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Basics of Immunology (31351 )
The immune system has the capacity to distinguish between body cells ( ‘self’ ) and foreign materials ( ‘non-self’ ) It will react to the presence of foreign materials with an immune response that eliminates the intruding material from the body The immunological concept of self A. Recognizing self The self Structures are absent from invasive microbial cells and may also be absent from some abnormal cells of the body (e.g., some cancer cells) and from cells of other individuals of the same species (e.g., a transplanted graft). Self markers (MHC class I) are present on the surface of all nucleated body cells and identify the cell as part of the organism. B. Recognizing the absence of self The absence of self indicators can trigger an attack on any cells that lack these indicators. certain cells (e.g., natural killer cells) of the innate immune system bear receptors that recognize stress signals expressed by infected or cancerous cells. killer cells examine the stressed cells to check if they possess sufficient levels of a particular set of cell surface molecules called MHC I that should be present on every normal nucleated cell of the body. Expression of MHC I molecules may be lost altogether in some cells as a result of viral infection or of becoming cancerous.
C. Recognizing non-self
The immune system recognize non-self structures by using the pattern recognition receptors and the somatically generated receptors.
- Via pattern recognition receptors : a genetically stable set of receptors PRRs are designed to recognize and bind to only nonself structures that are abundant in the microbial world but not typically expressed in normal host cells. Some PRRs (e. g. , the toll-like receptors) are found on the membranes of various cell types, whereas other PRRs (e. g. ,some molecules of the complement system) are soluble and found in the cytoplasm of body fluids.
2 .Via somatically generated receptors: A subset of white blood cells, the T and B lymphocytes, are the only cells capable of producing somatically generated receptors of the adaptive immune system. Each T or B cell uses the rearrangement of DNA to develop a unique receptor.
The Major histo-compatiabilitycomplex (MHC ) (
- Human leukocyte antigens (HLA) are the molecules that are identified when an individual is ‘tissue-typed’.
- They are the products of a group of genes known as the major histocompatibility complex (MHC).
- The genes are divided into three classes. Class I includes the A, B and C region genes, Class II includes the D region genes and Class III includes those genes which produce some of the enzymes and control elements involved in antigen processing and presentation and genes coding for members of a group of serum proteins known as complement. 1. Class I MHC genes :- encode glycoproteins expressed on the surface of nearly all nucleated cells ; the majo
MHC molecules class I and II
Antigen presentation by MHC I & II MHC Class I MHC Class II
Structure MHC class I molecules consist of one membrane-spanning α chain (heavy chain) produced by MHC genes, and one β chain (light chain or β2- microglobulin) produced by the β2-
MHC class II molecules consist of two membrane-spanning chains, α and β, of similar size and both produced by MHC genes.
Nature of Antigen Presentation
MHC class I glycoproteins present endogenous antigens that originate from the cytoplasm.
MHC II proteins present exogenou antigens that originate extracellularly from foreign bodies such as bacteria. Responsive T Cells
Present antigen to cytotoxic T cell lymphocytes (CD8+ T Cells).
Present antigen to helper T cell lymphocytes; (CD4+ T cells). Sources of Protein Antigens
Cytosolic proteins (mostly synthesized in the cell, may enter cytosol from phagosomes)
Endosomal/lysosomal proteins (mostly internalized from extracellular environment) Function Presentation of foreign-intracellular antigens or altered self-antigens; targets cell for destruction
Presentation of foreign extracellula antigens; induces antibody production, and attracts immune cells to area of infection
Recognition of microbes by the innate immune system
What does innate immunity recognize?
- Molecular structures that are produced by microbial Pathogens and often shared by classes of microbes ( Pathogen associated molecular patterns PAMPs)
- Endogenous molecules that are produced by or released from damaged and dying cells ( Damage associated molecular patterns DAMPs ) Can be produced as a result of cell damage caused by :- - infection. Also produced in response to sterile injury to cells. - chemical toxins, burns, trauma or low blood supply. - generally not released by cells dying from apoptosis.
Pattern recognition receptors (PRRs)
- Receptors of the innate immune system recognize broad structural motifs (similarities in design) that are generally not present within the host but are instead found on microbes.
- These receptors, pattern recognition receptors (PRRs) , are present in soluble forms (e.g., complement proteins ) or on host cell surfaces.
- They recognize pathogen-associated molecular patterns (PAMPs), which include combinations of sugars, some proteins, lipids, and nucleic acids broadly associated with microbes.
- PRR binding to PAMPs triggers various forms of inflammation intended to destroy the pathogens. Pattern recognition receptors (PRR) are present on macrophages, PMNs, dendritic cells, and some epithelial cells. ✓ Cellular PRRs include Toll-like receptors, NOD-like receptors, mannose receptors, scavenger receptors, and CD14. ✓ Soluble PRRs (Secreted PRRs) include MBL (a collectin), ficolins, and galectins. The acute phase protein, mannose-binding lectin (MBL), attaches to mannose on glycoproteins and glycolipids of microbes and induces complement activation via the lectin pathway. These receptors sense the “danger” signals given by invading microbes, but also are able to recognize some self components and are therefore important in recognition and clearance of dead (apoptotic) and dying cells. The body recognize molecules unique to groups of microorganisms and are not associated with human cells. These unique microbial molecules are called pathogen-associated molecular patterns or PAMPs. Unique molecules displayed on stressed, injured, infected, or transformed human cells also be recognized as a part of innate immunity. These are referred to as danger-associated molecular patterns or DAMPs.
- Nucleotide-binding oligomerization domain-like receptors (NLR) - Cytoplasmic (intracellular) PRRs. **- C-type lectin receptors (CLR) - Membrane bound PRRs.
- RIG-1 like receptors (RLR)** - Cytoplasmic (intracellular) PRRs.
There are present at the cell surface to recognise extracellular pathogens such as bacteria or fungi, in the endosomes where they sense intracellular invaders such as viruses and finally in the cytoplasm.
Microcidal action of secreted molecules from the body surfaces
- Various cells, including epithelial cells, Neutrophils, and Macrophages,in the skin and mucous membranes and Several tissues that are in contact with the environment synthesize and secrete various microcidal molecules that act to inhibit or kill microbes that are attempting to colonize.
- These peptides form channels in the cell membranes of bacteria, which cause the influx of certain ions and eventually bacterial death. Other molecules with microcidal functions include cathelicidin , lysozyme, DNases and RNases, and others.
1. Skin : The skin is protected in part by several antimicrobial peptides secreted by various cell types found within the skin. Among these are a-defensins, 13-defensins, and cathelicidin. All are able to inhibit microbial growth by direct action on the microbes, perhaps by damaging the microbial membranes and causing lysis.
tears. As part of protecting the eyes, the secretions of lacrimal glands contain lysozyme.
