elicit release of large amounts of cytokines particularly IFN-Y which in turn activates macrophages to express IL-1,IL-6 and TNF-a causing “cytokine storm” and leading to shock and organ failure.
Mechanism of Antigen recognition
Antigen ➡️ bound by APC ➡️ denatured/partial proteolysis within the endocytic vesicles of APC ➡️ fragments of antigen fuse with exocytic vesicles of APC containing MHC II ➡️ MHC II bound antigen is transported in the cell membrane for presentation